MAML2 Rearrangement in Primary Pulmonary Mucoepidermoid Carcinoma and the Correlation with FLT1 Expression

Introduction

Primary pulmonary mucoepidermoid carcinoma (PMEC) is an uncommon neoplasm with remarkable resemblance to mucoepidermoid carcinoma of the salivary glands. The latter has been shown to harbor t(11,19) resulting in MECT1-MAML2 fusion, which may be of diagnostic and prognostic values. However, the importance of such feature in PMEC has not been well studied.

Methods

We detected MAML2 rearrangement using fluorescence in situ hybridization (FISH) in tissue samples from 42 cases of PMEC and 40 of adenosquamous carcinoma (ASC), and the expression of potential downstream targets of MECT1-MAML2, including HES1, FLT1 and NR4A2 with immunohistochemistry (IHC). The findings were then examined regarding the clinicopathological parameters and patient outcomes.

Results

FISH analysis revealed MAML2 rearrangement in 50% of the PMEC cases, and such property was prominent in considerable younger patients (33 versus 60 years; p = 0.001) and restricted to cases of low and intermediate grades. IHC analysis showed that FLT1 and HES1 were expressed at lower level in MAML2 rearranged group than MAML2 non-rearranged group (p<0.001 and p = 0.023, respectively). Survival analysis showed significant correlation between MAML2 rearrangement and overall survival (p = 0.023) or disease-free survival (p = 0.027) as well as correlation between FLT1 and overall survival (p = 0.009).

Conclusions

MAML2 rearrangement appears frequent in PMEC and specific with this tumor. Both the presence of MAML2 rearrangement and absence of FLT1 tend to confer a favorable clinical outcome. These findings suggest that molecular detection of MAML2 rearrangement combined with FLT1 may be of important clinical value for PMEC.     

Pulmonary Sarcomatoid Carcinoma with ALK Rearrangement: Frequency,Clinical-Pathologic Characteristics,and Response to ALK Inhibitor

PURPOSE: The incidence of anaplastic lymphoma kinase (ALK) rearrangement in pulmonary sarcomatoid carcinoma (PSC) is controversial. In this study, we aimed to reveal the reliable frequency and the clinical-pathologic characteristics of pulmonary sarcomatoid carcinoma (PSC) with ALK rearrangement in Chinese population, and to provide insight into the translatability of anti-ALK treatment in this treatment-refractory disease. METHODS: Immunohistochemistry (IHC) using a Ventana anti-ALK (D5F3) rabbit monoclonal antibody was performed in 141 PSC specimens collected from multiple medical centers. IHC-positive cases were then confirmed using ALK fluorescent in situ hybridization (FISH). The incidence rates and clinical-pathologic characteristics of ALK-rearranged PSC were then analyzed. Response to ALK inhibitor crizotinib in a patient with ALK-rearranged PSC was evaluated according to the response evaluation criteria for solid tumors (RECIST) version 1.1. RESULTS: Five of 141 (3.5%) of PSCs showed ALK rearrangement-positive by IHC and then were confirmed by FISH. Two were carcinosarcomas and the other three were pulmonary pleomorphic carcinoma (PPC). Strong positive ALK rearrangement was observed in both the epithelioid and sarcomatoid components. The median age of ALK-positive patients was younger than that of ALK-negative patients. PSCs in never-smokers were more likely to harbor ALK rearrangement than those in former or current smokers (P < .05). A 40-year-old woman diagnosed with ALK-rearranged PPC experienced a partial response (?32%) to the ALK inhibitor crizotinib. CONCLUSIONS: The incidence rates of ALK rearrangement in PSC in the Chinese population are similar to those of other subtypes of NSCLC. PSCs in younger never-smokers are more often to harbor ALK rearrangement. ALK inhibitors may serve as an effective treatment for ALK-rearranged PSC.     

Anaplastic Lymphoma Kinase Gene Copy Number Gain in Inflammatory Breast Cancer (IBC): Prevalence,Clinicopathologic Features and Prognostic Implication

Background

Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer, and its molecular pathogenesis still remains to be elucidated. This study aimed to evaluate the prevalence and implication of anaplastic lymphoma kinase (ALK) copy number change in IBC patients.

