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The first edition of ‘A Standardized Pathology Report for Gastric Cancer’ was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.
ABSTRACT
The first edition of ‘A Standardized Pathology Report for Gastric Cancer’ was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements.The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.
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Background/Aims@#The incidence and prognosis of gastric cancer (GC) shows sex difference.This study aimed to evaluate the effect of body mass index (BMI) on GC survival depending on sex. @*Methods@#The sex, age, location, histology, TNM stages, BMI, and survival were analyzed in GC patients from May 2003 to February 2020 at the Seoul National University Bundang Hospital. @*Results@#Among 14,688 patients, there were twice as many males (66.6%) as females (33.4%).However, under age 40 years, females (8.6%) were more prevalent than males (3.1%). Cardia GC in males showed a U-shaped distribution for underweight (9.6%), normal (6.4%), overweight (6.1%), obesity (5.6%), and severe obesity (9.3%) but not in females (p=0.003). Females showed decreased proportion of diffuse-type GC regarding BMI (underweight [59.9%], normal [56.8%], overweight [49.5%], obesity [44.8%], and severe obesity [41.7%]), but males did not (p<0.001). Both sexes had the worst prognosis in the underweight group (p<0.001), and the higher BMI, the better prognosis in males, but not females. Sex differences in prognosis according to BMI tended to be more prominent in males than in females in subgroup analysis of TNM stages I, II, and III and the operative treatment group. @*Conclusions@#GC-specific survival was affected by BMI in a sex-dependent manner. These differences may be related to genetic, and environmental, hormonal factors; body composition; and muscle mass (Trial registration number: NCT04973631).
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Purpose@#Universal screening for Lynch syndrome (LS) refers to routine tumor testing for microsatellite instability (MSI) among all patients with colorectal cancer (CRC). Despite its widespread adoption, real-world data on the yield is lacking in Korean population. We studied the yield of adopting universal screening for LS in comparison with pedigree-based screening in a tertiary center. @*Materials and Methods@#CRC patients from 2007-2018 were reviewed. Family histories were obtained and were evaluated for hereditary nonpolyposis colorectal cancer (HNPCC) using Amsterdam II criteria. Tumor testing for MSI began in 2007 and genetic testing was offered using all available clinicopathologic data. Yield of genetic testing for LS was compared for each approach and step. @*Results@#Of the 5,520 patients, tumor testing was performed in 4,701 patients (85.2%) and family histories were obtained from 4,241 patients (76.8%). Hereditary CRC (LS or HNPCC) was present in 69 patients (1.3%). MSI-high was present in 6.9%, and 25 patients had confirmed LS. Genetic testing was performed in 41.2% (47/114) of MSI-high patients, out of which 40.4% (19/47) were diagnosed with LS. There were six additional LS patients found outside of tumor testing. For pedigree-based screening, Amsterdam II criteria diagnosed 55 patients with HNPCC. Fifteen of these patients underwent genetic testing, and 11 (73.3%) were diagnosed with LS. Two patients without prior family history were diagnosed with LS and relied solely on tumor testing results. @*Conclusion@#Despite widespread adoption of routine tumor testing for MSI, this is not a fail-safe approach to screen all LS patients. Obtaining a thorough family history in combination with universal screening provides a more comprehensive ‘universal’ screening method for LS.
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Purpose@#Hypoxaemia is a significant adverse event during endoscopic retrograde cholangiopancreatography (ERCP) under monitored anaesthesia care (MAC); however, no model has been developed to predict hypoxaemia. We aimed to develop and compare logistic regression (LR) and machine learning (ML) models to predict hypoxaemia during ERCP under MAC. @*Materials and Methods@#We collected patient data from our institutional ERCP database. The study population was randomly divided into training and test sets (7:3). Models were fit to training data and evaluated on unseen test data. The training set was further split into k-fold (k=5) for tuning hyperparameters, such as feature selection and early stopping. Models were trained over k loops; the i-th fold was set aside as a validation set in the i-th loop. Model performance was measured using area under the curve (AUC). @*Results@#We identified 6114 cases of ERCP under MAC, with a total hypoxaemia rate of 5.9%. The LR model was established by combining eight variables and had a test AUC of 0.693. The ML and LR models were evaluated on 30 independent data splits. The average test AUC for LR was 0.7230, which improved to 0.7336 by adding eight more variables with an l 1 regularisation-based selection technique and ensembling the LRs and gradient boosting algorithm (GBM). The high-risk group was discriminated using the GBM ensemble model, with a sensitivity and specificity of 63.6% and 72.2%, respectively. @*Conclusion@#We established GBM ensemble model and LR model for risk prediction, which demonstrated good potential for preventing hypoxaemia during ERCP under MAC.
