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Purpose@#Mutations in the PIK3CA gene occur frequently in breast cancer patients. Activating PIK3CA mutations confer resistance to human epidermal growth factor receptor 2 (HER2)-targeted treatments. In this study, we investigated whether PIK3CA mutations were correlated with treatment response or duration in patients with HER2-positive (HER2+) breast cancer. @*Materials and Methods@#We retrospectively reviewed the clinical information of patients with HER2+ breast cancer who received HER2-targeted therapy for early-stage or metastatic cancers. The pathologic complete response (pCR), progression-free survival (PFS), and overall survival were compared between patients with wild-type PIK3CA (PIK3CAw) and those with mutated PIK3CA (PIK3CAm). Next-generation sequencing was combined with examination of PFS associated with anti-HER2 monoclonal antibody (mAb) treatment. @*Results@#Data from 90 patients with HER2+ breast cancer were analyzed. Overall, 34 (37.8%) patients had pathogenic PIK3CA mutations. The pCR rate of the PIK3CAm group was lower than that of the PIK3CAw group among patients who received neoadjuvant chemotherapy for early-stage cancer. In the metastatic setting, the PIK3CAm group showed a significantly shorter mean PFS (mPFS) with first-line anti-HER2 mAb. The mPFS of second-line T-DM1 was lower in the PIK3CAm group than that in the PIK3CAw group. Sequencing revealed differences in the mutational landscape between PIK3CAm and PIK3CAw tumors. @*Conclusion@#Patients with HER2+ breast cancer with activating PIK3CA mutations had lower pCR rates and shorter PFS with palliative HER2-targeted therapy than those with wild-type PIK3CA. Precise targeted-therapy is needed to improve survival of patients with HER2+/PIK3CAm breast cancer.
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Purpose@#BRCA1 and BRCA2 are among the most important genes involved in DNA repair via homologous recombination (HR). Germline BRCA1/2 (gBRCA1/2)-related cancers have specific characteristics and treatment options but conducting gBRCA1/2 testing and interpreting the genetic imprint are sometimes complicated. Here, we describe the concordance of gBRCA1/2 derived from a panel of clinical tumor tissues using next-generation sequencing (NGS) and genetic aspects of tumors harboring gBRCA1/2 pathogenic variants. @*Materials and Methods@#Targeted sequencing was performed using available tumor tissue from patients who underwent gBRCA1/2 testing. Comparative genomic analysis was performed according to gBRCA1/2 pathogenicity. @*Results@#A total of 321 patients who underwent gBRCA1/2 testing were screened, and 26 patients with gBRCA1/2 pathogenic (gBRCA1/2p) variants, eight patients with gBRCA1/2 variants of uncertain significance (VUS; gBRCA1/2v), and 43 patients with gBRCA1/2 wild-type (gBRCA1/2w) were included in analysis. Mutations in TP53 (49.4%) and PIK3CA (23.4%) were frequently detected in all samples. The number of single-nucleotide variants (SNVs) per tumor tissue was higher in the gBRCA1/2w group than that in the gBRCA1/2p group (14.81 vs. 18.86, p=0.278). Tumor mutation burden (TMB) was significantly higher in the gBRCA1/2w group than in the gBRCA1/2p group (10.21 vs. 13.47, p=0.017). Except for BRCA1/2, other HR-related genes were frequently mutated in patients with gBRCA1/2w. @*Conclusion@#We demonstrated high sensitivity of gBRCA1/2 in tumors analyzed by NGS using a panel of tumor tissues. TMB value and aberration of non-BRCA1/2 HR-related genes differed significantly according to gBRCA1/2 pathogenicity in patients with breast cancer.
