Atypical Gradenigo's syndrome in a pediatric case: A critical review of neuroimaging.

Gradenigo's syndrome, a rare but serious complication of otitis media, encompasses a triad of symptoms including otalgia, facial palsy, and abducens nerve palsy, pointing to the involvement of the petrous apex. This case report presents an 11-year-old boy with an atypical manifestation of Gradenigo's syndrome, characterized by the absence of classic features such as abducens nerve palsy and purulent otorrhea. MRI findings were significant for petrous apicitis extending to Meckel's cave and the cavernous sinus, along with abscess formation and clivus osteomyelitis. The report highlights the critical role of advanced neuroimaging, particularly MRI, in the diagnosis and management of this condition. It underscores the importance of recognizing atypical presentations of Gradenigo's syndrome and the effectiveness of imaging-guided conservative treatment strategies in pediatric otological cases.

Digital Validation in Breast Cancer Needle Biopsies: Comparison of Histological Grade and Biomarker Expression Assessment Using Conventional Light Microscopy, Whole Slide Imaging, and Digital Image Analysis.

Given the widespread use of whole slide imaging (WSI) for primary pathological diagnosis, we evaluated its utility in assessing histological grade and biomarker expression (ER, PR, HER2, and Ki67) compared to conventional light microscopy (CLM). In addition, we explored the utility of digital image analysis (DIA) for assessing biomarker expression. Three breast pathologists assessed the Nottingham combined histological grade, its components, and biomarker expression through the immunohistochemistry of core needle biopsy samples obtained from 101 patients with breast cancer using CLM, WSI, and DIA. There was no significant difference in variance between the WSI and CLM agreement rates for the Nottingham grade and its components and biomarker expression. Nuclear pleomorphism emerged as the most variable histologic component in intra- and inter-observer agreement (kappa ≤ 0.577 and kappa ≤ 0.394, respectively). The assessment of biomarker expression using DIA achieved an enhanced kappa compared to the inter-observer agreement. Compared to each observer's assessment, DIA exhibited an improved kappa coefficient for the expression of most biomarkers with CLM and WSI. Using WSI to assess prognostic and predictive factors, including histological grade and biomarker expression in breast cancer, is acceptable. Furthermore, incorporating DIA to assess biomarker expression shows promise for substantially enhancing scoring reproducibility.

A Nationwide Study on HER2-low Breast Cancer in South Korea: Its Incidence of 2022 Real World Data and the Importance of Immunohistochemical Staining Protocols.

Purpose: Notable effectiveness of trastuzumab deruxtecan (T-DXd) in patients with HER2-low advanced breast cancer (BC) has focused pathologists' attention. We studied the incidence and clinicopathologic characteristics of HER2-low BC, and the effects of immunohistochemistry (IHC) associated factors on HER2 IHC results. Materials and Methods: The Breast Pathology Study Group of the Korean Society of Pathologists conducted a nationwide study using real-world data on HER2 status generated between January 2022 and December 2022. Information on HER2 IHC protocols at each participating institution was also collected. Results: Total 11,416 patients from twenty-five institutions included in this study. Of these patients, 40.7% (range: 6.0%-76.3%) were classified as HER2-zero, 41.7% (range: 10.5%-69.1%) as HER2-low, and 17.5% (range: 6.7%-34.0%) as HER2-positive. HER2-low tumors were associated with positive ER and PR statuses (p<0.001 and p<0.001, respectively). Antigen retrieval times (≥ 36 min vs. < 36 min) and antibody incubation times (≥ 12 min vs. < 12 min) affected on the frequency of HER2 IHC 1+ BC at institutions using the PATHWAY HER2 (4B5) IHC assay and BenchMark XT or Ultra staining instruments. Furthermore, discordant results between core needle biopsy (CNB) and subsequent resection specimen HER2 statuses were observed in 24.1% (787/3259) of the patients. Conclusion: The overall incidence of HER2-low BC in South Korea concurs with those reported in previously published studies. Significant inter-institutional differences in HER2 IHC protocols were observed, and it may have impact on HER2-low status. Thus, we recommend standardizing HER2 IHC conditions to ensure precise patient selection for targeted therapy.

