Ju Sik Yun

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.

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).

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.

Epithelioid Hemangioendothelioma Arising from Interanl Jugular Vein Mimicking Cervical Metastatic Lymphadenopathy.

Epithelioid hemangioendothelioma (EHE) is a relatively rare and moderately aggressive type of vascular tumor. We describe a case of EHE that presented in a 24-year-old woman as a palpable nodule in the left cervical area. Radiological examinations and fine-needle aspiration cytology led to a preliminary diagnosis of metastatic lymphadenopathy with an unknown primary site. However, during surgery, we determined that the nodule was an intra-vascular tumor arising from the left internal jugular vein. The histopathological examination revealed cords of epithelioid endothelial cells distributed in a hyaline stroma, compatible with a diagnosis of EHE.

Mixed squamous cell and glandular papilloma of the lung in a 64-year-old woman.

Mixed squamous cell and glandular papilloma of the lung is an extremely rare benign epithelial tumor showing a mixture of squamous and glandular epithelium. Here, we report a case of mixed squamous cell and glandular papilloma that presented as a solitary nodule in the left lower lobe of a 64-year-old woman. Chest computed tomography demonstrated a lobulated mass in the basal segment of the left lower lobe. The patient underwent a lobectomy under the suspicion of lung malignancy. The histopathological diagnosis was mixed squamous cell and glandular papilloma.

Metastatic Pulmonary Ameloblastoma Misdiagnosed as Primary Squamous Cell Carcinoma Preoperatively

Ameloblastomas are rare odontogenic epithelial tumors that occur mainly in the mandible. Despite their benign histologic appearance, they are locally aggressive with a high recurrence rate. However, a metastasizing ameloblastoma has been rarely reported. According to the current World Health Organization classification system, the definitive diagnosis of metastasizing ameloblastoma can only be carried out in retrospect, after the event of metastasis. This case report describes a patient with metastatic pulmonary ameloblastoma, 17 years after the surgical excision of an odontogenic tumor, preoperatively misdiagnosed as primary squamous cell carcinoma.

Combined Epithelioid Trophoblastic Tumor and Contralateral Synchronous Adenocarcinoma of the Lungs in a 69-Year-Old Man

An epithelioid trophoblastic tumor (ETT) is a form of gestational trophoblastic neoplasms that arise from trophoblasts. The tumor generally occurs in women of reproductive age and has a characteristic growth pattern and immunohistochemical profile. We present an extremely rare case of a primary ETT occurring in the lungs with an adenocarcinoma in the contralateral lung as synchronous double primary lung cancers in a 69-year-old man who had no history of a remote malignancy. He underwent adjuvant radiotherapy to both lungs after a staged thoracoscopic wedge resection and was doing well without recurrence or metastasis up to last follow-up.

Surgery for hemoptysis in patients with benign lung disease

Background Hemoptysis can be a life-threatening condition that requires urgent treatment. Surgery still plays an important role in managing this critical situation, although previous reports have reported high postoperative morbidity and mortality rates. We report our experience with surgical resection for hemoptysis caused by benign lung diseases. Methods We reviewed the retrospectively collected data from 94 patients undergoing pulmonary resection for various benign lung diseases with hemoptysis at a single institution from 2010 to 2016. Baseline characteristics, surgical factors, and postoperative outcomes (morbidity and mortality rates) were analyzed. Results The ratio of male to female patients was 1:1, and the mean age was 58.2±11.1 (range, 29-79) years. The etiology of hemoptysis included aspergilloma in 58 patients (61.7%), bronchiectasis in 10, tuberculosis in 7, necrotizing bronchiolitis in 6, and other inflammatory disease in 13. A total of 21 patients (22.3%) underwent emergency operation, and 73 (77.7%) had an elective operation. Pulmonary resection was performed by thoracotomy (n=53, 56.4%) and video-assisted thoracoscopic surgery (VATS) (n=41, 43.6%). Sublobar resection (n=50, 53.2%, segmentectomy in 19 and wedge resection in 31) was performed more often than lobectomy (n=35, 37.2%). Pneumonectomy was performed in 7 patients, and bilobectomy was performed in 2. Postoperative morbidity occurred in 23 patients (24.5%), with prolonged air leak being the most frequent complication (n=14, 14.9%). The in-hospital mortality rate was 3.2% (n=3). Complications were less frequent in patients undergoing an elective operation, VATS, and sublobar resection. Multivariate analysis showed that patients treated with VATS had a decreased risk of postoperative complications (odds ratio, 12.8; 95% confidence interval, 1.29-127.9; P=0.03). Conclusions Surgical resection for hemoptysis in patients with benign lung diseases is the mainstay of effective treatment with acceptable morbidity and mortality rates. If applicable, we recommend elective (planned) sublobar resection using VATS in order to improve postoperative outcomes.