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Background and Objectives@#Paroxysmal atrial fibrillation (AF) is a major potential cause of embolic stroke of undetermined source (ESUS). However, identifying AF remains challenging because it occurs sporadically. Deep learning could be used to identify hidden AF based on the sinus rhythm (SR) electrocardiogram (ECG). We combined known AF risk factors and developed a deep learning algorithm (DLA) for predicting AF to optimize diagnostic performance in ESUS patients. @*Methods@#A DLA was developed to identify AF using SR 12-lead ECG with the database consisting of AF patients and non-AF patients. The accuracy of the DLA was validated in 221 ESUS patients who underwent insertable cardiac monitor (ICM) insertion to identify AF. @*Results@#A total of 44,085 ECGs from 12,666 patient were used for developing the DLA. The internal validation of the DLA revealed 0.862 (95% confidence interval, 0.850–0.873) area under the curve (AUC) in the receiver operating curve analysis. In external validation data from 221 ESUS patients, the diagnostic accuracy of DLA and AUC were 0.811 and 0.827, respectively, and DLA outperformed conventional predictive models, including CHARGE-AF,C2HEST, and HATCH. The combined model, comprising atrial ectopic burden, left atrial diameter and the DLA, showed excellent performance in AF prediction with AUC of 0.906. @*Conclusions@#The DLA accurately identified paroxysmal AF using 12-lead SR ECG in patients with ESUS and outperformed the conventional models. The DLA model along with the traditional AF risk factors could be a useful tool to identify paroxysmal AF in ESUS patients.
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Objective@#: This study compared the quality of recovery (QoR) after minicraniotomy for clipping of unruptured intracranial aneurysms (UIAs) between patients with and without scalp nerve block (SNB). @*Methods@#: Patients were randomly assigned to the SNB (SNB using ropivacaine with epinephrine, n=27) and control (SNB using normal saline, n=25) groups. SNB was performed at the end of surgery. To assess postoperative QoR, the QoR-40, a patient-reported questionnaire, was used. The QoR-40 scores were measured preoperatively, 1–3 days postoperatively, at hospital discharge, and 1 month postoperatively. Pain and intravenous patient-controlled analgesia (IV-PCA) consumption were evaluated 3, 6, 9, and 12 hours and 1–3 days postoperatively. @*Results@#: All QoR-40 scores, including those measured 1 day postoperatively (primary outcome measure; 155.0 [141.0–176.0] vs. 161.0 [140.5–179.5], p=0.464), did not significantly differ between the SNB and control groups. The SNB group had significantly less severe pain 3 (numeric rating scale [NRS]; 3.0 [2.0–4.0] vs. 5.0 [3.5–5.5], p=0.029), 9 (NRS; 3.0 [2.0–4.0] vs. 4.0 [3.0–5.0], p=0.048), and 12 (NRS; 3.0 [2.0–4.0] vs. 4.0 [3.0–5.0], p=0.035) hours postoperatively. The total amount of IV-PCA consumed was significantly less 3 hours postoperatively in the SNB group (2.0 [1.0–4.0] vs. 4.0 [2.0–5.0] mL, p=0.044). @*Conclusion@#: After minicraniotomy for clipping of UIAs, SNB reduced pain and IV-PCA consumption in the early postoperative period but did not improve the QoR-40 scores.
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The cervical spine plays a critical role in supporting the skull, maintaining horizontal gaze, and facilitating walking. Its unique characteristics, including the widest range of motion among spinal segments, have led to extensive research on cervical sagittal alignment. Various parameters have been proposed to evaluate cervical alignment, with studies investigating their clinical significance, correlation with symptoms, and implications for surgical interventions. Recent findings suggest that cervical sagittal alignment not only impacts the cervical spine but also influences global spine-pelvic alignment through compensatory mechanisms. This comprehensive review examines classical and new parameters of cervical sagittal alignment and considers the dynamic and muscular factors associated with it.
