Sang Yun Song

Integrative and Comparative Genomic Analysis of Lung Squamous Cell Carcinomas in East Asian Patients

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.

Learning curves of minimally invasive esophageal cancer surgery

BACKGROUND Minimally invasive esophageal cancer surgery (MIES) has been performed at some experienced health centers. MIES has shown to be feasible and safe in esophageal cancer surgery. However, there are a few reports concerning the learning curve of MIES. METHODS From 2004 to 2007, MIES was performed in 28 patients by a single surgeon. This amount includes total MIES that contained thoracoscopic esophagectomy, laparoscopic gastric preparation, cervical anastomosis and hybrid MIES that contained only one scope surgery. Surgical outcomes and clinical factors in the first 14 patients (group A) and the other 14 patients (group B) were compared. RESULTS There were no differences in clinical factors between the two groups. Total MIES was completed in 14 patients, while 13 patients underwent hybrid MIES. There were 6 cases of emergent conversion to open procedures; one case was a thoracotomy and 5 cases were a laparotomy. Chest, abdominal, and total operation time were shorter in group B (p<0.05). The amount of red cell transfusions and intensive care unit stay times were less in the total MIES group (p<0.05). There was one hospital mortality due to acute respiratory distress syndrome. Postoperative complication rate was 43%. CONCLUSIONS As cases increase, surgical outcomes have improved. We think that this report showed a substantial learning curve for a complex surgery such as MIES.

Tension Pneumothorax after Endoscopic Retrograde Pancreatocholangiogram

We report a case of tension pneumothorax after an endoscopic sphincterotomy. A 78-yr-old woman presented with progressing dyspnea. She had undergone an endoscopic retrograde cholangiopancreatogram three days before due to acute cholecystitis. She underwent endoscopic sphincterotomy for stone extraction, but the procedure failed. On arrival to our hospital, she complained about severe dyspnea and she had subcutaneous emphysema. A computed tomogram scan revealed severe subcutaneous emphysema, right-side tension pneumothorax, and pneumoretroperitoneum. Contrast media injected through a transnasal biliary drainage catheter spilled from the second portion of the duodenum. A second abdominal computed tomogram showed multiple air densities in the retroperitoneum and peritoneal cavity, which were consistent with panperitonitis. We recommended an emergent laparotomic exploration, but the patients guardians refused. She died eventually due to septic shock. Endoscopic retrograde cholangiopancreatogram is a popular procedure for biliary and pancreatic diseases, but it can cause severe complications such as intestinal perforation. Besides perforations, air can spread through the abdominal cavity, retroperitoneum, mediastinum, and the neck soft tissue, eventually causing pneumothorax. Early recognition and appropriate management is crucial to an optimal output of gastrointestinal perforation and pneumothorax.

Factors influencing oncological outcomes in patients who develop pulmonary metastases after curative resection of colorectal cancer.

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.

Retrospective Analysis of Thoracoscopic Surgery for Esophageal Submucosal Tumors

Background Surgical enucleation is the treatment of choice for esophageal submucosal tumors (SMTs) with symptomatic, larger, or ill-defined lesions. The enucleation of SMTs has traditionally been performed via thoracotomy. However, minimally invasive approaches have recently been introduced and successfully applied. In this study, we present our experiences with the thoracotomic and thoracoscopic approaches to treating SMTs. Methods We retrospectively reviewed 53 patients with SMTs who underwent surgical enucleation between August 1996 and July 2013. Demographic and clinical features, tumor-related factors, the surgical approach, and outcomes were analyzed. Results There were 36 males (67.9%) and 17 females (32.1%); the mean age was 49.2±11.8 years (range, 16 to 79 years). Histology revealed leiomyoma in 51 patients, a gastrointestinal stromal tumor in one patient, and schwannoma in one patient. Eighteen patients (34.0%) were symptomatic. Fourteen patients underwent a planned thoracotomic enucleation. Of the 39 patients for whom a thoracoscopic approach was planned, six patients required conversion to thoracotomy because of overly small tumors or poor visualization in five patients and accidental mucosal injury in one patient. No mortality or major postoperative complications occurred. Compared to thoracotomy, the thoracoscopic approach had a slightly shorter operation time, but this difference was not statistically significant (120.0±45.6 minutes vs. 161.5±71.1 minutes, p=0.08). A significant difference was found in the length of the hospital stay (9.0±3.2 days vs. 16.5±5.4 days, p<0.001). Conclusion The thoracoscopic enucleation of submucosal esophageal tumors is safe and is associated with a shorter length of hospital stay compared to thoracotomic approaches.

Mediastinal thoracic duct cyst adjacent to left pericardium

Fig. 1. A chest computed tomography showed a 5.5 4.5 cm sized, homogeneous, non-enhancing cystic mass with a well-defined border, situated beside the left pericardium superior to the diaphragm (A, B). Thoracoscopic view of the cyst, located at the left cardiophrenic angle which was adherent to the diaphragm and pericardium anterior to the phrenic nerve. The wall was smooth and somewhat transparent (C). The retrieved cyst filled with saline (D) (P: pericardium, L: collapsed lung, and Arrow: phrenic nerve).

Integrative analysis for the discovery of lung cancer serological markers and validation by MRM-MS

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.

Predictive Value of Procalcitonin for Infection and Survival in Adult Cardiogenic Shock Patients Treated with Extracorporeal Membrane Oxygenation

Procalcitonin (PCT) is a predictive marker for the occurrence of bacterial infection and the decision to terminate antibiotic treatment in critically ill patients. An unusual increase in PCT, regardless of infection, has been observed during extracorporeal membrane oxygenation (ECMO) support. We evaluated trends and the predictive value of PCT levels in adult cardiogenic shock during treatment with ECMO. We reviewed the clinical records of 38 adult cardiogenic shock patients undergoing veno-arterial ECMO support between January 2014 and December 2016. The exclusion criteria were age <18 years, pre-ECMO infection, and less than 48 hours of support. The mean patient age was 56.7±14.7 years and 12 (31.6%) patients were female. The mean duration of ECMO support was 9.0±7.6 days. The rates of successful ECMO weaning and survival to discharge were 55.3% (n=21) and 52.6% (n=20), respectively. There were 17 nosocomial infections in 16 (42.1%) patients. Peak PCT levels (mean 25.6±9.4 ng/mL) were reached within 48 hours after initiation of ECMO support and decreased to ≤5 ng/mL within one week. The change in PCT levels was not useful in predicting the occurrence of new nosocomial infections during the ECMO run. However, a PCT level >10 ng/mL during the first week of ECMO support was significantly associated with mortality (p<0.01). The change in PCT level was not useful in predicting new infection during ECMO support. However, higher PCT levels within the first week of the ECMO run are associated with significantly higher mortality.

Nosocomial Infection in Adult Patients Undergoing Veno-Arterial Extracorporeal Membrane Oxygenation

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.

Diffuse Large B-cell Lymphoma Arising from Chronic Tuberculous Empyema.

Pyothorax-associated lymphoma is a relatively rare type of lymphoma that occurs in patients who have long histories of tuberculous pleuritis or induced pneumothorax. It is a type of non-Hodgkin’s lymphoma of mainly the B-cell phenotype and is strongly associated with Epstein–Barr virus infection. A majority of these cases have been reported in Japan, although some cases have occurred in Western countries. Here, we describe a case of pyothorax-associated lymphoma in a patient with a 30-year history of chronic tuberculous empyema. The patient underwent decortication under the impression of chronic empyema with fistula. The histopathologic diagnosis was a diffuse large B-cell lymphoma associated chronic inflammation.