A B S T R A C T PurposeLung squamous cell carcinoma (SCC) is the second most prevalent type of lung cancer. Currently, no targeted therapeutics are approved for treatment of this cancer, largely because of a lack of systematic understanding of the molecular pathogenesis of the disease. To identify therapeutic targets and perform comparative analyses of lung SCC, we probed somatic genome alterations of lung SCC by using samples from Korean patients. Patients and MethodsWe performed whole-exome sequencing of DNA from 104 lung SCC samples from Korean patients and matched normal DNA. In addition, copy-number analysis and transcriptome analysis were conducted for a subset of these samples. Clinical association with cancer-specific somatic alterations was investigated. ResultsThis cancer cohort is characterized by a high mutational burden with an average of 261 somatic exonic mutations per tumor and a mutational spectrum showing a signature of exposure to cigarette smoke. Seven genes demonstrated statistical enrichment for mutation: TP53, RB1, PTEN, NFE2L2, KEAP1, MLL2, and PIK3CA). Comparative analysis between Korean and North American lung SCC samples demonstrated a similar spectrum of alterations in these two populations in contrast to the differences seen in lung adenocarcinoma. We also uncovered recurrent occurrence of therapeutically actionable FGFR3-TACC3 fusion in lung SCC. ConclusionThese findings provide new steps toward the identification of genomic target candidates for precision medicine in lung SCC, a disease with significant unmet medical needs.

BackgroundPrimary cardiac tumors are rare and myxoma constitutes the majority. The present study summarizes our 30-year clinical outcomes of surgical myxoma resection.MethodsBetween January 1986 and December 2015, 93 patients (30 men, 63 women; mean age, 54.7 ± 16.6 years) underwent surgical myxoma resection. The most common origin site was the left atrium. Surgery was performed via a biatrial approach in 74.2%, atrial septotomy through right atriotomy in 17.2%, and left atriotomy only in 8.6%. Mean myxoma size based on longest length was 4.73 ± 1.92 cm (range, 1.2–11.0 cm).ResultsThe mean follow-up duration was 9.9 ± 7.8 years (range, 0–29 years). In-hospital mortality was 3.2%. The most common postoperative complication was atrial fibrillation (4.3%). The 5-, 10-, and 30-year survival rates were 92.9%, 87.2%, and 75.5%, respectively. Recurrence occurred in two patients (2.1%), which were detected at 20 and 79 months after the first surgery, respectively.ConclusionsLong-term survival after myxoma resection was excellent and recurrence was rare. Based on our experience, surgical method did not affect the outcome.

Data on the frequency of nosocomial infections during extracorporeal membrane oxygenation (ECMO) in adult populations remain scarce. We investigated the risk factors for nosocomial infections in adult patients undergoing venoarterial ECMO (VA-ECMO) support. From January 2011 to December 2015, a total of 259 patients underwent ECMO. Of these, patients aged 17 years or less and patients undergoing ECMO for less than 48 hours were excluded. Of these, 61 patients diagnosed with cardiogenic shock were evaluated. Mean patient age was 60.6 ± 14.3 years and 21 (34.4%) patients were female. The mean preoperative Sequential Organ Failure Assessment (SOFA) score was 8.6 ± 2.2. The mean duration of ECMO support was 6.8 ± 7.4 days. The rates of successful ECMO weaning and survival to discharge were 44.3% and 31.1%, respectively. There were 18 nosocomial infections in 14 (23.0%) patients. These included respiratory tract infections in 9 cases and bloodstream infections in a further 9. In multivariate analysis, independent predictors of infection during ECMO were the preoperative creatinine level (hazard ratio [HR], 2.176; 95% confidence interval [CI], 1.065–4.447; P = 0.033) and the duration of ECMO support (HR, 1.400; 95% CI, 1.081–1.815; P = 0.011). A higher preoperative creatinine level and an extended duration of ECMO support are risk factors for infection. Therefore, to avoid the development of nosocomial infections, strategies to shorten the length of ECMO support should be applied whenever possible.

Objective Oesophageal squamous cell carcinoma (ESCC) is a heterogeneous disease with variable outcomes that are challenging to predict. A better understanding of the biology of ESCC recurrence is needed to improve patient care. Our goal was to identify small non-coding RNAs (sncRNAs) that could predict the likelihood of recurrence after surgical resection and to uncover potential molecular mechanisms that dictate clinical heterogeneity. Design We developed a robust prediction model for recurrence based on the analysis of the expression profile data of sncRNAs from 108 fresh frozen ESCC specimens as a discovery set and assessment of the associations between sncRNAs and recurrence-free survival (RFS). We also evaluated the mechanistic and therapeutic implications of sncRNA obtained through integrated analysis from multiple data sets. Results We developed a risk assessment score for recurrence (RAS) with three sncRNAs (miR-223, miR-1269a, and nc886) whose expression was significantly associated with RFS in the discovery cohort (N=108). RAS was validated in an independent cohort of 512 patients. In multivariable analysis, RAS was an independent predictor of recurrence (hazard ratio, 2.27; 95% confidence interval, 1.26 to 4.09; P=0.007). This signature implies the expression of ΔNp63 and multiple alterations of driver genes like PIK3CA. We suggested therapeutic potentials of immune checkpoint inhibitors in low-risk patients, and Polo-like kinase, mTOR, and HDAC inhibitors in high-risk patients. Conclusion We developed an easy-to-use prognostic model with three sncRNAs as robust prognostic markers for postoperative recurrence of ESCC. We anticipate that such a stratified and systematic, tumor-specific biologic approach will potentially contribute to significant improvement in ESCC treatment.

BackgroundResults of studies to predict prolonged air leak (PAL; air leak longer than 5 days) after pulmonary lobectomy have been inconsistent and are of limited use. We developed a new scale representing the amount of early postoperative air leak and determined its correlation with air leak duration and its potential as a predictor of PAL.MethodsWe grade postoperative air leak using a 5-grade scale. All 779 lobectomies from January 2005 to December 2009 with available medical records were reviewed retrospectively. We devised six ‘SUM’ variables using air leak grades in the initial 72 h postoperatively.ResultsExcluding unrecorded cases and postoperative broncho-pleural fistulas, there were 720 lobectomies. PAL occurred in 135 cases (18.8%). Correlation analyses showed each SUM variable highly correlated with air leak duration, and the SUM4to9, which was the sum of six consecutive values of air leak grades for every 8 h record on postoperative days 2 and 3, was proved to be the most powerful predictor of PAL; PAL could be predicted with 75.7% and 77.7% positive and negative predictive value, respectively, when SUM4to9 ≥ 16. When 4 predictors derived from multivariable logistic regression of perioperative variables were combined with SUM4to9, there was no significant increase in predictability compared with SUM4to9 alone.ConclusionsThis simple new method to predict PAL using SUM4to9 showed that the amount of early postoperative air leak is the most powerful predictor of PAL, therefore, grading air leak after pulmonary lobectomy is a useful method to predict PAL.