Clinical characteristics of persistent postural-perceptual dizziness and its visual subtype in Korean patients: A multicenter cross-sectional study.

OBJECTIVES: Persistent postural-perceptual dizziness (PPPD) is a chronic functional vestibular disorder for which the Bárány Society has established diagnostic criteria. This nationwide multicenter study aims to investigate the clinical features of individuals with definite PPPD and clinical variant PPPD who do not fully meet the diagnostic criteria, with a particular focus on visual exaggeration. METHODS: Between September 2020 and September 2021, a total of 76 individuals with definite PPPD and 109 individuals with clinical variant PPPD who did not meet all three exacerbating factors outlined in Criterion B were recruited from 18 medical centers in South Korea. The study gathered information on demographic factors, clinical manifestations, balance scales, and personality assessments. RESULTS: Comparative analysis between groups with definite PPPD and clinical variant with visual exacerbation revealed no significant differences in sociodemographic characteristics, clinical course, dizziness impact, and specific precipitants. Only disease duration was significantly longer in definite PPPD compared with variant with visual exacerbation. However, the variant without visual exacerbation displayed significantly reduced rates of panic disorder, diminished space-motion discomfort, lesser impact of dizziness, and decreased prevalence of depression when compared with the definitive PPPD. CONCLUSION: This is the first comprehensive nationwide study examining clinical features of both definite PPPD patients and its clinical variants, considering visual exacerbating factors. Differences in dizziness and personality traits emerged between definite PPPD and its potential variant without visual issues. Our results highlight the possibility of a distinct clinical variant of PPPD influenced by visual dependency.

Comparison between Peritumoral and Intratumoral Budding in Colorectal Cancer.

Tumor budding (TB) is classified, based on location, into peritumoral budding (PTB) or intratumoral budding (ITB). This study aimed to evaluate the relationship between PTB and ITB in colorectal cancers (CRCs). PTB and ITB were investigated and subsequently divided into high and low groups. CRCs were divided into three groups: (1) high PTB/ITB, (2) high PTB or ITB, and (3) low PTB/ITB. The clinicopathological and prognostic significances were evaluated according to the three tumor budding (TB) groups. High PTB/ITB and low PTB/ITB were identified in 32 (12.0%) and 135 (50.8%) patients, respectively. A total of 99 patients (37.2%) were found to have high PTB or ITB. TB was significantly correlated with lymphatic and perineural invasion, lymph node metastasis, metastatic lymph node ratio, distant metastasis, and a higher pTNM stage. A significant correlation was found between high PTB and high ITB (p = 0.010). The amount of PTB was found to increase significantly with the amount of ITB (p < 0.001) in a linear regression test. Patients with high PTB/ITB had worse overall and recurrence-free survival than those with high PTB or ITB. Conversely, patients with low PTB/ITB had better overall and recurrence-free survival rates than those with high PTB or ITB. However, there was no significant difference in overall and recurrence-free survival between patients with high PTB/low ITB and high ITB/low PTB (p = 0.336 and p = 0.623, respectively). In summary, the presence of TB, regardless of PTB or ITB, was significantly correlated with aggressive tumor behavior and a worse prognosis than the absence of TB. Additionally, the present study demonstrated that it is feasible to stratify the prognosis of patients based on whether they have both PTB and ITB or only one of the two.

Spiritual Care Guide in Hospice∙Palliative Care.

The Spiritual Care Guide in Hospice∙Palliative Care is evidence-based and focuses on the universal and integral aspects of human spirituality-such as meaning and purpose, interconnectedness, and transcendence-which go beyond any specific religion. This guide was crafted to improve the spiritual well-being of adult patients aged 19 and older, as well as their families, who are receiving end-of-life care. The provision of spiritual care in hospice and palliative settings aims to assist patients and their families in finding life's meaning and purpose, restoring love and relationships, and helping them come to terms with death while maintaining hope. It is recommended that spiritual needs and the interventions provided are periodically reassessed and evaluated, with the findings recorded. Additionally, hospice and palliative care teams are encouraged to pursue ongoing education and training in spiritual care. Although challenges exist in universally applying this guide across all hospice and palliative care organizations in Korea-due to varying resources and the specific environments of medical institutions-it is significant that the Korean Society for Hospice and Palliative Care has introduced a spiritual care guide poised to enhance the spiritual well-being and quality of care for hospice and palliative care patients.