Methods

We retrospectively collected formalin-fixed, paraffin-embedded tumor tissues and medical records of IBC patients from several institutes in Korea. ALK gene copy number change and rearrangement were assessed by fluorescence in situ hybridization (FISH) assay, and ALK expression status was evaluated by immunohistochemical (IHC) staining.

Results

Thirty-six IBC patients including those with HER2 (+) breast cancer (16/36, 44.4%) and triple-negative breast cancer (13/36, 36.1%) were enrolled in this study. ALK copy number gain (CNG) was observed in 47.2% (17/36) of patients, including one patient who harbored ALK gene amplification. ALK CNG (+) patients showed significantly worse overall survival compared to ALK CNG (-) patients in univariate analysis (24.9 months vs. 38.1 months, p = 0.033). Recurrence free survival (RFS) after curative mastectomy was also significantly shorter in ALK CNG (+) patients than in ALK CNG (-) patients (n = 22, 12.7 months vs. 43.3 months, p = 0.016). Multivariate Cox regression analysis with adjustment for HER2 and ER statuses showed significantly poorer RFS for ALK CNG (+) patients (HR 5.63, 95% CI 1.11–28.44, p = 0.037).

Conclusion

This study shows a significant presence of ALK CNG in IBC patients, and ALK CNG was associated with significantly poorer RFS.     

Anaplastic Lymphoma Kinase Rearrangement in Digestive Tract Cancer: Implication for Targeted Therapy in Chinese Population

Background

Anaplastic lymphoma kinase (ALK) rearrangements define a subgroup of lung cancer which is eligible to targeted kinase inhibition. The aim of this study is to observe the incidence rate of ALK fusion in a large cohort of Chinese digestive tract cancer patients.

Patients and Methods

Tissue microarray (TMA) was constructed from 808 digestive tract cancer cases, including 169 esophageal squamous cell carcinoma, 182 gastric cancer and 457 colorectal cancer (CRC) cases. We tested all cases for ALK expression via a fully automated immunohistochemistry (IHC) assay. The IHC-positive cases were subjected to fluorescence in situ hybridization (FISH), real-time polymerase chain reaction (qRT-PCR), target gene enrichment and sequencing for confirmation of ALK gene rearrangement and discovery of novel fusion partner.

Results

Among the tested cases, 2 (0.44%) CRC cases showed positive both by IHC and FISH. By qRT-PCR, EML4–ALK fusion was found in one IHC-positive CRC case. In another IHC-positive CRC case, target gene enrichment and sequencing revealed ALK was fused to a novel partner, spectrin beta non-erythrocytic 1 (SPTBN1). One gastric cancer case showed partially positive IHC result, but no fusion was found by FISH and gene sequencing.

Conclusions

The incidence rate of ALK gene fusion in Chinese CRC patients was 0.44%,but not detectable in gastric and esophageal cancers. The novel SPTBN1 -ALK fusion, together with other ALK fusion genes, may become a potential target for anti-ALK therapy.     

Clinicopathological Characteristics and Survival Outcomes of Primary Signet Ring Cell Carcinoma in the Stomach: Retrospective Analysis of Single Center Database

Purpose

To investigate the clinicopathological features and prognosis of signet ring cell carcinoma of the stomach (SRC).

Methods

A total of 1464 gastric cancer patients who underwent curative gastrectomy from 2000 to 2008 at a single center were evaluated. Signet ring cell carcinoma (SRC) was defined as the presence of at least 50% signet ring cells in the pathologic specimen. The clinicopathological parameters and prognosis of SRC were analyzed by comparing with non-signet ring cell carcinoma (NSRC).

Results

Of 1464 patients, 138 patients (9.4%) were classified as SRC. There were significant differences in gender, age, tumor location, TNM stage, p21 expression, and p53 expression between SRC and NSRC. The 5-year survival rates of SRC and NSRC were 36.2% and 49.5%, respectively. The prognosis of SRC was poorer than that of NSRC (P <0.001). Multivariate analysis showed that SRC histology was an independent factor for poor prognosis (P <0.001).

Conclusion

Patients with SRC tend to present with a more advanced stage and poorer prognosis than patients with other types of gastric carcinoma.     

Cerebral Lipiodol Embolism in Hepatocellular Carcinoma Patients Treated with Transarterial Embolization/Chemoembolization

Background and Purpose

Liver cancer is the third leading cause of cancer mortality worldwide. The aim of this study was to investigate the frequency and characteristics of cerebral lipiodol embolism (CLE) in patients with hepatocellular carcinoma (HCC) receiving transarterial embolization/chemoembolization (TAE/TACE).

