The effect of afatinib in a pretreated patient with invasive mucinous adenocarcinoma of the lung harboring HER2 YVMA insertion: a case report.

Background: Invasive mucinous adenocarcinoma (IMA) is an uncommon variant of lung adenocarcinoma. The survival data and therapeutic methods for IMAs are limited. The frequency of human epidermal growth factor receptor 2 (HER2) mutations in IMAs is low, and the clinical benefit of HER2 inhibitors in patients with IMA is still being explored. Afatinib is a pan-HER inhibitor and the studies of afatinib treatment in IMA patients are very limited. Case Description: Herein, we present the case of a 49-year-old female, never-smoker stage IVa IMA patient with persistent cough and sputum expectoration diagnosed with stage IVa IMA. Polymerase chain reaction (PCR) and next-generation sequencing (NGS) were utilized to detect mutations for targeted therapies on lung biopsy, but no mutation was found. After treatment failures of chemotherapy and a multiple-kinase inhibitor, liquid biopsy identified HER2 exon 20 insertion p.A775_G776insYVMA with NGS. The patient was then treated with afatinib as the third-line treatment. Following administration for one month, the patient's symptoms of coughing, sputum expectoration, and dyspnea improved. Stable disease (SD) was observed, and the patient achieved durable clinical benefit with prolonged progression-free survival (PFS) of 20 months. Her overall survival was 5.8 years. Conclusions: This is the first report of afatinib treatment achieving long-lasting and stable disease control in an IMA patient with a HER2 exon 20 YVMA insertion. Our results will help to improve the treatment of IMA.

Spirometric prediction equations and the relationship between metabolic syndrome and spirometric parameters from an island in Fujian, China.

BACKGROUND: We investigated risk factors for decreased lung function among Chinese island residents (≥30 years) to determine the relationship between metabolic syndrome (MS) and decreased lung function. METHODS: From October 17, 2011 to November 1, 2011, 2607 residents aged ≥30 years who lived on the Huangqi Peninsula of Fujian were enlisted by random cluster sampling. They completed a questionnaire designed according to the Burden of Obstructive Lung Disease (BOLD) questionnaire, and underwent physical examination, blood test, and lung function evaluation. We constructed spirometric prediction equations for forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), determined the lower limits of normal for FVC, FEV1 and FEV1/FVC, and examined the relationship between lung function and MS. RESULTS: Prediction equations for normal island residents were as follows: FVC (L) = -0.023 × age (years) + 0.042 × height (cm) + 0.641 × weight (kg) - 3.607 (males); FVC (L) = -0.017 × age (years) + 0.030 × height (cm) + 0.009 × weight (kg) - 1.741 (females); FEV1 (L) = -0.023 × age (years) + 0.040 × height (cm) + 0.010 × weight (kg) - 2.999 (males); FEV1 (L) = -0.017 × age (years) + 0.026 × height (cm) + 0.007 × weight (kg) -1.135 (females). The odds ratio for MS for increased risk of decreased FVC was 4.623 (95%CI =3.626-5.894, P<0.001), and for increased risk of decreased FEV1 was 3.043 (95%CI =2.447-3.785, P<0.001). CONCLUSIONS: MS is a risk factor for decreased lung function in island residents ≥30 years old.

[The application of loop-mediated isothermal amplification for detection of common pathogenic bacteria in lower respiratory tract infections].

OBJECTIVE: To investigate the spectrum of common pathogenic bacteria of low respiratory tract infection by loop-mediated isothermal amplification (LAMP) of nucleic acid test and to prove the clinical significance of this method. METHODS: A total of 289 qualified sputum samples from patients with lower respiratory tract infections in Fujian Province were detected by LAMP technique, and then the distribution of pathogenic bacteria was analyzed. The positive cases (the patients whose specific bacterial copies in their sputum samples > 1×10(3) copies/ml) were divided into 2 groups according to whether their treatment had covered this pathogen or not. The underlying diseases, duration of anti-bacterial treatment, the hospital days, and the effectiveness of initial treatment and cure rate were compared. RESULTS: The culture method in the 289 patients showed that 44 (15.2%) were positive. Tests by the LAMP method with a bacteria concentration > 1×10(3) copies/ml as cutoff value, showed positive results in 124 patients (43.0%). The lower respiratory tract pathogens included 144 strains of bacteria (77.8%), and 41 strains of atypical pathogens (22.2%). Gram-negative bacteria were the predominant pathogens, such as Pseudomonas aeruginosa, H. influenzae, Klebsiella pneumoniae, and Streptococcus pneumoniae. In 95 cases the initial therapy had covered the pathogens, while in 29 cases the initial therapy had not. The effectiveness of the initial treatment (χ(2) = 31.0, P < 0.01) and the total days of hospital stay (t = -2.083, P = 0.039) in the group whose antibiotics had covered the pathogens were significantly higher than those of the other group. However, there were no significant difference in duration of anti-bacterial treatment (t = -1.073, P = 0.285)and cure rates (χ(2) = 0.6, P = 0.4) between the 2 groups. CONCLUSIONS: LAMP method can detect the nuclear acid of the bacteria in the sputum much more rapidly and sensitively than the routine culture method. LAMP technique may be helpful to know the pathogenic bacteria before treatment, and therefore may improve the choice of initial antibiotic therapy.

[Association between polymorphisms of insulin-like growth factor receptor gene and susceptibility to non-small-cell lung cancer in Fujian Chinese].