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Purpose@#According to the American Joint Committee on Cancer cancer staging system, positive peritoneal washing cytology (PWC) indicates stage IV gastric cancer. However, rapid intraoperative diagnosis of PWC has no established reliable method. This study evaluated and compared the diagnostic accuracy of the Shorr and the modified ultrafast Papanicolaou (MUFP) methods for intraoperative PWC. @*Materials and Methods@#This study included patients with gastric cancer who were clinically diagnosed with stage cT3 or higher. The Shorr and MUFP methods were performed on all PWC specimens, and the results were compared with those of conventional Papanicolaou (PAP) staining with carcinoembryonic antigen immunohistochemistry. Sensitivity, specificity, and partial likelihood tests were used to compare the 2 methods. @*Results@#Forty patients underwent intraoperative PWC between November 2019 and August 2021. The average time between specimen reception and slide preparation using Shorr and MUFP methods was 44.4±4.5 minutes, and the average time between specimen reception and pathologic diagnosis was 53.9±8.9 minutes. Eight patients (20.0%) had positive cytology in PAP staining. The Shorr method had a sensitivity of 75.0% and specificity of 93.8%; the MUFP method had 62.5% sensitivity and 100.0% specificity. The area under the curve was 0.844 for Shorr and 0.813 for MUFP. In comparing the C-indices of each method with overall survival, no difference was found among the Shorr, MUFP, and conventional PAP methods. @*Conclusions@#The Shorr and MUFP methods are acceptable for the intraoperative diagnosis of PWC in advanced gastric cancer.
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Purpose@#In this study, polymerase chain reaction (PCR)-based microsatellite instability (MSI) testing was comprehensively analyzed and compared with immunohistochemistry (IHC) for mismatch repair (MMR) protein expression in patients with gastric cancer (GC). @*Materials and Methods@#In 5,676 GC cases, PCR-based MSI testing using five microsatellites (BAT-26, BAT-25, D5S346, D2S123, and D17S250) and IHC for MLH1 were performed. Reevaluation of MSI testing/MLH1 IHC and additional IHC for MSH2, MSH6, and PMS2 were performed in discordant/indeterminate cases. @*Results@#Of the 5,676 cases, microsatellite stable (MSS)/MSI-low and intact MLH1 were observed in 5,082 cases (89.5%), whereas MSI-high (MSI-H) and loss of MLH1 expression were observed in 502 cases (8.8%). We re-evaluated the remaining 92 cases (1.6%) with a discordant/ indeterminate status. Re-evaluation showed 1) 37 concordant cases (0.7%) (18 and 19 cases of MSI-H/MMR-deficient (dMMR) and MSS/MMR-proficient (pMMR), respectively), 2) 6 discordant cases (0.1%) (3 cases each of MSI-H/pMMR and MSS/dMMR), 3) 14 MSI indeterminate cases (0.2%) (1 case of dMMR and 13 cases of pMMR), and 4) 35 IHC indeterminate cases (0.6%) (22 and 13 cases of MSI-H and MSS, respectively). Finally, MSI-H or dMMR was observed in 549 cases (9.7%), of which 47 (0.8%) were additionally confirmed as MSI-H or dMMR by reevaluation. Sensitivity was 99.3% for MSI testing and 95.4% for MMR IHC. @*Conclusions@#Considering the low incidence of MSI-H or dMMR, discordant/indeterminate results were occasionally identified in GCs, in which case complementary testing is required.These findings could help improve the accuracy of MSI/MMR testing in daily practice.
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Purpose@#We compared heart rate variability parameters between patients with spina bifida and a control group during urodynamic studies, with the goal of evaluating the autonomic nervous system dysfunction present in spina bifida. @*Methods@#Continuous heart rate variability parameters were recorded during 3 successive periods (P0, the 2 minutes prior to the start of filling; P1, from the start of filling to the first desire to void; and P2, from P1 to the end of filling or the start of voiding). The control group consisted of children with vesicoureteral reflux who had undergone video-urodynamic studies. Our study included 11 patients with spina bifida and 9 control participants. @*Results@#At baseline, patients with spina bifida exhibited lower values for the root mean square of successive differences in NN intervals, the percentage of successive R-R interval differences exceeding 50 msec relative to the total number of intervals, and high frequency (HF). In contrast, the low frequency (LF)/HF ratio was elevated in these patients (5.04 ± 4.75 vs. 0.67 ± 0.42, P = 0.014). During bladder filling, LF/HF values increased in the control group (P0, 0.67 ± 0.42; P1, 0.89 ± 0.34; P2, 1.21 ± 0.64; P = 0.018), while they declined in patients with spina bifida (P0, 5.04 ± 4.75; P1, 3.96 ± 4.35; P2, 3.26 ± 4.03; P < 0.001). The HF values were significantly elevated in children with spina bifida during bladder filling (P = 0.002). In the time domain, the standard deviations of all NN intervals were elevated only in the control group during bladder filling. Parasympathetic activity domains were reduced in the children with spina bifida at the initial assessment. @*Conclusions@#During the bladder filling phase, parasympathetic activity increased along with fixed sympathetic activity in the spina bifida group. In contrast, the control group exhibited a shift towards a sympathetic preponderance at the conclusion of bladder filling. These observations may be associated with the pathophysiology of neurogenic bladder in spina bifida.
