The recent approval of trastuzumab deruxtecan for human epidermal growth factor receptor 2 (HER2)–low and HER2-ultralow breast cancer mandates an adequate assessment of these categories. Methods: Seven breast pathologists from the Breast Pathology Study Group of the Korean Society of Pathologists held an on-site expert consensus meeting. Fifteen sets of virtual whole slide images (WSI) of hematoxylin and eosin stain and HER2 immunohistochemistry were provided. The pathologists were given 60 minutes to submit their diagnosis of HER2 expression into null, ultralow, 1+, 2+, or 3+. Afterwards, in-depth discussion and consensus diagnoses were made by real-time visualization of the WSI. Results: After the consensus meeting, unanimous 100% agreements were seen only in five (33.3%) of the examined cases, which consisted of three 1+ cases and two 2+ cases. Two cases (13.3%) had mild disagreement, with only one pathologist’s disagreement. Of note, eight cases (53.3%) showed significant disagreement, defined by more than two pathologists’ disagreement. All HER2-null cases were reclassified as ultralow after consensus review, suggesting potential widespread underclassification of ultralow cases in clinical practice. Conclusions: Experts had significant discrepancies in interpreting HER2-low/ultralow status. It is important to assess if the distinction between HER2-low and ultralow is strictly required and if HER2-null breast cancer exists in reality.

Background: Programmed death ligand 1 (PD-L1) expression cannot currently be predicted through radiological findings. This study aimed to develop a prediction model capable of differentiating between positive and negative PD-L1 expression through a radiomics-based investigation of computed tomography (CT) images in patients with urothelial carcinoma. Methods: Sixty-four patients with urothelial carcinoma who underwent immunohistochemical testing for PD-L1 were retrospectively reviewed. The number of patients in the positive and negative PD-L1 groups (PD-L1 expression >5%) was 14 and 50, respectively. CT images obtained 90 seconds after contrast medium administration were selected for radiomic extraction. For all tumors, 1,691 radiomic features were extracted from CT using a manually segmented three-dimensional volume of interest. Univariate and multivariate logistic regression analyses were performed to identify radiomic features that were significant predictors of PD-L1 expression. For the radiomics-based model, a receiver operating characteristic (ROC) analysis was performed. Results: Among 64 patients, 14 were included in the PD-L1 positive group. Logistic regression analysis found that the following radiomic features significantly predicted PD-L1 expression: wavelet-low-pass, low-pass, and high-pass filters (LLH)_gray-level size-zone matrix (GLSZM)_SmallAreaEmphasis, wavelet-LLH_firstorder_Energy, log-sigma-0-5-mm-3D_GLSZM_SmallAreaHighGrayLevelEmphasis, original_shape_Maximum2DDiameterColumn, wavelet-low-pass, low-pass, and low-pass filters (LLL)_gray-level run-length matrix (GLRLM)_ShortRunEmphasis, and exponential_firstorder_Kurtosis. The radiomics signature was –4.0934+21.6224 (wavelet-LLH_GLSZM_SmallAreaEmphasis)+0.0044 (wavelet-LLH_firstorder_Energy)–4.7389 (log-sigma-0-5-mm-3D_GLSZM_SmallAreaHighGrayLevelEmphasis)+0.0573 (original_shape_Maximum2DDiameterColumn)–29.5892 (wavelet-LLL_GLRLM_ShortRunEmphasis)–0.4324 (exponential_firstorder_Kurtosis). The area under the ROC curve model representing the radiomics signature for differentiating cases that were deemed PD-L1 positive based on immunohistochemistry was 0.96. Conclusions This preliminary radiomics model derived from contrast-enhanced CT predicted PD-L1 positivity in patients with urothelial cancer.

Objectives: The aim of this study was to determine the most effective treatment approach by comparing the impacts of various otolith reduction techniques in patients with apogeotropic lateral semicircular canal benign paroxysmal positional vertigo (LC-BPPV). Methods: We performed a multicenter randomized prospective study from January to December 2015, involving 72 consecutive patients with apogeotropic LC-BPPV. The patients were divided into three treatment groups: therapeutic head-shaking (group A), the Gufoni-Appiani maneuver (group B), and the cupulolith repositioning maneuver (CuRM; group C). Each group underwent evaluation and treatment up to the fourth week. Treatment success was defined as the disappearance of positional vertigo and nystagmus. Results: This study included 72 patients (49 male and 23 female), with a mean (±standard deviation) age of 55.4±13.5 years. The mean duration of vertigo experienced prior to treatment was 3.9±4.4 days. The mean latency and duration of nystagmus were 2.7±3.0 seconds and 47.9±15.8 seconds, respectively. The overall treatment frequency was 2.0±0.9. The number of treatments differed significantly among the three groups (P<0.05). After 4 weeks, the success rates for groups A, B, and C were 90.5%, 92.3%, and 100%, respectively. No significant difference was observed in the success rate across treatment methods and periods (P>0.05). However, CuRM was the only method with a 100% treatment success rate. Conclusion While no clear difference was observed among the three treatments for LC-BPPV, CuRM was found to be superior to the other approaches in the long term.

