Impact of the COVID-19 Pandemic on the Diagnosis and Surgery of Breast Cancer: A Multi-Institutional Study / 한국유방암학회지

Purpose@#The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the rates of screening, case identification, and referral for cancer diagnosis. We investigated the diagnosis and surgery status of breast cancer before and after the COVID-19 pandemic at a multi-institutional level. @*Methods@#We collected breast cancer data from the clinical data warehouse which contained the medical records of patients from six academic institutions in South Korea. Patients were divided into two groups: February to April (period A) and May to July (period B). The data from the two groups were then compared against the same periods in 2019 and 2020. The primary objective was to investigate the differences in breast cancer stages before and after the COVID-19 pandemic. @*Results@#Among 3,038 patients, there was a 9.9% reduction in the number of diagnoses in 2020. This decrease was more significant during period A than period B. The breast cancer stage was not statistically different in period A (p = 0.115), but it was in period B (p = 0.001). In the subset analysis according to age, there was a statistical difference between 2019 and 2020 in period B for patients under the age of 65 years (p = 0.002), but no difference was observed in the other groups. @*Conclusion@#The number of breast cancer cases declined during the pandemic, and the staging distribution has changed after the pandemic peak.

A study on the disaster medical response in the fire accident at the women’s hospital

Objective@#The purpose of this study is to report the activities of Disaster Medical Assistance Team and national emergency medical center in the fire at a women’s hospital on December 14, 2019, and to suggest an improvement plan for the special disastrous situation. @*Methods@#We reviewed the transfer records of national emergency medical center, medical records of regional emergency medical center, and records of each patient’s prognosis of the women’s hospital, retrospectively. Triage of casualties was conducted according to SALT (Sort, Assess, Lifesaving Interventions, Treatment/Transport) method. @*Results@#The fire was extinguished early and there was no victim with significant carbon monoxide intoxication. Among 228 casualties, there were 143 patients of the women’s hospital. Two patients were classified as immediate, 55 patients including pregnant women, newborns, and mothers were classified as delayed, and 171 casualties including newborns and mothers were classified as minimal. Among 66 newborns, 40 newborns were transferred to the regional Emergency Medical Center, and a second triage was conducted by doctors there. @*Conclusion@#Although there was no significant victim, physically and socially susceptible people such as pregnant women, newborns, and mothers were included in this accident. We recommend establishing a standard of disaster response for special population and improving our capability at a national level.

Clinical outcome and predictive factors for docetaxel and epirubicin neoadjuvant chemotherapy of locally advanced breast cancer

Background/Aims@#We evaluated the efficacy of docetaxel and epirubicin as neoadjuvant chemotherapy in locally advanced breast cancer and assessed the predictive factors for response to neoadjuvant chemotherapy and prognostic factors related to relapse-free survival. @*Methods@#Forty patients who received docetaxel and epirubicinas neoadjuvant chemotherapy for locally advanced breast cancer were evaluated retrospectively. Neoadjuvant chemotherapy consisted of intravenous injection of 75 mg/m2 docetaxel and 60 mg/m2 epirubucin on day 1, every 21 days, and two to six cycles. @*Results@#Twenty-five (62.5%) patients showed a partial response, and 15 (37.5%) patients showed a stable disease in the first response evaluation after two or three cycles of neoadjuvant chemotherapy. In the second response evaluation of nine patients who received six cycles of neoadjuvant chemotherapy, one patient achieved a complete response, but two patients with hormone receptor-negative, human epidermal growth factor receptor 2-positive breast cancer experienced disease progression. Twenty-five (62.5%) patients experienced downstaging after neoadjuvant chemotherapy. Patients with > 20% pretreatment Ki-67 and decrease of Ki-67 between pre- and post-neoadjuvant chemotherapy showed a trend for better response. In multivariate analysis, advanced pathological stage showed a significant negative effect on relapse-free survival. @*Conclusions@#Docetaxel and epirubicin neoadjuvant chemotherapy showed a good response in locally advanced breast cancer. Pretreatment Ki-67 and change of Ki-67 may play a role as predictive factor for response to neoadjuvant chemotherapy.