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Background/Aims@#There are few reports regarding mixed carcinoma, defined as a mixture of glandular and poorly cohesive components, in patients with gastric cancer (GC). The aim of this study was to evaluate the proportion and characteristics of mixed carcinoma in GC patients. @*Methods@#A total of 7,215 patients diagnosed with GC at Seoul National University Bundang Hospital were enrolled from March 2011 to February 2020. GC was divided into four groups (wellmoderately differentiated GC, poorly differentiated GC, poorly cohesive carcinoma, and mixed carcinoma). The proportion of each GC type and the clinicopathological features were analyzed and divided into early GC and advanced GC. @*Results@#The proportion of mixed carcinoma was 10.9% (n=787). In early GC, submucosal invasion was the most common in poorly differentiated (53.7%), and mixed carcinoma ranked second (41.1%). Mixed carcinoma showed the highest proportion of lymph node metastasis in early GC (23.0%) and advanced GC (78.3%). In advanced GC, the rate of distant metastasis was 3.6% and 3.9% in well-moderately differentiated GC and mixed carcinoma, respectively, lower than that in poorly differentiated GC (6.4%) and poorly cohesive carcinoma (5.7%), without statistical significance. @*Conclusions@#Mixed carcinoma was associated with lymph node metastasis compared to other histological GC subtypes. And it showed relatively common submucosal invasion in early GC, but the rates of venous invasion and distant metastasis were lower in advanced GC. Further research is needed to uncover the mechanism underlying these characteristics of mixed carcinoma (Trial registration number: NCT04973631).
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Background/Aims@#Programmed death-ligand 1 (PD-L1) expression in tumor cells is associated with a poor biliary tract cancer (BTC) prognosis; tumor-infiltrating immune cells in the tumor microenvironment are associated with a better prognosis. The effect of PD-L1 expression on immune cells on survival is unclear. We investigated the relationship between PD-L1 expression in immune cells and BTC prognosis. @*Methods@#PD-L1 expression was evaluated using an anti-PD-L1 22C3 mouse monoclonal primary antibody, and its relationships with clinical characteristics and prognosis were analyzed using the Cox proportional hazard model to investigate the prognostic performance of PD-L1 in BTC. @*Results@#Among 144 analyzed cases, patients with positive PD-L1 expression in tumor cells and negative PD-L1 expression in immune cells showed poorer overall survival rates than those exhibiting other expressions (tumor cells: hazard ratio [HR]=1.023, p<0.001; immune cells: HR=0.983, p=0.021). PD-L1 expression in tumor cells was an independent predictor of poor overall survival (HR=1.024, p<0.001). In contrast, PD-L1 expression in immune cells was a predictive marker of good prognosis (HR=0.983, p=0.018). @*Conclusions@#PD-L1 expression in immune cells may be used as an independent factor to evaluate the prognosis of patients with BTC.
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Background/Aims@#Transarterial radioembolization (TARE) has shown promising results in treating advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). However, whether TARE can provide superior or comparable outcomes to tyrosine kinase inhibitor (TKI) in patients with HCC and PVTT remains unclear. We compared the outcomes of TARE and TKI therapy in treatment-naïve patients with locally advanced HCC and segmental or lobar PVTT. @*Methods@#This multicenter study included 216 patients initially treated with TARE (n=124) or TKI (sorafenib or lenvatinib; n=92) between 2011 and 2021. Baseline characteristics were balanced using propensity score matching (PSM) or inverse probability of treatment weighting (IPTW). The primary outcome was overall survival (OS). The secondary outcomes included progression-free survival (PFS) and objective response rate (ORR). @*Results@#In the unmatched cohort, the median OS of the TARE and TKI groups were 28.2 and 7.2 months, respectively (p<0.001), and the TARE group experienced significantly and independently longer OS compared to the TKI group (adjusted hazard ratio=0.41, 95% confidence interval=0.28–0.60, p<0.001). Similar results were observed in the study cohorts balanced with IPTW (p=0.003) or PSM (p=0.004). Although PFS was comparable between the two groups, the TARE group showed a trend of prolonged PFS in a subpopulation of patients with Vp1 or Vp2 PVTT (p=0.052). In the matched cohorts, the ORR of the TARE group was 53.0–56.7%, whereas that of the TKI group was 12.3–15.0%. @*Conclusions@#For patients with advanced HCC with segmental or lobar PVTT and well-preserved liver function, TARE may provide superior OS compared to sorafenib or lenvatinib.
