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BACKGROUND Left atrial venting through atrial septotomy in patients with decreased left ventricular (LV) contractility after venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a simple and effective method for treating LV decompression. MATERIALS & METHODS We report a case of prosthetic mitral valve thrombosis after left atrial venting in a patient with VA-ECMO. RESULTS In patients undergoing mitral valve replacement, left atrial venting reduces the flow through the mitral valve and forms a prosthetic thrombosis. DISCUSSION Therefore, excessive left atrial venting should be avoided. Other venting methods that can maintain the flow through the mitral valve should be considered after mitral valve replacement.

Background This study aimed to confirm the effectiveness of thoracoscopic metastasectomy for colorectal cancer (CRC) and determine its prognostic factors. Methods Of the 181 patients who underwent video‐assisted thoracoscopic surgery (VATS) for pulmonary metastases from CRC between 2011 and 2017, 173 were retrospectively reviewed. Surgical outcomes, long‐term survival, and the factors affecting the prognosis were analyzed. Results The patients in the study were predominantly male (n = 104, 60.1%), and the median age was 65 years (range, 25–83 years). The median follow‐up time was 46 months (range, 0–114 months). The surgical procedures were 156 wedge resections, five segmentectomies, and 12 lobectomies. Conversion to thoracotomy was required in nine patients. The postoperative complication rate was 2.9%, and the in‐hospital mortality rate was 1.2%. The overall 1‐, 3‐, and 5‐year survival rates were 94.8%, 70.6%, and 51.8%, respectively. Univariate analysis showed that the prognostic factors for survival were age (p = 0.027), pathological stage of CRC (p = 0.019), prior extrathoracic metastasis (p = 0.005), preoperative carcinoembryonic antigen level (p = 0.020), number of pulmonary metastases (p = 0.011), and disease‐free interval (p = 0.026). In the multivariate analysis, two factors were related to prognosis: age (hazard ratio [HR], 1.881; 95% confidence interval [CI]; 1.189–2.976; p = 0.007) and prior extrathoracic metastasis (HR, 2.170; 95% CI; 1.269–3.711; p = 0.005). Conclusions VATS for pulmonary metastasectomy for CRC can be performed relatively safely, and our results regarding long‐term survival are comparable with those of other studies. In this study, older age (≥70 years) and prior extrathoracic metastasis were independent prognostic factors of poor prognosis., VATS for pulmonary metastasectomy for CRC can be performed relatively safely, and our results regarding long‐term survival are comparable with those of other studies. In this study, older age (≥70 years) and prior extrathoracic metastasis were independent prognostic factors of poor prognosis.

We aimed to examine the usefulness of serum glutathione peroxidase 3 (GPx3) as a biomarker of lung cancer recurrence after complete resection. We prospectively collected serial serum samples at the baseline, as well as 3, 6 and 12 months after surgery from complete resection cases in 2013. GPx3 levels were measured by enzyme-linked immunosorbent assay. Statistical tests including t-tests and Cox proportional hazard regression analyses were performed. Totally, 135 patients were enrolled, and 39 (28.9%) showed relapse during the median follow-up period (63.60 months, range, 0.167&ndash, 81.867). The mean GPx3 change was significantly higher in the recurrence group at 6 months (0.32 &plusmn, 0.38 vs. 0.15 &plusmn, 0.29, p = 0.016) and 12 months (0.40 &plusmn, 0.37 vs. 0.13 &plusmn, 0.28, p = 0.001). The high GPx3 change group showed significantly higher 60-months recurrence rates than the low group (48.1% vs. 25.2% at 3 months, p = 0.005, 54.5% vs. 28.9% at 6 months, p = 0.018, 38.3% vs. 18.3% at 12 months, p = 0.035). High GPx3 change at 3 months were independent risk factors of recurrence (hazard ratio (HR) 3.318, 95% confidence interval (CI), 1.582&ndash, 6.960, p = 0.002) and survival (HR 3.150, 95% CI, 1.301&ndash, 7.628, p = 0.011). Therefore, serum GPx3 changes after surgery may be useful predictive biomarkers for recurrence in lung cancer. Larger-scale validation studies are warranted to confirm these findings.

There is limited evidence for effectiveness of adjuvant chemotherapy in esophageal squamous cell carcinoma. We conducted a multi-center randomized controlled trial to assess whether adjuvant Capecitabine and Cisplatin improve survival compared with surgery only among patients with resectable esophageal squamous cell carcinoma. Methods This is a multicenter randomized controlled trials conducted at five hospitals in Korea from Mar 2005 to Dec 2018. Patients were eligible if they underwent curative resection for esophageal squamous cell carcinoma and diagnosed with pathologic T2–3 or N1 stage, according to 6th edition of TNM cancer staging system. Patients who were diagnosed with cervical esophageal cancer, had previous history of cancer, or received neoadjuvant therapy were excluded. Intervention group received 4 cycles of adjuvant chemotherapy (Capecitabine 1,000 mg/m2 b.i.d for 14 days and intravenous Cisplatin 75 mg/m2 at Day1, every 3 weeks). The primary endpoint was disease free survival. Results 136 patients were randomly assigned to adjuvant chemotherapy group (n = 68) or surgery alone group (n = 68). Seven patients who rejected chemotherapy after randomization were excluded from the final analysis. The cumulative incidence of recurrence within 18 months after surgery was significantly lower in the adjuvant chemotherapy group compared to the surgery alone group (Hazard Ratio (HR), 0.45; 95% Confidence Interval (CI), 0.22–0.91). After long-term follow-up (median 3.3 years, maximum 14 years), disease free survival and overall survival were not different between two groups. (HR, 0.77; 95% CI, 0.49–1.18 and HR, 0.85; 95% CI, 0.55–1.34, respectively.) Conclusion Adjuvant chemotherapy after curative resection in patients with esophageal squamous cell carcinoma reduced early recurrence but this does not extend to long-term disease free and overall survival due to limited sample size. Additional randomized controlled trials with larger sample would be necessary to confirm the effectiveness of adjuvant chemotherapy in esophageal squamous cell carcinoma.

