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Gastric cancer (GC) is the fourth leading cause of cancer-related deaths worldwide. Under the standard of care, patients with advanced GC (AGC) have a median survival time of approximately 12–15 months. With the emergence of immunotherapy as a key therapeutic strategy in medical oncology, relevant changes are expected in the systemic treatment of GC. In the phase III ATTRACTION-2 trial, nivolumab, a monoclonal anti-programmed cell death 1 (PD-1) antibody, as a third- or later-line treatment improved overall survival (OS) compared with placebo in patients with AGC. Furthermore, nivolumab in combination with 5-fluorouracil and platinum as a first-line treatment improved OS in patients with human epidermal growth factor receptor-2 (HER2)-negative AGC in the global phase III CheckMate-649 study. Another anti-PD-1 antibody, pembrolizumab, in combination with trastuzumab and cytotoxic chemotherapy as a first-line treatment, significantly improved the overall response rate in patients with HER2-positive AGC. Therefore, immune checkpoint inhibitors (ICIs) are essential components of the current treatment of GC. Subsequent treatments after ICI combination therapy, such as ICI rechallenge or combination therapy with agents having other modes of action, are being actively investigated to date. On the basis of the success of immunotherapy in the treatment of AGC, various clinical trials are underway to apply this therapeutic strategy in the perioperative and postoperative settings for patients with early GC. This review describes recent progress in immunotherapy and potential immunotherapy biomarkers for GC.
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Objective@#To evaluate the computed tomography (CT) features for diagnosing metastatic cervical lymph nodes (LNs) in patients with differentiated thyroid cancer (DTC) and validate the CT-based risk stratification system suggested by the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) guidelines. @*Materials and Methods@#A total of 463 LNs from 399 patients with DTC who underwent preoperative CT staging and ultrasound-guided fine-needle aspiration were included. The following CT features for each LN were evaluated: absence of hilum, cystic changes, calcification, strong enhancement, and heterogeneous enhancement. Multivariable logistic regression analysis was performed to identify independent CT features associated with metastatic LNs, and their diagnostic performances were evaluated. LNs were classified into probably benign, indeterminate, and suspicious categories according to the K-TIRADS and the modified LN classification proposed in our study. The diagnostic performance of both classification systems was compared using the exact McNemar and Kosinski tests. @*Results@#The absence of hilum (odds ratio [OR], 4.859; 95% confidence interval [CI], 1.593–14.823; P = 0.005), strong enhancement (OR, 28.755; 95% CI, 12.719–65.007; P < 0.001), and cystic changes (OR, 46.157; 95% CI, 5.07–420.234; P = 0.001) were independently associated with metastatic LNs. All LNs showing calcification were diagnosed as metastases. Heterogeneous enhancement did not show a significant independent association with metastatic LNs. Strong enhancement, calcification, and cystic changes showed moderate to high specificity (70.1%–100%) and positive predictive value (PPV) (91.8%–100%). The absence of the hilum showed high sensitivity (97.8%) but low specificity (34.0%). The modified LN classification, which excluded heterogeneous enhancement from the K-TIRADS, demonstrated higher specificity (70.1% vs. 62.9%, P = 0.016) and PPV (92.5% vs. 90.9%, P = 0.011) than the K-TIRADS. @*Conclusion@#Excluding heterogeneous enhancement as a suspicious feature resulted in a higher specificity and PPV for diagnosing metastatic LNs than the K-TIRADS. Our research results may provide a basis for revising the LN classification in future guidelines.