Methods

We reviewed all HCC patients who received TAE/TACE during the period of 2007 and 2013 at a university medical center. The frequency of CLE per procedure and the clinical manifestations of CLE, including the review of previous reported cases (n = 24), were analyzed.

Results

During the study period, a total of 7855 TAE/TACE procedures were conducted on 3277 patients. There were 8 patients (mean age 59±11 years; 5 males and 3 females) who developed CLE. The frequency of TAE/TACE-related CLE was 1.02 (95% CI, 0.44–2.01) per 1000 procedures. Acute disturbance of consciousness and respiratory distress after TAE/TACE were the most common presentations of CLE. All patients had disseminated infarcts involving both the anterior and posterior cerebral circulations. For 3 patients with shunting between the tumor feeding artery and the pulmonary vein, a specific imaging pattern of coexisting scattered hyperdense spots was found. Furthermore, combined with our 8 cases, the total of 32 cases indicated that old age and female sex were the two risk factors for poor outcome after CLE.

Conclusions

CLE is a rare but potentially serious complication in HCC patients receiving TAE/TACE. The clinical characteristics of CLE summarized in our study would help facilitate the ability of clinicians to provide timely diagnosis and management.     

The Molecular Detection and Clinical Significance of ALK Rearrangement in Selected Advanced Non-Small Cell Lung Cancer: ALK Expression Provides Insights into ALK Targeted Therapy

Background

This study aimed to elucidate clinical significance of anaplastic lymphoma kinase (ALK) rearrangement in selected advanced non-small cell lung cancer (NSCLC), to compare the application of different ALK detection methods, and especially evaluate a possible association between ALK expression and clinical outcomes in crizotinib-treated patients.

Methods

ALK status was assessed by fluorescent in situ hybridization (FISH), immunohistochemistry (IHC) and quantitative RT-PCR (qRT-PCR) in 173 selected advanced NSCLC patients. Clinicopathologic data, genotype status and survival outcomes were analyzed. Moreover, the association of ALK expression with clinical outcomes was evaluated in ALK FISH-positive crizotinib-treated patients including two patients with concurrent epidermal growth factor receptor (EGFR) mutation.

Results

The positivity detection rate of ALK rearrangement by FISH, IHC and qRT-PCR was 35.5% (59/166), 35.7% (61/171), and 27.9% (34/122), respectively. ALK rearrangement was observed predominantly in young patients, never or light smokers, and adenocarcinomas, especially with signet ring cell features and poor differentiation. Median progression-free survival (PFS) of crizotinib-treated patients was 7.6 months. The overall survival (OS) of these patients was longer compared with that of crizotinib-naive or wild-type cohorts, but there was no significant difference in OS compared with patients with EGFR mutation. ALK expression did not associate with PFS; but, when ALK expression was analyzed as a dichotomous variable, moderate and strong ALK expression had a decreased risk of death (P = 0.026). The two patients with concomitant EGFR and ALK alterations showed difference in ALK expression, response to EGFR and ALK inhibitors, and overall survival.

Conclusions

Selective enrichment according to clinicopathologic features in NSCLC patients could highly improve the positivity detection rate of ALK rearrangement for ALK-targeted therapy. IHC could provide more clues for clinical trial design and therapeutic strategies for ALK-positive NSCLC patients including patients with double genetic aberration of ALK and EGFR.     

A Genome Wide Study of Copy Number Variation Associated with Nasopharyngeal Carcinoma in Malaysian Chinese Identifies CNVs at 11q14.3 and 6p21.3 as Candidate Loci

Background

Nasopharyngeal carcinoma (NPC) is a neoplasm of the epithelial lining of the nasopharynx. Despite various reports linking genomic variants to NPC predisposition, very few reports were done on copy number variations (CNV). CNV is an inherent structural variation that has been found to be involved in cancer predisposition.

Methods

A discovery cohort of Malaysian Chinese descent (NPC patients, n = 140; Healthy controls, n = 256) were genotyped using Illumina^® HumanOmniExpress BeadChip. PennCNV and cnvPartition calling algorithms were applied for CNV calling. Taqman CNV assays and digital PCR were used to validate CNV calls and replicate candidate copy number variant region (CNVR) associations in a follow-up Malaysian Chinese (NPC cases, n = 465; and Healthy controls, n = 677) and Malay cohort (NPC cases, n = 114; Healthy controls, n = 124).

