Recent Developments in the Therapeutic Landscape of Advanced or Metastatic Hormone Receptor–Positive Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

Hormone receptor–positive (HR+) disease is the most frequently diagnosed subtype of breast cancer. Among tumor subtypes, natural course of HR+ breast cancer is indolent with favorable prognosis compared to other subtypes such as human epidermal growth factor protein 2–positive disease and triple-negative disease. HR+ tumors are dependent on steroid hormone signaling and endocrine therapy is the main treatment option. Recently, the discovery of cyclin-dependent kinase 4/6 inhibitors and their synergistic effects with endocrine therapy has dramatically improved treatment outcome of advanced HR+ breast cancer. The demonstrated efficacy of additional nonhormonal agents, such as targeted therapy against mammalian target of rapamycin and phosphatidylinositol 3-kinase signaling, poly(ADP-ribose) polymerase inhibitors, antibody-drug conjugates, and immunotherapeutic agents have further expanded the available therapeutic options. This article reviews the latest advancements in the treatment of HR+ breast cancer, and in doing so discusses not only the development of currently available treatment regimens but also emerging therapies that invite future research opportunities in the field.

Overcoming the Challenges in the Development and Implementation of Artificial Intelligence in Radiology:A Comprehensive Review of Solutions Beyond Supervised Learning

Artificial intelligence (AI) in radiology is a rapidly developing field with several prospective clinical studies demonstrating its benefits in clinical practice. In 2022, the Korean Society of Radiology held a forum to discuss the challenges and drawbacks in AI development and implementation. Various barriers hinder the successful application and widespread adoption of AI in radiology, such as limited annotated data, data privacy and security, data heterogeneity, imbalanced data, model interpretability, overfitting, and integration with clinical workflows. In this review, some of the various possible solutions to these challenges are presented and discussed; these include training with longitudinal and multimodal datasets, dense training with multitask learning and multimodal learning, self-supervised contrastive learning, various image modifications and syntheses using generative models, explainable AI, causal learning, federated learning with large data models, and digital twins.

Progesterone Receptor Expression as a Prognostic Factor in Luminal B Breast Cancer

Purpose@#The luminal subtype of breast cancer has heterogeneous biological characteristics with respect to the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor-2 (HER2), and Ki-67. We analyzed luminal B breast cancer subcategorized by PR expression and identified clinically relevant prognostic factors. @*Methods@#We collected the clinical and pathologic data of 247 breast cancer patients (stage 1-4) who were diagnosed with luminal B subtype, defined as ER- and/or PR-positive and/or HER2-positive and with a high Ki-67 proliferation index (>14%). We classified them into PR intact and PR low groups according to PR expression pattern. We also analyzed the clinical and pathological data of each group, including age at diagnosis, tumor size, node metastasis, breast and axillary operative method, margin involvement, tumor-node-metastasis (TNM) stage, histological grade, nuclear grade, number of tumors, and expression of ER, PR, Ki-67, and Bcl-2; evaluated recurrence or metastatic characteristics; and analyzed disease-free survival (DFS) and overall survival (OS) in both groups. @*Results@#Among the 247 luminal B breast cancer patients (stage 1-4), 141 were classified into the PR intact group (57.1%) and 106 into the PR low group (42.9%). The PR low group was associated with age >50 years (p=0.001), low Bcl-2 expression (p<0.001), and high proportion of mastectomies (p<0.001). DFS and OS were significantly lower in the PR low group (p=0.025 and 0.024, respectively). @*Conclusion@#This study showed that decreased in PR expression (PR low group) in luminal B breast cancer was related to poor prognosis compared to normal PR expression (PR intact group).

Acute Cerebral Infarction and Epilepsy in Duchenne Muscular Dystrophy / 대한신경근육질환학회지

Duchenne muscular dystrophy (DMD) is a progressive form of muscular dystrophy caused by mutations in the dystrophin gene. Patients with DMD are more likely to have cerebral infarction than normal populations, possibly due to low ejection fraction and cardiomyopathy, and also higher epilepsy prevalence. Careful history taking and neurological examination are needed for differentiating new symptoms from preexisting weakness in DMD. Here, we present a young male with DMD and acute ischemic stroke followed by recurrent seizures.

Egg phospholipids exert an inhibitory effect on intestinal cholesterol absorption in mice