OBJECTIVE: To assess the association between polymorphisms of insulin-like growth factor receptor (IGF-1R and IGF-2R) and genetic susceptibility and non-small-cell lung cancer (NSCLC). METHODS: A case-control study of 260 patients with NSCLC and 258 cancer-free subjects from Fujian was carried out. Genotypes of polymorphisms of IGF-1R +1013 and IGF-2R +1619 were determined by DNA sequencing and polymerase chain reaction-restrictive fragment length polymorphism. RESULTS: (1) Significant differences in allele frequency and genotypes distribution of IGF-1R +1013 (G/A) were found between the two groups (P<0.05). On multivariate analysis after controlling age and gender, compared with GG genotype of the IGF-1R +1013 (G/A), the risk of lung cancer for individuals with GA genotype was increased by 0.80 times (95%CI: 1.24-2.59, P = 0.002), those with AA genotype was increased by 2.56 times (95%CI: 1.78-7.26, P = 0.000), and those with the polymorphic A variant (GA or AA) was increased by 0.98 times (95%CI: 1.39-2.83, P = 0.000). No significant differences in genotypic or allelic frequencies of IGF-2R +1619 (G/A) were found between the two groups (P> 0.05). (2) After stratification of the clinical status, the IGF-1R +1013 A allele increased the risk of lung squamous cell carcinoma (OR = 3.20, 95%CI: 1.75-5.84, P = 0.000), lung adenocarcinoma (OR = 1.55, 95%CI: 1.00-2.41, P = 0.049) and other types of lung cancer (OR = 1.96, 95% CI: 1.10-3.49, P = 0.023), but no association was found between the two SNPs and other clinical features. (3) IGF-1R +1013 (G/A) and IGF-2R +1619(G/A) polymorphisms showed a synergic effect (P = 0.003). CONCLUSION: The common IGF-1R gene polymorphism G1013A may influence the risk of lung cancer. The polymorphisms of IGF-1R +1013 (G/A) and IGF-2R +1619 (G/A) have synergistic influence on the risk of lung cancer.

[Relationship of insulin-like growth factor receptor single nucleotide polymorphism (SNP) with platinum-based chemotherapy outcomes in advanced non-small cell lung cancer].

BACKGROUND AND OBJECTIVE: It has been proven that the insulin-like growth factor 1 receptor (IGF-1R) gene is an important regulator of many aspects of growth, differentiation, and development. The insulin-like growth factor 2 receptor (IGF-2R) gene is a negative mediator for carcinogenesis. The aim of this study is to investigate the relationship of IGF-1R+1013(G/A) and IGF-2R+1619(G/A) single nucleotide polymorphism (SNP) with platinum-based chemotherapy outcomes in advanced non-small cell lung cancer (NSCLC). METHODS: A total of 132 patients with NSCLC were routinely treated with platinum-based chemotherapy, and their clinical responses were evaluated after four cycles of chemotherapy. IGF-1R+1013(G/A) and IGF-2R+1619(G/A) were genotyped using polymerase chain reaction-restrictive fragment length polymorphism. The relationship between IGF-1R+1013(G/A) and IGF-2R+1619(G/A) genotypes and the clinical benefit rate, as well as the median survival time (MST), was analyzed. RESULTS: No significant association was found between IGF-1R+1013(G/A) and IGF-2R+1619(G/A) polymorphisms with clinical benefit (P>0.05). Further, we found that the two SNPs could not work together (P=0.975). The MST of patients with IGF-1R+1013(G/A) genotypes with A allele (GA+AA) was significantly shorter than that of GG genotype carriers (P=0.017). There was no significant difference in MST in patients with IGF-2R+1619(G/A) A allele (GA+AA) carrier and GG genotype carrier (P=0.575). The two SNPs showed a synergistic effect on MST. Patients who carried a mutant allele A of IGF-1R+1013(G/A) and a mutant allele A of IGF-2R+1619(G/A) had a MST of 12 months, which was significantly shorter than that of patients with other genotypes (P<0.05). Estimation by the Cox proportional hazards model showed that IGF-1R+1013(G/A) polymorphism is an independent prognostic factor (P=0.020), and IGF-1R+1013(G/A) polymorphism in combination with IGF-2R +1619(G/A) polymorphism is an independent prognostic factor in advanced NSCLC (P=0.025). CONCLUSIONS: IGF-1R+1013(G/A) polymorphism alone or in combination with IGF-2R +1619(G/A) polymorphism was associated with the overall survival period in patients with advanced NSCLC after treatment with platin-based chemotherapy, which might be a prognostic factor in platin-treated patients with advanced NSCLC.

No association between APOE ε 4 allele and multiple sclerosis susceptibility: a meta-analysis from 5472 cases and 4727 controls.

BACKGROUND: Apolipoprotein E (APOE) gene ε4, 2 alleles have been reported to be associated with multiple sclerosis (MS), but results were conflicting. In order to derive a more precise estimation of the associations, a meta-analysis was performed. METHODS: The PubMed, EBSCO and BIOSIS databases were searched to identify eligible studies published in English before March, 2011. Data were extracted using standardized forms. The association was assessed by odds ratio (OR) with 95% confidence intervals (CIs). Begg's test was used to measure publication bias. RESULTS: A total of 20 case-control studies, containing 5472 patients/4727 controls for ε4 allele and 4636 patients/4047 controls for ε2 allele were included. The associations between APOE ε4, 2 alleles and MS were not found in overall population (OR(ε4)=0.997, 95% CI=0.861-1.156; OR(ε2)=1.097, 95% CI=0.940-1.279). Subgroup analysis revealed that APOE ε4, 2 alleles were not associated with an increased risk of MS in Caucasian population (OR(c-ε4)=0.924, 95% CI=0.819-1.041; OR(c-ε2)=1.127, 95% CI=0.955-1.331). There was no evidence of publication bias according to Begg's regression test. CONCLUSIONS: This meta-analysis suggests that APOE ε4, 2 alleles are not associated with MS susceptibility. However, large sample, representative population-based studies with homogeneous MS patients, and well matched controls are warranted to confirm this finding.