Results

Six putative CNVRs overlapping GRM5, MICA/HCP5/HCG26, LILRB3/LILRA6, DPY19L2, RNase3/RNase2 and GOLPH3 genes were jointly identified by PennCNV and cnvPartition. CNVs overlapping GRM5 and MICA/HCP5/HCG26 were subjected to further validation by Taqman CNV assays and digital PCR. Combined analysis in Malaysian Chinese cohort revealed a strong association at CNVR on chromosome 11q14.3 (P_combined = 1.54x10^-5; odds ratio (OR) = 7.27; 95% CI = 2.96–17.88) overlapping GRM5 and a suggestive association at CNVR on chromosome 6p21.3 (P_combined = 1.29x10^-3; OR = 4.21; 95% CI = 1.75–10.11) overlapping MICA/HCP5/HCG26 genes.

Conclusion

Our results demonstrated the association of CNVs towards NPC susceptibility, implicating a possible role of CNVs in NPC development.     

The Immediate Effect of Sildenafil on Right Ventricular Function in Patients with Heart Failure Measured by Cardiac Magnetic Resonance: A Randomized Control Trial

Background

Studies have demonstrated that phosphodiesterase 5 (PDE5) inhibition is associated with right ventricle (RV) functional improvement in patients with primary pulmonary hypertension. This study aims to demonstrate the immediate impact of Sildenafil, a PDE5 inhibitor, on RV function, measured by cardiovascular magnetic resonance (CMR), in patients with heart failure (HF).

Methods

We conducted a randomized double-blind controlled trial. Inclusion criteria: diagnosis of HF functional class I-III; left ventricle ejection fraction < 35%. Patients underwent CMR evaluation and were then equally randomly assigned to either 50 mg of Sildenafil or Placebo groups. One hour following drug administration, they were submitted to a second scan examination.

Results

26 patients were recruited from a tertiary reference center in Brazil and 13 were allocated to each study group. The median age was 61.5 years (50–66.5 years). Except for the increase in RV fractional area change following the administration of sildenafil (Sildenafil [before vs. after]: 34.3 [25.2–43.6]% vs. 42.9 [28.5–46.7]%, p = 0.04; Placebo [before vs. after]: 28.1 [9.2–34.8]% vs. 29.2 [22.5–38.8]%, p = 0.86), there was no statistically significant change in parameters. There was no improvement in left ventricular parameters or in the fractional area change of the pulmonary artery.

Conclusion

This study demonstrated that a single dose of Sildenafil did not significantly improve RV function as measured by the CMR.

Trial Registration

ClinicalTrials.gov NCT01936350     

Long-Term Cochlear Implant Outcomes in Children with GJB2 and SLC26A4 Mutations

Objectives

To investigate speech and language outcomes in children with cochlear implants (CIs) who had mutations in common deafness genes and to compare their performances with those without mutations.

Study Design

Prospective study.

Methods

Patients who received CIs before 18 years of age and had used CIs for more than 3 years were enrolled in this study. All patients underwent mutation screening of three common deafness genes: GJB2, SLC26A4 and the mitochondrial 12S rRNA gene. The outcomes with CIs were assessed at post-implant years 3 and 5 using the Categories of Auditory Performance (CAP) scale, Speech Intelligibility Rating (SIR) scale, speech perception tests and language skill tests.

Results

Forty-eight patients were found to have confirmative mutations in GJB2 or SLC26A4, and 123 without detected mutations were ascertained for comparison. Among children who received CIs before 3.5 years of age, patients with GJB2 or SLC26A4 mutations showed significantly higher CAP/SIR scores than those without mutations at post-implant year 3 (p = 0.001 for CAP; p = 0.004 for SIR) and year 5 (p = 0.035 for CAP; p = 0.038 for SIR). By contrast, among children who received CIs after age 3.5, no significant differences were noted in post-implant outcomes between patients with and without mutations (all p > 0.05).

Conclusion

GJB2 and SLC26A4 mutations are associated with good post-implant outcomes. However, their effects on CI outcomes may be modulated by the age at implantation: the association between mutations and CI outcomes is observed in young recipients who received CIs before age 3.5 years but not in older recipients.     