PTEN Mutation Identified in Patient Diagnosed with Simultaneous Multiple Cancers / Journal of the Korean Cancer Association, 대한암학회지

PTEN hamartoma tumor syndrome is a spectrum of disorders characterized by unique phenotypic features including multiple hamartomas caused by mutations of the tumor suppressor gene PTEN. Cowden syndrome and Bannayan–Riley–Ruvalcaba syndrome are representative diseases, and both have several common clinical features and differences. Because PTEN mutations are associated with an increased risk of malignancy including breast, thyroid, endometrial, and renal cancers, cancer surveillance is an important element of disease management. We report a germline mutation of the PTEN (c.723dupT, exon 7) identified in a young woman with a simultaneous occurrence of breast cancer, dermatofibrosarcoma protuberans, and follicular neoplasm. This case suggests that it is critical for clinicians to recognize the phenotypic features associated with these syndromes to accurately diagnose them and provide preventive care.

Downregulation of SIRT2 by Chronic Stress Reduces Expression of Synaptic Plasticity-related Genes through the Upregulation of Ehmt2

Silent information regulator 2 (Sirtuin2 / SIRT2) is a NAD⁺-dependent deacetylase that regulates the cellular oxidative stress response. It modulates transcriptional silencing and protein stability through deacetylation of target proteins including histones. Previous studies have shown that SIRT2 plays a role in mood disorders and hippocampus-dependent cognitive function, but the underlying neurobiological mechanism is poorly understood. Here, we report that chronic stress suppresses SIRT2 expression in the hippocampus. Molecular and biochemical analyses indicate that the stress-induced decrease in the SIRT2 expression downregulates synaptic plasticity-related genes in the hippocampus through the increase of euchromatic histone-lysine N-methyltransferase 2 (Ehmt2) (also known as G9a). shRNA-mediated knockdown of SIRT2 in the dentate gyrus alters the expression of synaptic plasticity-related genes in a way similar to those induced by chronic stress, and produces depression-like behaviors. Our results indicate that SIRT2 plays an important role in the response to stress, thereby modulating depression-like behaviors.

Apoptosis and Cell Cycle Arrest in Two Human Breast Cancer Cell Lines by Dieckol Isolated from Ecklonia cava

PURPOSE: Dieckol, a phlorotannin compound isolated from Ecklonia cava, has been reported to have antioxidant, antiviral, anti-inflammatory, and anticancer properties. The purpose of this study was to investigate its anticancer effects on human breast cancer cell lines. METHODS: In this study, the viability of two human breast cancer cell lines SK-BR-3 and MCF-7 was investigated after dieckol treatment using a WST-1 assay. Apoptosis and cell cycle distribution were assayed via Annexin V-fluorescein isothiocyanate and propidium iodide staining followed by flow cytometric analysis. Immunoblotting analysis was also performed using Bax/Bcl-2 to determine whether the dieckol-induced apoptosis was mediated by the intrinsic apoptotic pathway. RESULTS: In a dose dependent manner, dieckol reduced the number of viable cells and increased the number of apoptotic cells. The effect of dieckol on the cell cycle distribution was analyzed using flow cytometry. Dieckol treatment significantly increased the percentage of MCF-7 and SK-BR-3 in the G2/M phase. Immunoblot analysis revealed that 24 hours of dieckol exposure increased the Bax/Bcl-2 ratio. CONCLUSION: Dieckol induced cytotoxicity in MCF-7 and SK-BR-3 human breast cancer cells inducing apoptosis and cell cycle arrest. Therefore, it is suggested that dieckol may be a potential therapeutic agent for breast cancer.