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Purpose@#K-MASTER project is a Korean national precision medicine platform that screened actionable mutations by analyzing next-generation sequencing (NGS) of solid tumor patients. We compared gene analyses between NGS panel from the K-MASTER project and orthogonal methods. @*Materials and Methods@#Colorectal, breast, non–small cell lung, and gastric cancer patients were included. We compared NGS results from K-MASTER projects with those of non-NGS orthogonal methods (KRAS, NRAS, and BRAF mutations in colorectal cancer [CRC]; epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK] fusion, and reactive oxygen species 1 [ROS1] fusion in non–small cell lung cancer [NSCLC], and Erb-B2 receptor tyrosine kinase 2 (ERBB2) positivity in breast and gastric cancers). @*Results@#In the CRC cohort (n=225), the sensitivity and specificity of NGS were 87.4% and 79.3% (KRAS); 88.9% and 98.9% (NRAS); and 77.8% and 100.0% (BRAF), respectively. In the NSCLC cohort (n=109), the sensitivity and specificity of NGS for EGFR were 86.2% and 97.5%, respectively. The concordance rate for ALK fusion was 100%, but ROS1 fusion was positive in only one of three cases that were positive in orthogonal tests. In the breast cancer cohort (n=260), ERBB2 amplification was detected in 45 by NGS. Compared with orthogonal methods that integrated immunohistochemistry and in situ hybridization, sensitivity and specificity were 53.7% and 99.4%, respectively. In the gastric cancer cohort (n=64), ERBB2 amplification was detected in six by NGS. Compared with orthogonal methods, sensitivity and specificity were 62.5% and 98.2%, respectively. @*Conclusion@#The results of the K-MASTER NGS panel and orthogonal methods showed a different degree of agreement for each genetic alteration, but generally showed a high agreement rate.
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Purpose@#Next-generation sequencing (NGS) can facilitate precision medicine approaches in metastatic colorectal cancer (mCRC) patients. We investigated the molecular profiling of Korean mCRC patients under the K-MASTER project which was initiated in June 2017 as a nationwide precision medicine oncology clinical trial platform which used NGS assay to screen actionable mutations. @*Materials and Methods@#As of 22 January 2020, total of 994 mCRC patients were registered in K-MASTER project. Targeted sequencing was performed using three platforms which were composed of the K-MASTER cancer panel v1.1 and the SNUH FIRST Cancer Panel v3.01. If tumor tissue was not available, cell-free DNA was extracted and the targeted sequencing was performed by Axen Cancer Panel as a liquid biopsy. @*Results@#In 994 mCRC patients, we found 1,564 clinically meaningful pathogenic variants which mutated in 71 genes. Anti-EGFR therapy candidates were 467 patients (47.0%) and BRAF V600E mutation (n=47, 4.7%), deficient mismatch repair/microsatellite instability–high (n=15, 1.5%), HER2 amplifications (n=10, 1.0%) could be incorporated with recently approved drugs. The patients with high tumor mutation burden (n=101, 12.7%) and DNA damaging response and repair defect pathway alteration (n=42, 4.2%) could be enrolled clinical trials with immune checkpoint inhibitors. There were more colorectal cancer molecular alterations such as PIK3CA, KRAS G12C, atypical BRAF, and HER2 mutations and even rarer but actionable genes that approved or ongoing clinical trials in other solid tumors. @*Conclusion@#K-MASTER project provides an intriguing background to investigate new clinical trials with biomarkers and give therapeutic opportunity for mCRC patients.
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Background@#Various types of miniplates have been developed and used for the reduction of facial bone fractures. We introduced Yang’s Keyhole (YK) plate, and reported on its short-term stability. The purpose of this study was to evaluate the long-term stability of the YK plate, as a follow-up study, by examining the patients who had used the YK plate among the patients with the reduction of mandible fractures and who visited for plate removal. @*Methods@#We reviewed the medical records of 16 patients who underwent mandibular fracture fixation using a YK plate (group I) and 17 patients who underwent mandibular fracture fixation using a conventional plate (group II). Assessment was then made on malunion, occlusal stability, discomfort during the application, and clinical symptoms. @*Results@#From January 2015 to December 2017, a total of 36 patients underwent mandibular fracture surgery using a YK plate. A total of 16 patients received plate removal. Among them, 15 were male and 1 female. The average age was 26 years. The applied surgical sites were the 12 on mandibular angle, 4 on mandibular symphysis, and 2 on subcondyle. The application period of YK plate was an average of 335 days. During the same period, 45 people underwent surgery on the conventional plate. A total of 17 patients received plate removal. Among them, 15 were male and 2 females. The average age was 36 years. The applied surgical sites were the 8 on mandibular angle, 4 on mandibular symphysis, and 2 on subcondyle. The application period of the conventional plate was an average of 349 days. No malocclusion occurred at the time of removal, and occlusion was stable. No patient complained of joint disease or discomfort. @*Conclusion@#The YK plate system, in which the screw was first inserted and the plate was applied, for clinical convenience did not cause any particular problem and no significant difference from the conventional plate.