Accurate Identification of ALK Positive Lung Carcinoma Patients: Novel FDA-Cleared Automated Fluorescence In Situ Hybridization Scanning System and Ultrasensitive Immunohistochemistry

Background

Based on the excellent results of the clinical trials with ALK-inhibitors, the importance of accurately identifying ALK positive lung cancer has never been greater. However, there are increasing number of recent publications addressing discordances between FISH and IHC. The controversy is further fuelled by the different regulatory approvals. This situation prompted us to investigate two ALK IHC antibodies (using a novel ultrasensitive detection-amplification kit) and an automated ALK FISH scanning system (FDA-cleared) in a series of non-small cell lung cancer tumor samples.

Methods

Forty-seven ALK FISH-positive and 56 ALK FISH-negative NSCLC samples were studied. All specimens were screened for ALK expression by two IHC antibodies (clone 5A4 from Novocastra and clone D5F3 from Ventana) and for ALK rearrangement by FISH (Vysis ALK FISH break-apart kit), which was automatically captured and scored by using Bioview''s automated scanning system.

Results

All positive cases with the IHC antibodies were FISH-positive. There was only one IHC-negative case with both antibodies which showed a FISH-positive result. The overall sensitivity and specificity of the IHC in comparison with FISH were 98% and 100%, respectively.

Conclusions

The specificity of these ultrasensitive IHC assays may obviate the need for FISH confirmation in positive IHC cases. However, the likelihood of false negative IHC results strengthens the case for FISH testing, at least in some situations.     

Cough Aerosol Cultures of Mycobacterium tuberculosis: Insights on TST / IGRA Discordance and Transmission Dynamics

Rationale

The diagnosis of latent tuberculosis (TB) infection (LTBI) is complicated by the absence of a gold standard. Discordance between tuberculin skin tests (TST) and interferon gamma release assays (IGRA) occurs in 10–20% of individuals, but the underlying mechanisms are poorly understood.

Methods

We analyzed data from a prospective household contact study that included cough aerosol culture results from index cases, environmental and contact factors. We assessed contacts for LTBI using TST and IGRA at baseline and six weeks. We examined TST/IGRA discordance in qualitative and quantitative analyses, and used multivariable logistic regression analysis with generalized estimating equations to analyze predictors of discordance.

Measurements and Results

We included 96 TB patients and 384 contacts. Discordance decreased from 15% at baseline to 8% by six weeks. In adjusted analyses, discordance was related to less crowding (p = 0.004), non-cavitary disease (OR 1.41, 95% CI: 1.02–1.96; p = 0.03), and marginally with BCG vaccination in contacts (OR 1.40, 95% CI: 0.99–1.98, p = 0.06).

Conclusions

We observed significant individual variability and temporal dynamism in TST and IGRA results in household contacts of pulmonary TB cases. Discordance was associated with a less intense infectious exposure, and marginally associated with a BCG-mediated delay in IGRA conversion. Cough aerosols provide an additional dimension to the assessment of infectiousness and risk of infection in contacts.     

Reproducibility of Circulating MicroRNAs in Stored Plasma Samples

Background

Most studies of microRNA (miRNA) and disease have examined tissue-specific expression in limited numbers of samples. The presence of circulating miRNAs in plasma samples provides the opportunity to examine prospective associations between miRNA expression and disease in initially healthy individuals. However, little data exist on the reproducibility of miRNAs in stored plasma.

Methods

We used Real-Time PCR to measure 61 pre-selected microRNA candidates in stored plasma. Coefficients of variation (CVs) were used to assess inter-assay reliability (n = 15) and within-person stability over one year (n = 80). Intraclass correlation coefficients (ICCs) and polychoric correlation coefficients were used to assess within-person stability and delayed processing reproducibility (whole blood stored at 4°C for 0, 24 and 48 hours; n = 12 samples).

Results

Of 61 selected miRNAs, 23 were detected in at least 50% of samples and had average CVs below 20% for inter-assay reproducibility and 31 for delayed processing reproducibility. Ten miRNAs were detected in at least 50% of samples, had average CVs below 20% and had ICCs above 0.4 for within-person stability over 1–2 years, six of which satisfied criteria for both interassay reproducibility and short-term within-person stability (miR-17-5p, -191-5p, -26a-5p, -27b-3p, -320a, and -375) and two all three types of reproducibility (miR-27b-3p and -26a-5p). However, many miRNAs with acceptable average CVs had high maximum CVs, most had low expression levels, and several had low ICCs with delayed processing.