Clinical Differences in Triple-Positive Operable Breast Cancer Subtypes in Korean Patients: An Analysis of Korean Breast Cancer Registry Data / 한국유방암학회지

PURPOSE: Triple-positive breast cancer is defined by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) positivity. Several systemic breast cancer therapies target hormonal and HER2 responsiveness. We compared clinical outcomes of triple-positive disease with those of HER2-enriched and luminal HER2-negative disease and investigated the clinical efficacy of anti-HER2 therapy for triple-positive disease. METHODS: We retrospectively compared overall and recurrence-free survival among cases included in the Korean Breast Cancer Society (KBCS) and Seoul St. Mary's Hospital breast cancer registries and the therapeutic efficacy of trastuzumab for triple-positive and HER2-enriched cases. RESULTS: KBCS registry data (2006–2010; median follow-up, 76 months) indicated that patients with triple-positive breast cancer had intermediate survival between those with luminal A and HER2-enriched subtypes (p < 0.001). Trastuzumab did not improve overall survival among patients with triple-positive breast cancer (p=0.899) in contrast to the HER2-enriched subtype (p=0.018). Seoul St. Mary's Hospital registry data indicated similar recurrence-free survival outcomes (p < 0.001) and a lack of improvement with trastuzumab among patients with triple-positive breast cancer (median follow-up, 33 months; p=0.800). Multivariate analysis revealed that patients with triple-positive breast cancer had better overall survival than those with HER2-enriched disease and similar survival as those with the luminal A subtype (triple-positive: hazard ratio, 1.258, p=0.118; HER2-enriched: hazard ratio, 2.377, p < 0.001). CONCLUSION: Our findings showed that anti-HER2 therapy was less beneficial for treatment of triple-positive breast cancer than for HER2-enriched subtypes of breast cancer, and the triple-positive subtype had a distinct prognosis.

Capsaicin upregulates HDAC2 via TRPV1 and impairs neuronal maturation in mice

Transient receptor potential vanilloid 1 (TRPV1) affects mood and neuroplasticity in the brain, where its role is poorly understood. In the present study we investigated whether capsaicin (8-methyl-N-vanillyl-trans-6-nonenamide), an agonist of TRPV1, induced chromatin remodeling and thereby altered gene expression related to synaptic plasticity. We found that capsaicin treatment resulted in upregulation of histone deacetylase 2 (HDAC2) in the mouse hippocampus and HDAC2 was enriched at Psd95, synaptophysin, GLUR1, GLUR2 promoters. Viral-mediated hippocampal knockdown of HDAC2 induced expression of Synapsin I and prevented the detrimental effects of capsaicin on Synapsin I expression in mice, supporting the role of HDAC2 in regulation of capsaicin-induced Synapsin I expression. Taken together, our findings implicate HDAC2 in capsaicin-induced transcriptional regulation of synaptic molecules and support the view that HDAC2 is a molecular link between TRPV1 activity and synaptic plasticity.

Combined Extracts of Artemisia and Green Tea, Mitigated Alcoholic Gastritis Via Enhanced Heat-shock Protein 27 / 대한소화기학회지

BACKGROUND/AIMS: Several lines of evidence from epidemiologic and laboratory studies have shown that the consumption of Artemisia or green tea extracts (MPGT) is inversely associated with the risk of alcohol-induced damage and other chronic diseases. Supported by previous studies showing that the combined extract of Artemisia and green tea, MPGT, exerted significantly either antioxidative or anti-inflammatory actions against Helicobacter pylori-associated gastric diseases, it was hypothesized that MPGT can offer protection against alcoholic gastritis. METHODS: Ethanol was administered to induce gastric damage in Wistar rats, which had been pretreated with various doses of MPGT, to measure the rescuing action of a MPGT pretreatment against ethanol-induced gastric damage. In addition, the molecular mechanisms for the preventive effects were examined. RESULTS: The MPGT pretreatment (100, 300, and 500 mg/kg) alleviated the ethanol-induced gastric damage, which was evidenced by the significant decrease in calcium-dependent phospholipase A2, MAPKs, and NF-κB levels compared to ethanol alone. Furthermore, the MPGT pretreatment preserved 15-prostaglandin dehydrogenase, whereas cyclooxygenase-2 was decreased significantly. All of these biochemical changes led to the significant alleviation of alcohol-associated gastric mucosal damage. Ethanol significantly increased the TUNEL positivity in the stomach, but MPGT decreased the apoptotic index significantly, which was associated with significantly lower pathological scores of ethanol-induced mucosal ulcerations. The significant protective changes observed alcoholic gastritis with MPGT were related to the increased expression of cytoprotective genes, such as heat-shock protein (HSP)27, HSP60, and PDGF. CONCLUSIONS: The efficient anti-inflammatory, anti-apoptotic, and regenerative actions of MPGT make it a potential nutrient phytoceutical to rescue the stomach from alcoholic gastritis.