Myxoma is the most common type of primary cardiac tumors and is usually benign and asymptomatic, although it has been reported with fatal complications due to extracardiac manifestations. Extracorporeal cardiopulmonary resuscitation, a rescue therapy for cardiac arrest, yields favorable outcomes, only if complications have a reversible origin. Herein, we report the first case of abdominal aortic occlusion due to total myxoma detachment who was successfully treated with extracorporeal cardiopulmonary resuscitation.

BACKGROUND: IBM Watson for Oncology (WFO) is a cognitive computing system helping physicians quickly identify key information in a patient’s medical record, surface relevant evidence, and explore treatment options. This study assessed the possibility of using WFO for clinical treatment in lung cancer patients. METHODS: We evaluated the level of agreement between WFO and multidisciplinary team (MDT) for lung cancer. From January to December 2018, newly diagnosed lung cancer cases in Chonnam National University Hwasun Hospital were retrospectively examined using WFO version 18.4 according to four treatment categories (surgery, radiotherapy, chemoradiotherapy, and palliative care). Treatment recommendations were considered concordant if the MDT recommendations were designated ‘recommended’ by WFO. Concordance between MDT and WFO was analyzed by Cohen’s kappa value. RESULTS: In total, 405 (male 340, female 65) cases with different histology (adenocarcinoma 157, squamous cell carcinoma 132, small cell carcinoma 94, others 22 cases) were enrolled. Concordance between MDT and WFO occurred in 92.4% (k=0.881, P

BACKGROUND This multicenter study was performed to develop a prognosis-prediction model incorporating genetic polymorphism with pathologic stage for surgically treated non-small cell lung cancer (NSCLC) patients. METHODS A replication study including 720 patients and a panel of eight single nucleotide polymorphisms (SNPs), which predicted the prognosis of surgically treated NSCLC in our previous study, was conducted. Using the combined cohort of current and previous studies including 1534 patients, a nomogram for predicting overall survival was made using Cox proportional hazards regression. RESULTS Among the eight SNPs, C3 rs2287845, GNB2L1 (alias RACK1), and rs3756585 were significantly associated with overall survival. A nomogram was constructed based on pathologic stage and the genotypes of the two SNPs, and the risk score was calculated for each patient in the combined cohort. Using the prognosis-prediction model, we categorized patients into low, intermediate, and high-risk groups, which had greater accuracy in predictive ability (log-rank statistics = 54.66) than the conventional tumor node metastasis staging (log-rank statistics = 39.56). Next, we generated a prognosis-prediction model for stage I to identify a subgroup of potential candidates for adjuvant chemotherapy. Notably, 97 out of 499 stage IB patients were classified as high-risk patients with a similar prognosis to stage II patients, suggesting the benefit of adjuvant chemotherapy. CONCLUSIONS This prognosis-prediction model incorporating genetic polymorphism with pathologic stage may lead to more precise prognostication in surgically resected NSCLC patients. In particular, this model may be useful in selecting a subgroup of stage IB patients who may benefit from adjuvant chemotherapy.

We evaluated the association between genetic variants in the Notch pathway and survival outcomes of patients with surgically resected NSCLC. Sixty-four single nucleotide polymorphisms (SNPs) in the Notch pathway genes were evaluated in the discovery study (n = 354) and two sequential validation studies (n = 772 and n = 746, respectively). The association of genotype with overall survival (OS) and disease-free survival (DFS) was evaluated. Of the 64 SNPs analyzed in the discovery study, 9 were significantly associated with OS or DFS. Among them, the association remained significant only for Deltex-1 (DTX1) rs1732786A>G in the first validation study. The second validation study confirmed again the association between DTX1 rs1732786A>G and survival outcomes. In the combined analysis, rs1732786A>G was significantly associated with better OS and DFS (adjusted HR ·aHR· for OS, 0.75; 95% CI 0.64–0.87; P = 0.0002; aHR for DFS, 0.79; 95% CI 0.71–0.89; P = 0.0001). In vitro luciferase assay showed that the rs1732786G allele was associated with higher promoter activity compared to rs1732786A allele. Consistently, relative mRNA expression level of DTX1 showed significant positive correlation with rs1732786 A-to-G change (Ptrend = 0.02) in tumor tissues. These results suggest that DTX1 rs1732786 is a potential prognostic factor that may have clinical utility in the management of early stage NSCLC.

The aim of this retrospective, multicenter study was to develop a recurrence risk-scoring model in patients with curatively resected stage I lung adenocarcinoma (ADC). Clinicopathologic and outcome data for a development cohort of 1,700 patients with pathologic stage I ADC from four institutions resected between January 2000 and December 2009 were evaluated. A phantom study was performed for correction of inter-institutional differences in positron emission tomography-standardized uptake value (PET-SUV). A nomogram for recurrence prediction was developed using Cox proportional hazards regression. This model was validated in a cohort of 460 patients in two other hospitals. The recurrence rate was 21.0 % for the development cohort and 22.1 % for the validation cohort. In multivariable analysis, three independent predictors for recurrence were identified: pathologic tumor size (hazard ratio [HR] 1.03, 95 % CI 1.017–1.048; p

