Purpose: Neuroendocrine carcinomas (NECs) of the stomach are extremely rare, but fatal. However, our understanding of the genetic alterations in gastric NECs is limited. We aimed to evaluate genomic and clinicopathological characteristics of gastric NECs and mixed adenoneuroendocrine carcinomas (MANECs). Materials and Methods: Fourteen gastric NECs, three gastric MANECs, and 1,381 gastric adenocarcinomas were retrieved from the departmental next-generation sequencing database between 2017 and 2022. Clinicopathological parameters and next-generation sequencing test results were retrospectively collected and reviewed. Results: Gastric NECs and MANECs frequently harbored alterations of TP53, RB1, SMARCA4, RICTOR, APC, TOP1, SLX4, EGFR, BRCA2, and TERT. In contrast, gastric adenocarcinomas exhibited alterations of TP53, CDH1, LRP1B, ARID1A, ERBB2, GNAS, CCNE1, NOTCH, and MYC. Mutations of AKT3, RB1, and SLX4; amplification of BRCA2 and RICTOR; and deletion of ADAMTS18, DDX11, KLRC3, KRAS, MAX, NFKBIA, NUDT7, and RB1 were significantly more frequent in gastric NECs and MANECs than in gastric adenocarcinomas. The presence of LRP1B mutation was significantly associated with longer overall survival (OS), whereas RB1 mutation and advanced TNM stage were associated with shorter OS. Conclusion We identified frequently mutated genes and potential predictors of survival in patients with gastric NECs and MANECs.

Purpose: Neuroendocrine carcinomas (NECs) of the stomach are extremely rare, but fatal. However, our understanding of the genetic alterations in gastric NECs is limited. We aimed to evaluate genomic and clinicopathological characteristics of gastric NECs and mixed adenoneuroendocrine carcinomas (MANECs). Materials and Methods: Fourteen gastric NECs, three gastric MANECs, and 1,381 gastric adenocarcinomas were retrieved from the departmental next-generation sequencing database between 2017 and 2022. Clinicopathological parameters and next-generation sequencing test results were retrospectively collected and reviewed. Results: Gastric NECs and MANECs frequently harbored alterations of TP53, RB1, SMARCA4, RICTOR, APC, TOP1, SLX4, EGFR, BRCA2, and TERT. In contrast, gastric adenocarcinomas exhibited alterations of TP53, CDH1, LRP1B, ARID1A, ERBB2, GNAS, CCNE1, NOTCH, and MYC. Mutations of AKT3, RB1, and SLX4; amplification of BRCA2 and RICTOR; and deletion of ADAMTS18, DDX11, KLRC3, KRAS, MAX, NFKBIA, NUDT7, and RB1 were significantly more frequent in gastric NECs and MANECs than in gastric adenocarcinomas. The presence of LRP1B mutation was significantly associated with longer overall survival (OS), whereas RB1 mutation and advanced TNM stage were associated with shorter OS. Conclusion We identified frequently mutated genes and potential predictors of survival in patients with gastric NECs and MANECs.

Purpose: Neuroendocrine carcinomas (NECs) of the stomach are extremely rare, but fatal. However, our understanding of the genetic alterations in gastric NECs is limited. We aimed to evaluate genomic and clinicopathological characteristics of gastric NECs and mixed adenoneuroendocrine carcinomas (MANECs). Materials and Methods: Fourteen gastric NECs, three gastric MANECs, and 1,381 gastric adenocarcinomas were retrieved from the departmental next-generation sequencing database between 2017 and 2022. Clinicopathological parameters and next-generation sequencing test results were retrospectively collected and reviewed. Results: Gastric NECs and MANECs frequently harbored alterations of TP53, RB1, SMARCA4, RICTOR, APC, TOP1, SLX4, EGFR, BRCA2, and TERT. In contrast, gastric adenocarcinomas exhibited alterations of TP53, CDH1, LRP1B, ARID1A, ERBB2, GNAS, CCNE1, NOTCH, and MYC. Mutations of AKT3, RB1, and SLX4; amplification of BRCA2 and RICTOR; and deletion of ADAMTS18, DDX11, KLRC3, KRAS, MAX, NFKBIA, NUDT7, and RB1 were significantly more frequent in gastric NECs and MANECs than in gastric adenocarcinomas. The presence of LRP1B mutation was significantly associated with longer overall survival (OS), whereas RB1 mutation and advanced TNM stage were associated with shorter OS. Conclusion We identified frequently mutated genes and potential predictors of survival in patients with gastric NECs and MANECs.