The potential theragnostic (diagnostic+therapeutic) application of exosomes in diverse biomedical fields

Exosomes are membranous vesicles of 30-150 nm in diameter that are derived from the exocytosis of the intraluminal vesicles of many cell types including immune cells, stem cells, cardiovascular cells and tumor cells. Exosomes participate in intercellular communication by delivering their contents to recipient cells, with or without direct contact between cells, and thereby influence physiological and pathological processes. They are present in various body fluids and contain proteins, nucleic acids, lipids, and microRNAs that can be transported to surrounding cells. Theragnosis is a concept in next-generation medicine that simultaneously combines accurate diagnostics with therapeutic effects. Molecular components in exosomes have been found to be related to certain diseases and treatment responses, indicating that they may have applications in diagnosis via molecular imaging and biomarker detection. In addition, recent studies have reported that exosomes have immunotherapeutic applications or can act as a drug delivery system for targeted therapies with drugs and biomolecules. In this review, we describe the formation, structure, and physiological roles of exosomes. We also discuss their roles in the pathogenesis and progression of diseases including neurodegenerative diseases, cardiovascular diseases, and cancer. The potential applications of exosomes for theragnostic purposes in various diseases are also discussed. This review summarizes the current knowledge about the physiological and pathological roles of exosomes as well as their diagnostic and therapeutic uses, including emerging exosome-based therapies that could not be applied until now.

The antidepressant action of 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid is mediated by phosphorylation of histone deacetylase 5

3-(2-Carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, produces rapid antidepressant-like effects in animal models of depression. However, the molecular mechanisms underlying these behavioral actions remain unknown. Here, we demonstrate that CPP rapidly stimulates histone deacetylase (HDAC) 5 phosphorylation and nuclear export in rat hippocampal neurons. These effects are accompanied by calcium/calmodulin kinase II (CaMKII) and protein kinase D (PKD) phosphorylation. Behavioral experiments revealed that viral-mediated hippocampal knockdown of HDAC5 blocked the antidepressant effects of CPP in stressed animals. Taken together, our results imply that CPP acts via HDAC5 and suggest that HDAC5 is a common regulator contributing to the antidepressant actions of NMDA receptor antagonists such as CPP.

Spontaneous Bleeding from Internal Pudendal Artery associated with Abciximab after Primary Percutaneous Coronary Intervention: Successful Treatment with Percutaneous Gel-Foam Embolization

We describe a case of spontaneous bleeding from a branch of the right internal pudendal artery that resulted in massive scrotal swelling in a patient who had underwent primary percutaneous coronary intervention with the use of abciximab concurrent with conventional anticoagulation and dual antiplatelet therapies for the treatment of acute ST-segment elevation myocardial infarction. This unusual complication was promptly identified by percutaneous peripheral arteriography and successfully treated with gel-foam embolization.

Misconceived Retropharyngeal Calcific Tendinitis during Management of Myofascial Neck Pain Syndrome

Differential diagnosis of posterior neck pain is very challenging based on symptoms and physical examination only. Retropharyngeal calcific tendinitis is a rare and frequently misdiagnosed entity in various causes of neck pain. It results from calcium hydroxyapatite deposition in the longus colli muscle which is characterized by severe neck pain, painful restriction of neck movement, dysphagia, and odynophagia. We herein report a case of a patient with acute retropharyngeal calcific tendinitis, who complained of posterior neck pain, initially diagnosed and treated as a myofascial neck pain syndrome.