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Purpose@#The purpose of this study was to identify the concordant or discordant genomic profiling between primary and matched metastatic tumors in patients with colorectal cancer (CRC) and to explore the clinical implication. @*Materials and Methods@#Surgical samples of primary and matched metastatic tissues from 158 patients (335 samples) with CRC at Korea University Anam Hospital were evaluated using the Ion AmpliSeq Cancer Hotspot Panel. We compared genetic variants and classified them as concordant, primary-specific, and metastasis-specific variants. We used a combination of principal components analysis and clustering to find genomic groups. Kaplan-Meier curves were used to appraise survival between genomic groups. We used machine learning to confirm the correlation between genetic variants and metastatic sites. @*Results@#A total of 282 types of deleterious non-synonymous variants were selected for analysis. Of a total of 897 variants, an average of 40% was discordant. Three genomic groups were yielded based on the genomic discrepancy patterns. Overall survival differed significantly between the genomic groups. The poorest group had the highest proportion of concordant KRAS G12V and additional metastasis-specific SMAD4. Correlation analysis between genetic variants and metastatic sites suggested that concordant KRAS mutations would have more disseminated metastases. @*Conclusion@#Driver gene mutations were mostly concordant; however, discordant or metastasis-specific mutations were present. Clinically, the concordant driver genetic changes with additional metastasis-specific variants can predict poor prognosis for patients with CRC.
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PURPOSE: Abdominal pain is the most common symptom of patients visiting the emergency department (ED). Abdominal pain is caused by a variety of causes, so it is difficult for a triage nurse to determine the urgency of a patient, but it is still a must. The purpose of this study was to identify the related factors to the urgent diseases of patients with abdominal pain visiting ED.METHODS: This study was a retrospective descriptive study. The study setting was an ED in a tertiary hospital in Korea. Data were collected from September 1, 2017 to October 15, 2017. During the study period, of a total of 6,181 patients visiting the ED, 731 complained of abdominal pain. Patients with obvious cause of pain and patients who could not express detailed symptoms were excluded. The 573 patients were included in the final analysis. We collected demographics, clinical characteristics, and final diagnosis. We divided final diagnoses into urgent diseases which were more likely to be life-threatening without treatment and non-urgent diseases. We identified the related factors to the urgent diseases of patients with abdominal pain using the logistic regression.RESULTS: 173 (30.2%) patients had urgent diseases. Age (OR=1.02, 95% CI=1.00~1.03), referral from other clinics (OR=2.92, 95% CI=1.86~4.60), ambulance utilization (OR=2.00, 95% CI=1.27~3.15), diarrhea (OR=0.44, 95% CI=0.25~0.76), and tachycardia (OR=2.27, 95% CI=1.44~3.58) were related to urgent diseases.CONCLUSION: Triage nurse should take into account the patient's age, mode of visiting, and route of visiting ED; and check the symptom of tachycardia or diarrhea.