Background We conducted this study to identify genetic variants in cancer-related pathway genes which can predict prognosis of NSCLC patients after surgery, using a comprehensive list of regulatory single nucleotide polymorphisms (SNPs) prioritized by RegulomeDB. Method A total of 509 potentially functional SNPs in cancer-related pathway genes selected from RegulomeDB were evaluated. These SNPs were analyzed in a discovery set (n = 354), and a replication study was performed in an independent set (n = 772). The association of the SNPs with overall survival (OS) and disease-free survival (DFS) were analyzed. Results In the discovery set, 76 SNPs were significantly associated with OS or DFS. Among the 76 SNPs, the association was consistently observed for 5 SNPs (ERCC1 rs2298881C > A, BRCA2 rs3092989G > A, NELFE rs440454C > T, PPP2R4 rs2541164G > A, and LTBP4 rs3786527G > A) in the validation set. In combined analysis, ERCC1 rs2298881C > A, BRCA2 rs3092989, NELFE rs440454C > T, and PPP2R4 rs2541164G > A were significantly associated with OS and DFS (adjusted HR ·aHR· for OS = 1.46, 0.62, 078, and 0.76, respectively; P = 0.003, 0.002, 0.007, and 0.003 respectively; and aHR for DFS = 1.27, 0.69, 0.86, and 0.82, respectively; P = 0.02, 0.002, 0.03, and 0.008, respectively). The LTBP4 rs3786527G > A was significantly associated with better OS (aHR = 0.75; P = 0.003). Conclusion Our results suggest that five SNPs in the cancer-related pathway genes may be useful for the prediction of the prognosis in patients with surgically resected NSCLC.

Background We selected glutathione peroxidase 3 (GPx3) as a specific candidate that is down regulated in patients with lung cancer. In this study, we examined the diagnostic value of serum GPx3, which is an extracellular protein and readily detectable in blood. Methods We collected serum samples from 342 patients with lung cancer and 126 controls (normal healthy people and patients with benign diseases or other malignancies). We measured serum GPx3 levels using the enzyme-linked immunosorbent assay. Results Mean serum GPx3 levels were significantly lower in the patient group compared with the control group (10.1 ± 5.0 μg/mL vs. 13.0 ± 5.8 μg/mL, P < 0.001). In addition, mean serum GPx3 levels tended to be lower in the patients without metastasis compared with those with metastasis (9.6 ± 4.5 μg/mL vs. 10.7 ± 5.7 μg/mL, P = 0.051). Furthermore, mean serum GPx3 levels had a significant difference according to initial treatments (P < 0.001). In other words, mean serum GPx3 levels were significantly lower in the surgery group (8.2 ± 4.1 μg/mL) compared with the concurrent chemoradiotherapy (11.5 ± 4.6 μg/mL, P < 0.001), chemotherapy (10.7 ± 5.6 μg/mL, P < 0.001), and supportive care groups (10.9 ± 4.8 μg/mL, P = 0.002). Conclusion Our results showed that serum GPx3 levels were significantly lower in the patients who underwent surgery, which indicates that the serum may have diagnostic value in patients at an operable stage of lung cancer, rather than those at a locally advanced or metastatic stage.

Purpose Lung 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 Methods We 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. Results This 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. Conclusion These findings provide new steps toward the identification of genomic target candidates for precision medicine in lung SCC, a disease with significant unmet medical needs.

Purpose Locally advanced esophageal cancers are generally treated with neoadjuvant chemoradiotherapy, followed by surgery in operable candidates. However, even if the patients were diagnosed as operable disease, surgery could not be performed on patients with poor condition or other comorbidity. In this case, definitive chemoradiotherapy (dCRT) is the other option for localized esophageal cancer. Therefore, the purpose of this study was to evaluate the efficacy and clinical prognostic factors for dCRT in locally advanced esophageal cancer. Materials and methods We conducted a review of patients who received dCRT for locally advanced squamous esophageal cancer from 2004 to 2010, focusing on stages III and IVa. All patients received at least two cycles of platinum-based chemotherapy during radiation, and all tumor burdens were included in the radiation field. The treatment results were analyzed for patterns of failure and prognostic factors associated with survival. Results In total, 63 patients were enrolled in this study. The overall response rate was 84.1%. Relief from dysphagia after dCRT was achieved in 48 patients. The most frequent failure was local recurrence. The median overall survival (OS) was 23.0 months, and the 2-year survival rate was 45.4%. Similar results were observed for elderly study patients. Significant prognostic factors for OS were duration of smoking, high grade of dysphagia (score of 3 or 4), and shorter duration of progression-free and dysphagia-free survival. Maintenance chemotherapy after dCRT did not influence OS. However, "good risk" patients receiving maintenance chemotherapy showed better OS than those who did not receive maintenance chemotherapy (30.4 months vs. 12.0 months, p=0.002). Conclusion dCRT has a major role in improving survival and palliation of dysphagia in inoperable advanced esophageal cancer, even in elderly patients. Maintenance chemotherapy after dCRT may be effective in prolonging survival in "good risk" patients.

Background Coronary artery bypass grafting (CABG) with a composite Y-graft made of the left internal thoracic artery (LITA) and another arterial graft has a risk for hypoperfusion. Changes over time in the diameter of the LITA anastomosed to the left anterior descending coronary artery (LAD) are not known. Methods Data were collected for 71 patients who had undergone coronary angiography (CAG) immediately and at 1 year following off-pump CABG with a composite Y-graft made of the LITA and either the radial artery or the right gastroepiploic artery. These patients were divided into 2 groups depending on the degree of LAD stenosis. Group 1 (n = 28) consisted of patients with complete occlusion of the LAD. Group 2 (n = 43) consisted of patients with

Background The association between the anatomy of a single coronary artery (SCA) and the surgical risk of aortic valve replacement (AVR) remains unclear due to a lack of studies on this topic. Case presentation A 73-year-old woman underwent AVR for aortic stenosis. Preoperative coronary angiography results showed a SCA arising from the left coronary sinus. The Manouguian procedure was performed for a small aortic annulus. Intraoperatively, an extracorporeal membrane oxygenator (ECMO) was needed for bypass weaning failure due to newly developed right ventricular dysfunction. Coronary angiography was performed on postoperative day 4, and the findings showed a right coronary artery occlusion just after its origin. After emergent coronary artery bypass surgery, she could be weaned from the ECMO. She was discharged on postoperative day 70 and followed up without complications for 12 months. Conclusions AVR with the annular enlargement procedure in those with a SCA can result in an unexpected coronary artery occlusion, which should be, therefore, suspected when unexplained myocardial dysfunction occur. For reducing this risk, the use of a small prosthesis should be considered over the annular enlargement procedure when performing AVR in those with a small aortic annulus and a SCA. Electronic supplementary material The online version of this article (doi:10.1186/s13019-016-0542-8) contains supplementary material, which is available to authorized users.

