Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that culminates in respiratory failure and death due to irreversible scarring of the distal lung. While initially considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now acknowledged as playing a central role in the pathophysiology of IPF. This study aimed to investigate the regenerative capacity of alveolar type 2 (AT2) cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity. Methods: Lung tissues from three pneumothorax patients and six IPF patients (early and advanced stages) were obtained through video-assisted thoracoscopic surgery and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-epithelial cell adhesion molecule (EpCAM)+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immunostaining was used to verify the presence of AT2 cells. Results: FACS sorting yielded approximately 1% of AT2 cells in early IPF tissue, and the number decreased as the disease progressed, in contrast to 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller and less numerous compared to those from pneumothorax patients. The colony forming efficiency decreased as the disease advanced. Immunostaining results showed that the IPF organoids expressed less surfactant protein C (SFTPC) compared to the pneumothorax group and contained keratin 5+ (KRT5+) cells. Conclusion This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, with IPF-derived AT2 cells inherently exhibiting functional abnormalities and altered differentiation plasticity.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that culminates in respiratory failure and death due to irreversible scarring of the distal lung. While initially considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now acknowledged as playing a central role in the pathophysiology of IPF. This study aimed to investigate the regenerative capacity of alveolar type 2 (AT2) cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity. Methods: Lung tissues from three pneumothorax patients and six IPF patients (early and advanced stages) were obtained through video-assisted thoracoscopic surgery and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-epithelial cell adhesion molecule (EpCAM)+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immunostaining was used to verify the presence of AT2 cells. Results: FACS sorting yielded approximately 1% of AT2 cells in early IPF tissue, and the number decreased as the disease progressed, in contrast to 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller and less numerous compared to those from pneumothorax patients. The colony forming efficiency decreased as the disease advanced. Immunostaining results showed that the IPF organoids expressed less surfactant protein C (SFTPC) compared to the pneumothorax group and contained keratin 5+ (KRT5+) cells. Conclusion This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, with IPF-derived AT2 cells inherently exhibiting functional abnormalities and altered differentiation plasticity.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that culminates in respiratory failure and death due to irreversible scarring of the distal lung. While initially considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now acknowledged as playing a central role in the pathophysiology of IPF. This study aimed to investigate the regenerative capacity of alveolar type 2 (AT2) cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity. Methods: Lung tissues from three pneumothorax patients and six IPF patients (early and advanced stages) were obtained through video-assisted thoracoscopic surgery and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-epithelial cell adhesion molecule (EpCAM)+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immunostaining was used to verify the presence of AT2 cells. Results: FACS sorting yielded approximately 1% of AT2 cells in early IPF tissue, and the number decreased as the disease progressed, in contrast to 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller and less numerous compared to those from pneumothorax patients. The colony forming efficiency decreased as the disease advanced. Immunostaining results showed that the IPF organoids expressed less surfactant protein C (SFTPC) compared to the pneumothorax group and contained keratin 5+ (KRT5+) cells. Conclusion This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, with IPF-derived AT2 cells inherently exhibiting functional abnormalities and altered differentiation plasticity.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that culminates in respiratory failure and death due to irreversible scarring of the distal lung. While initially considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now acknowledged as playing a central role in the pathophysiology of IPF. This study aimed to investigate the regenerative capacity of alveolar type 2 (AT2) cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity. Methods: Lung tissues from three pneumothorax patients and six IPF patients (early and advanced stages) were obtained through video-assisted thoracoscopic surgery and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-epithelial cell adhesion molecule (EpCAM)+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immunostaining was used to verify the presence of AT2 cells. Results: FACS sorting yielded approximately 1% of AT2 cells in early IPF tissue, and the number decreased as the disease progressed, in contrast to 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller and less numerous compared to those from pneumothorax patients. The colony forming efficiency decreased as the disease advanced. Immunostaining results showed that the IPF organoids expressed less surfactant protein C (SFTPC) compared to the pneumothorax group and contained keratin 5+ (KRT5+) cells. Conclusion This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, with IPF-derived AT2 cells inherently exhibiting functional abnormalities and altered differentiation plasticity.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that culminates in respiratory failure and death due to irreversible scarring of the distal lung. While initially considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now acknowledged as playing a central role in the pathophysiology of IPF. This study aimed to investigate the regenerative capacity of alveolar type 2 (AT2) cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity. Methods: Lung tissues from three pneumothorax patients and six IPF patients (early and advanced stages) were obtained through video-assisted thoracoscopic surgery and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-epithelial cell adhesion molecule (EpCAM)+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immunostaining was used to verify the presence of AT2 cells. Results: FACS sorting yielded approximately 1% of AT2 cells in early IPF tissue, and the number decreased as the disease progressed, in contrast to 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller and less numerous compared to those from pneumothorax patients. The colony forming efficiency decreased as the disease advanced. Immunostaining results showed that the IPF organoids expressed less surfactant protein C (SFTPC) compared to the pneumothorax group and contained keratin 5+ (KRT5+) cells. Conclusion This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, with IPF-derived AT2 cells inherently exhibiting functional abnormalities and altered differentiation plasticity.

