Fetal lung interstitial tumor (FLIT), which is characterized by immature interstitial cells resembling the fetal lung parenchyma of 20 to 24 weeks of gestation, is a rare respiratory neoplasm. This study presents the first reported FLIT in Korea. It also aims to refine the diagnostic method of FLIT and increase the accuracy of prognostic assessment by using next-generation sequencing to check for anaplastic lymphoma receptor tyrosine kinase (anaplastic lymphoma kinase) gene rearrangement. Although the initial prognosis for FLIT has been promising since its first report in 2010, certain pathological features are associated with poorer outcomes. Therefore, achieving an accurate diagnosis of FLIT is crucial for avoiding unnecessary treatments beyond surgical resection.

Purpose: Few studies have reported the prevalence of inflammatory bowel disease unclassified (IBDU) among Korean pediatric IBD (PIBD) population. To address this gap, we used two tertiary centers and nationwide population-based healthcare administrative data to estimate the prevalence of Korean pediatric IBDU at the time of diagnosis. Methods: We identified 136 patients aged 2–17 years with newly diagnosed IBD (94 Crohn’s disease [CD] and 42 ulcerative colitis [UC]) from two tertiary centers in Korea between 2005 and 2017. We reclassified these 136 patients using the revised Porto criteria. To estimate the population-based prevalence, we analyzed Korean administrative healthcare data between 2005 and 2016, which revealed 3,650 IBD patients, including 2,538 CD and 1,112 UC. By extrapolating the reclassified results to a population-based dataset, we estimated the prevalence of PIBD subtypes. Results: Among the 94 CD, the original diagnosis remained unchanged in 93 (98.9%), while the diagnosis of one (1.1%) patient was changed to IBDU. Among the 42 UC, the original diagnosis remained unchanged in 13 (31.0%), while the diagnoses in 11 (26.2%), 17 (40.5%), and one (2.4%) patient changed to atypical UC, IBDU, and CD, respectively. The estimated prevalences of CD, UC, atypical UC, and IBDU in the Korean population were 69.5%, 9.4%, 8.0%, and 13.1%, respectively. Conclusion This study is the first in Korea to estimate the prevalence of pediatric IBDU.This prevalence (13.1%) aligns with findings from Western studies. Large-scale prospective multicenter studies on PIBDU are required to examine the clinical features and outcomes of this condition.

Background/Aims: Astragalin (kaempferol-3-O-β-D-glucoside) is a flavonoid isolated from the leaves of persimmon or Rosa agrestis. Astragalin exhibits various anti-inflammatory properties; however, little is known about its therapeutic potential for inflammatory bowel disease (IBD). This study aims to investigate the anti-inflammatory effect of astragalin via blockade of the nuclear factor κB (NF-κB) signaling pathway in human colonic epithelial cells and a murine colitis model. Methods: HCT-116 and HT-29 human colonic epithelial cells were pretreated with astragalin and stimulated with tumor necrosis factor-α (TNF-α). Cell viability was assessed by the MTS assay. Real-time reverse transcription polymerase chain reaction was used to analyze the messenger RNA expression of the inflammatory cytokines interleukin (IL)-6 and IL-8. The effect of astragalin on the NF-κB pathway was evaluated by Western blot analysis of inhibitor of NF-κB alpha (IκBα) phosphorylation/degradation and by electrophoretic mobility shift assay. Dextran sulfate sodium (DSS)-induced acute murine colitis model was used for in vivo experiments. Results: Astragalin strongly suppressed the expression of proinflammatory cytokines in human colonic epithelial cells in a dose-dependent manner. Western blot analysis showed that astragalin inhibited IκBα phosphorylation/degradation. Additionally, astragalin reduced the DNA binding ac-tivity of NF-κB. Astragalin alleviated colon shortening and improved the pathologic scores in DSSinduced acute murine colitis model. Furthermore, astragalin reduced the level of phosphorylated IκBα and decreased the production of the inflammatory cytokines IL-6, IL-8, and TNF-α in the DSS-treated colon mucosa. Conclusions Astragalin exerted an anti-inflammatory effect through NF-κB pathway inhibition and attenuated murine colitis. Astragalin is thus a potential therapeutic agent for IBD.