Objectives SR-splicing factors (SRSFs) play important roles in oncogenesis. However, the expression of SRSF 5–7 proteins in lung cancer (LC) is unclear, and their use in the diagnosis of pleural diseases has never been assessed. We evaluated SRSF 5–7 protein levels in LC and their diagnostic potential for cancer cells in lung and pleural effusion (PE) and, for the dysregulated SRSFs, investigated their neutralization effect on LC. Materials and methods SRSF 5–7 levels in lung tissue and PE cell lysate samples ( n =453) were compared with the results of conventional tumor markers. Knockdown of SRSF gene expression was performed using small interfering RNAs on small-cell LC (SCLC) cell lines. Results In lung tissue analysis, SRSF 5–7 levels were up-regulated in LC samples compared with non-tumoral lung tissue samples; they were markedly higher in SCLC than in adenocarcinoma or squamous cell carcinoma. SRSF5 showed the highest detection accuracy (89%) for total LC, and it was superior to that (74%) of carcinoembryonic antigen [CEA, a commonly used non-SCLC (NSCLC) marker]. Notably, the detection accuracies of the three SRSFs for SCLC were all 100% and higher than that (69%) of a pro-gastrin-releasing peptide (a well-known SCLC marker). In PE cell analysis, the detection accuracy (86%) of SRSF5 for malignant cells was highest among SRSFs and comparable to that (83%) of CEA. SRSF5 additionally detected 70% of CEA-missed non-NSCLC cases. Down-regulation of the SRSFs induced mild (SRSF5 and SRSF7) to remarkably (SRSF6) reduced cell proliferation. Conclusions Our results demonstrated the up-regulated expression of SRSF 5–7 proteins in LC with much more profound up-regulation in SCLC than in NSCLC and suggest that up-regulation of the SRSFs is related to SCLC proliferation. Moreover, we identified SRSF5 as a novel detection marker for SCLC and pleural metastatic cancer cells.

Concurrent chemoradiotherapy (CRT) is a main treatment option for patients with advanced oesophageal cancer. However, improvement of survival outcomes and toxicities according to the selected treatment is still needed. This phase II trial was conducted to assess the efficacy and safety of concurrent CRT with weekly docetaxel and cisplatin in advanced oesophageal cancer.Patients with unresectable oesophageal cancer due to advanced stage or patients medically unfit for surgery were enrolled. Patients received 20 mg/m(2) docetaxel and 25 mg/m(2) cisplatin in weeks 1, 2, 3, 5, 6, and 7 with concurrent 54-Gy radiotherapy at 200 cGy/day.Thirty-six patients with oesophageal squamous cell carcinoma were enrolled from December 2007 to December 2009. Among them, the toxicity and response rate of 35 were evaluated. Thirty-five patients completed radiotherapy as planned, and 33 completed chemotherapy as planned. Grade 3 or 4 toxicity during CRT included leucopenia (5.7 %), febrile neutropenia (2.9 %), oesophagitis (22.9 %), and tracheo-oesophageal fistula (5.7 %). After CRT, 8 patients (22.9 %) had a complete response, 22 (62.9 %) had a partial response, 4 (11.4 %) had stable disease, and 1 (2.9 %) had progressive disease. Improvement of dysphagia was observed in 85.3 %. At a median follow-up of 26.7 months, the median time to progression was 13.5 months, and median overall survival was 26.9 months. The 3-year progression-free survival rate was 16.7 %, and survival rate was 27.8 %.Concurrent CRT with weekly docetaxel and cisplatin was well tolerated and is a convenient combination with promising efficacy. This result indicated favourable activity in terms of both tumour and symptom control.

Background The prognostic factors after pulmonary resection in patients with colorectal pulmonary metastases remain controversial. Objective The study aimed to identify the predicting factors for oncological outcomes after curative resection in patients with colorectal cancer and pulmonary metastases. Design This study is a retrospective review of prospectively collected data. Setting This study was conducted at a tertiary care hospital/referral center in South Korea. Patients Between January 2000 and June 2010, 105 patients who developed pulmonary metastases after curative resection for colorectal cancer were enrolled. Forty-eight patients underwent pulmonary resection, and the remaining 58 were given chemotherapy and/or best supportive care. Main outcome measures The primary outcomes measured were the predictive factors of survival and recurrence. Results During the 35.9-month median follow-up period, 3- and 5-year overall survival rates were 54.6% and 30.4%. On multivariate analysis, absence of adjuvant chemotherapy after pulmonary metastases (p = 0.003), presence of extrapulmonary metastases (p = 0.001), elevated prelaparotomy serum CEA level (p = 0.015), and absence of pulmonary resection (p = 0.048) were independent prognostic factors for poor overall survival. In patients who underwent pulmonary resection, the 3-year pulmonary recurrence-free survival rate was 78.3%. On multivariate analysis, elevated prelaparotomy serum CEA level (p = 0.018) and disease-free interval ≤ 12 months (p = 0.008) were independent risk factors associated with pulmonary re-recurrence after pulmonary resection. Limitations This study took place at a single institution and had a small sample size. Conclusion Although we admit, to some degree, the benefits of the selection mechanism, pulmonary metastasectomy from colorectal cancer may improve survival after curative resection of colorectal cancer. Adjuvant chemotherapy, extrapulmonary metastases, and prelaparotomy CEA value are independent prognostic factors for overall survival. Prelaparotomy serum CEA level may be an especially reliable predictor of both overall survival and recurrence-free survival after pulmonary metastasectomy in patients who undergo curative resection for colorectal cancer.

