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INTRODUCTION AND OBJECTIVES: Adjuvant platinum-based chemotherapy for completely resected non-small cell lung cancer is associated with modest improvement in survival; nevertheless, no validated biomarker exists for predicting the benefit or harm of adjuvant platinum-based chemotherapy. MATERIALS AND METHODS: We simultaneously measured 27 cytokines in operative tumor specimens from a discovery cohort (n = 97) by multiplex immunoassay; half of the patients received adjuvant platinum-based chemotherapy, and the other half were observed. We tested possible prognostic and predictive factors in multivariate Cox models for overall survival (OS) and relapse-free survival (RFS), and a tree-based method was applied to detect predictive factors with respect to RFS. The results were validated in an independent validation cohort (n = 93). RESULTS: Fifty-two of 97 (54 %) patients in the discovery cohort and 50 of 93 (54 %) in the validation cohort received adjuvant chemotherapy; forty-four (85 %) patients in the discovery cohort and 37 (74 %) in the validation cohort received four cycles as planned. In patients with low IL-1ß-expressing tumors, RFS and OS were worse after adjuvant chemotherapy than after observation. The limited effect of adjuvant chemotherapy for patients with low IL-1ß-expressing tumors was confirmed in the validation cohort. Additionally, RFS and OS were prolonged by adjuvant chemotherapy only in patients with high IL-1ß-expressing tumors in the validation cohort. CONCLUSIONS: This study identified and validated low tumor IL-1ß expression as a potential biomarker of a limited response to adjuvant platinum-based chemotherapy after complete resection of pulmonary adenocarcinoma. This finding has the potential to inform adjuvant treatment decisions.
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INTRODUCTION: Surgical treatment of type I hiatal sliding hernias aims to control the gastroesophageal reflux symptoms and prevention of hernia recurrence. Usually, a cruroplasty is performed to narrow the hiatal orifice. Here, it remains controversial if a mesh reinforcement of the cruroplasty should be performed, since benefits as well as mesh-associated complications have been described. METHODS: We performed a propensity-score matching analysis with data derived from the Herniamed registry comparing patients undergoing laparoscopic type I hiatal hernia repair with and without synthetic mesh. We analyzed perioperative, intraoperative, and postoperative data including data derived from the 1-year follow-up in the registry. RESULTS: 6.533 patients with an axial, type I hiatal hernia and gastroesophageal reflux are included in this analysis. Mesh augmentation of the hiatoplasty was performed in n = 1.252/6.533 (19.2%) of patients. The defect size in the subgroup of patients with mesh augmentation was with mean 16.3 cm2 [14.5; 18.2] significantly larger as in the subgroups without mesh augmentation with 10.8 cm2 [8.7; 12.9]; (p < 0.001). In patients with mesh hiatoplasty n = 479 (38.3%) Nissen and n = 773 (61.7%) Toupet fundoplications are performed. 1.207 matched pairs could be analyzed. The mean defect size after matching was with 15.9 cm2 comparable in both groups. A significant association was seen regarding recurrence (4.72% mesh vs. 7.29% non-mesh hiatoplasty, p = 0.012). The same relation can be seen for pain on exertion (8.78% vs 12.10%; p = 0.014) and pain requiring treatment (6.13% vs 9.11%; p = 0.010). All other outcome parameter showed no significant correlation. CONCLUSIONS: Our data demonstrate that mesh-reinforced laparoscopic type I hiatal hernia repair in larger defects is associated with significantly lower rates for recurrence, pain on exertion and pain requiring treatment.
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Asthma is a heterogenous disease characterized by airway inflammation and variable expiratory airflow limitation resulting in variable respiratory symptoms. Characterization of airway inflammation is important to choose the optimal treatment for severe asthma patients eligible for biological treatment. However, counting cells in induced sputum samples are a time-consuming process, highly dependent on personal skills. Replacing eosinophil and neutrophil cell counting with qPCR for transcripts of selected mast cell, and basophil genes may provide more reproducible results. Aims: The objective of this study was to compare qPCR with microscopy in asthma endotyping. Methods: A qPCR method measuring five mast cell/basophil genes was applied on induced sputum samples from 30 severe asthma patients and compared with microscopy. Target gene Ct-values (CPA3, GATA2, HDC, MS4A2, TPSAB1/TPSB2) were referenced to household ß-actin Ct values as a measure of relative mRNA abundance of the target in each sample. Target/ß-actin-ratios in eosinophilic and non-eosinophilic groups determined by microscopy with an eosinophil threshold of 3% in 400 cells were compared using Mann-Whitney U Test. Spearman´s correlations were used to test for correlation between targets vs. FENO and targets vs. blood eosinophil counts. Results: The study demonstrated a statistical difference in relative mRNA abundance for four mast cell/basophil specific genes. CPA3, GATA2, HDC and MS4A2 were elevated in eosinophilic asthma versus non-eosinophilic asthma patients. The study found that GATA2, CPA3, MS4A2 and TPSAB1/TPSB2 transcripts are positively correlated with FENO. Neither the five mast cell genes nor the five-gene signature correlated with blood eosinophils. The five-gene signature with a target/ß-actin-ratio cut-off ≥2 generated sensitivity = 87%, specificity = 94%, NPV = 88% and PPV = 92% compared to microscopy. Conclusion: This study confirms the contribution of mast cells in the pathogenesis of EA and suggests that mast cell mRNA markers could be one of the biomarkers used to identify EA.