Background: Complex regional pain syndrome (CRPS) is an intractable pain disease with various symptoms. Here, we investigated the disease status, work life, sleep problems, medical insurance, economic status, psychological problems, and quality of life (QOL) of CRPS patients. Methods: CRPS patients from 37 university hospitals in South Korea were surveyed.The survey questionnaire consisted of 24 questions on the following aspects of CRPS patients: sex, age, occupation, cause of injury, activities of daily living (ADL), pain severity, sleep disturbance, level of education, economic status, therapeutic effect, and suicidal ideation. Additionally, the abbreviated World Health Organization Quality of Life (WHOQOL-BREF) questionnaire, consisting of 26 questions, was used to identify the status of QOL. Results: A total of 251 patients completed the questionnaire. According to the survey, 54.2% patients could not perform ADL on their own. Over the previous week, the mean pain score was 7.15 ± 1.78 (out of a total of 10 points); 92.1% of patients had sleep disorders and 80.5% had suicidal ideation, with most patients suffering from psychological problems. The average for each domain of WHOQOL-BREF was as follows: 21.74 ± 14.77 for physical, 25.22 ± 17.66 for psychological, 32.02 ± 22.36 for social relationship, and 30.69 ± 15.83 for environmental (out of a total of 100 points each). Occupation, ADL, sleep time, therapeutic effect, and suicidal ideation were statistically correlated with multiple domains. Conclusions Most patients had moderate to severe pain, economic problems, limitations of their ADL, sleep problems, psychological problems, and a low QOL score.

Background and Objectives: Proximal submandibular stone is not a rare disease. The aim of this study is to evaluate the surgical outcomes of 3 different ways to treat proximal submandibular stone: intraoral removal of stone (IORS) with sublingual gland (SLG) resection, IORS without SLG resection and submandibular gland (SMG) resection. Subjects and Methods: We prospectively reviewed the surgical outcomes of IORS with SLG resection group (22 patients), IORS without SLG resection group (35 patients) and SMG resection group (22 patients). To evaluate the surgical outcomes, we analyzed the location and size of stones, mean operation time, mean hospital stay, mean postoperative degree of pain based on a visual analog scale (0–10), and incidence of complications. Results: There were no significant differences between the mean diameter of stones and lengthfrom the hilum to stones. The mean operation time was shorter in the IORS without SLG re-section group than that in IORS without SLG resection group, and was significantly shorter than that of the SMG resection group. The mean hospital stay of the IORS without SLG resection group was also shorter than that of IORS with SLG resection group, and was significantly short-er than the SMG resection group. IORS without SLG resection group felt less pain than IORS with SLG resection group and SMG resection group. Four patients who underwent IORS without SLG resection experienced transient and mild SMG swelling, and mild paresthesia was noted on the same side. All patients recovered within 3 months. Intraoral removal of proximal SMG stones exhibited several advantages over SMG resection in terms of hospital stay, mean operation, time and postoperative pain. Conclusion Based on our results, we suggest that IORS without SLG resection be selected as the primary procedure for the removal of proximal submandibular stones rather than SMG resection.

Purpose: Adjuvant radiotherapy (RT) has been performed to reduce locoregional failure (LRF) following radical cystectomy for locally advanced bladder cancer; however, its efficacy has not been well established. We analyzed the locoregional recurrence patterns of post-radical cystectomy to identify patients who could benefit from adjuvant RT and determine the optimal target volume. Materials and Methods: We retrospectively reviewed 160 patients with stage ≥ pT3 bladder cancer who were treated with radical cystectomy between January 2006 and December 2015. The impact of pathologic findings, including the stage, lympho-vascular invasion, perineural invasion, margin status, nodal involvement, and the number of nodes removed on failure patterns, was assessed. Results: Median follow-up period was 27.7 months. LRF was observed in 55 patients (34.3%), 12 of whom presented with synchronous local and regional failures as the first failure. The most common failure pattern was distant metastasis (40%). Among LRFs, the most common recurrence site was the cystectomy bed (15.6%). Patients with positive resection margins had a significantly higher recurrence rate compared to those without (28% vs. 10%, p=0.004). The pelvic nodal recurrence rate was < 5% in pN0 patients; the rate of recurrence in the external and common iliac nodes was 12.5% in pN+ patients. The rate of recurrence in the common iliac nodes was significantly higher in pN2–3 patients than in pN0–1 patients (15.2% vs. 4.4%, p=0.04). Conclusion Pelvic RT could be beneficial especially for those with positive resection margins or nodal involvement after radical cystectomy. Radiation fields should be optimized based on the patient-specific risk factors.

Background: Complex regional pain syndrome (CRPS) is an intractable pain disease with various symptoms. Here, we investigated the disease status, work life, sleep problems, medical insurance, economic status, psychological problems, and quality of life (QOL) of CRPS patients. Methods: CRPS patients from 37 university hospitals in South Korea were surveyed.The survey questionnaire consisted of 24 questions on the following aspects of CRPS patients: sex, age, occupation, cause of injury, activities of daily living (ADL), pain severity, sleep disturbance, level of education, economic status, therapeutic effect, and suicidal ideation. Additionally, the abbreviated World Health Organization Quality of Life (WHOQOL-BREF) questionnaire, consisting of 26 questions, was used to identify the status of QOL. Results: A total of 251 patients completed the questionnaire. According to the survey, 54.2% patients could not perform ADL on their own. Over the previous week, the mean pain score was 7.15 ± 1.78 (out of a total of 10 points); 92.1% of patients had sleep disorders and 80.5% had suicidal ideation, with most patients suffering from psychological problems. The average for each domain of WHOQOL-BREF was as follows: 21.74 ± 14.77 for physical, 25.22 ± 17.66 for psychological, 32.02 ± 22.36 for social relationship, and 30.69 ± 15.83 for environmental (out of a total of 100 points each). Occupation, ADL, sleep time, therapeutic effect, and suicidal ideation were statistically correlated with multiple domains. Conclusions Most patients had moderate to severe pain, economic problems, limitations of their ADL, sleep problems, psychological problems, and a low QOL score.