BACKGROUND/OBJECTIVES: Consumption of cholesterol-rich foods, such as eggs, has a minimal effect on circulating cholesterol levels in healthy humans. To gain insight, we investigated whether phospholipids rich in eggs (EPL) interfere with intestinal cholesterol absorption in vivo. MATERIALS/METHODS: To investigate the acute effect of EPL on intestinal cholesterol absorption, male C57BL/6J mice were orally administered with 6, 11, or 19 mg of EPL for three days. We also tested the effect of chronic EPL consumption on cholesterol metabolism in the small intestine and the liver in mice with diet-induced hypercholesterolemia. Male C57BL/6J mice were fed a high fat/high cholesterol (HF/HC; 35% fat, 0.25% cholesterol, w/w) diet for 4 weeks to induce hypercholesterolemia, and subsequently the mice were either fed 0, 0.4 or 0.8% (w/w) of EPL for 6 weeks. RESULTS: Intestinal cholesterol absorption was significantly decreased by the highest dose of acute EPL administration compared to control. Chronic EPL supplementation did not significantly alter intestinal cholesterol absorption nor plasma levels of total cholesterol and low-density lipoprotein cholesterol. In the small intestine and the liver, EPL supplementation minimally altered the expression of genes which regulate cellular cholesterol levels. CONCLUSION: Although chronic EPL consumption was not able to counteract hypercholesterolemia in HF/HC-fed mice, acute EPL administration decreased intestinal cholesterol absorption. This study provides in vivo evidence that acute administration of PLs in eggs prevent cholesterol absorption in the intestine, suggesting a mechanism for a minimal effect of egg consumption on circulating cholesterol levels.

Usefulness of the Patient Health Questionnaire-2 in Screening for Depression

BACKGROUND: While various screening tools are available for depression, they are not feasible in clinical practice because of their excessive number of questions. The Patient Health Questionnaire-2 (PHQ-2) consists of two questions gauging the frequency of depressed mood and anhedonia over the past two weeks. This study aimed to assess the usefulness of the PHQ-2 as a brief screening tool for depression.METHODS: This study used Korean National Health and Nutrition Examination Survey data from 2014, and the study population consisted of 4,946 individuals. We analyzed the validity of the PHQ-2 compared with ‘depression by PHQ-9,’ and obtained the optimal cut point for screening depression. The agreement between PHQ-2 and depression by PHQ-9 and the agreement between PHQ-2 and ‘currently diagnosed as depression’ were analyzed using Cohen's kappa. The correlation between EuroQol-5D (EQ-5D) index scores and PHQ-2 scores was analyzed using Student's t-test.RESULTS: Using ‘depression by PHQ-9’ as the criterion standard, PHQ-2 scores ≥2 had a sensitivity of 89% and a specificity of 87%, and a receiver operating characteristic analysis identified PHQ-2≥2 as the optimal cut point for screening. The agreement between PHQ-2 and depression by PHQ-9 was 0.430 when PHQ-2 ≥2 was used as a cut point. The agreement between PHQ-2 and ‘depression by questionnaire’ was poor. The EQ-5D index score of the depressive group was significantly lower than that of the normal group.CONCLUSION: The PHQ-2 is an effective measure for screening depression and is expected to be useful in busy clinical settings.

Dietary Patterns Assessed by the Diet Quality Index-International Among Cancer Survivors Compared with Healthy Control Subjects: Using the Korea National Health and Nutrition Examination Surveys 2013–2015

BACKGROUND: Dietary patterns have a significant impact on prognosis, recurrence, and survival in patients with cancer. This study investigated dietary patterns using the Diet Quality Index-International (DQI-I) in cancer survivors compared to those in the general population without cancer.METHODS: Using the Korea National Health and Nutrition Examination Survey VI data, cancer survivors were defined as those diagnosed with cancer more than 1 year before the survey. The associations between possible predictors and the DQI-I score were examined using t-tests and analysis of variance. Adjusted multiple linear regression analysis was performed to compare the differences in DQI-I scores between cancer survivors and controls.RESULTS: In univariate analysis of 9,351 subjects (433 cancer survivors and 8,918 controls), age, sex, body mass index, marital status, education level, income, residential area, smoking status, and alcohol consumption were associated with the DQI-I score (each P-value < 0.05). After adjustment, cancer survivors showed higher DQI-I scores than the controls (67.40±8.90 vs. 65.50±9.40, P-value=0.007). In subgroup analysis, cancer survivors within 5 years after cancer diagnosis showed higher DQI-I scores than the controls (68.70±8.30 vs. 65.50±9.40, P-value=0.034), whereas those who survived beyond 5 years post-diagnosis did not show significant differences from the controls (66.70±9.20 vs. 65.50±9.40, P-value=0.063).CONCLUSION: Cancer survivors within 5 years of cancer diagnosis showed better dietary patterns than those in the general population. However, the differences were not observed after 5 years post-diagnosis. To reduce the risks of second primary cancer and mortality, targeted inventions for dietary habits are necessary for long-term survivors of cancer.

Status epilepticus due to cerebral air embolism after the Valsalva maneuver

BACKGROUND: Cerebral air embolism is uncommon but potentially causes catastrophic events such as cardiac damage or even death. However, due to a low overall incidence, it may go undiagnosed. CASE REPORT: A 56-year-old man with a medical history of right upper lobectomy due to lung cancer showed changes in mental status after the Valsalva maneuver, followed by status epilepticus during admission. Brain and chest computed tomography showed cerebral air embolism and accidental pneumothorax in the right major fissure. After antiepileptic drug infusion and oxygen therapy, he recovered completely. CONCLUSION: Since cerebral air embolism may result in fatal outcomes, it should be suspected in patients with sudden neurological deterioration after routine medical procedures.