Background and objective: Expression of excision repair cross-complementation group 1 (ERCC1) is recognized as a favourable prognostic marker in patients who have undergone surgical resection of non-small cell lung cancer (NSCLC). However, in patients treated with adjuvant chemotherapy after surgical resection, ERCC1 correlated with poor prognosis. Class III beta tubulin (TUBB3) is also known to be a predictive marker of the efficacy of treatment with taxanes or vinorelbine. Methods: Tumour tissues (n = 363) from patients with surgically resected NSCLC were analysed retrospectively. Tissue sections were labelled with ERCC1- and TUBB3-specific antibodies. Using genomic DNA from 262 patients, single nucleotide polymorphisms of the ERCC1 gene (T19007C and C8092A) were genotyped by PCR-restriction fragment length polymorphism analysis. Results: Only 5.9% of patients with stage I disease (14/238) and 61.6% of patients with stages II–III disease (77/125) received adjuvant chemotherapy. Relapses were noted in 30.6% (111) of patients, and among these, 31 ultimately succumbed. The relapse rate (RR) was 24.8% for stage I disease, and 41.6% for stages II–III disease. The RR was significantly lower in ERCC1-positive (24.3%) as compared with ERCC1-negative patients (36.3%, P = 0.014) and was lower in patients with the AA/CA genotype at the ERCC1 C8092A locus (29.5%) compared with those with the CC genotype (42.1%, P = 0.034). The median disease-free survival (DFS) time was 62.3 months. DFS was significantly greater in ERCC1-positive patients (62.3 months) than in ERCC1-negative patients (48.0 months, P = 0.042). In a multivariate analysis, ERCC1 expression and the C8092A polymorphism were independent prognostic factors in patients with stage I disease who were naive to chemotherapy. Conclusions: ERCC1 expression and the AA/CA genotype at the C8092A locus were correlated with a good prognosis in patients who had undergone surgical resection of NSCLC.

Non-small-cell lung cancer (NSCLC) constitutes approximately 80% of all diagnosed lung cancers, and diagnostic markers detectable in the plasma/serum of NSCLC patients are greatly needed. In this study, we established a pipeline for the discovery of markers using 9 transcriptome datasets from publicly available databases and profiling of six lung cancer cell secretomes. Thirty-one out of 312 proteins that overlapped between two-fold differentially expressed genes and identified cell secretome proteins were detected in the pooled plasma of lung cancer patients. To quantify the candidates in the serum of NSCLC patients, multiple-reaction-monitoring mass spectrometry (MRM-MS) was performed for five candidate biomarkers. Finally, two potential biomarkers (BCHE and GPx3; AUC = 0.713 and 0.673, respectively) and one two-marker panel generated by logistic regression (BCHE/GPx3; AUC = 0.773) were identified. A validation test was performed by ELISA to evaluate the reproducibility of GPx3 and BCHE expression in an independent set of samples (BCHE and GPx3; AUC = 0.630 and 0.759, respectively, BCHE/GPx3 panel; AUC = 0.788). Collectively, these results demonstrate the feasibility of using our pipeline for marker discovery and our MRM-MS platform for verifying potential biomarkers of human diseases.

With the introduction of high pressure balloon inflations and antiplatelet therapy, the incidence of stent thrombosis has been markedly reduced, but the incidence of late stent restenosis has not. A new strategy may be local drug delivery, which maintains sustained local concentration and limits systemic complications. To evaluate the efficacy of local nitric oxide (NO) donor delivery on stent thrombosis and complications, local NO donor delivery was performed in stented patients. NO donor (2.0-mg molsidomine) was delivered (1.0 mL/min > 10 min) using the Dispatch Catheter after predilation of target lesions in 13 patients (6 angina, 7 myocardial infarction, age 53.1 ± 11.4 years). After local NO donor delivery, Palmaz-Schutz stents were placed using standard methods. Follow-up coronary angiograms were performed 48 hours and 6 months after stenting. None of the patients had hypotensive effects, ischemic symptoms, or ECG changes during and after local NO donor delivery. APTT and CK values were unchanged at 3 and 24 hours after local NO donor delivery and stenting. Follow-up coronary angiograms at 48 hours and 6 months showed all stents patent with TIMI III flow and without intrastent thrombus. No target lesion revascularization and 100% event-free survival were observed during the 6-month clinical follow-up period. Intracoronary stenting may be performed safely and effectively by local NO donor delivery prior to stent implantation.

One of the major limitations in coronary intervention is restenosis. This study was aimed to identify clinical, angiographic, and procedural factors that may be related to the second restenosis (SR). We studied 101 patients who underwent more than two follow-up coronary angiograms after two coronary interventions between January 1996 and December 1998 in Chonnam University Hospital (out of 4,092 total coronary interventions in 3,030 patients during the same period). The patients were divided into two groups according to the evidence of SR. Fifty-two patients (group A: 57 ± 10 years, M:F = 44:8) who had SR and the other 49 patients (group B: 54 ± 9 years, M:F = 44:5) without SR were analyzed. Clinical features, angiographic characteristics, coronary interventional procedures, and other risk factors were compared between two groups by univariate analysis and multivariate stepwise logistic regression analysis was performed for the predictive factors for SR. The clinical variables of age, sex, clinical diagnosis, and risk factors were not different between two groups. The lesion severer than B 2 by AHA/ACC classification were associated with SR (P < 0.05). Recurrent angina as an indication for follow-up angiography was associated with SR (P < 0.01). Predictive factors associated with SR were patient's subjective symptom and lesion severer than type B 2 according to AHA/ ACC classification.

We treated a patient with non-small cell lung cancer (NSCLC) and an isolated hepatic metastasis. He was a 56-year-old male who underwent right pneumonectomy after concurrent chemoradiation therapy (etoposide+cisplatin) with the diagnosis of stage IIIA squamous cell lung carcinoma. Seven months later, an isolated hepatic metastasis was found on a PET-CT scan. Hepatic segmentectomy was performed, and the pathology showed squamous cell carcinoma. Adjuvant chemotherapy with five cycles of gemcitabine and cisplatin was also given. The patient has been followed with PET-CT and CT scanning every 6 months, and there is no evidence of relapse at more than 5 years after the diagnosis of NSCLC. This shows that the surgical resection of an isolated hepatic metastasis may be an option in carefully selected patients with NSCLC without evidence of disease outside the liver.

