Kook Joo Na

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.

Predictive factors for the second restenosis after coronary interventions

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 B2 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 patients subjective symptom and lesion severer than type B2 according to AHA/ACC classification. Cathet. Cardiovasc. Intervent. 50:34–39, 2000.

Integrated genomic analysis of recurrence-associated small non-coding RNAs in oesophageal cancer

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 datasets. Results We developed a risk assessment score (RAS) for recurrence with three sncRNAs (microRNA (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 (HR, 2.27; 95% CI, 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 inhibitors, mammalian target of rapamycin (mTOR) inhibitors, and histone deacetylase 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, tumour-specific biological approach will potentially contribute to significant improvement in ESCC treatment.

Traumatic rupture of the coronary sinus following blunt chest trauma: a case report

Cardiac rupture is rare but potentially life-threatening complication after chest trauma. We present the case of a 57-year-old male who developed cardiac arrest because of extensive pericardial tamponade after a falling injury. We decided to perform an exploratory sternotomy in the operating room (OR). The patient was transported to the OR on extracorporeal membrane oxygenation (ECMO) support. We found a rupture of the coronary sinus after evacuation of an extensive hematoma in the pericardium and primarily repaired the injured site. After 2 days, the patient died due to refractory cardiogenic shock. To our knowledge, this is the first reported case of rupture of the coronary sinus after blunt chest trauma.

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.

Chemical Pleurodesis Using Mistletoe Extraction (ABNOVAviscum® Injection) for Malignant Pleural Effusion

PURPOSE Malignant pleural effusion (MPE) is common in patients with advanced cancer. Chemical pleurodesis can be considered for MPE that do not respond to chemotherapy, radiotherapy, or therapeutic thoracentesis. However, it is not yet clear which agent is more effective and safer in chemical pleurodesis. METHODS This study was designed as a single arm, multicenter, and open-label phase III clinical trial to evaluate efficacy and safety of chemical pleurodesis using mistletoe extraction (ABNOVAviscum(®) Injection). References of other agents in chemical pleurodesis were investigated to compare efficacy and safety. Efficacy was evaluated by followed up chest X-ray and changes of clinical symptoms and Karnofsky performance scale. Safety was evaluated by serious adverse event (SAE) and changes of laboratory findings. A follow-up period was 4 weeks after last pleurodesis. RESULTS Of 62 patients, 49 (79.0%) had complete response, 11 (17.7%) had partial response, and two had no response. Mean response rate was significantly different in this study comparing with reference response rate which was 64% (p <0.0001). There were two SAEs, but all were recovered without sequelas. CONCLUSION The results of this study suggest that mistletoe extraction (ABNOVAviscum(®) Injection) could be an effective and safe agent of chemical pleurodesis in patients with MPE.

Timing in resolution of left heart dilation according to the degree of mitral regurgitation in children with ventricular septal defect after surgical closure

OBJECTIVE Children with ventricular septal defects (VSD) can have chronic volume overload, which can result in changes of left heart echocardiographic parameters. To evaluate the changes before and after surgical closure, the children were divided into three groups according to the degree of mitral regurgitation (MR), and their echocardiographic characteristics were reviewed at serial follow-up after surgical closure. METHODS The preoperative, and one-, three-, and 12-month postoperative echocardiographic data of 40 children who underwent surgical closure of VSD were retrospectively reviewed. Left ventricular end-diastolic volume (LVEDV), left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD), mitral valvular characteristics, including degree of MR and mitral valve annulus, and left atrial (LA) characteristics, including volume and dimensions, were observed. RESULTS Preoperative LVEDV, LVEDD, LVESD, mitral valvular annulus, LA volume, and LA dimensions were significantly larger in children with MR. Additionally, there were significant decreases in LVEDV, LVEDD, LA volume, and LA dimensions at one, three, and 12 months postoperatively. The degree of MR also improved to a lower grade after surgical closure of the VSD without additional mitral valve repair. CONCLUSION The echocardiographic parameters of left heart dilation and MR in children with VSD improved within the first year after surgical closure without additional mitral valve repair. Furthermore, in all of the patients with VSD, regardless of MR, LA dilation was reduced within three months after surgical closure of the VSD; however, LV and mitral valve annular dilatation decreased within 12 months.

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).