Mucocutaneous ulcer positive for Epstein-Barr virus, misdiagnosed as a small bowel adenocarcinoma: A case report.

BACKGROUND: Epstein-Barr virus (EBV)-positive mucocutaneous ulcers (MCUs) are an uncommon disorder characterized by ulcerative lesions in the skin, oral cavity or gastrointestinal tract in patients with iatrogenic or aging-induced immunosuppression. The nonspecific lesions are difficult to differentiate from small bowel adenocarcinomas. We present the case of a 69-year-old woman who was initially misdiagnosed with a small bowel adenocarcinoma but was later surgically diagnosed with and treated for EBV-MCU. Through this case, we aim to emphasize the importance of accurately distinguishing between the two conditions. CASE SUMMARY: The patient presented with an incidental finding of a small bowel tumor during computed tomography (CT) examination performed for hematuria. The CT scan showed irregular thickening of the distal ileum, which was suggestive of a malignant small bowel tumor. An exploratory laparotomy revealed an 8-cm mass in the distal ileum; thus, a segment of the small intestine, including the mass, was resected. Histopathological analysis revealed an ulceroinfiltrative mass-like lesion with luminal narrowing, marked inflammatory cell infiltration, and large atypical lymphoid cells (positive for EBV-encoded small RNA). A final diagnosis of an EBV-MCU was established. The postoperative course was uneventful, and the patient was discharged on postoperative day 7. The patient remained recurrence-free until 12 mo after surgery. CONCLUSION: This case highlights the diagnostic challenges for EBV-MCUs and emphasizes the importance of comprehensive evaluation and accurate histopathological analysis.

The prognostic value of a combined immune score in tumor and immune cells assessed by immunohistochemistry in triple-negative breast cancer.

BACKGROUND: This study aimed to develop a novel combined immune score (CIS)-based model assessing prognosis in triple-negative breast cancer (TNBC). METHODS: The expression of eight immune markers (PD-1, PD-L1, PD-L2, IDO, TIM3, OX40, OX40L, and H7-H2) was assessed with immunohistochemistry on the tumor cells (TCs) and immune cells (ICs) of 227 TNBC cases, respectively, and subsequently associated with selected clinicopathological parameters and survival. Data retrieved from The Cancer Genome Atlas (TCGA) were further examined to validate our findings. RESULTS: All immune markers were often expressed in TCs and ICs, except for PD-1 which was not expressed in TCs. In ICs, the expression of all immune markers was positively correlated between one another, except between PD-L1 and OX40, also TIM3 and OX40. In ICs, PD-1, PD-L1, and OX40L positive expression was associated with a longer progression-free survival (PFS; p = 0.040, p = 0.020, and p = 0.020, respectively). In TCs, OX40 positive expression was associated with a shorter PFS (p = 0.025). Subsequently, the TNBC patients were classified into high and low combined immune score groups (CIS-H and CIS-L), based on the expression levels of a selection of biomarkers in TCs (TCIS-H or TCIS-L) and ICs (ICIS-H or ICIS-L). The TCIS-H group was significantly associated with a longer PFS (p < 0.001). Furthermore, the ICIS-H group was additionally associated with a longer PFS (p < 0.001) and overall survival (OS; p = 0.001), at significant levels. In the multivariate analysis, both TCIS-H and ICIS-H groups were identified as independent predictors of favorable PFS (p = 0.012 and p = 0.001, respectively). ICIS-H was also shown to be an independent predictor of favorable OS (p = 0.003). The analysis of the mRNA expression data from TCGA also validated our findings regarding TNBC. CONCLUSION: Our novel TCIS and ICIS exhibited a significant prognostic value in TNBC. Additional research would be needed to strengthen our findings and identify the most efficient prognostic and predictive biomarkers for TNBC patients.

Identification of the Plant Family Caryophyllaceae in Korea Using DNA Barcoding.