Purpose: Stem cell transplantation (SCT) has historically played a major role in the long-term remission of mantle cell lymphoma (MCL), an incurable hematological malignancy. Using data from the Korean Society of Bone and Marrow Transplantation registry, we retrospectively analyzed the role of autologous (auto) and allogeneic (allo) SCT in longterm MCL survival. Methods: This study analyzed data from 188 patients (age ≥ 19 years at the time of transplantation) who underwent a transplant for MCL from 2011 to 2020. Progression-free survival (PFS) was defined as the time from transplantation to disease progression, relapse, or death from any cause. Overall survival (OS) was defined as the time from transplan‑ tation to death from any cause or the last follow-up. Results: In total, 109 patients underwent consolidative SCT after first-line chemotherapy. The 3-year PFS and OS rates were 65.4% and 78.5%, respectively, in the auto-SCT group, and 66.7% and 71.4%, respectively, in the allo-SCT group. The PFS and OS did not differ significantly between the auto- and allo-SCT groups. As part of salvage treatment, 52 patients with relapsed or refractory disease underwent auto- or allo-SCT. Patients who underwent auto-SCT with complete remis‑ sion/partial remission status reported better outcomes. In patients with refractory status, allogeneic transplantation using human leukocyte antigen (HLA) fully matched donors was a significantly favorable factor for PFS and OS. Conclusion The long-term survival of patients who underwent consolidative transplantation was similar to that reported in previous studies. Auto-SCT may be beneficial in patients who respond to salvage therapy, whereas allo-SCT with HLA-matched donors may be an alternative for patients with refractory disease. 

Purpose: Next-generation sequencing (NGS)-based tumor panel testing has been reimbursed by the Korean government since 2017. We evaluated the use of NGS-based tumor panel testing in real-world clinical practice, focusing on molecular profiling (MP)-guided breast cancer treatment. Methods: A total of 137 breast cancer patients underwent NGS panel testing between December 2017 and July 2020 at Seoul National University Bundang Hospital (SNUBH).Samples from patients were profiled using an in-house SNUBH pan-cancer panel. Sixty-four patients were profiled on SNUBH Pan_Cancer v1.0, targeting 89 genes, while 73 patients were profiled on SNUBH Pan_Cancer v2.0, targeting 546 genes. Results: Breast cancer subtypes included hormone receptor+/human epidermal growth factor receptor 2 (HER2)− (n = 87), triple-negative (n = 44), and HER2+ (n = 6). Most patients had locally advanced or metastatic cancers (92%). Approximately 92% (126/137) of the patients had significant genomic alterations (tiers I and II), and 62% (85/137) had targetable genomic alterations. The most common targetable genomic alterations were PIK3CA (39%) and ESR1 mutations (9%), followed by ERBB2 (7%), PTEN (7%), BRCA2 (6%), and BRCA1 mutations (4%). Of the 81 patients with locally advanced/metastatic breast cancer with targetable genomic alterations, 6 (7.4%) received MP-guided treatments, including PARP inhibitor (n = 4), ERBB2-directed therapy (n = 1), and PI3K inhibitor (n = 1). Among these 6 patients, 4 participated in clinical trials, 1 underwent treatment at their own expense, and 1 received drugs through an expanded access program. The remaining 66 patients (81%) with targetable genomic alteration did not receive MP-guided treatment due to lack of matched drugs and/or clinical trials, poor performance status, and/or financial burden. Conclusion NGS panel testing allowed MP-guided treatment in only 4.7% (6/127) of patients with advanced breast cancer in a real-world setting. The availability of matched drugs is critical for the realistic implementation of personalized treatment.

