Keon Hyon Jo

Alterations of Fas-pathway genes associated with nodal metastasis in non-small cell lung cancer.

Many types of cancer cells are resistant to Fas-mediated apoptosis by several mechanisms, including the mutations of the genes involved in Fas-mediated apoptosis. In this study, to explore the possibility that the mutations of the genes involved in the proximal pathway of Fas-mediated apoptosis (Fas, FADD, caspase 8 and caspase 10) are involved in cancer metastasis, we have analysed somatic mutation and deletion of these genes in 80 non-small cell lung cancers (NSCLCs) with (n=43) and without (n=37) metastasis to the regional lymph nodes. We found 12 mutations (four Fas, four FADD, and four caspase 10 mutations) in 11 of 80 NSCLCs (13.8%). Interestingly, of these mutations, most mutations (10 out of 12) were detected in the NSCLCs with metastasis, and the frequency in the metastasis lesions (23%) was higher than that in the primary lesions of the NSCLCs without metastasis (5.4%). Furthermore, transfection study revealed that the tumor-derived mutants have decreased apoptosis inductions compared to the wild types. These data suggest that the inactivating mutations of the genes in the proximal pathway of Fas-mediated apoptosis may lead to a decreased cancer cell death and play a role in the metastasis of NSCLC.

What Factors Predict Recurrence after an Initial Episode of Primary Spontaneous Pneumothorax in Children

PURPOSE Recurrence is the most common complication after an initial episode of primary spontaneous pneumothorax (PSP). However, preventive surgery in children remains a controversial issue. The purpose of this study was to determine predictive factors of recurrence to better inform early surgical referrals. METHODS We retrospectively reviewed all consecutive patients under 18 years of age who conservatively treated for an initial episode of PSP between March 2005 and September 2011. RESULTS One hundred fourteen patients were included in this study. The mean follow-up period was 43.1 months. Ipsilateral and contralateral recurrence developed in 47.3% and 14.0% of patients. The risk of ipsilateral recurrence for patients with or without air-containing lesions according to high-resolution computed tomography (HRCT) was 60.3% and 31.4%. In the multivariate analysis, the presence of air-containing lesions on HRCT scans and bullae on chest X-rays were independent risk factors for ipsilateral recurrence. CONCLUSION The presence of bleb or bullae on HRCT scans or chest X-rays after an initial episode of PSP was significantly related to the ipsilateral recurrence in children. If the risk factors are clarified in further studies, hospital stays and the recurrence of PSP after the first episode could be reduced with early video-assisted thoracoscopic surgery.

Thoracic Air-leak Syndromes In Hematopoietic Stem Cell Transplant Recipients with Graft-versus-Host Disease: A Possible Sign for Poor Response to Treatment and Poor Prognosis

Bronchiolitis obliterans (BO) or bronchiolitis obliterans organizing pneumonia (BOOP) is one of manifestations of graft-versus-host disease (GVHD), a complication of hematopoietic stem cell transplantation (HSCT). Recently there are reports about thoracic air-leakage syndrome (TALS), but real incidence, clinical course, and implications of TALS remain unclear. Retrospective review of 18 TALS patients among 2,177 patients who received allogeneic HSCT between January 2000 to July 2007 was done. Clinical manifestations, treatments, and outcomes of TALS were reviewed. The incidence of TALS was 0.83% (18/2,177). The onset of TALS was mean 425.9±417.8 days (60-1,825 days) after HSCT, and the duration was mean 16.3±21 days (2-90 days). The most common types of TALS were spontaneous pneumothroax (n=14), followed by subcutaneous emphysema (n=6), pneumomediastinum (n=5), interstitial emphysema (n=2), and pneumopericardium (n=1). TALS persisted in six patients, who died during the same hospitalization. The 12 patients recovered from TALS, but only 2 survived, while others died due to aggravation of GVHD. TALS may complicate BO/BOOP and be an initial manifestation of BO/BOOP. TALS is hard to be resolved, and even after the recovery, patients die because of aggravation of GVHD. We suggest specifically in HSCT patients, when once developed, TALS seems hard to be cured, and as a result, be related to high fatality.