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BACKGROUND/AIMS: The annual risk of transformation of non-hypervascular magnetic resonance (MR) hepatobiliary phase imaging (HBPI) hypointense nodules into hypervascular hepatocellular carcinomas (HCCs) was evaluated. METHODS: Cirrhotic patients with non-hypervascular HBPI hypointense nodules were retrospectively analyzed if they were diagnosed as HCC and MR followed up longer than 1 year during the period from January 2010 to October 2016 with regular intervals of 3 to 6 months. Risk factors for transformation into hypervascular HCCs were analyzed using the Cox proportional hazard model. RESULTS: Among the 103 non-hypervascular HBPI hypointense nodules meeting the inclusion criteria, transformation into hypervascular HCCs occurred in 44 tumors (42.7%). The median follow-up period was 24 months. Multivariate analysis revealed that hyperintensity on T2-weighted images (T2WI) and diffusion-weighted images (DWI) were the two independent predictors of transformation into hypervascular HCCs (p=0.036 and p=0.041, respectively). Most tumors with hyperintensity on T2WI or DWI on the initial or follow-up MR were transformed into hypervascular HCCs within the first year. Among the 22 nodules (21.3%) showing a new change in dynamic phases during follow-up, 14 nodules (13.6%) showed malignant transformations. CONCLUSIONS: The transformation rates of HBPI hypointense nodules into hypervascular HCCs could be predicted according to the initial or serial MRI findings.
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Humans , Carcinoma, Hepatocellular , Follow-Up Studies , Hepatocytes , Liver Neoplasms , Magnetic Resonance Imaging , Multivariate Analysis , Proportional Hazards Models , Retrospective Studies , Risk FactorsABSTRACT
BACKGROUND: The objective of this study was to evaluate the changes in gene expression after incubation of cells with proteins released from different silk mat layers. METHODS: A silk cocoon from Bombyx mori was separated into four layers of equal thickness. The layers were numbered from 1 to 4 (from the inner to the outer layer). The proteins were released by sonication of a silk mat layer in normal saline. The concentration of proteins was determined by spectrophotometry. They were incubated with RAW264.7 cells, and changes in the expression of genes were evaluated by cDNA microarray analysis and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). RESULTS: Layer 1 and 4 groups had higher protein concentrations compared to those in layer 2 and 3 groups. The genes associated with inflammation and angiogenesis showed significantly higher expression in layer 1 and 4 groups. The results of qRT-PCR were in agreement with those of the cDNA microarray analysis. CONCLUSIONS: The silk mat from the middle portion of the silkworm cocoon yielded a lower protein release and caused an insignificant change in the expression of genes that are associated with inflammation and angiogenesis.
Subject(s)
Angiogenesis Inducing Agents , Bombyx , Gene Expression , Inflammation , Macrophages , Oligonucleotide Array Sequence Analysis , Silk , Sonication , SpectrophotometryABSTRACT
BACKGROUND: This study aimed to evaluate the mechanical, biological, and esthetic stability of a zirconium abutment according to evidence-based dentistry. MAIN TEXT: An electronic search was performed. Domestic studies were found using the keywords “zirconia abutments” and “zirconium abutment” in KMbase, KoreaMed, and the National Assembly Library, and international studies were found using the same keywords in PubMed. All identified studies were divided by evidence level from the viewpoint of the research type utilizing the evidence-based review manual. A total of 102 domestic studies (with Korean language) were found, and 9 of these studies were selected. In these nine studies, 3 had evidence level 3 and 6 had evidence level 4. A total of 97 international studies (with English language) were found, and 19 were selected. Among these 19 studies, 5 had evidence level 2 and 7 had evidence level 3, whereas the remainder had evidence level 4. According to the studies, zirconium abutments are mechanically, biologically, and esthetically stable, but the evidence level of these studies is low, and the follow-up duration is no longer than 5 years. CONCLUSIONS: All examined studies verified the mechanical stability of zirconium abutments for a period no longer than 5 years. Therefore, a long-term clinical observation is needed. Zirconium abutments are thought to be biologically stable, but they are not superior to titanium abutments. As the esthetic stability of such abutments had a low evidence level in the studies that examined here, a much higher evidence level is needed.