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Background@#Thyroid cancer mortality has been largely overlooked as relatively stable given the large gap between thyroid cancer incidence and mortality. This study evaluated long-term trends in age-standardized mortality rates (ASMRs) throughout Korea and compared them with mortality data reported by the Surveillance, Epidemiology, and End Results (SEER). @*Methods@#Cancer-specific mortality data from 1985 to 2020 were obtained from Statistics Korea. ASMRs from thyroid cancer were calculated based on the Korean mid-year resident registration population of 2005. We assessed SEER*Explorer and downloaded the mortality data. @*Results@#The ASMR increased from 0.19 to 0.77/100,000 between 1985 and 2002 but decreased continuously to 0.36/100,000 in 2020. The annual percent change (APC) in the ASMR between 1985 and 2003 and between 2003 and 2020 was 6.204 and −4.218, respectively, with similar patterns observed in both men and women. The ASMR of the SEER showed a modest increase from 1988 to 2016 and then stabilized. In subgroup analysis, the ASMR of the old age group (≥55 years) increased significantly from 0.82 in 1985 to 3.92/100,000 in 2002 (APC 6.917) but then decreased again to 1.86/100,000 in 2020 (APC −4.136). ASMRs according to the age group in the SEER showed a relatively stable trend even in the elderly group. @*Conclusion@#The ASMR of thyroid cancer in Korea had increased from 1985 to 2002 but has since been steadily decreasing. This trend was mainly attributed to elderly people aged 55 or over. The absolute APC value of Korea was much higher than that of the SEER.
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Purpose@#The aim of this study was to assess the diagnostic role of fine-needle aspiration cytology (FNAC) and analyze factors associated with false-negative FNAC results in patients with parathyroid incidentaloma who were referred for ultrasonography (US)-guided fine-needle aspiration (FNA) of thyroid nodules. @*Methods@#In this study, 121 patients with suspected parathyroid lesions were enrolled. The patients underwent US-guided FNAC with measurements of washout parathyroid hormone (PTH) between January 2015 and May 2020. The diagnostic performance of FNAC for the diagnosis of parathyroid lesions was assessed using surgical results and elevated washout PTH as a reference standard. The clinical and radiologic features associated with false-negative results on FNAC for the diagnosis of parathyroid lesions were evaluated. @*Results@#Among the 121 nodules assessed, 38 were parathyroid lesions (31.4%), and 83 were non-parathyroid lesions (68.6%). The diagnostic performance of FNAC for parathyroid incidentaloma showed a sensitivity of 31.6% (12/38), specificity of 100% (83/83), positive predictive values of 100% (12/12), negative predictive values of 76.1% (83/109), and accuracy of 78.5% (95/121). The FNAC results of non-parathyroid lesions included thyroid nodules, lymph nodes, neurogenic tumors, and fat tissue. True-positive results on FNAC were significantly associated with performing FNA twice (58.3% vs. 23.1%, P=0.043). @*Conclusion@#Considering the low sensitivity of FNAC, measuring washout PTH in addition to FNAC may help accurately diagnose parathyroid incidentaloma on thyroid US. Further, the falsenegative rate for FNAC can be reduced by obtaining two or more FNA samples.
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Gastric cancer is one of the most common cancers in Korea and the world. Since 2004, this is the 4th gastric cancer guideline published in Korea which is the revised version of previous evidence-based approach in 2018. Current guideline is a collaborative work of the interdisciplinary working group including experts in the field of gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology and guideline development methodology. Total of 33 key questions were updated or proposed after a collaborative review by the working group and 40 statements were developed according to the systematic review using the MEDLINE, Embase, Cochrane Library and KoreaMed database. The level of evidence and the grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation proposition. Evidence level, benefit, harm, and clinical applicability was considered as the significant factors for recommendation. The working group reviewed recommendations and discussed for consensus. In the earlier part, general consideration discusses screening, diagnosis and staging of endoscopy, pathology, radiology, and nuclear medicine. Flowchart is depicted with statements which is supported by meta-analysis and references. Since clinical trial and systematic review was not suitable for postoperative oncologic and nutritional follow-up, working group agreed to conduct a nationwide survey investigating the clinical practice of all tertiary or general hospitals in Korea. The purpose of this survey was to provide baseline information on follow up. Herein we present a multidisciplinary-evidence based gastric cancer guideline.
