The Role of Adjuvant Therapy Following Surgical Resection of Small Cell Lung Cancer: A Multi-Center Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This multi-center, retrospective study was conducted to evaluate the long-term survival in patients who underwent surgical resection for small cell lung cancer (SCLC) and to identify the benefit of adjuvant therapy following surgery. @*Materials and Methods@#The data of 213 patients who underwent surgical resection for SCLC at four institutions were retrospectively reviewed. Patients who received neoadjuvant therapy or an incomplete resection were excluded. @*Results@#The mean patient age was 65.29±8.93 years, and 184 patients (86.4%) were male. Lobectomies and pneumonectomies were performed in 173 patients (81.2%), and 198 (93%) underwent systematic mediastinal lymph node dissections. Overall, 170 patients (79.8%) underwent adjuvant chemotherapy, 42 (19.7%) underwent radiotherapy to the mediastinum, and 23 (10.8%) underwent prophylactic cranial irradiation. The median follow-up period was 31.08 months (interquartile range, 13.79 to 64.52 months). The 5-year overall survival (OS) and disease-free survival were 53.4% and 46.9%, respectively. The 5-year OS significantly improved after adjuvant chemotherapy in all patients (57.4% vs. 40.3%, p=0.007), and the survival benefit of adjuvant chemotherapy was significant in patients with negative node pathology (70.8% vs. 39.7%, p=0.004). Adjuvant radiotherapy did not affect the 5-year OS (54.6% vs. 48.5%, p=0.458). Age (hazard ratio [HR], 1.032; p=0.017), node metastasis (HR, 2.190; p < 0.001), and adjuvant chemotherapy (HR, 0.558; p=0.019) were associated with OS. @*Conclusion@#Adjuvant chemotherapy after surgical resection in patients with SCLC improved the OS, though adjuvant radiotherapy to the mediastinum did not improve the survival or decrease the locoregional recurrence rate.

Relative infectivity of the SARS-CoV-2 Omicron variant in human alveolar cells

With the emergence of multiple highly transmissible SARS-CoV-2 variants during the recent pandemic, the comparison of their infectivity has become a substantially critical issue for public health. However, a direct assessment of these viral characteristics has been challenging due to the lack of appropriate experimental models and efficient methods. Here, we integrated human alveolar organoids and single-cell transcriptome sequencing techniques to facilitate the evaluation. In a proof-of-concept study using the assay with four highly transmissible SARS-CoV-2 variants, including GR (B.1.1.119), Alpha (B.1.1.7), Delta (B.1.617.2), and Omicron (BA.1), a rapid evaluation of the relative infectivity was possible. Our results demonstrate that the Omicron (BA.1) variant is 3-5-fold more infectious to human alveolar cells than the other SARS-CoV-2 variants at the early phase of infection. To our knowledge, this study provides the first direct measurement of the infectivity of the Omicron variant and new experimental procedures that can be applied for monitoring newly emerging viral variants.

Discovery of potential imaging and therapeutic targets for severe inflammation in COVID-19 patients

The COVID-19 pandemic has caused more than 540,000 deaths globally. Hyperinflammation mediated by dysregulated monocyte/macrophage function is considered to be the key factor that triggers severe illness in COVID-19. However, no specific targeting molecule has been identified for detecting or treating hyperinflammation related to dysregulated macrophages in severe COVID-19. Herein, we suggest candidate targets for imaging and therapy in severe COVID-19 by analyzing single-cell RNA-sequencing data based on bronchoalveolar lavage fluid of COVID-19 patients. We found that expression of SLC2A3, which can be imaged by [18F]fluorodeoxyglucose, was higher in macrophages from severe COVID-19 patients. Furthermore, by integrating the surface target database and drug-target binding database with RNA-sequencing data of severe COVID-19, we identified CCR1 and FPR1 as surface and druggable targets for drug delivery as well as molecular imaging. Our results provide a resource for candidate targets in the development of specific imaging and therapy for COVID-19-related hyperinflammation.

Robust three-dimensional expansion of human adult alveolar stem cells and SARS-CoV-2 infection

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), which is the cause of a present global pandemic, infects human lung alveolar cells (hACs). Characterising the pathogenesis is crucial for developing vaccines and therapeutics. However, the lack of models mirroring the cellular physiology and pathology of hACs limits the study. Here, we develop a feeder-free, long-term three-dimensional (3D) culture technique for human alveolar type 2 (hAT2) cells, and investigate infection response to SARS-CoV-2. By imaging-based analysis and single-cell transcriptome profiling, we reveal rapid viral replication and the increased expression of interferon-associated genes and pro-inflammatory genes in infected hAT2 cells, indicating robust endogenous innate immune response. Further tracing of viral mutations acquired during transmission identifies full infection of individual cells effectively from a single viral entry. Our study provides deep insights into the pathogenesis of SARS-CoV-2, and the application of long-term 3D hAT2 cultures as models for respiratory diseases.

