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: To evaluate the efficacy and toxicities of skin-directed radiotherapy (RT) in primary cutaneous T-cell lymphoma (CTCL). Materials and Methods: We retrospectively analyzed 57 CTCL lesions treated with skin-directed RT between January 2000 and December 2022. Lesions were categorized into three distinct groups: early-stage disease treated with local RT, advanced-stage disease treated with local RT, and advanced-stage disease treated with total skin electron beam therapy (TSEBT). Treatment outcomes, including response rates, recurrence patterns, and local progression probability, were assessed for each group. Results: Mycosis fungoides (MF) constituted 90.9% of the advanced-stage pathologies, while CD4+ primary cutaneous small/medium T-cell lymphoproliferative disorder was common in the early stage lesions (55%). Median RT doses were 30.6 Gy, 27 Gy, and 32 Gy for the local RT with early stage, the local RT with advanced stage, and TSEBT with advanced stage, respectively. The complete response rates were high across the groups: 95.5%, 70.8%, and 90.9%, respectively. Seven local recurrences (29.2%) occurred in the local RT group with advanced stage, while seven patients (63.6%) in the TSEBT group experienced local failure. All recurrences were observed in lesions and patients with MF. Acute toxicities were mainly grade 1 or 2, with no grade 3 or higher events. No significant association between RT dose and local progression rates in MF lesions was found. Conclusion Skin-directed RT in CTCL is effective for local control and well-tolerated with less toxicity.

Purpose: To evaluate the efficacy and toxicities of skin-directed radiotherapy (RT) in primary cutaneous T-cell lymphoma (CTCL). Materials and Methods: We retrospectively analyzed 57 CTCL lesions treated with skin-directed RT between January 2000 and December 2022. Lesions were categorized into three distinct groups: early-stage disease treated with local RT, advanced-stage disease treated with local RT, and advanced-stage disease treated with total skin electron beam therapy (TSEBT). Treatment outcomes, including response rates, recurrence patterns, and local progression probability, were assessed for each group. Results: Mycosis fungoides (MF) constituted 90.9% of the advanced-stage pathologies, while CD4+ primary cutaneous small/medium T-cell lymphoproliferative disorder was common in the early stage lesions (55%). Median RT doses were 30.6 Gy, 27 Gy, and 32 Gy for the local RT with early stage, the local RT with advanced stage, and TSEBT with advanced stage, respectively. The complete response rates were high across the groups: 95.5%, 70.8%, and 90.9%, respectively. Seven local recurrences (29.2%) occurred in the local RT group with advanced stage, while seven patients (63.6%) in the TSEBT group experienced local failure. All recurrences were observed in lesions and patients with MF. Acute toxicities were mainly grade 1 or 2, with no grade 3 or higher events. No significant association between RT dose and local progression rates in MF lesions was found. Conclusion Skin-directed RT in CTCL is effective for local control and well-tolerated with less toxicity.

Purpose: To evaluate the efficacy and toxicities of skin-directed radiotherapy (RT) in primary cutaneous T-cell lymphoma (CTCL). Materials and Methods: We retrospectively analyzed 57 CTCL lesions treated with skin-directed RT between January 2000 and December 2022. Lesions were categorized into three distinct groups: early-stage disease treated with local RT, advanced-stage disease treated with local RT, and advanced-stage disease treated with total skin electron beam therapy (TSEBT). Treatment outcomes, including response rates, recurrence patterns, and local progression probability, were assessed for each group. Results: Mycosis fungoides (MF) constituted 90.9% of the advanced-stage pathologies, while CD4+ primary cutaneous small/medium T-cell lymphoproliferative disorder was common in the early stage lesions (55%). Median RT doses were 30.6 Gy, 27 Gy, and 32 Gy for the local RT with early stage, the local RT with advanced stage, and TSEBT with advanced stage, respectively. The complete response rates were high across the groups: 95.5%, 70.8%, and 90.9%, respectively. Seven local recurrences (29.2%) occurred in the local RT group with advanced stage, while seven patients (63.6%) in the TSEBT group experienced local failure. All recurrences were observed in lesions and patients with MF. Acute toxicities were mainly grade 1 or 2, with no grade 3 or higher events. No significant association between RT dose and local progression rates in MF lesions was found. Conclusion Skin-directed RT in CTCL is effective for local control and well-tolerated with less toxicity.

Purpose: Oligoprogressive lesions are observed in a subset of patients who progress to castration-resistant prostate cancer (CRPC), while other lesions remain controlled by systemic therapy. This study evaluates the impact of progression-directed therapy (PDT) on these oligoprogressive lesions. Materials and Methods: This retrospective study included 40 patients diagnosed with oligoprogressive CRPC. PDT was performed for treating all progressive sites using radiotherapy. Fifteen patients received PDT using radiotherapy for all progressive sites (PDT group) while 25 had additional first-line systemic treatments (non-PDT group). In PDT group, 7 patients underwent PDT and unchanged systemic therapy (PDT-A group) and 8 patients underwent PDT with additional new line of systemic therapy on CRPC (PDT-B group). The Kaplan–Meier method was used to assess treatment outcomes. Results: The prostate specific antigen (PSA) nadir was significantly lower in PDT group compare to non-PDT group (p=0.007). A 50% PSA decline and complete PSA decline were observed in 13 patients (86.7%) and 10 patients (66.7%) of PDT group and in 18 patients (72.0%) and 11 patients (44.0%) of non-PDT group, respectively. The PSA-progression free survival of PDT-B group was significantly longer than non-PDT group. The median time to failure of first-line systemic therapy on CRPC was 30.2 months in patients in PDT group and 14.9 months in non-PDT group (p=0.014). PDT-B group showed a significantly longer time to progression than non-PDT group (p=0.025). Minimal PDT-related adverse events were observed. Conclusions PDT can delay progression of disease and enhance treatment efficacy with acceptable tolerability in oligoprogressive CRPC.

Purpose: To evaluate the efficacy and toxicities of skin-directed radiotherapy (RT) in primary cutaneous T-cell lymphoma (CTCL). Materials and Methods: We retrospectively analyzed 57 CTCL lesions treated with skin-directed RT between January 2000 and December 2022. Lesions were categorized into three distinct groups: early-stage disease treated with local RT, advanced-stage disease treated with local RT, and advanced-stage disease treated with total skin electron beam therapy (TSEBT). Treatment outcomes, including response rates, recurrence patterns, and local progression probability, were assessed for each group. Results: Mycosis fungoides (MF) constituted 90.9% of the advanced-stage pathologies, while CD4+ primary cutaneous small/medium T-cell lymphoproliferative disorder was common in the early stage lesions (55%). Median RT doses were 30.6 Gy, 27 Gy, and 32 Gy for the local RT with early stage, the local RT with advanced stage, and TSEBT with advanced stage, respectively. The complete response rates were high across the groups: 95.5%, 70.8%, and 90.9%, respectively. Seven local recurrences (29.2%) occurred in the local RT group with advanced stage, while seven patients (63.6%) in the TSEBT group experienced local failure. All recurrences were observed in lesions and patients with MF. Acute toxicities were mainly grade 1 or 2, with no grade 3 or higher events. No significant association between RT dose and local progression rates in MF lesions was found. Conclusion Skin-directed RT in CTCL is effective for local control and well-tolerated with less toxicity.