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Background@#The purpose of this longitudinal prospective cohort study was to investigate the role of chronotype in the incidence of chemotherapy-induced peripheral neuropathy (CIPN) among women with breast cancer. @*Methods@#We recruited women with breast cancer awaiting adjuvant chemotherapy, including four cycles of docetaxel. Participants reported peripheral neuropathy symptoms of numbness/ tingling at the baseline, and at 4weeks after completion of chemotherapy. Candidate psychiatric factors associated with CIPN were assessed at the baseline, using the Composite Scale of Morningness, the Pittsburgh Sleep Quality Index, and the Hospital Anxiety and Depression Scale. To examine the association between chronotype and CIPN, we built logistic regression models, adjusting for demographic, clinical, and other psychiatric variables. @*Results@#Among 48 participants, 29 participants developed CIPN. The morning chronotype was inversely associated with CIPN (odds ratio, 0.06; confidence interval, 0.01–0.74; P = 0.028) after adjusting for age, BMI, education, type of operation, alcohol use, smoking, sleep quality, depression, and anxiety. @*Conclusion@#Our results suggest that the morning chronotype is a protective factor against the development of CIPN in patients with breast cancer who were treated with docetaxel.
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Purpose@#Radiofrequency ablation (RFA) and ethanol ablation (EA) are effective and safe for benign symptomatic thyroid nodules (BSTNs). However, relatively little is known about the effects of these procedures on patients’ quality of life (QoL). This prospective, multicenter study evaluated the effects of RFA and EA on changes in thyroid-specific QoL in patients with BSTNs and assessed the volume reduction and safety of these procedures. @*Methods@#Eighty-six consecutive patients with 86 BSTNs were prospectively included from two medical centers. RFA was performed for 55 BSTNs with solidity ≥50% and EA was performed for 31 BSTNs with solidity <50%. QoL was evaluated using an 11-scale, multiple-choice thyroid-specific QoL questionnaire. Nodule characteristics and QoL were evaluated at diagnosis and 1, 6, and 12 months after treatment. Overall QoL was rated from 0 (good) to 4 (poor). @*Results@#The mean longest size and volume of the index nodule were 4.2±1.5 cm and 21.6±22.1 mL, respectively. Patients received 1.1 treatments on average (range, 1 to 2). Significant post-treatment volume reductions were noted; however, the EA group showed a higher volume reduction than the RFA group at 1 (78.7%-16.1% vs. 49.1%-15.8%), 6 (86.3%-21.7% vs. 73.0%-14.5%), and 12 (90.9%-14.9% vs. 80.3%-12.4%) months. The score for each scale of the QoL questionnaire improved significantly during follow-up (all P<0.001). Overall QoL improved significantly, from 1.7±0.9 at diagnosis to 0.6±0.7 at the 12-month follow-up (P<0.001). There were no major complications. @*Conclusion@#Both RFA and EA are safe and effective in reducing nodule volume and improving thyroid-specific QoL in patients with BSTNs.
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Purpose@#Up to 20% of patients with biliary tract cancer (BTC) have alterations in DNA damage response (DDR) genes, including homologous recombination (HR) genes. Therefore, the DDR pathway could be a promising target for new drug development in BTC. We aim to investigate the anti-tumor effects using poly(ADP-ribose) polymerase (PARP) and WEE1 inhibitors in BTC. @*Materials and Methods@#We used 10 BTC cell lines to evaluate an anti-tumor effect of olaparib (a PARP inhibitor) and AZD1775 (a WEE1 inhibitor) in in vitro. Additionally, we established SNU869 xenograft model for in vivo experiments. @*Results@#In this study, we observed a modest anti-proliferative effect of olaparib. DNA double-strand break (DSB) and apoptosis were increased by olaparib in BTC cells. However, olaparib-induced DNA DSB was repaired through the HR pathway, and G2 arrest was induced to secure the time for repair. As AZD1775 typically regulates the G2/M checkpoint, we combined olaparib with AZD1775 to abrogate G2 arrest. We observed that AZD1775 downregulated p-CDK1, a G2/M cell cycle checkpoint protein, and induced early mitotic entry. AZD1775 also decreased CtIP and RAD51 expression and disrupted HR repair. In xenograft model, olaparib plus AZD1775 treatment reduced tumor growth more potently than did monotherapy with either drug. @*Conclusion@#This is the first study to suggest that olaparib combined with AZD1775 can induce synergistic anti-tumor effects against BTC. Combination therapy that blocks dual PARP and WEE1 has the potential to be further clinically developed for BTC patients.