The monoamine hypothesis has significantly improved our understanding of mood disorders and their treatment by linking monoaminergic abnormalities to the pathophysiology of mood disorders. Even 50 years after the monoamine hypothesis was established, some patients do not respond to treatments for depression, including selective serotonin reuptake drugs. Accumulating evidence shows that patients with treatment-resistant depression (TRD) have severe abnormalities in the neuroplasticity and neurotrophic factor pathways, indicating that different treatment approaches may be necessary. Therefore, the glutamate hypothesis is gaining attention as a novel hypothesis that can overcome monoamine restrictions. Glutamate has been linked to structural and maladaptive morphological alterations in several brain areas associated with mood disorders. Recently, ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, has shown efficacy in TRD treatment and has received the U.S. Food and Drug Administration approval, revitalizing psychiatry research. However, the mechanism by which ketamine improves TRD remains unclear. In this review, we re-examined the glutamate hypothesis, bringing the glutamate system onboard to join the modulation of the monoamine systems, emphasizing the most prominent ketamine antidepressant mechanisms, such as NMDAR inhibition and NMDAR disinhibition in GABAergic interneurons. Furthermore, we discuss the animal models used in preclinical studies and the sex differences in the effects of ketamine.

Background/Aims: The prospective Crohn’s Disease Clinical Network and Cohort Study is a nationwide multicenter cohort study of patients with Crohn’s disease (CD) in Korea, aiming to prospectively investigate the clinical features and long-term prognosis associated with CD. Methods: Patients diagnosed with CD between January 2009 and September 2019 were prospectively enrolled. They were divided into two cohorts according to the year of diagnosis: cohort 1 (diagnosed between 2009 and 2011) versus cohort 2 (between 2012 and 2019). Results: A total of 1,175 patients were included, and the median follow-up duration was 68 months (interquartile range, 39.0 to 91.0 months). The treatment-free durations for thiopurines (p<0.001) and anti-tumor necrosis factor agents (p=0.018) of cohort 2 were shorter than those of cohort 1. Among 887 patients with B1 behavior at diagnosis, 149 patients (16.8%) progressed to either B2 or B3 behavior during follow-up. Early use of thiopurine was associated with a reduced risk of behavioral progression (adjusted hazard ratio [aHR], 0.69; 95% confidence interval [CI], 0.50 to 0.90), and family history of inflammatory bowel disease was associated with an increased risk of behavioral progression (aHR, 2.29; 95% CI, 1.16 to 4.50). One hundred forty-one patients (12.0%) underwent intestinal resection, and the intestinal resection-free survival time was significantly longer in cohort 2 than in cohort 1 (p=0.003). The early use of thiopurines (aHR, 0.35;95% CI, 0.23 to 0.51) was independently associated with a reduced risk of intestinal resection. Conclusions The prognosis of CD in Korea appears to have improved over time, as evidenced by the decreasing intestinal resection rate. Early use of thiopurines was associated with an improved prognosis represented by a reduced risk of intestinal resection.

A 60-year-old man diagnosed with unresectable hepatocellular carcinoma (HCC) presented to the hospital with pain in the perineal region. He had been taking lenvatinib every day for 2 months after he was diagnosed with HCC with metastases to the lymph node, small bowel mesentery, and retroperitoneal space. Enhanced abdominal computed tomography revealed mild elevation in intensity in the perineal subcutaneous tissue with subcutaneous emphysema. The patient was diagnosed with Common Terminology Criteria for Adverse Events grade 3, skin ulceration of stage IV with full-thickness skin loss and tissue necrosis in the muscular layer. The patient was taken off the medication with prescription of antibiotics, and after 3 weeks, the skin has fully recovered. This is the first report of an HCC patient who presented with a skin ulceration of stage IV after lenvatinib treatment. We recommend stopping the medication immediately and changing to alternative treatments with appropriate supportive care.

A 60-year-old man diagnosed with unresectable hepatocellular carcinoma (HCC) presented to the hospital with pain in the perineal region. He had been taking lenvatinib every day for 2 months after he was diagnosed with HCC with metastases to the lymph node, small bowel mesentery, and retroperitoneal space. Enhanced abdominal computed tomography revealed mild elevation in intensity in the perineal subcutaneous tissue with subcutaneous emphysema. The patient was diagnosed with Common Terminology Criteria for Adverse Events grade 3, skin ulceration of stage IV with full-thickness skin loss and tissue necrosis in the muscular layer. The patient was taken off the medication with prescription of antibiotics, and after 3 weeks, the skin has fully recovered. This is the first report of an HCC patient who presented with a skin ulceration of stage IV after lenvatinib treatment. We recommend stopping the medication immediately and changing to alternative treatments with appropriate supportive care.

Purpose: Our study aimed to evaluate the predictive value of multiparametric magnetic resonance imaging (mpMRI)to assess the capsular extension of prostate cancer. Risk factors for extraprostatic invasion or microscopic invasionof bladder neck (pT3a stage) in the cases showing localized disease findings on MRI scan were also identified. Materials and Methods: We identified 198 patients who underwent robot-assisted or conventional laparoscopicradical prostatectomy in our institute between June, 2016 and May, 2018. Altogether, 170 patients withpreoperational mpMRI scans and complete pathologic data were included. Positive and negative predictive valuesof mpMRI to detect capsular extension were estimated. Chi-square test was performed for ratio variables. Logisticregression analysis was performed to identify capsular invasion risk factors. Results: Median age and prostate-specific antigen level were 68 years and 7.5 ng/mL, respectively. Based onfindings, 16 patients (9.4%) were identified as cT3a stage (unilateral or bilateral extraprostatic extension), whereas37 patients (21.8%) as pT3a stage. Positive and negative predictive values of mpMRI to detect capsular extensionwere 75.0% and 73.9%, respectively. In the logistic regression analysis, positive biopsy core rate was the significantpredictor for pT3a disease in the patients with negative capsular invasion findings on mpMRI (p<0.001). Accordingto receiver-operating characteristic curve (area under the curve=0.691, p=0.001), the positive biopsy core rateof 0.275 was the best threshold. Conclusions Multiparametric MRI is an appropriate test to predict pT3a disease preoperatively. The patients withpositive core rate over 0.275 may have pT3a diseases despite negative image findings.