An Autopsy Case of Epstein-Barr Virus–Associated Diffuse Large B-Cell Lymphoma of the Central Nervous System in an Immunocompromised Host

Lymphomas arising in the central nervous system (CNS) of immunocompromised hosts are most commonly non-Hodgkin’s lymphomas and are highly associated with Epstein-Barr virus (EBV). Here we report an autopsy case of EBV-associated CNS diffuse large B-cell lymphoma (DLBCL) in a host suffering from systemic lupus erythematosus who underwent immunosuppressive therapy. After autopsy, EBV-associated CNS DLBCL as well as pulmonary mixed aspergillosis and Pneumocystis jirovecii pneumonia were added to the cause of clinical manifestations of complicated pneumonia and cerebral hemorrhage in this immunocompromised patient. In conclusion, complex disease processes were revealed by autopsy in this case, indicating that the clinicopathological correlations observed through autopsy can improve our understanding of disease progression and contribute to the management of similar patients in the future.

Aggressive Supratentorial Ependymoma, RELA Fusion-Positive with Extracranial Metastasis: A Case Report

Ependymoma is the third most common pediatric primary brain tumor. Ependymomas are categorized according to their locations and genetic abnormalities, and these two parameters are important prognostic factors for patient outcome. For supratentorial (ST) ependymomas, RELA fusion-positive ependymomas show a more aggressive behavior than YAP1 fusion-positive ependymomas. Extracranial metastases of intra-axial neuroepithelial tumors are extremely rare. In this paper, we report a case of aggressive anaplastic ependymoma arising in the right frontoparietal lobe, which had genetically 1q25 gain, CDKN2A homozygous deletion, and L1CAM overexpression. The patient was a 10-year-old boy who underwent four times of tumor removal and seven times of gamma knife surgery. Metastatic loci were scalp and temporalis muscle overlying primary operation site, lung, liver, buttock, bone, and mediastinal lymph nodes. He had the malignancy for 10 years and died. This tumor is a representative case of RELA fusion-positive ST ependymoma, showing aggressive behavior.

Use of Bioelectrical Impedance Analysis for the Assessment of Nutritional Status in Critically Ill Patients

Malnutrition is common in the critically ill patients and known to cause a variety of negative clinical outcomes. However, various conventional methods for nutrition assessment have several limitations. We hypothesized that body composition data, as measured using bioelectrical impedance analysis (BIA), may have a significant role in evaluating nutritional status and predicting clinical outcomes in critically ill patients. We gathered clinical, biochemical, and BIA data from 66 critically ill patients admitted to an intensive care unit. Patients were divided into three nutritional status groups according to their serum albumin level and total lymphocyte counts. The BIA results, conventional indicators of nutrition status, and clinical outcomes were compared and analyzed retrospectively. Results showed that the BIA indices including phase angle (PhA), extracellular water (ECW), and ECW/total body water (TBW) were significantly associated with the severity of nutritional status. Particularly, PhA, an indicator of the health of the cell membrane, was higher in the well-nourished patient group, whereas the edema index (ECW/TBW) was higher in the severely malnourished patient group. PhA was positively associated with albumin and ECW/TBW was negatively associated with serum albumin, hemoglobin, and duration of mechanical ventilation. In non-survivors, PhA was significantly lower and both ECW/TBW and %TBW/fat free mass were higher than in survivors. In conclusion, several BIA indexes including PhA and ECW/TBW may be useful for nutritional assessment and represent significant prognostic factors in the care of critically ill patients.

Paraneoplastic Extralimbic Encephalitis Presenting with Partial Motor Clonic Seizure in a Patient with Invasive Thymoma

Paraneoplastic encephalitis presenting with partial clonic seizure is rare. We report a 57-year-old man with clonic seizure in his left arm. He had past medical history of recurrent thymoma and thymomectomy. Magnetic resonance imaging showed multiple brain lesions, but none of them were congruent with the partial seizure. His symptoms and brain lesions resolved after steroid therapy. This is the first reported case extralimbic encephalitis presenting as partial seizure with invasive thymoma in Korea.

Paraneoplastic Extralimbic Encephalitis Presenting with Partial Motor Clonic Seizure in a Patient with Invasive Thymoma

Paraneoplastic encephalitis presenting with partial clonic seizure is rare. We report a 57-year-old man with clonic seizure in his left arm. He had past medical history of recurrent thymoma and thymomectomy. Magnetic resonance imaging showed multiple brain lesions, but none of them were congruent with the partial seizure. His symptoms and brain lesions resolved after steroid therapy. This is the first reported case extralimbic encephalitis presenting as partial seizure with invasive thymoma in Korea.

Anti-LGI1 Antibody Autoimmune Encephalitis Which Manifests Faciobrachial Dystonic Seizure

Anti-LGI1 (leucine-rich glioma inactivated-1) antibody encephalitis is one of autoimmune encephalitis. We report a 66-year-old man who presented with frequent, brief dystonic seizures which involve predominantly ipsilateral face and arm without cognitive impairment. Brain MRI showed normal finding. Serum and CSF tests revealed anti-LGI1 antibody. His symptom was not relieved by antiepileptic drugs, but completely controlled after immunotherapy. This case indicates that recognition of the brief, dystonic seizures should do tests for anti-LGI1 antibodies.