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Purpose@#We aimed to assess the real-world efficacy of nab-paclitaxel in metastatic breast cancer patients. @*Materials and Methods@#This is a retrospective study performed in two tertiary referral hospitals in Korea. Patients with metastatic breast cancer treated with nab-paclitaxel (Abraxane®) between March 2016 and March 2020 were enrolled. @*Results@#A total of 102 patients with metastatic breast cancer were included. Patients were heavily pre-treated with a median of four prior lines of chemotherapy (5 lines when including endocrine therapy in hormone-receptor-positive patients), and 66 patients (64.7%) were exposed to taxanes in the metastatic setting. According to St. Gallen molecular subtypes, 36 patients (35.3%) were luminal A, 28 (27.5%) were luminal B, 18 (17.7%) were human epidermal growth factor receptor 2–positive and 20 (19.6%) had triple-negative disease. Fifty patients (49.0%) were treated with a 3-weekly regimen (260 mg/m2 on day 1 every 3 weeks), and 52 (51.0%) were treated with a weekly regimen (100 mg/m2 every week). Objective response rate was 22.9%. After a median follow-up of 22.0 months, median progression-free survival (PFS) was 4.0 months (95% confidence interval [CI], 2.6 to 4.8) and median overall survival was 8.7 months (95% CI, 7.5 to 11.2). Patients treated with weekly regimen had longer PFS compared to 3-weekly regimen (5.5 vs. 2.3 months, p < 0.001). Multivariate analysis revealed the treatment regimen as an independent prognostic factor for PFS. There was no grade 3 or 4 hypersensitivity reaction. @*Conclusion@#This real-world data shows that nab-paclitaxel is a reasonable treatment option in heavily pre-treated and/or taxane-exposed metastatic breast cancer patients.
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Background@#Hürthle cell carcinoma (HCC), a type of thyroid carcinoma, is rare in South Korea, and few studies have investigated its prognosis. @*Methods@#This long-term multicenter retrospective cohort study evaluated the clinicopathological features and clinical outcomes in patients with HCC who underwent thyroid surgery between 1996 and 2009. @*Results@#The mean age of the 97 patients included in the study was 50.3 years, and 26.8% were male. The mean size of the primary tumor was 3.2±1.8 cm, and three (3.1%) patients had distant metastasis at initial diagnosis. Ultrasonographic findings were available for 73 patients; the number of nodules with low-, intermediate-, and high suspicion was 28 (38.4%), 27 (37.0%), and 18 (24.7%), respectively, based on the Korean-Thyroid Imaging Reporting and Data System. Preoperatively, follicular neoplasm (FN) or suspicion for FN accounted for 65.2% of the cases according to the Bethesda category, and 13% had malignancy or suspicious for malignancy. During a median follow-up of 8.5 years, eight (8.2%) patients had persistent/recurrent disease, and none died of HCC. Older age, gross extrathyroidal extension (ETE), and widely invasive types of tumors were significantly associated with distant metastasis (all P<0.01). Gross ETE (hazard ratio [HR], 27.7; 95% confidence interval [CI], 2.2 to 346.4; P=0.01) and widely invasive classification (HR, 6.5; 95% CI, 1.1 to 39.4; P=0.04) were independent risk factors for poor disease-free survival (DFS). @*Conclusion@#The long-term prognosis of HCC is relatively favorable in South Korea from this study, although this is not a nation-wide data, and gross ETE and widely invasive cancer are significant prognostic factors for DFS. The diagnosis of HCC by ultrasonography and cytopathology remains challenging.
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Pelizaeus-Merzbacher disease (PMD) is a X-linked recessive disorder with dysmyelination in central nervous system caused by proteolipid protein 1 (PLP1) gene mutation. We report a case of PMD with PLP1 exon 1 duplication, previously misdiagnosed as cerebral palsy (CP).A 25-year-old male previously diagnosed as CP visited our clinic with progressive weakness and spasticity of bilateral lower limbs. Next generation sequencing revealed hemizygous duplication of exon 1 in PLP1. Additionally, multiplex ligation-dependent probe amplification assay of the patient's mother showed the same mutation, which could finally confirm the diagnosis as PMD. This patient received comprehensive rehabilitation program, and helped the patient to achieve functional improvement. Proper diagnosis and therapeutic plan will be needed for the patients with PMD, before diagnosing CP rashly.