Background/Aims: The proposed eosinophilic esophagitis (EoE) endoscopic reference score serves to diagnose and evaluate treatment responses in EoE.Nevertheless, the validated reference score thresholds for diagnosis and treatment response in Asian patients are yet to be established.This study aims to establish these thresholds for the first time among Asian patients with EoE. Methods: Patients presenting with ≥ 15 eosinophils/high power field and esophageal dysfunction symptoms between August 2007 andNovember 2021 were included. Age- and sex-matched non-EoE controls were also enrolled. Baseline characteristics, endoscopic reference score features, and scores were compared between patients and controls. Among patients, endoscopic reference score features and scores, along with peak eosinophil counts, were evaluated both before and after treatment. The optimal threshold was determined based on sensitivity, specificity, and the Youden index. Results: Overall, 102 patients were enrolled (74.5% men; mean age, 46.9 years). The mean endoscopic reference score was 2.65 and 0.52 for patients and controls, respectively (P < 0.001). An endoscopic reference score ≥ 2 was identified as the optimal diagnostic threshold for EoE (sensitivity, 0.79; specificity, 0.86; Youden index, 0.66). Post-treatment data regarding endoscopic findings and histology wereavailable for 30 patients. Regarding histologic response, an endoscopic reference score of ≤ 3 demonstrated the optimal threshold(sensitivity, 0.95; specificity, 0.88; Youden index, 0.83). Conclusions The optimal diagnostic and treatment response thresholds were determined to be endoscopic reference scores of ≥ 2 and ≤ 3,respectively. Further studies involving a larger patient cohort are necessary to validate these findings.

Background/Aims: The proposed eosinophilic esophagitis (EoE) endoscopic reference score serves to diagnose and evaluate treatment responses in EoE.Nevertheless, the validated reference score thresholds for diagnosis and treatment response in Asian patients are yet to be established.This study aims to establish these thresholds for the first time among Asian patients with EoE. Methods: Patients presenting with ≥ 15 eosinophils/high power field and esophageal dysfunction symptoms between August 2007 andNovember 2021 were included. Age- and sex-matched non-EoE controls were also enrolled. Baseline characteristics, endoscopic reference score features, and scores were compared between patients and controls. Among patients, endoscopic reference score features and scores, along with peak eosinophil counts, were evaluated both before and after treatment. The optimal threshold was determined based on sensitivity, specificity, and the Youden index. Results: Overall, 102 patients were enrolled (74.5% men; mean age, 46.9 years). The mean endoscopic reference score was 2.65 and 0.52 for patients and controls, respectively (P < 0.001). An endoscopic reference score ≥ 2 was identified as the optimal diagnostic threshold for EoE (sensitivity, 0.79; specificity, 0.86; Youden index, 0.66). Post-treatment data regarding endoscopic findings and histology wereavailable for 30 patients. Regarding histologic response, an endoscopic reference score of ≤ 3 demonstrated the optimal threshold(sensitivity, 0.95; specificity, 0.88; Youden index, 0.83). Conclusions The optimal diagnostic and treatment response thresholds were determined to be endoscopic reference scores of ≥ 2 and ≤ 3,respectively. Further studies involving a larger patient cohort are necessary to validate these findings.

Background/Aims: The proposed eosinophilic esophagitis (EoE) endoscopic reference score serves to diagnose and evaluate treatment responses in EoE.Nevertheless, the validated reference score thresholds for diagnosis and treatment response in Asian patients are yet to be established.This study aims to establish these thresholds for the first time among Asian patients with EoE. Methods: Patients presenting with ≥ 15 eosinophils/high power field and esophageal dysfunction symptoms between August 2007 andNovember 2021 were included. Age- and sex-matched non-EoE controls were also enrolled. Baseline characteristics, endoscopic reference score features, and scores were compared between patients and controls. Among patients, endoscopic reference score features and scores, along with peak eosinophil counts, were evaluated both before and after treatment. The optimal threshold was determined based on sensitivity, specificity, and the Youden index. Results: Overall, 102 patients were enrolled (74.5% men; mean age, 46.9 years). The mean endoscopic reference score was 2.65 and 0.52 for patients and controls, respectively (P < 0.001). An endoscopic reference score ≥ 2 was identified as the optimal diagnostic threshold for EoE (sensitivity, 0.79; specificity, 0.86; Youden index, 0.66). Post-treatment data regarding endoscopic findings and histology wereavailable for 30 patients. Regarding histologic response, an endoscopic reference score of ≤ 3 demonstrated the optimal threshold(sensitivity, 0.95; specificity, 0.88; Youden index, 0.83). Conclusions The optimal diagnostic and treatment response thresholds were determined to be endoscopic reference scores of ≥ 2 and ≤ 3,respectively. Further studies involving a larger patient cohort are necessary to validate these findings.