Current Issues in Minimally Invasive Esophagectomy

Minimally invasive esophagectomy (MIE) was first introduced in the 1990s. Currently, itis a widely accepted surgical approach for the treatment of esophageal cancer, as it isan oncologically sound procedure; its advantages when compared to open procedures,including reduction in postoperative complications, reduction in the length of hospitalstay, and improvement in quality of life, are well documented. However, debates are stillongoing about the safety and efficacy of MIE. The present review focuses on some of thecurrent issues related to conventional MIE and robot-assisted MIE based on evidence fromthe current literature.

Efficacy and Cost-effectiveness of Surgical Biopsy for Histologic Diagnosis of Indeterminate Nodules Suspected for Early Stage Lung Cancer: Comparison with Percutaneous Needle Biopsy

Background@#Indeterminate pulmonary nodules (IPN) suspected for early stage lung cancer mandate accurate diagnosis. Both percutaneous needle biopsy (PCNB) and surgical biopsy (SB) are valuable options. The present study aimed to compare the efficacy and cost-effectiveness between PCNB and SB for IPN suspected for early stage lung cancer. @*Methods@#During January–November 2018, patients who underwent operation for IPN suspected for early stage lung cancer (SB group, n = 245) or operation after PCNB (PCNB group, n = 113) were included. Patient-level cost data were extracted from medical bills from the institution. Propensity score matching was performed between the two groups from a retrospectively-collected database. @*Results@#Fifteen patients (11.5%) had complications after PCNB; thirteen (11.5%) were not confirmed to have lung cancer through PCNB but underwent operation for IPN. In SB group, 172 (70.2%) and 7 (2.9%) patients underwent wedge resection and segmentectomy for SB, respectively; 66 patients (26.9%) underwent direct lobectomy without SB. After propensity score matching, 58 paired samples were produced. Most patients in PCNB group were admitted twice (n = 55, 94.8%). The average hospital stay was longer in PCNB group (12.9 ± 5.3 vs. 7.3 ± 3.0, P < 0.001). Though the cost of the operation was comparable (USD 12,509 ± 2,909 vs. 12,669 ± 3,334; P = 0.782), the total cost was higher for PCNB group (USD 14,403 ± 3,085 vs. 12,669 ± 3,334; P = 0.006). The average subcategory cost, which increases proportional to hospital stay, was higher in PCNB group, whereas the cost of operation and surgical materials were comparable between the two groups. @*Conclusion@#Lung cancer operation following SB for IPN was associated with lesser cost, shorter hospital stays, and lesser admission time than lung cancer operation after PCNB. The increased cost and longer hospital stay appear largely related to the admission for PCNB.

Primary Extraskeletal Osteosarcoma in the Anterior Mediastinum: A Case Report and Review

Extraskeletal osteosarcoma (ESOS) is a malignant soft tissue neoplasm producing osteoid, without any continuity with the bone or periosteum. Primary ESOS presenting in the mediastinum is an extremely rare, yet aggressive malignant tumor associated with a poor prognosis. We report a case of primary ESOS arising from the thymus in a 63-year-old male patient.

Primary Extraskeletal Osteosarcoma in the Anterior Mediastinum: A Case Report and Review / 대한흉부외과학회지

Extraskeletal osteosarcoma (ESOS) is a malignant soft tissue neoplasm producing osteoid, without any continuity with the bone or periosteum. Primary ESOS presenting in the mediastinum is an extremely rare, yet aggressive malignant tumor associated with a poor prognosis. We report a case of primary ESOS arising from the thymus in a 63-year-old male patient.

The Importance of Complete Pericardiectomy and the Role of the Apical Suction Device in Chronic Constrictive Pericarditis

BACKGROUND: The aim of this study was to analyze the preoperative attributes and clinical impacts of complete pericardiectomy in chronic constrictive pericarditis. METHODS: A total of 26 patients were treated from January 2001 to December 2013. The pericardium was resected as widely as possible. When excessive bleeding or hemodynamic instability occurred intraoperatively, a cardiopulmonary bypass (CPB; n=3, 11.5%) or an apical suction device (n=8, 30.8%) was used. Patients were divided into 2 groups: those who underwent ≥ 80% resection of the pericardium (group A, n=18) and those who underwent <80% resection of the pericardium (group B, n=8). RESULTS: The frequency of CPB use was not significantly different between groups A and B (n=2, 11.1% vs. n=1, 12.5%; p=1.000). However, the apical suction device was more frequently applied in group A than group B (n=8, 30.8% vs. n=0, 0.0%; p=0.031). The postoperative New York Heart Association functional classification improved more in group A (p=0.030). Long-term follow-up echocardiography also showed a lower frequency of unresolved constriction in group A than in group B (n=1, 5.60% vs. n=5, 62.5%; p=0.008). CONCLUSION: Patients with chronic constrictive pericarditis demonstrated symptomatic improvement through complete pericardiectomy. Aggressive resection of the pericardium may correct constrictive physiology and an apical suction device can facilitate the approach to the posterolateral aspect of the left ventricle and atrioventricular groove area without the aid of CPB.