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Purpose@#To identify important features of lymph node metastasis (LNM) and develop a prediction model for early gastric cancer (EGC) using a gradient boosting machine (GBM) method. @*Materials and Methods@#The clinicopathologic data of 2556 patients with EGC who underwent gastrectomy were used as training set and the internal validation set (set 1) at a ratio of 8:2. Additionally, 548 patients with EGC who underwent endoscopic submucosal dissection (ESD) as the initial treatment were included in the external validation set (set 2). The GBM model was constructed, and its performance was compared with that of the Japanese guidelines. @*Results@#LNM was identified in 12.6% (321/2556) of the gastrectomy group (training set & set 1) and 4.3% (24/548) of the ESD group (set 2). In the GBM analysis, the top five features that most affected LNM were lymphovascular invasion, depth, differentiation, size, and location. The accuracy, sensitivity, specificity, and the area under the receiver operating characteristics of set 1 were 0.566, 0.922, 0.516, and 0.867, while those of set 2 were 0.810, 0.958, 0.803, and 0.944, respectively. When the sensitivity of GBM was adjusted to that of Japanese guidelines (beyond the expanded criteria in set 1 [0.922] and eCuraC-2 in set 2 [0.958]), the specificities of GBM in sets 1 and 2 were 0.516 (95% confidence interval, 0.502-0.523) and 0.803 (0.795-0.805), while those of the Japanese guidelines were 0.502 (0.488-0.509) and 0.788 (0.780-0.790), respectively. @*Conclusion@#The GBM model showed good performance comparable with the eCura system in predicting LNM risk in EGCs.
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Background@#The Global Initiative for Chronic Obstructive Lung Disease (GOLD) update 2023 proposed new definitions of chronic obstructive pulmonary disease (COPD) and COPD exacerbation. However, an agreement on the definitions has not been made, either internationally or domestically. This study aimed to reach an agreement between experts on the new definitions of COPD and COPD exacerbation in South Korea. @*Methods@#A modified Delphi method was used to make an agreement on the definitions of COPD and COPD exacerbation proposed by the GOLD update 2023. We performed two rounds of the survey including 15 Korean experts on COPD, asthma, and tuberculosis. @*Results@#More than two-thirds of the experts agreed on 12 of the 13 statements related to the definitions of COPD and COPD exacerbation in the two rounds of the survey. The experts agreed on the definitions of COPD and COPD exacerbation that should be revised in line with the definitions proposed by the GOLD update 2023. However, the experts showed an uncertain opinion on the statement that the definition of COPD includes patients with persistent airflow obstruction due to bronchiectasis. @*Conclusion@#Based on this Delphi survey, experts’ agreement was made on the definitions of COPD and COPD exacerbation proposed by the GOLD update 2023.
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Objective@#To identify factors associated with swallowing recovery in patients with dysphagia after ischemic stroke. @*Methods@#Patients admitted to Kangbuk Samsung Hospital from 2011 to 2019 for first acute ischemic stroke and dysphagia, as confirmed by a videofluoroscopic swallowing study (VFSS), were enrolled in this retrospective study. Patients whose Dysphagia Outcome and Severity Scale (DOSS) level was ＜6 as determined by VFSS were monitored in a dysphagia clinic and additional VFSS was performed periodically until one year after stroke. Follow-up was discontinued when the DOSS level reached 6 or 7. The main study outcomes were full recovery and tube removal rate. Cox regression analysis was used to identify prognostic factors of dysphagia. The Kaplan-Meier method was used to generate curves of the proportions of patients that achieved full recovery. @*Results@#One hundred and thirteen patients were enrolled. Multivariate analysis showed that only initial DOSS was significantly associated with swallowing recovery (13.0% for non-oral feeding vs. 35.6 % for a modified diet). @*Conclusion@#Initial swallowing status (as determined by VFSS findings) is strongly associated with swallowing recovery in post-ischemic stroke patients. Assessments of dysphagia are important for predicting dysphagia recovery and planning management strategies.