Lung Cancer Associated with Sarcoidosis - A case report -

Sarcoidosis is a somewhat common pulmonary disease, but the concurrence of lung cancer and sarcoidosis in the same patient is very rare. Because sarcoidosis usually presents as mediastinal lymphadenopathies, this concurrence in a lung cancer patient detected radiologically is apt to be misunderstood to be mediastinal metastases, and it is thus considered to be an unresectable disease. We report a case of lung cancer associated with sarcoidosis that developed in a 65-year-old woman who underwent surgery. Radiological studies revealed a 1.9×1.7 cm mass in the left upper lobe with multiple enlarged bilateral mediastinal lymph nodes (2R, 3a, 4R, 4L, 5, 6, 7, 8R). Pathologic findings showed that the mass was a well-differentiated adenocarcinoma and all of the enlarged mediastinal lymph nodes were granulomas without cancer metastasis. We report this case with a review of the literature.

Adventitial fibroblast abormality in thoracic aortic aneurysms and aortic dissections.

Background Development of thoracic aortic aneurysms and aortic dissections (TAAD) is attributed to unbearable wall tension superimposed on defective aortic wall integrity and impaired aortic repair mechanisms. Central to this repair mechanisms are well-balanced and adequately functional cellular components of the aortic wall, including endothelial cells, smooth muscle cells (SMCs), inflammatory cells, and adventitial fibroblasts. Adventitial fibroblasts naturally produce aortic extracellular matrix (ECM), and, when aortic wall is injured, they can be transformed into SMCs, which in turn are involved in aortic remodeling. We postulated the hypothesis that adventitial fibroblasts in patients with TAAD may have defects in ECM production and SMC transformation. Materials and Methods Adventitial fibroblasts were procured from the adventitial layer of fresh aortic tissues of patients with TAAD (Group I) and of multi-organ donors (Group II), and 4-passage cell culture was performed prior to the experiment. To assess ECM production, cells were treated with TNF-α (50 pM) and the expression of MMP-2 / MMP-3 was analyzed using western blot technique. To assess SMC transformation capacity, cells were treated with TGF-β1 and expression of SM α-actin, SM-MHC, Ki-67 and SM calponin was evaluated using western blot technique. Fibroblasts were then treated with TGF-β1 (10 pM) for up to 10 days with TGF-β1 supplementation every 2 days, and the proportion of transformed SMC in the cell line was measured using immunofluorescence assay for fibroblast surface antigen every 2 days. Results MMP-3 expression was significantly lower in group I than in group II. TGF-β1-stimulated adventitial fibroblasts in group I expressed less SM α-actin, SM-MHC, and Ki-67 than in group II. SM-calponin expression was not different between the two groups. Presence of fibroblast was observed on immunofluorescence assay after more than 6 days of TGF-β1 treatment in group I, while most fibroblasts were transformed to SMC within 4 days in group II. Conclusion ECM production and SMC transformation are compromised in adventitial fibroblasts from patients with TAAD. This result suggests that functional restoration of adventitial fibroblasts could well be a novel approach for the prevention and treatment of TAAD.

Neurologic outcomes after early surgery for infective endocarditis in patients with combined cerebral septic embolism

Objectives This study followed the results of any development of neurologic outcomes according to the presence or absence of cerebral stroke in infective endocarditis patients after early cardiac surgery. We also analysed the neurologic outcomes regardless of cerebral microbleeds in cerebral embolic patients after cardiac surgery. Methods We retrospectively studied 55 patients with left-sided infective endocarditis who underwent early surgery and hospitalization between May 2010 and May 2015. Preoperatively, there were 33 patients in the cerebral embolic group and 22 patients in the non-embolic event group. Among the cerebral embolic patients, 13 patients had additional cerebral microbleeds on brain imaging. Results After cardiac surgery, intracranial haemorrhage and haemorrhagic complications occurred in 2 patients (9.1%) in the non-embolic group and 5 patients (15.1%) in the embolic group. There was no statistically significant difference in postoperative neurologic problems between the non-embolic group and the embolic group (22.7% vs 30.3%, respectively, P  = 0.54). Early mortality was 4.5% in the non-embolic group and 9.1% in the embolic group ( P  = 1.00). In the cerebral microbleeds combined with septic embolism group, the neurologic problem rate (38.5%) was higher than in the non-cerebral microbleeds group (20.0%), but the difference was not statistically significant. Conclusions Our analysis showed that the rate of postoperative neurologic problems was not high in patients with cerebral septic embolism. Despite this, early surgery is not contraindicated in cerebral septic emboli patients. Cerebral microbleeds related to septic embolism were suspected to increase the rate of neurologic problems after cardiac surgery. So, further studies are needed to assess about the influence of cerebral microbleeds in cardiac operation.