Diagnosis of diaphragmatic paralysis using ultrasound in a cervical herpes zoster patient: A case report

Herpes zoster is a varicella-zoster virus reactivation that is characterized by pain and rash. It can cause motor paresis on affecting muscles, but diaphragmatic paralysis is a rare complication. Methods of evaluation of diaphragmatic paralysis include plain radiography, fluoroscopy and electroneurography. The direct movement of diaphragmatic muscles on ultrasound can also be used to diagnose diaphragmatic paralysis. We reported a case of a 72-year-old woman who developed left hemidiaphragmatic paralysis after herpes zoster. The diaphragmatic paralysis occurred 3 weeks after appearance of a typical skin rash on the left C4-5 dermatomes. We diagnosed diaphragmatic paralysis using ultrasound.

MUC Expression in Gallbladder Epithelial Tissues in Cholesterol-Associated Gallbladder Disease

BACKGROUND/AIMS: Gallstone pathogenesis is linked to mucin hypersecretion and bacterial infection. Several mucin genes have been identified in gallbladder epithelial cells (GBECs). We investigated MUC expression in cholesterol-associated gallbladder disease and evaluated the relationship between mucin and bacterial infection. METHODS: The present study involved 20 patients with cholesterol stones with cholecystitis, five with cholesterol stones with cholesterolosis, six with cholesterol polyps, two with gallbladder cancer, and six controls. Canine GBECs treated with lipopolysaccharide were also studied. MUC3, MUC5AC, MUC5B, and MUC6 antibodies were used for dot/slot immunoblotting and immunohistochemical studies of the gallbladder epithelial tissues, canine GBECs, and bile. Reverse-transcription polymerase chain reaction was performed to evaluate MUC3 and MUC5B expression. RESULTS: MUC3, MUC5AC, MUC5B, and MUC6 were expressed in the normal gallbladder epithelium, and of those, MUC3 and MUC5B exhibited the highest expression levels. Greatly increased levels of MUC3 and MUC5B expression were observed in the cholesterol stone group, and slightly increased levels were observed in the cholesterol polyp group; MUC3 and MUC5B mRNA was also upregulated in those groups. Canine GBECs treated with lipopolysaccharide also showed upregulation of MUC3 and MUC5B. CONCLUSIONS: The mucin genes with the highest expression levels in gallbladder tissue in cholesterol-associated diseases were MUC3 and MUC5B. Cholesterol stones and gallbladder infections were associated with increased MUC3 and MUC5B expression.

Prognostic Impact and Clinicopathological Correlation of CD133 and ALDH1 Expression in Invasive Breast Cancer / 한국유방암학회지

PURPOSE: CD133 and aldehyde dehydrogenase 1 (ALDH1) expression are reliable poor-prognosis markers associated with the presence of adverse biomarkers and subtypes of breast cancer. The aim of our study was to investigate and compare the clinical impact of CD133 and ALDH1 expression in invasive breast cancer. METHODS: A total of 291 consecutive patients with invasive breast cancer who underwent breast cancer operations from 2005 to 2010 at a single institution were included in this retrospective review. CD133 and ALDH1 expression were determined by immunohistochemistry. RESULTS: CD133 and ALDH1 expression were positive in 24.7% and 22.0% of the patients, respectively, and were associated with tumor size, cancer stage, estrogen receptor negativity, nonluminal subtype, triple-negative breast cancer, and recurrence. CD133 expression was significantly associated with lymph node metastasis, progesterone receptor negativity, human epidermal growth factor receptor 2 positivity, chemotherapy, and poor disease-free (p=0.002) and overall survival (p=0.014), but ALDH1 expression was not. Cancer stage (p<0.001) was an independent prognostic factor for disease-free survival in multivariate analysis. Cancer stage (p<0.001) and receipt of radiotherapy (p=0.045) were independent prognostic factors for overall survival in multivariate analysis. CONCLUSION: CD133 or the combination of CD133 and ALDH1 expression were more widely associated with the presence of adverse biomarkers and subtypes of breast cancer, compared to ALDH1 expression alone, and these markers may have a potential predictive role and be a helpful tool in the management for patients with invasive breast cancer.