Objectives Prosthetic valve dehiscence after aortic valve surgery in Behcet's disease patients is common. We aimed to validate the usefulness of our new technique 'subannular endomyocardial implantation of valve prosthesis' designed to prevent prosthetic valve dehiscence. Methods Subannular endomyocardial implantation of valve prosthesis involves suturing the sewing cuff of the valve prosthesis in the endomyocardium below the aortic annulus, which is based on the idea that annular tissue should be excluded from the suture line in Behcet's disease patients. Medical records of 7 patients in whom the new technique was performed between 2002 and 2014 were reviewed. Results Five men and two women were included (median age, 44 years). Aortic root replacement was performed in 6 cases, and aortic valve replacement in 1. No operative mortality occurred. Postoperatively, complete atrioventricular block developed in 3 cases, and permanent pacemakers were implanted in 2. No reoperation was performed for prosthetic valve dehiscence during the median 7.8-year follow-up. One late death occurred due to sudden cardiac arrest 8.4 years after surgery. One additional permanent pacemaker was implanted for complete atrioventricular block, which developed at 4.2 years postoperatively. The last echocardiography (median, 6.7 years after surgery) revealed no paravalvular leakages. Conclusions Subannular endomyocardial implantation of valve prosthesis seems useful for preventing prosthetic valve dehiscence after aortic valve surgery for Behcet's disease. It poses a risk of complete atrioventricular block, but considering the high reoperation rate and mortality due to prosthetic valve dehiscence after conventional aortic valve surgery, this risk seems reasonable.

Background and Objectives Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels play an important role in myocardial protection. We examined the effects of thromboxane A2 on the regulation of KATP channel activity in single ventricular myocytes. Subjects and Methods Single ventricular myocytes were isolated from the hearts of adult Institute of Cancer Research (ICR) mice by enzymatic digestion. Single channel activity was recorded by excised inside-out and cell-attached patch clamp configurations at −60 mV holding potential during the perfusion of an ATP-free K-5 solution. Results In the excised inside-out patches, the thromboxane A2 analog, U46619, decreased the KATP channel activity in a dose-dependent manner; however, the thromboxane A2 receptor antagonist, SQ29548, did not significantly attenuate the inhibitory effect of U46619. In the cell-attached patches, U46619 inhibited dinitrophenol (DNP)-induced KATP channel activity in a dose-dependent manner, and SQ29548 attenuated the inhibitory effects of U46619 on DNP-induced KATP channel activity. Conclusion Thromboxane A2 may inhibit KATP channel activity, and may have a harmful effect on ischemic myocardium.

Atherosclerotic disease of the coronary artery may simultaneously involve the subclavian artery, and a significant stenosis of the left subclavian artery may result in recurrent myocardial ischemia in patients with patent left internal mammary artery (LIMA) grafts because of 'coronary steal' through the LIMA. Isometric exercise of the left arm may improve myocardial perfusion through vertebral - subclavian steal by flow reversal in the ipsilateral vertebral artery because of the change in the pressure gradient between the circle of Willis and the distal subclavian artery. The present patient had coronary steal through a LIMA after coronary artery bypass surgery and a transient vertebral - subclavian steal with improved myocardial perfusion as a result of exercise of the left arm.

A combination of docetaxel (D) and cisplatin (P) is one of the standard regimens for the initial treatment of advanced non-small cell lung cancer (NSCLC). Yet, the toxicity of D administered at 75 mg/m(2) in three weekly doses to patients is a concern. The aim of this study was to assess the efficacy of a lower combination dose, 60 mg/m(2) of D and 60 mg/m(2) of cisplatin (P), as a treatment for NSCLC. In this randomized, phase III trial, we compared the response rates (RRs) and toxicity profiles of two combination regimens, D/P 75/60 vs. 60/60 mg/m(2), to patients with stage IIIB or IV NSCLC. A total of 132 patients were randomized to the 75/60 (n=65) or 60/60 (n=67) dosage group. Non-inferiority of 60/60 group compared to the 75/60 group was confirmed by the RR (38.5% for the 75/60 group and 40.3% for the 60/60 group, 95% confidence interval -14.8 to 18.5, meeting the predefined non-inferiority criterion). The dose reduction rate and incidence of grade 3-4 neutropenia were significantly higher in the 75/60 group. The incidence of neutropenia was significantly higher in those with the non-expressing genotype (GG) compared to the AG or AA genotypes of CYP3A5. We determined that DP 60/60 was not inferior to DP 75/60 in RR, and that the reduced combination dosage provides a better safety profile for patients.

This study was performed to determine the feasibility and safety of salvage chemotherapy, using docetaxel and cisplatin in 5-fluorouracil (5-FU) and cisplatin-pretreated esophageal cancer.Patients with metastatic or recurrent esophageal squamous cell carcinoma that had previously been treated with 5-FU and cisplatin chemotherapy or chemoradiotherapy were eligible for this study. Docetaxel (70 mg/m²) and cisplatin (75 mg/m²) were given as a 1-hour intravenous infusion on day 1, and the treatment was repeated every 3 weeks.Thirty-eight male patients were enrolled, and 35 patients were available for evaluation. The median age was 64.5 years; Eastern Cooperative Oncology Group performance status was 0/1/2 = 2/18/18. The median and total numbers of cycles delivered were 3.5 (range, 1-9 cycles) and 162, respectively. One patient (2.6%) achieved complete response, 12 (31.6%) achieved partial response, 12 (31.6%) had stable disease, and 10 (26.3%) had progressive disease. The overall response rate was 34.2% (95% confidence interval, 19.6-51.3). The median progression-free survival and overall survival times were 4.5 ± 1.3 months (95% CI, 4.1-4.9) and 7.4 ± 0.4 months (95% CI, 7.3-7.5), respectively. The main hematological toxicities greater than grade 3 were neutropenia and leucopenia in 20 (52.6%) and 18 patients (47.3%), respectively. Nonhematological toxicities greater than grade 3 included asthenia in 12 patients (31.6%), nausea in 7 patients (18.4%), and peripheral neuropathy in 6 patients (15.8%).Chemotherapy with docetaxel and cisplatin was an effective and feasible treatment following treatment with 5-FU and cisplatin, and would be considered as a salvage option for patients with refractory esophageal cancer.