Caryophyllaceae is a large angiosperm family, with many species being utilized as ornamental or medicinal plants in Korea, in addition to several endangered species that are managed by the government. In this study, we used DNA barcoding for the accurate identification of Korean Caryophyllaceae. A total of 78 taxa (n = 215) were sequenced based on three chloroplast regions (rbcL, matK, and psbA-trnH) and nuclear ribosomal internal transcribed spacers (ITS). In the neighbor-joining tree, a higher accuracy of identification was generally observed when using ITS (>73%) rather than chloroplast regions (<62%). The highest resolution was found for rbcL + ITS (77.6%), although resolution varied according to the genus. Among the genera that included two and more species, five genera (Eremogone, Minuartia, Pseudostellaria, Sagina, and Stellaria) were successfully identified. However, the species of five other genera (Cerastium, Gypsophila, Dianthus, Silene, and Spergularia) showed relatively low resolutions (0-61.1%). In the cases of Cerastium, Dianthus, and Silene, ambiguous taxonomic relationships among unidentified species may have been a factor contributing to such low resolutions. However, in contrast to these results, Gypsophila and Spergularia have been identified well in previous studies. Our findings indicate the need of taxonomic reconsideration in Korea.

FAM83H Expression Is Associated with Tumor-Infiltrating PD1-Positive Lymphocytes and Predicts the Survival of Breast Carcinoma Patients.

BACKGROUND: FAM83H has been implicated in cancer progression, and PD1 is an important target for anti-cancer immune checkpoint therapy. Recent studies suggest an association between FAM83H expression and immune infiltration. However, studies on the roles of FAM83H and its relationship with PD1 in breast carcinomas have been limited. METHODS: Immunohistochemical expression of FAM83H and PD1 and their prognostic significance were evaluated in 198 breast carcinomas. RESULTS: The expression of FAM83H in cancer cells was significantly associated with the presence of PD1-positive lymphoid cells within breast carcinoma tissue. Individual and co-expression patterns of nuclear FAM83H and PD1 were significantly associated with shorter survival of breast carcinomas in univariate analysis. In multivariate analysis, the expression of nuclear FAM83H (overall survival, p < 0.001; relapse-free survival, p = 0.003), PD1 (overall survival, p < 0.001; relapse-free survival, p = 0.003), and co-expression patterns of nuclear FAM83H and PD1 (overall survival, p < 0.001; relapse-free survival, p < 0.001) were the independent indicators of overall survival and relapse-free survival of breast carcinoma patients. CONCLUSIONS: This study suggests a close association between FAM83H expression and the infiltration of PD1-positive lymphoid cells in breast carcinomas and their expression as the prognostic indicators for breast carcinoma patients, and further studies are needed to clarify this relationship.

Round-window delivery of lithium chloride regenerates cochlear synapses damaged by noise-induced excitotoxic trauma via inhibition of the NMDA receptor in the rat.

Noise exposure can destroy the synaptic connections between hair cells and auditory nerve fibers without damaging the hair cells, and this synaptic loss could contribute to difficult hearing in noisy environments. In this study, we investigated whether delivering lithium chloride to the round-window can regenerate synaptic loss of cochlea after acoustic overexposure. Our rat animal model of noise-induced cochlear synaptopathy caused about 50% loss of synapses in the cochlear basal region without damaging hair cells. We locally delivered a single treatment of poloxamer 407 (vehicle) containing lithium chloride (either 1 mM or 2 mM) to the round-window niche 24 hours after noise exposure. Controls included animals exposed to noise who received only the vehicle. Auditory brainstem responses were measured 3 days, 1 week, and 2 weeks post-exposure treatment, and cochleas were harvested 1 week and 2 weeks post-exposure treatment for histological analysis. As documented by confocal microscopy of immunostained ribbon synapses, local delivery of 2 mM lithium chloride produced synaptic regeneration coupled with corresponding functional recovery, as seen in the suprathreshold amplitude of auditory brainstem response wave 1. Western blot analyses revealed that 2 mM lithium chloride suppressed N-methyl-D-aspartate (NMDA) receptor expression 7 days after noise-exposure. Thus, round-window delivery of lithium chloride using poloxamer 407 reduces cochlear synaptic loss after acoustic overexposure by inhibiting NMDA receptor activity in rat model.

Broad spectrum of phenotype and genotype in Korean α-dystroglycan related muscular dystrophy presenting to a tertiary pediatric neuromuscular center.