Clinical Implication of Aortic Wall Biopsy in Aortic Valve Disease with Bicuspid Valve Pathology

BACKGROUND: Although unique aortic pathology related to bicuspid aortic valve (BAV) has been previously reported, clinical implications of BAV to aortopathy risk have yet to be investigated. We looked for potential differences in matrix protein expressions in the aortic wall in BAV patients. METHODS: Aorta specimens were obtained from 31 patients: BAV group (n=27), tricuspid aortic valve (TAV) group (n=4). The BAV group was categorized into three subgroups: left coronary sinus-right coronary sinus (R+L group; n=13, 42%), right coronary sinus-non-coronary sinus (R+N group; n=8, 26%), and anteroposterior (AP group; n=6, 19%). We analyzed the expression of endothelial nitric oxide synthase (eNOS), matrix metalloproteinase (MMP)-9, and tissue inhibitor of matrix metalloproteinase (TIMP)-2. RESULTS: Based on the mean value of the control group, BAV group showed decreased expression of eNOS in 72.7% of patients, increased MMP-9 in 82.3%, and decreased TIMP in 79.2%. There was a higher tendency for aortopathy in the BAV group: eNOS (BAV:TAV)= 53%±7%:57%±11%, MMP-9 (BAV:TAV)=48%±10%:38%±1%. The AP group showed lower expression of eNOS than the fusion (R+L, R+N) group did; 48%±5% vs. 55%±7% (p=0.081). CONCLUSION: Not all patients with BAV had expression of aortopathy; however, for patients who had a suspicious form of bicuspid valve, aortic wall biopsy could be valuable to signify the presence of aortopathy.

Wrapping of an Ascending Aortic Aneurysm with the Multiple Boot-Straps Technique in a Patient Undergoing Off-Pump Coronary Artery Bypass Grafting

Ascending aortic aneurysms are usually treated with graft replacement under cardiopulmonary bypass. However, if a candidate for off-pump coronary artery bypass grafting has an enlarged ascending aorta, surgeons may consider wrapping it without cardiopulmonary bypass. Here, we report a 78-year-old female who underwent successful wrapping of the ascending aorta concomitant with off-pump coronary artery bypass grafting, using a new wrapping technique that involves multiple bootstraps.

Multiple Aortic Operations in Loeys-Dietz Syndrome: Report of 2 Cases

Due to its low prevalence and because there is lack of awareness about it, Loeys-Dietz syndrome is often mis-diagnosed as Marfan syndrome, which has similar skeletal abnormalities and aortic pathology. However, the differential diagnosis between these two connective tissue diseases is critical because they correspond to different surgical indications and surgical decision-making. We report two cases of successful thoracoabdominal aortic replacement in patients with previously undiagnosed Loeys-Dietz syndrome.

Anaortic Off-pump Coronary Artery Bypass Grafting in Patients with Takayasu's Arteritis

BACKGROUND: Coronary involvement in Takayasu's arteritis is a rare but fatal disease. The aim of this study was to evaluate the early and mid-term results of Takayasu's arteritis patients who underwent coronary artery bypass grafting (CABG). MATERIALS AND METHODS: Of 2,280 patients who underwent isolated CABG from January 1998 to June 2012, Takayasu's arteritis was identified in 5 patients. There were 3 female patients, and the mean age was 58+/-9 years. Takayasu's arteritis was diagnosed during preoperative evaluation for coronary artery disease in 4 patients, and the initial manifestation was angina pectoris in 4 patients. All of the patients underwent anaortic off-pump CABG (OPCAB) using the in situ left or right internal thoracic arteries (ITA); 3 patients had severe stenosis of the proximal left subclavian artery and the in situ right ITA was used instead. Medical treatment for inflammatory arteritis during the perioperative and follow-up period was performed if indicated. Early, 1-year, and 5-year angiographic results and clinical outcomes were analyzed. RESULTS: There was no surgical mortality, and all of the patients were discharged without complications on postoperative 8+/-2 days. Early postoperative (postoperative 2+/-1 days) angiography demonstrated a graft patency of 100% (12 of 12 distal anastomoses). One-year (13+/-3 months) angiography was performed in 4 patients, and all of the grafts were patent (100%, 9 of 9 distal anastomoses). CONCLUSION: By performing anaortic OPCAB in patients with Takayasu's arteritis, we were able to avoid complications associated with manipulating an atherosclerotic and severely calcified ascending aorta. The early and mid-term graft patency of OPCAB in Takayasu's arteritis was maintained when concomitant with medical treatment.

Radial Arteriovenous Fistula Developed Late after Coronary Angiography: A Case Report

Transradial access is a widely accepted method for percutaneous coronary diagnostic and interventional procedures, and it has dramatically reduced access site vascular complications compared to transfemoral access. Arteriovenous fistula formation at the access site is an especially rare complication in transradial access. We report an extremely rare case of delayed radial arteriovenous fistula that developed one year after transradial coronary angiography, which was successfully treated by surgical repair.