Pyogenic Liver Abscess: Changes in Clinical Features over the Last 10 Years / 대한내과학회지

BACKGROUND/AIMS: A pyogenic liver abscess is an acute bacterial infection that can potentially lead to life-threatening sepsis. This study examined the clinical features and changing trends of pyogenic liver abscess over the last 10 years. METHODS: We investigated patient characteristics, laboratory findings, blood and abscess culture results, location and characteristics of the abscess, and treatment modality in the medical records of 146 patients. We divided them into three groups by period: period 1, 23 patients in 2002-2003; period 2, 46 patients in 2007-2008; and period 3, 77 patients in 2012-2013. RESULTS: The mean patient age was 64.3 +/- 15.1 years and 87 of the 146 patients were male (59.6%). Period 2 had a higher prevalence of chronic alcoholics (30.4% vs. 10.4%) and lower prevalence of fever and chills (73.9% vs. 92.2%) compared with period 3. Klebsiella pneumoniae was the most commonly cultured bacteria and the microbiological findings did not differ among the three periods. Pyogenic liver abscesses were more common in the right liver. The lengths of hospital stay and treatment modalities were similar in all three periods. CONCLUSIONS: Although there were slight differences in symptoms among the periods, there were no changes in the liver abscess characteristics, i.e., location, size, and culture results. As there were no changes, the treatment strategy also did not change. We should continue to investigate the clinical features of liver abscess.

Nerve injury in an undiagnosed adult tethered cord syndrome patients following spinal anesthesia: A case report

Spinal anesthesia is a safe and widely used procedure. Spinal cord injury is a rare but serious complication from spinal anesthesia occurs, unexpectedly. Risks of direct neural injury from spinal anesthesia increase in tethered cord syndrome that the spinal cord is tethered by the inelastic structure and is, also, extended to the lower lumbar vertebra. A 52-years-old female patient undergoing anti-incontinence surgery developed neurologic symptoms following spinal anesthesia. The low-lying conus (L5 body level) and tethered cord were found during the assessment of neurological symptoms.

Pancreatitis with Pseudocyst Arising from Ectopic Pancreas in a Chronic Alcoholism / 대한소화기학회지

No abstract available.

High Sodium Intake in Women with Metabolic Syndrome

BACKGROUND AND OBJECTIVES: Metabolic syndrome and high sodium intake are associated with frequent cardiovascular events. Few studies have estimated sodium intake in subjects with metabolic syndrome by 24-hour urine sodium excretion. We evaluated sodium intake in individuals with metabolic syndrome. SUBJECTS AND METHODS: Participants were recruited by random selection and through advertisement. Twenty four-hour urine collection, ambulatory blood pressure measurements, and blood test were performed. Sodium intake was estimated by 24-hour urine sodium excretion. Participants receiving antihypertensive medications were excluded from analysis. RESULTS: Among the 463 participants recruited, subjects with metabolic syndrome had higher levels of 24-hour urine sodium excretion than subjects without metabolic syndrome (p=0.0001). There was a significant relationship between the number of metabolic syndrome factors and 24-hour urine sodium excretion (p=0.001). The proportion of subjects with metabolic syndrome was increased across the tertile groups of 24-hour urine sodium excretion (p<0.0001). The association of high sodium intake and metabolic syndrome was significant only among women. Among the factors related to metabolic syndrome, body mass index had an independent association with 24-hour urine sodium excretion (p<0.0001). CONCLUSION: Women with metabolic syndrome exhibited significantly higher sodium intake, suggesting that dietary education to reduce sodium consumption should be emphasized for women with metabolic syndrome.