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Objective@#This study aimed to evaluate the efficacy of a bougie and glidescope video laryngoscope (GVL) for ground intubation by novice prehospital caregivers. We hypothesized that the intubation outcome using a bougie or GVL was superior to that using the Macintosh laryngoscope (MCL) with a stylet (MCLS) in ground intubation. @*Methods@#A randomized crossover manikin study was conducted. Studied groups were categorized into 4 according to the intubation devices used; MCLS, Macintosh laryngoscope with bougie (MCLB), glidescope video laryngoscope with a stylet (GVLS), and glidescope video laryngoscope with bougie (GVLB). The primary outcome was the total endotracheal intubation time and the secondary outcome was the success rate for endotracheal intubation. @*Results@#The use of a bougie did not cause a significant difference in the intubation time (MCLS vs. MCLB, P=0.213; GVLS vs. GVLB, P=0.633) and the success rate of endotracheal intubation (MCLS vs. MCLB, P>0.990; GVLS vs. GVLB, P=0.077) was compared with the use of a stylet in MCL and GVL. The use of GVL showed a longer endotracheal intubation time compared with MCLS (MCLS vs. GVLS, P<0.001; MCLS vs. GVLB, P<0.001). GVLB showed a decreased success rate of endotracheal intubation compared with the use of MCL (MCLS vs. GVLB, P=0.004; MCLB vs. GVLB, P<0.001). @*Conclusion@#The use of the GVL and a bougie could not affect the performance of endotracheal intubation on the ground. The use of MCL and a stylet for ground intubation could increase the intubation success rate and shorten intubation time compared with the use of a bougie or the use of GVL.
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Objective@#Overcrowded emergency departments (ED) are a worldwide problem, which could cause treatment delays and increased mortality of patients. This study aimed at evaluating the effect of admission decisions by emergency physicians without consultation of an internal medicine doctor on the emergency department length of stay (ED LOS) and survival rate of patients diagnosed with medical disease. @*Methods@#The study was a retrospective observational study comparing the ED LOS of patients admitted to the internal medicine (IM) department before and after the policy change regarding admission decisions, implemented in July 2017. During and after the policy change, emergency physicians took decisions on the arrangements and treatment for patients by processing their admission and providing follow-up care without further specialist consultations. The ED LOS and rate of admission to the IM department were compared between the study period (October 2017 to October 2018) and the control period (June 2016 to June 2017). @*Results@#The median ED LOS of patients admitted to the IM department decreased from 164.0 minutes (interquartile range [IQR], 118.0-234.0) in the control period to 114.0 minutes (IQR, 104.0-208.0) in the study period. After propensity score matching, the median ED LOS of patients admitted to the IM department decreased from 187.0 minutes (IQR, 136.0-253.0) in the control period to 144.0 minutes (IQR, 104.0-208.0) in the study period. @*Conclusion@#The admission decisions made by emergency physicians reduced the ED and hospital LOS of patients visiting the ED and diagnosed with medical disease.
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Active surveillance (AS) for low-risk papillary thyroid microcarcinoma (PTMC) has been accepted worldwide as safe and effective. Despite the growing acceptance of AS in the management of low-risk PTMCs, there are barriers to AS in real clinical settings, and it is important to understand and establish appropriate AS protocol from initial evaluation to follow-up. PTMC management strategies should be decided upon after careful consideration of patient and tumor characteristics by a multidisciplinary team of thyroid cancer specialists. Patients should understand the risks and benefits of AS, participate in decision-making and follow structured monitoring strategies. In this review, we discuss clinical outcomes of AS from previous studies, optimal indications and follow-up strategies for AS, and unresolved questions about AS.