α-Dystroglycanopathies are a clinically and genetically heterogeneous group of muscular dystrophies associated with the defective glycosylation of α-dystroglycan (α-DG). Eighteen genes associated with α-dystroglycanopathies have been identified, and the relative prevalence of genetic subtypes varies with ethnicity. Here, we investigated the clinical and genetic characteristics of α-DG-related muscular dystrophy in the Korean pediatric population. We analyzed the clinical characteristics and variant profiles of 42 patients with α-DG-related muscular dystrophies diagnosed by either reduced glycosylation of α-DG and/or genetic confirmation. Genotype-phenotype correlations were explored by a retrospective medical record review. The muscle-eye-brain disease/Fukuyama congenital muscular dystrophy was the most common phenotype (28/42, 66.7%). Homozygous or compound heterozygous variants were detected in 37 patients belonging to 34 unrelated families (37/42; 88.1%). Pathogenic variants were identified in FKTN (n = 24), POMGNT1 (n = 4), GMPPB (n = 4), FKRP (n = 2), POMT1 (n = 2), and ISPD (n = 1). Compound heterozygous retrotransposal insertions and deep-intronic variants in FKTN were the most common genotypes and were associated with severe phenotypes. This study suggests that α-DG-related muscular dystrophy has a wide range of genotypes and phenotypes according to ethnicity. A stratified genetic test according to ethnicity should be considered to diagnose α-DG-related muscular dystrophy.

Prevalence, Trend, and Risk Factors for Early Chronic Obstructive Pulmonary Disease: An Analysis of the Nationwide Population-Based Survey from 2010 to 2019 in South Korea.

This study aimed to evaluate the prevalence, trends, and risk factors of early chronic obstructive pulmonary disease (COPD) by using a nationally representative sample. The datasets of the Korea National Health and Nutrition Examination Survey 2010-2019 were used, where 80,860 individuals were identified; of these, 9,045 participants aged 40-49 years who underwent spirometry with no missing data were analyzed. Early COPD was defined as forced expiratory volume in 1 s /forced vital capacity ratio < the lower limit of normal (2.5th percentile) in individuals aged <50 years without a history of asthma, inhaler therapy, or persistent respiratory symptoms. The prevalence and trend of early COPD were estimated according to features such as smoking status and pack-years. Joinpoint regression analysis was used to analyze the significant annual change in the trend according to sex, smoking status, and pack-years. A complex sample multivariable-adjusted regression model was used to identify factors affecting early COPD. The estimated population size during 2010-2019 was 82,326,178. Early COPD was present in 4.5% of patients (6.5% of men and 2.3% of women). It was present in 7.7% of current smokers, followed by former and never smokers. Among smokers with ≥ 10 pack-years, early COPD was present in 8.2%, whereas it was present in 2.6% of smokers with < 10 pack-years. Joinpoint regression analyses found a recent decrease in the trend of prevalence in males who were former and current smokers. The multivariable-adjusted logistic regression model showed that being male, lower educational level, smoking status, and pack-years were factors that affected the presence of early COPD. Continued surveillance of this pre-disease condition is required, and further research are warrant.

Transition-Metal-Free Upscaling of 2,5-Furandicarboxylic Acid Synthesis and Investigation of the Reaction Mechanism.

An environmentally friendly oxidation system has proposed for the practical and scalable production of value-added 2,5-furandicarboxylic acid from 1 kg of 5-hydroxymethylfurfural. The system is composed of a simple base, oxygen, and a green solvent, thereby providing a sustainable and economical approach to organic synthesis. To gain insight into the mechanism of this oxidation process, NMR spectroscopic analysis and kinetic study are used for the mechanistic investigation of this environmentally friendly oxidation process.

Outcomes of Endoscopic Tympanoplasty for Large Perforations: A Multicenter Retrospective Study in South Korea.