Emerging Fixation Technique to Prevent Pectus Bar Displacement: Needlescope-Assisted 3-Point Fixation

BACKGROUND Bar flipping displacement is one of the most common complications after the Nuss procedure for pectus excavatum. We evaluated the results of a modified Nuss procedure with needlescope-assisted bar fixation. METHODS The records of 41 patients with pectus excavatum who underwent single pectus bar insertion with the Nuss procedure between July 2011 and August 2014 were retrospectively reviewed. The patients were divided into two groups: those who did not undergo 3-point fixation (group A) and those who did undergo 3-point fixation (group B). RESULTS There were 36 male patients and 5 female patients with a mean age of 10.7 ± 8.3 years (range: 3-36 years). The postoperative Haller index (HI) (2.61 ± 0.42) was significantly lower than the preoperative HI (3.91 ± 1.07; p < 0.01). The angle of the initial bar position was 5.59 ± 7.37 degrees in group A and 8.52 ± 9.61 degrees in group B, with no significant difference between the groups (p > 0.05). The rate of reoperation to correct bar displacement was lower in group B (3.3%) than in group A (9.1%). CONCLUSION Needlescope-assisted 3-point fixation of the bar was performed without an additional skin incision and showed a low rate of reoperation to correct displacement of the pectus bar.

Extracorporeal Life Support in Patients with Hematologic Malignancies: A Single Center Experience

Background Extracorporeal life support (ECLS) in patients with hematologic malignancies is considered to have a poor prognosis. However, to date, there is only one case series reported in the literature. In this study, we compared the in-hospital survival of ECLS in patients with and without hematologic malignancies. Methods We reviewed a total of 66 patients who underwent ECLS for treatment of acute respiratory failure from January 2012 to December 2014. Of these patients, 22 (32%) were diagnosed with hematologic malignancies, and 13 (59%) underwent stem cell transplantation before ECLS. Results The in-hospital survival rate of patients with hematologic malignancies was 5% (1/22), while that of patients without malignancies was 26% (12/46). The number of platelet transfusions was significantly higher in patients with hematologic malignancies (9.69±7.55 vs. 3.12±3.42 units/day). Multivariate analysis showed that the presence of hematologic malignancies was a significant negative predictor of survival to discharge (odds ratio, 0.07; 95% confidence interval, 0.01–0.79); p=0.031). Conclusion ECLS in patients with hematologic malignancies had a lower in-hospital survival rate, compared to patients without hematologic malignancies.

Open Surgical Repair Using the Femoral Vein for a Mycotic Superior Mesenteric Artery Aneurysm

Superior mesenteric artery (SMA) aneurysms are rare and often fatal. A 72-year-old man had previously been admitted to the emergency room with epigastric pain and heart murmur. The echocardiographic diagnosis was vegetation on the aortic and mitral valves, with moderate regurgitation from both valves due to infective endocarditis. No aneurysm was detected on abdominal computed tomography, and emergency double-valve replacement was performed. On postoperative day 25, the patient experienced abrupt abdominal pain, and computed tomography revealed a mycotic SMA aneurysm. Open surgical repair of the SMA aneurysm was performed using the femoral vein, and the patient’s postoperative course was uneventful.

Surgical Management of a Coronary-Bronchial Artery Fistula Combined with Myocardial Ischemia Revealed by 13 N-Ammonia Positron Emission Tomography

A 71-year-old male with known bronchiectasis and atrial fibrillation was admitted to Seoul St. Mary’s Hospital with recurrent transient ischemic attack. Radiofrequency ablation was performed to resolve the patient’s atrial fibrillation, but failed. However, a fistula between the left circumflex artery and the bilateral bronchial arteries was found on computed tomography. Fistula ligation and a left-side maze operation were planned due to his recurrent symptom of dizziness, and these procedures were successfully performed. After the operation, the fistula was completely divided and no recurrence of atrial fibrillation took place. A coronary-bronchial artery fistula is a rare anomaly, and can be safely treated by surgical repair.