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Background@#Serum calcitonin measurement contains various clinical and methodological aspects. Its reference level is wide and unclear despite sensitive calcitonin kits are available. This study aimed to identify the specific reference range in the healthy Korean adults. @*Methods@#Subjects were ≥20 years with available calcitonin (measured by a two-site immunoradiometric assay) data by a routine health checkup. Three groups were defined as all eligible subjects (group 1, n=10,566); subjects without self or family history of thyroid disease (group 2, n=5,152); and subjects without chronic kidney disease, autoimmune thyroid disease, medication of proton pump inhibitor/H2 blocker/steroid, or other malignancies (group 3, n=4,638). @*Results@#This study included 6,341 male and 4,225 female subjects. Males had higher mean calcitonin than females (2.3 pg/mL vs. 1.9 pg/mL, P<0.001) in group 1. This gender difference remained similar in groups 2 and 3. Calcitonin according to age or body mass index was not significant in both genders. Higher calcitonin in smoking than nonsmoking men was observed but not in women. Sixty-nine subjects had calcitonin higher than the upper reference limit (10 pg/mL) and 64 of them had factors associated with hypercalcitoninemia besides medullary thyroid cancer. Our study suggests the reference intervals for men who were non, ex-, current smokers, and women (irrespective of smoking status) as <5.7, <7.1, <7.9, and <3.6 pg/mL, respectively. @*Conclusion@#Specific calcitonin reference range should be provided considering for sex and smoking status. Taking account for several factors known to induce hypercalcitoninemia can help interpret the gray zone of moderately elevated calcitonin.
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Objective@#This study aimed to evaluate the efficacy of a bougie and glidescope video laryngoscope (GVL) for ground intubation by novice prehospital caregivers. We hypothesized that the intubation outcome using a bougie or GVL was superior to that using the Macintosh laryngoscope (MCL) with a stylet (MCLS) in ground intubation. @*Methods@#A randomized crossover manikin study was conducted. Studied groups were categorized into 4 according to the intubation devices used; MCLS, Macintosh laryngoscope with bougie (MCLB), glidescope video laryngoscope with a stylet (GVLS), and glidescope video laryngoscope with bougie (GVLB). The primary outcome was the total endotracheal intubation time and the secondary outcome was the success rate for endotracheal intubation. @*Results@#The use of a bougie did not cause a significant difference in the intubation time (MCLS vs. MCLB, P=0.213; GVLS vs. GVLB, P=0.633) and the success rate of endotracheal intubation (MCLS vs. MCLB, P>0.990; GVLS vs. GVLB, P=0.077) was compared with the use of a stylet in MCL and GVL. The use of GVL showed a longer endotracheal intubation time compared with MCLS (MCLS vs. GVLS, P<0.001; MCLS vs. GVLB, P<0.001). GVLB showed a decreased success rate of endotracheal intubation compared with the use of MCL (MCLS vs. GVLB, P=0.004; MCLB vs. GVLB, P<0.001). @*Conclusion@#The use of the GVL and a bougie could not affect the performance of endotracheal intubation on the ground. The use of MCL and a stylet for ground intubation could increase the intubation success rate and shorten intubation time compared with the use of a bougie or the use of GVL.
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Objective@#Overcrowded emergency departments (ED) are a worldwide problem, which could cause treatment delays and increased mortality of patients. This study aimed at evaluating the effect of admission decisions by emergency physicians without consultation of an internal medicine doctor on the emergency department length of stay (ED LOS) and survival rate of patients diagnosed with medical disease. @*Methods@#The study was a retrospective observational study comparing the ED LOS of patients admitted to the internal medicine (IM) department before and after the policy change regarding admission decisions, implemented in July 2017. During and after the policy change, emergency physicians took decisions on the arrangements and treatment for patients by processing their admission and providing follow-up care without further specialist consultations. The ED LOS and rate of admission to the IM department were compared between the study period (October 2017 to October 2018) and the control period (June 2016 to June 2017). @*Results@#The median ED LOS of patients admitted to the IM department decreased from 164.0 minutes (interquartile range [IQR], 118.0-234.0) in the control period to 114.0 minutes (IQR, 104.0-208.0) in the study period. After propensity score matching, the median ED LOS of patients admitted to the IM department decreased from 187.0 minutes (IQR, 136.0-253.0) in the control period to 144.0 minutes (IQR, 104.0-208.0) in the study period. @*Conclusion@#The admission decisions made by emergency physicians reduced the ED and hospital LOS of patients visiting the ED and diagnosed with medical disease.