Conclusions

About a tenth of miRNAs plausibly related to chronic disease were reliably detected in stored samples of healthy adults.     

Prognostic Impact of Tricuspid Regurgitation in Patients Undergoing Aortic Valve Surgery for Aortic Stenosis

Background

The prognostic significance of tricuspid regurgitation (TR) and right ventricular (RV) function in patients undergoing aortic valve replacement (AVR) for severe aortic stenosis (AS) is unknown. The aim of the present study was to evaluate the impact of TR and RV systolic dysfunction on early and late mortality in this setting.

Methods

This was a prospective single-center observational study. 465 consecutive patients who were referred to AVR for severe AS were investigated. Significant TR was defined as TR≥moderate by transthoracic echocardiography.

Results

At baseline, significant TR was present in 26 (5.6%) patients. Patients with TR presented with a higher EuroSCORE I (p = 0.001), a higher incidence of previous cardiac surgery (p<0.001), pulmonary hypertension (p = 0.003), more dilated RVs (p = 0.001), and more frequent RV dysfunction (p = 0.001). Patients were followed for an average of 5.2 (±2.8 SD) years. By multivariable Cox regression analysis TR (p = 0.014), RV dysfunction (p = 0.046), age (p = 0.001) and concomitant coronary artery bypass graft surgery (CABG, p = 0.003) were independently associated with overall mortality. By Kaplan-Meier analysis, survival rates were significantly worse in patients with significant than with non-significant TR (log rank p = 0.001).

Conclusions

TR, RV dysfunction, age, and concomitant CABG are associated with outcome in patients undergoing AVR for severe AS. This finding underlines the importance of a thorough echocardiographic evaluation with particular consideration of the right heart in these patients.     

Reversed Halo Sign: Presents in Different Pulmonary Diseases

Objective

To observe the incidence of reversed halo sign in different pulmonary diseases and the pathological correspondence of reversed halo sign.

Methods

Retrospectively studied the high resolution computer tomography scans of all the patients who were admitted in our department with abnormal pulmonary imaging, from 1st of January 2011 to 31st of December 2013, and all the cases with reversed halo sign on the high resolution computer tomography were collected. Clinical data such as pathological findings and confirmed diagnosis of the patients with reversed halo sign on the high resolution computer tomography scan were collected and summarized.

Results

Of 1546 abnormal High resolution computer tomography scans 108 had a reverse halo sign present, including 108 cases were observed with reversed halo sign in the high resolution computer tomography, including 40 cases of pulmonary tuberculosis, 43 cases of cryptogenic organizing pneumonia, 16 cases of lung cancer, 7 cases of sarcoidosis, and 1 case of pulmonary cryptococcosis, 1 case of granulomatosis with polyangiitis. Reversed halo sign had a higher incidence in granulomatous diseases (16.28%) compared with non-granulomatous diseases (9.97%).

Conclusions

Reversed halo sign is relatively non specific; it can be observed in different lung diseases, and different phases of diseases; reversed halo sign is more commonly found in granulomatous diseases compared with non-granulomatous diseases, and is most commonly observed in pulmonary tuberculosis among the granulomatous diseases, and in cryptogenic organizing pneumonia among the non-granulomatous diseases.     

Clinical Features and Gene Mutations of Lung Cancer Patients 30 Years of Age or Younger

Purpose

Few studies examining the clinical features and gene mutations in lung cancer patients 30 years of age or younger have been published. A trend towards increasing morbidity has been noted in young patients; thus, an urgent need exists to explore this subgroup of patients.

Methods

Patients aged ≤30 years with pathologically diagnosed lung cancer were retrospectively evaluated. We reviewed the clinical features, gene mutations and prognosis of each patient.