OBJECTIVES: Endoscopic tympanoplasty (ET) provides minimally invasive transcanal access to the middle ear and improves middle ear visibility for the treatment of tympanic membrane (TM) perforations. However, the literature on surgical outcomes for large TM perforations is lacking and limited to small series. This study aimed to evaluate the clinical benefits of ET for large TM perforations. METHODS: This retrospective cohort study was conducted at nine tertiary referral hospitals in South Korea, where 252 patients who underwent ET as primary surgery from September 2019 to August 2021 were included. The outcome measures included the graft success rate and pre- and postoperative audiometric data. RESULTS: In 239 patients, the graft success rate of ET for large or subtotal perforations was 86.2% (206 patients), while the graft failure rate was 13.8% (33 patients). The graft failure rate was directly correlated with surgical techniques, including overlay and medial or lateral underlay tympanoplasty (P=0.027). Lateral underlay tympanoplasty showed the most favorable. RESULTS: Sex, laterality, etiology, site and size of perforation, operation time, and graft materials did not vary significantly between the graft success and failure groups (P>0.05). The mean air-bone gap (ABG) improved significantly in both groups (graft success group: 10.0±0.6 dB and graft failure group: 7.7±0.3 dB; P<0.001). However, the ABG improvement did not significantly differ between the groups. Analysis of covariance revealed that the postoperative 500-Hz bone conduction threshold improved after successful ET (adjusted coefficient, -11.351; 95% confidence interval, -21.491 to -1.212; P=0.028). CONCLUSION: This study involved the largest population to date of large TM perforations treated by ET. The study findings suggest that ET is feasible and effective in treating large TM perforations.

Distinct Clinical and Laboratory Features of COVID-19 in Children During the Pre-Delta, Delta and Omicron Wave.

BACKGROUND: The SARS-CoV-2 variants of concern exhibit distinct features in terms of transmissibility and virulence. This study compared the clinical characteristics of COVID-19 in children during pre-Delta, Delta and Omicron waves. METHODS: Medical records of 1163 children <19 years of age with COVID-19 admitted to a designated hospital in Seoul, South Korea, were analyzed. Clinical and laboratory findings during the pre-Delta (March 1, 2020, to June 30, 2021; 330 children), Delta (July 1, 2021, to December 31, 2021; 527 children) and Omicron (January 1, 2022, to May 10, 2022; 306 children) waves were compared. RESULTS: Children during the Delta wave were older and had a higher proportion of fever ≥5 days and pneumonia than children during the pre-Delta and Omicron waves. The Omicron wave was characterized by younger age and a higher proportion of fever ≥39.0 °C, febrile seizure and croup. More children <2 years of age and adolescents aged 10 to <19 years experienced neutropenia and lymphopenia, respectively, during the Delta wave. Children aged 2 to <10 years had a higher incidence of leukopenia and lymphopenia during the Omicron wave. CONCLUSIONS: Distinct features of COVID-19 were observed in children during the Delta and Omicron surges. Continuous scrutiny of the manifestations of variants of concern is needed for appropriate public health response and management.

Outcomes of Endoscopic Congenital Cholesteatoma Removal in South Korea.

Importance: Transcanal endoscopic ear surgery (TEES) provides minimally invasive transcanal access to the middle ear and improves middle ear visibility during cholesteatoma resection. However, the literature on outcomes following TEES alone for the removal of congenital cholesteatoma (CC) is lacking and limited to small series. Objective: To assess outcomes of TEES for CC limited to the middle ear and/or mastoid antrum and to explore the risk factors associated with recidivism (ie, recurrent and/or residual cholesteatoma). Design, Setting, and Participants: This cohort study evaluated retrospective, multicenter data for 271 children with CC who underwent TEES at 9 tertiary referral hospitals in South Korea between January 1, 2013, and December 31, 2021, and had a follow-up of at least 6 months after surgery. Main Outcomes and Measures: Outcomes included the incidence of residual cholesteatoma and audiometric data after TEES. A multivariable analysis using Cox proportional hazards regression models was used to assess associations between cholesteatoma characteristics and recidivism, with hazard ratios (HRs) and 95% CIs reported. Results: Of the 271 patients (mean [SD] age, 3.5 [2.9] years; 194 [71.6%] boys, 77 [28.4%] girls), 190 had Potsic stage I CC (70.1%), 21 (7.7%) had stage II, 57 (21.0%) had stage III, and 3 (1.1%) had stage IV. Thirty-six patients (13.3%) with residual cholesteatoma were found, including 15 (7.9%) with Potsic stage I, 3 (14.3%) with stage II, and 18 (31.6%) with stage III. In the multivariable analysis, invasion of the malleus (HR, 2.257; 95% CI, 1.074-4.743) and posterosuperior quadrant location (HR, 3.078; 95% CI, 1.540-6.151) were associated with the incidence of recidivism. Overall, hearing loss (>25 dB on auditory behavioral test or >30 dB of auditory evoked responses) decreased from 24.4% to 17.7% after TEES. Conclusions and Relevance: This cohort study involved the largest known population to date of CC removed by TEES. The findings suggest that TEES may be feasible and effective for the removal of CC limited to the middle ear and/or mastoid antrum in children.