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Purpose@#This study investigated the association of insulin, metformin, and statin use with survival and whether the association was modified by the hormone receptor status of the tumor in patients with breast cancer. @*Materials and Methods@#We studied 7,452 patients who had undergone surgery for breast cancer at Seoul National University Hospital from 2008 to 2015 using the nationwide claims database. Exposure was defined as a recorded prescription of each drug within 12 months before the diagnosis of breast cancer. @*Results@#Patients with prior insulin or statin use were more likely to be older than 50 years at diagnosis and had a higher comorbidity index than those without it (p < 0.01 for both). The hazard ratio (HR) for death with insulin use was 5.7 (p < 0.01), and the effect was attenuated with both insulin and metformin exposure with an HR of 1.2 (p=0.60). In the subgroup analyses, a heightened risk of death with insulin was further prominent with an HR of 17.9 (p < 0.01) and was offset by co-administration of metformin with an HR of 1.3 (p=0.67) in patients with estrogen receptor (ER)–negative breast cancer. Statin use was associated with increased overall mortality only in patients with ER-positive breast cancer with HR for death of 1.5 (p=0.05). @*Conclusion@#Insulin or statin use before the diagnosis of breast cancer was associated with an increase in all-cause mortality. Subsequent analyses suggested that metformin or statin use may have been protective in patients with ER-negative disease, which warrants further studies.
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Purpose@#The soluble form programmed death-ligand 1 (sPDL1) has immunosuppressive properties and is being studied as a candidate biomarker for immuno-oncology drug development. We measured the serum sPDL1 at pre-and post-chemotherapy and evaluated its prognostic implication and dynamics during chemotherapy in advanced gastric cancer (GC). @*Materials and Methods@#We prospectively enrolled 68 GC patients who were candidates for palliative standard first-line chemotherapy, and serially collected blood at baseline and after one cycle of chemotherapy, at the best response and after disease progression. sPDL1 was measured using an enzyme-linked immunosorbent assay. Response to chemotherapy, overall survival (OS), progressionfree survival (PFS) and other prognostic factors including neutrophil-lymphocyte ratio (NLR) were obtained. The cut-off value of sPDL1 levels for survival analysis was found using C-statistics. @*Results@#The median baseline sPDL1 was 0.8 ng/mL (range, 0.06 to 6.06 ng/mL). The median OS and PFS were 14.9 months and 8.0 months, respectively. sPDL1 and NLR showed a weak positive correlation (Spearman’s rho=0.301, p=0.013). Patients with low levels of sPDL1 at diagnosis (< 1.92 ng/mL) showed a better OS and PFS than patients with a high sPDL1. The baseline sPDL1 before treatment was higher in the progressive disease group than in the stable disease and partial response groups. Patients whose sPDL1 increased after the first cycle of chemotherapy showed worse PFS and OS. Following disease progression, sPDL1 increased compared with the baseline. @*Conclusion@#sPDL1 at prechemotherapy confers a prognostic value for PFS and OS in GC patients under palliative first-line chemotherapy. Dynamics of sPDL1 during chemotherapy correlates with disease progression.
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Active surveillance (AS) for low-risk papillary thyroid microcarcinoma (PTMC) has been accepted worldwide as safe and effective. Despite the growing acceptance of AS in the management of low-risk PTMCs, there are barriers to AS in real clinical settings, and it is important to understand and establish appropriate AS protocol from initial evaluation to follow-up. PTMC management strategies should be decided upon after careful consideration of patient and tumor characteristics by a multidisciplinary team of thyroid cancer specialists. Patients should understand the risks and benefits of AS, participate in decision-making and follow structured monitoring strategies. In this review, we discuss clinical outcomes of AS from previous studies, optimal indications and follow-up strategies for AS, and unresolved questions about AS.