The remarkable advances in our understanding of renal tumor pathogenesis, driven by the widespread application of molecular testing, are reflected in the latest 2022 World Health Organization classification. This updated classification categorizes renal cell carcinoma (RCC) into morphologically and molecularly defined RCCs. It includes updates to existing entities and introduces newly established and provisional entities. A standard macroscopic and microscopic evaluation is typically sufficient for diagnosing morphologically defined RCCs and serves as the initial step in the identification of molecularly defined entities. In cases where classification based solely on histologic examination is challenging, a limited panel of immunohistochemical stains can be employed to aid in the diagnosis, with molecular testing for validation if necessary. Therefore, this review explores the key clinical, pathological, and molecular features essential for classifying both the commonly encountered morphologically defined RCCs and the less common but clinically significant molecularly defined RCCs. The goal is to increase awareness of these RCC subtypes among clinicians and promote a deeper understanding of the pathological diagnostic process, ultimately improving patient care.

Glucagon like peptide-1 (GLP-1) stimulates glucose-dependent insulin secretion. Dipeptidyl peptidase-4 (DPP-4) inhibitors, which block inactivation of GLP-1, are currently in clinical use for type 2 diabetes mellitus. Recently, GLP-1 has also been reported to have neuroprotective effects in cases of cerebral ischemia. We therefore investigated the neuroprotective effects of GLP-1 receptor (GLP-1R) agonist, exendin-4 (ex-4), after cerebral ischemia-reperfusion injury. Transient middle cerebral artery occlusion (tMCAO) was induced in rats by intracerebroventricular (i.c.v.) administration of ex-4 or ex9-39. Oxygen-glucose deprivation was also induced in primary neurons, bEnd.3 cells, and BV-2. Ischemia-reperfusion injury reduced expression of GLP-1R. Additionally, higher oxidative stress in SOD2 KO mice decreased expression of GLP-1R. Downregulation of GLP-1R by ischemic injury was 70% restored by GLP-1R agonist, ex-4, which resulted in significant reduction of infarct volume. Levels of intracellular cyclic AMP, a second messenger of GLP-1R, were also increased by 2.7-fold as a result of high GLP-1R expression. Moreover, our results showed that ex-4 attenuated pro-inflammatory cyclooxygenase-2 (COX-2) and prostaglandin E₂ after MCAO. C-Jun NH₂ terminal kinase (JNK) signaling, which stimulates activation of COX-2, was 36% inhibited by i.c.v. injection of ex-4 at 24 h. Islet-brain 1 (IB1), a scaffold regulator of JNK, was 1.7-fold increased by ex-4. GLP-1R activation by ex-4 resulted in reduction of COX-2 through increasing IB1 expression, resulting in anti-inflammatory neuroprotection during stroke. Our study suggests that the anti-inflammatory action of GLP-1 could be used as a new strategy for the treatment of neuroinflammation after stroke accompanied by hyperglycemia.
Animals ; Brain Ischemia ; Cyclic AMP ; Cyclooxygenase 2 ; Diabetes Mellitus, Type 2 ; Down-Regulation ; Glucagon* ; Glucagon-Like Peptide 1 ; Glucagon-Like Peptide-1 Receptor ; Hyperglycemia ; Infarction, Middle Cerebral Artery ; Insulin ; Mice ; Neurons ; Neuroprotection ; Neuroprotective Agents ; Oxidative Stress ; Phosphotransferases ; Rats ; Reperfusion Injury ; Second Messenger Systems ; Stroke*

Paragonimiasis was one of the most common causes of cavitary lung lesions until the 1960s, but now it has become a very rare disease in Korea. A 16-year-old boy presented with hemoptysis and several days of cough. His plain chest radiograph showed nodular opacity with a cavity in the left upper lung region. Although his symptoms disappeared after taking antituberculous drugs, his plain chest radiograph and computed tomography images after completion of therapy showed a new nodule with a cavity in the left lung field. Through video-assisted thoracoscopic wedge resection, Paragonimus eggs were found in the lung tissues.
Adolescent ; Cough ; Eggs ; Hemoptysis ; Humans ; Korea ; Lung ; Male ; Ovum ; Paragonimiasis* ; Paragonimus ; Radiography, Thoracic ; Rare Diseases ; Tuberculosis, Pulmonary*

Paragonimiasis was one of the most common causes of cavitary lung lesions until the 1960s, but now it has become a very rare disease in Korea. A 16-year-old boy presented with hemoptysis and several days of cough. His plain chest radiograph showed nodular opacity with a cavity in the left upper lung region. Although his symptoms disappeared after taking antituberculous drugs, his plain chest radiograph and computed tomography images after completion of therapy showed a new nodule with a cavity in the left lung field. Through video-assisted thoracoscopic wedge resection, Paragonimus eggs were found in the lung tissues.
Adolescent ; Cough ; Eggs ; Hemoptysis ; Humans ; Korea ; Lung ; Male ; Ovum ; Paragonimiasis* ; Paragonimus ; Radiography, Thoracic ; Rare Diseases ; Tuberculosis, Pulmonary*