Results

Forty-one patients were included in this study. The mean age was 26.4±3.5 years. Cough, tightness/dyspnea and chest pain were common symptoms, and 58.5% of patients presented with advanced stages of lung cancer. Adenocarcinoma was the predominant histologic type noted in these young patients. Masses and nodules were the dominant imaging features observed upon lung computed tomography (CT). Thoracic lymphadenopathy occurred very frequently in these patients. Five of 6 patients with echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) gene fusions presented solid masses with no ground-glass opacity (GGO) and thoracic multifocal lymphadenopathy. Six of 22 (27.2%) cases contained EML4-ALK gene fusions. In addition, 5 of 22 (22.7%) patients harbored epidermal growth factor receptor (EGFR) mutations, and 2 of 17 patients exhibited KRAS and ROS1 gene mutations. The median survival times were 44.2 months for patients with early stage disease and 8 months for patients with advanced NSCLC disease. The one-year and 5-year survival rates were 56.6% and 38.6%, respectively.

Conclusions

Increased gene mutation frequencies are noted in these very young lung cancer patients. This finding indicates that the detection of gene mutations in these patients is important and will help to determine the appropriate targeted therapy.     

The Relationship between TTF-1 Expression and EGFR Mutations in Lung Adenocarcinomas

Objective

To explore the relationship between TTF-1 and EGFR mutations in lung adenocarcinoma tissues to guide clinical treatment timely and effectively.

Materials and Methods

we collected 664 tissue samples from patients with histologically confirmed lung adenocarcinoma from May 2010 to April 2013. All tumor tissues were collected prior to administering therapy. TTF-1 was detected byimmunohistochemistry and EGFR mutations by DNA direct sequencing. Finally, the correlation between TTF-1 expression and the presence of EGFR mutations was analyzed using χ² test or Fisher’s exact test with SPSS software version 18.0.

Results

Of the 664 lung adenocarcinoma tissue samples, 18 were partially positive for TTF-1 (+−), and 636 were positive for TTF-1 (+) resulting in a total positive rate of 98.49% (+,+−)(including partial positive). In only 10 cases was the TTF-1 negative (−); the negative rate was 1.51%. There were 402 cases without an EGFR mutation and 262 cases with EGFR mutations; the rate of mutations was 39.46%. The location of the EGFR mutation was exon 19 for 121 cases resulting in a mutation rate in exon 19 of 18.22%. The location of the EGFR mutation was exon 21 for 141 cases resulting in a mutation rate in exon 21 of 21.23%. Exon 18 and 20 detected by DNA direct sequencing no mutations.A Fisher’s exact test was used to determine the correlation between EGFR mutations and TTF-1 expression.for the whole, TTF-1 positive expression(including partial positive) has correlation with EGFR mutations (p<0.001),especially for Exon 21 expression,the correlation is significant (p = 0.008).

Conclusion

In lung adenocarcinomas, positive and partial positive TTF-1 expression has a significant positive correlation with EGFR mutations(exon 19 and 21). In clinical practice, TTF-1 expression combine with EGFR mutations, especially exon 21 mutation can guide clinical treatment timely for lung adenocarcinomas.     

Comparison of Astigmatic Correction after Femtosecond Lenticule Extraction and Small-Incision Lenticule Extraction for Myopic Astigmatism

Purpose

To compare postoperative astigmatic correction between femtosecond lenticule extraction (FLEx) and small-incision lenticule extraction (SMILE) in eyes with myopic astigmatism.

Methods

We examined 26 eyes of 26 patients undergoing FLEx and 26 eyes of 26 patients undergoing SMILE to correct myopic astigmatism (manifest astigmatism of 1 diopter (D) or more). Visual acuity, cylindrical refraction, the predictability of the astigmatic correction, and the astigmatic vector components using Alpin’s method, were compared between the two groups 3 months postoperatively.

Results

We found no statistically significant difference in manifest cylindrical refraction (p=0.74) or in the percentage of eyes within ± 0.50 D of their refraction (p=0.47) after the two surgical procedures. Moreover, no statistically significant difference was detected between the groups in astigmatic vector components, namely, surgically induced astigmatism (0.80), target induced astigmatism (p=0.87), astigmatic correction index (p=0.77), angle of error (p=0.24), difference vector (p=0.76), index of success (p=0.91), flattening effect (p=0.79), and flattening index (p=0.84).

Conclusions

Both FLEx and SMILE procedures are essentially equivalent in correcting myopic astigmatism using vector analysis, suggesting that the lifting or non-lifting of the flap does not significantly affect astigmatic outcomes after these surgical procedures.