Purpose: The value of the genomic profiling by targeted gene-sequencing on radiation therapy response prediction was evaluated through integrated analysis including clinical information. Radiation response prediction model was constructed based on the analyzed findings. Materials and Methods: Patients who had the tumor sequenced using institutional cancer panel after informed consent and received radiotherapy for the measurable disease served as the target cohort. Patients with irradiated tumor locally controlled for more than 6 months after radiotherapy were defined as the durable local control (DLC) group, otherwise, non-durable local control (NDLC) group. Significant genomic factors and domain knowledge were used to develop the Bayesian Network model to predict radiotherapy response. Results: Altogether, 88 patients were collected for analysis. Of those, 41 (43.6%) and 47 (54.4%) patients were classified as the NDLC and DLC group, respectively. Somatic mutations of NOTCH2 and BCL were enriched in the NDLC group, whereas, mutations of CHEK2, MSH2, and NOTCH1 were more frequently found in the DLC group. Altered DNA repair pathway was associated with better local failure–free survival (hazard ratio, 0.40; 95% confidence interval, 0.19 to 0.86; p=0.014). Smoking somatic signature was found more frequently in the DLC group. Area under the receiver operating characteristic curve of the Bayesian network model predicting probability of 6-month local control was 0.83. Conclusion Durable radiation response was associated with alterations of DNA repair pathway and smoking somatic signature. Bayesian network model could provide helpful insights for high precision radiotherapy. However, these findings should be verified in prospective cohort for further individualization.

Background/Aims: Narrow band imaging provides an accurate diagnosis of colonic polyps.However, these diagnostic modalities are not used as standard endoscopic tools in most institutions. This study aims to investigate whether the chicken skin mucosa (CSM) surrounding the colon polyp yields additional information about colorectal polyps, including histological differentiation of neoplastic and non-neoplastic polyps, under conventional white light colonoscopy. Methods: This study prospectively observed 173 patients who underwent endoscopic polypectomy and reviewed the clinical data and pathologic reports of 313 polyps from a university hospital. Two endoscopists each performed colonoscopy and polypectomy and assessed the CSM. The association between CSM surrounding colorectal polyps and histology was analyzed. Results: The majority (91.3%) of CSM-positive polyps were neoplastic (sensitivity, 37.90%;specificity, 86.15%; p<0.001). In logistic regression, the neoplastic polyps were associated with positive CSM (adjusted odds ratio [OR], 3.51; 95% confidence interval [CI], 1.45 to 9.25; p=0.007), protruded polyps (adjusted OR, 4.85; 95% CI, 1.65 to 17.23; p=0.008), and neoplastic histology–associated pit pattern (pit III, IV, and V) (adjusted OR, 10.14; 95% CI, 4.85 to 22.12; p=0.000). Furthermore, advanced adenomas were associated with positive CSM (adjusted OR, 5.64; 95% CI, 1.77 to 20.28; p=0.005), protruded polyps (adjusted OR, 3.30; 95% CI, 1.15 to 9.74; p= 0.026), and ≥10 cm polyp size (adjusted OR, 18.56; 95% CI, 3.89 to 147.01; p=0.001). Conclusions Neoplastic and advanced polyps were associated with CSM-positive polyps.These findings suggest that CSM is a useful marker in differentiating neoplastic polyps and advanced polyps under conventional white colonoscopy.

Purpose: Under the South Korea’s unique health insurance structure, any new surgical technology must be evaluated first by the government in order to consider whether that particular technology can be applied to patients for further clinical trials as categorized as ‘New Health Technology,’ then potentially covered by the insurance sometime later. The aim of this meta-analysis was to assess the safety and efficacy of transanal total mesorectal excision (TaTME) for rectal cancer, activated by the National Evidence-based Healthcare Collaborating Agency (NECA) TaTME committee. Methods: We systematically searched Ovid-MEDLINE, Ovid-Embase, Cochrane, and Korean databases (from their inception until August 31, 2019) for studies published that compare TaTME with laparoscopic total mesorectal excision (LaTME). End-points included perioperative and pathological outcomes. Results: Sixteen cohort studies (7 for case-matched studies) were identified, comprising 1,923 patients (938 TaTMEs and 985 LaTMEs). Regarding perioperative outcomes, the conversion rate was significantly lower in TaTME (risk ratio, 0.19; 95% confidence interval, 0.11–0.34; P < 0.001); whereas other perioperative outcomes were similar to LaTME. There were no statistically significant differences in pathological results between the 2 procedures. Conclusion Our meta-analysis showed comparable results in preoperative and pathologic outcomes between TaTME and LaTME, and indicated the benefit of TaTME with low conversion. Extensive evaluations of well-designed, multicenter randomized controlled trials are required to come to unequivocal conclusions, but the results showed that TaTME is a potentially beneficial technique in some specific cases. This meta-analysis suggests that TaTME can be performed for rectal cancer patients as a ‘New Health Technology’ endorsed by NECA in South Korea.