Purpose: Adjuvant radiotherapy (RT) has been performed to reduce locoregional failure (LRF) following radical cystectomy for locally advanced bladder cancer; however, its efficacy has not been well established. We analyzed the locoregional recurrence patterns of post-radical cystectomy to identify patients who could benefit from adjuvant RT and determine the optimal target volume. Materials and Methods: We retrospectively reviewed 160 patients with stage ≥ pT3 bladder cancer who were treated with radical cystectomy between January 2006 and December 2015. The impact of pathologic findings, including the stage, lympho-vascular invasion, perineural invasion, margin status, nodal involvement, and the number of nodes removed on failure patterns, was assessed. Results: Median follow-up period was 27.7 months. LRF was observed in 55 patients (34.3%), 12 of whom presented with synchronous local and regional failures as the first failure. The most common failure pattern was distant metastasis (40%). Among LRFs, the most common recurrence site was the cystectomy bed (15.6%). Patients with positive resection margins had a significantly higher recurrence rate compared to those without (28% vs. 10%, p=0.004). The pelvic nodal recurrence rate was < 5% in pN0 patients; the rate of recurrence in the external and common iliac nodes was 12.5% in pN+ patients. The rate of recurrence in the common iliac nodes was significantly higher in pN2–3 patients than in pN0–1 patients (15.2% vs. 4.4%, p=0.04). Conclusion Pelvic RT could be beneficial especially for those with positive resection margins or nodal involvement after radical cystectomy. Radiation fields should be optimized based on the patient-specific risk factors.

The purpose of this study was to evaluate the diagnostic performance of magnetic resonance (MR) radiomics-based machine learning algorithms in differentiating squamous cell carcinoma (SCC) from lymphoma in the oropharynx. MR images from 87 patients with oropharyngeal SCC (n=68) and lymphoma (n=19) were reviewed retrospectively. Tumors were semi-automatically segmented on contrast-enhanced T1-weighted images registered to T2-weighted images, and radiomic features (n=202) were extracted from contrast-enhanced T1- and T2-weighted images. The radiomics classifier was built using elastic-net regularized generalized linear model analyses with nested five-fold cross-validation. The diagnostic abilities of the radiomics classifier and visual assessment by two head and neck radiologists were evaluated using receiver operating characteristic (ROC) analyses for distinguishing SCC from lymphoma. Nineteen radiomics features were selected at least twice during the five-fold cross-validation. The mean area under the ROC curve (AUC) of the radiomics classifier was 0.750 [95% confidence interval (CI), 0.613–0.887], with a sensitivity of 84.2%, specificity of 60.3%, and an accuracy of 65.5%. Two human readers yielded AUCs of 0.613 (95% CI, 0.467–0.759) and 0.663 (95% CI, 0.531–0.795), respectively. The radiomics-based machine learning model can be useful for differentiating SCC from lymphoma of the oropharynx.

Pellino-1 is a ubiquitin (Ub) E3 ligase that plays a role in M1, but not M2a polarization of macrophages. However, it is unknown whether Pellino-1 regulates IL-10-mediated M2c polarization of macrophages. Here, we found that Pellino-1 attenuated tumor growth by inhibiting M2c polarization of macrophages. Upon IL-10 stimulation, Pellino-1-deificient bone marrow-derived macrophages (BMDMs) showed higher expression of M2c markers, but not M2a, and M2b markers than wild-type (WT) BMDMs, indicating that Pellino-1 inhibits M2c polarization of macrophages. Pellino-1-deficient BMDMs exhibited a defect in mitochondria respiration, but enhancement of glycolysis during M2c polarization. During M2c polarization of macrophages, Pellino-1 increased STAT1 phosphorylation via K63-linked ubiquitination of IL-1 receptor associated kinase 1 (IRAK1). Furthermore, Lysm-CrePellino-1(fl/fl) mice showed enhancement of tumor growth via regulating M2c polarization of tumor-associated macrophages. These results demonstrate that Pellino-1 inhibits IL-10-induced M2c macrophage polarization via K63-linked ubiquitination of IRAK1 and activation of STAT1, thereby inhibiting tumor growth in vivo.
Animals ; Glycolysis ; Interleukin-1 ; Interleukin-10 ; Macrophages ; Mice ; Mitochondria ; Phosphorylation ; Phosphotransferases ; Respiration ; Ubiquitin ; Ubiquitin-Protein Ligases ; Ubiquitination