Although various combinations of chemotherapy regimens have been tried for patients with esophageal cancer, their duration of survival is extremely poor. In this study, we investigated the safety and clinical efficacy of paclitaxel and cisplatin chemotherapy in metastatic or recurrent esophageal cancer. 32 patients enrolled in this study and the median age was 60 yr. Of all the 32, 28 patients (88%) had been treated previously, 22 of them with chemotherapy or radiation therapy. All patients in the study received biweekly paclitaxel (90 mg/m(2)) followed by cisplatin (50 mg/m(2)). One patient (3%) responded completely, and 12 patients (38%) showed a partial response; in 9 patients (28%) the disease remained stable, and in 10 patients (31%) it progressed. The objective response rate was 41%. The median duration of response was 4.8 months, and the median overall survival in all patients was 7 months. The 1-yr and 2-yr survival rates were 28.1% and 7.1%, respectively. Grade 3 or 4 of neutropenia and anemia were observed in 6 (19%) and 5 (16%) patients, respectively. The major non-hematologic toxicity was fatigue, but most of them could manageable. In conclusion, biweekly paclitaxel and cisplatin is effective in patients with metastatic or recurrent esophageal cancer.

Gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has a response rate of 10% to 20% in refractory non–small cell lung carcinoma. Although female gender, adenocarcinoma, and never having smoked are possible markers of a favorable response, mutations of the EGFR gene have also been reported to be highly significant predictors of response. Seventy patients with relapsed non–small cell lung carcinoma were enrolled in the Expanded Access Program. After the drug became available commercially, 28 more patients were treated with gefitinib. Response evaluations were feasible in 80 patients. Twenty-seven tumor specimens (8 responders and 19 nonresponders) were available for the sequence analysis of the EGFR gene. The response rate was 25% (20/80) and the disease control rate (remission + stable disease) was 47.5% (38/80). The response rate was significantly higher for adenocarcinoma (41.0%) versus non-adenocarcinoma (9.8%, P = 0.001), in those who never smoked (58.8%) versus smokers (15.9%, P < 0.001), and in females (42.1%) versus males (19.7%, P = 0.049). A deletion or mutation of the EGFR gene was found in six of eight responders. Remission was noted in all patients with a mutation, whereas the response rate was 9.5% (2/21) in patients without a mutation (P < 0.001). The predictors of response showed significant correlations with survival and time to progression. In a multivariate logistic analysis, the independent predictors of response were smoking history and adenocarcinoma. Given that 9.5% of smokers and 6.7% of those with non-adenocarcinoma showed a mutation of the EGFR gene, the genetic profile may replace those variables as an independent predictor of a response.

Purpose Belotecan (camtobell™) is a topoisomerase I inhibitor, and effective in small cell lung cancer (SCLC). The objective of this study is to compare the efficacy and safety of belotecan + cisplatin (BP) and etoposide + cisplatin (EP) in first line setting. Methods (materials) This is a multicenter, randomized, prospective controlled trial to prove non-inferiority of BP compared to standard EP regimen. The primary endpoint is overall response rate (ORR), and secondary endpoints are toxicity, overall survival (OS) and progression-free survival (PFS). BP was administrated by belotecan 0.5 mg/m2 for 4 days combined with cisplatin 60 mg/m2 only for first day. Treatment response was evaluated according to version 1.0 of Response Evaluation Criteria in Solid Tumors. Results We enrolled 129 (BP: 63, EP: 66) patients, and response evaluation was possible in 111 (BP: 50, EP: 61) patients. In BP group, there were 1 complete response, 32 partial responses (PR), 7 stable diseases (SD), and there were 33 PR and 11 SD in EP group. There were no significant differences in ORR (BP: 66.0%, EP: 54.1%, p = 0.25) and disease control rate (BP: 80.0%, EP: 72.1%, p = 0.38). Median OS (BP: 483, EP: 340 days, p = 0.21) and PFS (BP: 192, EP: 150 days, p = 0.08) were not significantly different. The frequency of grade ≥ 3 anemia (BP: 29.0%, EP: 7.5%, p Conclusions In this interim analysis, BP and EP have similar ORR, OS and PFS in extensive stage SCLC. Toxicity profiles except anemia and thrombocytopenia were similar between two groups. (ClinicalTrials.gov number, NCT00826644) Disclosure All authors have declared no conflicts of interest.

Purpose: Lung cancer has been the leading cause of death in South Korea since the year 2000. Adenocarcinoma became the most frequent type in the national survey of lung cancer since year 2005. Materials and Methods: We analyzed 5,456 cases with lung cancer from 2004 to 2012 in a community cancer center. The mean age was 69.9 years, and 78.9% was male. Results: Adenocarcinoma (ADC, 40.8%) was the most frequent type, followed by squamous cell carcinoma (SQC, 36.4%), small cell carcinoma (SCC, 14.8%) and non-small cell lung cancer (NSCLC) not otherwise specified (8.1%). In male patients, SQC was the most frequent type (43.5%), while ADC showed highest incidence in females (72.6%). Anatomic stage at diagnosis in NSCLC was I (10.3%), II (5.8%), IIIA (15.7%), IIIB (19.2%), and IV (49.0%). In SCC, 41.7% was in limited stage and 58.3% was diagnosed in extensive stage. The proportion of never smoker has been increased from 19.1% in 2004 ∼2008 to 25.4% in 2009∼2012. Never-smokers are more likely to be female (68.2% vs. 4.0%, p