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The hypoglossal canal (HC) is an unusual location of the posterior fossa dural arteriovenous fistula (AVF), which usually occurs in the transverse or sigmoid sinus. Herein, we report a case of HC dural AVF successfully treated with transvenous coil embolization using detachable coils in a 68-year-old woman who presented with headache and left pulsatile tinnitus for 2 months. Brain magnetic resonance imaging (MRI) and cerebral angiography revealed left HC dural AVF. The pulsatile bruit disappeared immediately after the procedure. Follow-up MRI showed complete disappearance of the fistula. Precise localization of the fistula through careful consideration of the anatomy and transvenous coil embolization using a detachable coil can facilitate the treatment for HC dural AVF.
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Purpose@#Triple-negative breast cancer (TNBC) does not have defined therapeutic targets and is currently treated with chemotherapy only. Kinase dysregulation triggers cancer cell proliferation and metastasis and is a crucial therapeutic target for cancer. In this study, targeted kinome sequencing of TNBC tumors was performed to assess the association between kinome gene alterations and disease outcomes in TNBC. @*Methods@#A kinome gene panel consisting of 612 genes was used for the targeted sequencing of 166 TNBC samples and matched normal tissues. Analyses of the significantly mutated genes were performed. Genomic differences between Asian and non-Asian patients with TNBC were evaluated using two Asian TNBC datasets (from Seoul National University Hospital [SNUH] and Fudan University Shanghai Cancer Center [FUSCC]) and three nonAsian TNBC datasets (The Cancer Genome Atlas [TCGA], METABRIC, and Gustave Roussy).The prognostic value of kinome gene mutations was evaluated using tumor mutational burden (TMB) and oncogenic pathway analyses. Mutational profiles from the TCGA were used for validation. @*Results@#The significantly mutated genes included TP53 (60% of patients), PIK3CA (21%), BRCA2 (8%), and ATM (8%). Compared with data from non-Asian public databases, the mutation rates of PIK3CA p.H1047R/Q were significantly higher in the SNUH cohort (p = 0.003, 0.048, and 0.032, respectively). This was verified using the FUSCC dataset (p = 0.003, 0.078, and 0.05, respectively). The TMB-high group showed a trend toward longer progression-free survival in our cohort and the TCGA TNBC cohort (p = 0.041 and 0.195, respectively). Kinome gene alterations in the Wnt pathway in patients with TNBC were associated with poor survival in both datasets (p = 0.002 and 0.003, respectively). @*Conclusion@#Comprehensive analyses of kinome gene alterations in TNBC revealed genomic alterations that offer therapeutic targets and should help identify high-risk patients more precisely in future studies.
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Purpose@#Smoking is a risk factor for the development of asthma and worsens the long-term prognosis of asthma. This study investigated the effect of cigarette smoke extract (CSE) on innate immune cells such as innate lymphoid cells (ILCs) and macrophages in a murine model of induced asthma. @*Methods@#Six-week-old female BALB/C mice were exposed to ovalbumin (OVA) via an intranasal route with or without CSE for 8 weeks to establish a chronic murine asthma model. Airway hyperresponsiveness (AHR), airway inflammatory cells from bronchoalveolar lavage fluid, and the population of CD4 + T cells, ILCs, and macrophages in the lungs were studied to evaluate the effect of chronic CSE exposure on asthma. @*Results@#Mice intranasally exposed to CSE along with OVA treatment (CSE/OVA) had significantly enhanced AHR, eosinophilic inflammation, increased IL-13 and IL-17 producing CD4 + T cells compared to mice intranasally exposed to OVA only. On the contrary, the frequency of Foxp3 + in CD4 + T cells was reduced in the CSE/OVA group. CSE enhanced the dendritic cell (DC) population, especially MHCII + DC with antigen-presenting capacity. Among ILCs, the CSE/OVA group showed a significant increase of IL-13-producing type 2 ILCs, but not interferon-γ+ ILC1s and IL-17 + ILC3s. . Among macrophages, alveolar macrophage and Ym-1 and FIZZ1 positive M2 macrophage populations were significantly induced by CSE exposure alone and when combined with OVA treatment. @*Conclusion@#In this study, we showed that long-term exposure to cigarette smoke contributes to the inception and aggravation of asthmatic inflammation by enhancing DCs, ILC2, and M2 alveolar macrophage populations in the mouse model.