Diagnostic Performance of the Newly Developed WellPrep® Liquid-Based Cytology System and Its Comparison with SurePathTM in Cervical Squamous Lesions.

INTRODUCTION: WellPrep® (WP), a fully automated, one-step liquid-based cytology (LBC) platform using an all-in-one closed chamber, has recently been developed as a next-generation LBC technology. This study aimed to evaluate the diagnostic performance and cytomorphologic features of WP regarding cervical cytology and also to compare WP with the SurePathTM (SP), one of the most widely used LBC systems used worldwide. METHODS: Cervicovaginal samples were taken from 212 females who enrolled in the study, and each sample was split and subsequently used for WP and SP LBC. Following the exclusion of seven cases with insufficient quality, a total of 205 cases were used for subsequent analysis. Among them, 75 (36.6%) received histologic follow-up. All cases were interpreted according to the Bethesda System, while three experienced pathologists evaluated their cytomorphologic features. RESULTS: The diagnostic concordance rate between the two LBC technologies was 84.4% (kappa = 0.776). Furthermore, the diagnostic concordance rates between SP and histology and between WP and histology were 73.3% (kappa = 0.516) and 70.7% (kappa = 0.497), respectively. The two LBC methods showed comparable sensitivity, specificity, and area under the curve (AUC) for histologic HSIL+ (SP: sensitivity 82.8%, specificity 84.8%, and AUC 0.838; WP: sensitivity 79.3%, specificity 87.0%, and AUC 0.831). No significant difference was found regarding the sensitivity, specificity, and AUC between SP and WP (p = 0.586, p = 0.670, and p = 0.924, respectively). In terms of cytomorphologic features, WP revealed more often than SP the presence of coarse chromatin (p = 0.031) and mitoses (p = 0.008) but less commonly perinuclear clearing (p = 0.001). CONCLUSION: This is the first study demonstrating that WP has a comparable performance to SP. In conclusion, WP may be an alternative LBC technology for cervical cancer screening.

Prognostic Implications of Intratumoral Budding in Colorectal Cancer: Detailed Analysis Based on Tumor-Infiltrating Lymphocytes.

BACKGROUND: This study aims to understand the clinical and pathological importance of intratumoral budding (ITB) in colorectal cancer (CRC) and its relationship with tumor-infiltrating lymphocytes (TILs). CRCs can be classified into hot (high immunoscore (IS)) and cold (low IS) tumors. METHODS: We investigated the number of ITBs in a hotspot area and categorized them into high-ITB (≥5) and low-ITB (<5) groups. The clinicopathological significance of ITB in human CRCs was evaluated, and a detailed analysis based on tumor-infiltrating lymphocytes (TILs) was also performed. RESULTS: High ITB was identified in 59 of 266 CRC cases (22.2%). High ITB significantly correlated with a poorly differentiated tumor, lympho-vascular invasion, perineural invasion, higher pT stage, lymph node metastasis, and higher metastatic lymph node ratio. High ITB was also significantly correlated with a low IS and low CD8-positive lymphocytic infiltrate. The number of ITBs was substantially higher in the low-IS group than in the high-IS group (3.28 ± 3.31 vs. 2.19 ± 2.59; p = 0.005). High ITB significantly correlated with worse overall survival (p = 0.004). In the low-IS group, CRCs with high ITB had a significantly worse prognosis than those with low ITB (p = 0.021). However, there was no significant difference in prognosis between the high- and low-ITB groups in the high-IS group (p = 0.498). CONCLUSIONS: Taken together, high ITB was significantly correlated with aggressive tumor behaviors and worse survival in patients with CRCs. In addition, ITB can be useful for the prognostic stratification of CRCs with low IS.