Background :A lthough smoking is a major cause of chronic obstructive pulmonary disease (COPD), only 10-20% of cigarette smokers develop symptomatic COPD, which suggests the presence of genetic susceptibility. This genetic susceptibility to COPD might depend on variations in the activities of the enzyme that detoxify hazardous chemical products, such as microsomal epoxide hydrolase (mEPHX) and glutathione-S transferase M1 subunit (GSTM1) genes. Methods : The genotypes of 58 patients with COPD, and 79 age matched control subjects, were determined by a polymerase chain reaction, followed by restriction fragment length polymorphism (PCR-RFLP) for the mEPHX, and multiplex PCR for the GSTM1. Results : GSTM1 was deleted in 53.3% of the subjects. There was no difference in GSTM1 deletion rates between the COPD patients (32/58, 55.2%) and the control subjects (41/79, 51.9%). The combination

A 61-yr-old male patient presented with severe chest pain with cardiogenic shock due to an extensive anterolateral myocardial infarction. Two-dimensional echocardiogram showed severe left ventricular systolic dysfunction (ejection fraction=17%). Emergent coronary angiogram obtained immediately after placing temporary pacing electrode revealed total thrombotic occlusion in the left main stem. We performed direct coronary intervention using kissing balloon technique with the aid of Abciximab (ReoPro) infusion. Residual stenosis with thrombus remained even after high pressure balloon dilatations, therefore we placed two stents, one in the ostia of left anterior descending (LAD) and the other in left circumflex artery (LCX). Coronary angiogram after kissing stents showed improved LAD and LCX flows without residual stenosis. Chest pain resolved and blood pressure normalized after coronary intervention. The whole procedure time was 15 min. Follow-up coronary angiogram taken one week later showed patent previous stented arteries, and echocardiography demonstrated 40% of left ventricular ejection fraction. The clinical course for one-year follow-up was uneventful.

Background:An antioxidant, probucol, prevents endothelial dysfunction and low density lipoprotein oxidation and also inhibits the secretion of interleukin-1 by macrophages. These effects of probucol may result in decreased production of matrix metalloproteinases by smooth muscle cells and thus modify remodeling of the extracellular matrix. Methods and Materials:We analyzed clinical events at 1 month and 6 months in 337 patients with 363 coronary arterial lesions after coronary stenting at Chonnam National University Hospital between January 1998 and May 1999. The patients were assigned to following four modalities:500 mg of tilcipidine daily (GroupI), 200 mg of cilostazol daily (Group II), 500 mg of probucol in addition to 500 mg of ticlipidine daily (Group III), and 500 mg of probucol in addition to 200 mg of cilostazol daily (Group IV). All patients received aspirin. Results:GroupIcomprised of 149 (104 M, 45 F, 62±10 years), Group II 96 (73 M, 23 F, 60±10 years), Group III 50 (32 M, 18 F, 61±10 years), and Group IV 42 (32 M, 10 F, 62±10 years) patients. Clinical diagnosis was not different among four groups. Major adverse cardiac events, including myocardial infarction, cardiac death, and repeated intervention, at 1 month were 7 (4.7%) in Group I, 2 (2.1%) in Group II, 0 (0%) in Group III, 2 patients (4.8%) in Group IV, and those at 6 months were 29 (19.5%) in GroupI, 17 (17.7%) in Group II, 9 (18.0%) in Group III, and 6 patients (14.3%) in Group IV. Conclusions:Probucol combined with aspirin and cilostazol has a tendency reducing the major cardiac events compared with aspirin and ticlopidine or cilostazol after stenting. (Korean Circulation J 2000;30(7):811-818)

Background: Glutathione peroxidase 3 (GPx3) which is an extracellular secretory protein is down regulated in patients with early stage lung cancer. We examined the usefulness of serum GPx3 as a biomarker for monitoring of relapse after surgery. Methods: We prospectively collected serial serum samples at baseline, 3 months (3m), 6 months (6m), and 12 months (12m) after operation from the patients who underwent surgery during the year 2013. GPx3 levels were measured three times per sample using the enzyme-linked immunosorbent assay, and the mean values were analyzed by t-test and paired t-test. Results: A total of 170 (100 adenocarcinoma, 41 squamous cell carcinoma, 29 others) patients were analyzed in this study. Mean age was 64.1 years old (range, 39-80) and 27 (15.9%) out of 165 lung cancer patients were confirmed relapse during the median follow-up period of 597.5 days (range, 5-938). The mean GPx3 value at postoperative 6m was significantly elevated in relapsed group than control group (7.90 ± 2.44 mg/mL vs. 6.99 ± 1.79 mg/mL, p1⁄40.047). The mean GPx3 differences were significantly higher in relapsed group than control group at 3m (-0.38 ± 0.39 mg/mL vs. -0.21 ± 0.36 mg/mL, p1⁄40.044), 6m (-0.37 ± 0.42 mg/mL vs. -0.19 ± 0.30 mg/mL, p1⁄40.024), and 12m (-0.38 ± 0.42 mg/mL vs. -0.19 ± 0.28 mg/mL, p1⁄40.012). The mean time to relapse was significantly shorter in high level of GPx3 group at postoperative 3m (694.83 ± 31.86 days vs. 839.05 ± 24.31 days, p1⁄40.007). The mean time to relapse was significantly shorter in high GPx3 difference group between baseline and postoperative 3m (729.76 ± 34.89 days vs. 838.18 ± 24.03 days, p1⁄40.002). Conclusion: Serum mean GPx3 value at postoperative 6m and the mean GPx3 difference were significantly elevated in relapsed lung cancer. The mean time to relapse was significantly shorter in high level of GPx3 group at postoperative 3m. More large scaled validation studies are warranted.