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Dental Implants , Evidence-Based Dentistry , Follow-Up Studies , Titanium , ZirconiumABSTRACT
BACKGROUND@#Silk mats have been approved for clinical trials by the Korean Food and Drug Administration as membranes for guided tissue regeneration (GTR). In this study, silk mat application was compared to high-density polytetrafluoroethylene (dPTFE) membrane application or no membrane group.@*METHODS@#To compare the silk mat group to the dPTFE group or the no membrane group, a retrospective sample collection was conducted. Bony defects were measured at the time of extraction (T0) and then at 3 months (T1) and 6 months after extraction (T2) on a digital panoramic view. Bone gain (BG) was calculated by subtracting from the bony defect at T0 to the bony defect at each follow-up.@*RESULTS@#The BG at T2 was 2.44 ± 2.49 mm, 4.18 ± 1.80 mm, and 4.24 ± 2.05 mm in the no membrane group, silk mat group, and dPTFE group, respectively. Both membrane groups had significantly higher BG than BG in the no membrane group at T2 (P < 0.05).@*CONCLUSIONS@#Both membrane groups showed higher BG than the no membrane group.
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PURPOSE@#To evaluate the effect of portal hypertension on the tumor recurrence in patients with hepatocellular carcinoma (HCC) and without hepatic decompression following radiofrequency ablation (RFA).@*MATERIALS AND METHODS@#Treatment-naïve HCC patients within the Milan criteria and with Child-Pugh class A were included in this study, who had performed RFA in our hospital between January 2010 and March 2017. Univariate and multivariate analyses using the Cox proportional hazard model were performed to find the predictors of local or distant tumor recurrence.@*RESULTS@#Overall, 178 patients were included in this study. Median follow-up period was 40.2 months. The difference in the local tumor progression rates depending on the absence or presence of portal hypertension was not statistically significant (p = 0.195). The 1-, 3-, and 5-year distant intrahepatic tumor spread rates were 6.6%, 29.5%, and 537% in patients without portal hypertension, and 23.4%, 51.9%, and 63.6% in patients with portal hypertension, respectively. The difference was statistically significant (p = 0.011). Univariate and multivariate analysis showed that portal hypertension was an independent predictor for distant intrahepatic tumor spread (p = 0.008).@*CONCLUSION@#For HCC patients with Child-Pugh class A, portal hypertension adversely affected distant intrahepatic tumor progression.
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BACKGROUND: The objective of this retrospective study was to show results from platform-switched narrow-diameter implants in the posterior edentulous region, which we followed up for more than 1 year after functional loading. METHODS: Ninety-eight narrow implants were inserted into 66 patients. After healing, fixed implant-supported prostheses were delivered to the patients, and Periotest and radiographic examinations were performed. After the first year of loading, the implant outcome was again evaluated clinically and radiographically using the Periotest analysis. Crestal bone loss and Periotest values (PTVs) were used to evaluate the effect of surgery, prosthesis, implant, and a host-related factor. A general linear model was used to statistically detect variables statistically associated with crestal bone loss and Periotest value. RESULTS: We followed up on the implants over 1 to 4 years after loading; their survival rate was 100%, and pronounced differences from PTVs were noted among jaw location, bone quality, and loading period. No difference was detected in bone loss among the variables studied. Bone loss after functional loading was 0.14 ± 0.39 mm. The stability value from the Periotest was −3.29 ± 0.50. CONCLUSIONS: Within the limitations of this study, judicious use of platform-switched narrow implants with a conical connection must be considered an alternative for wide-diameter implants to restore a posterior edentulous region.
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Humans , Dental Implant-Abutment Design , Jaw , Linear Models , Prostheses and Implants , Retrospective Studies , Survival RateABSTRACT
PURPOSE: Revisit to the pediatric emergency department (ED) in the short-term period may be due to inadequate evaluation during the previous visit, which may indicate a problem with quality in emergency care. The aims of this study are to analyze the characteristics of patients who revisited the pediatric ED within 48 hours after discharge and to evaluate the relation between overcrowding and revisit rates. METHODS: Retrospectively, we reviewed the charts of patients who returned within 48 hours after visiting a PED during a one-year period between June 1st, 2011 and December 31st, 2011. We determined the rate of return visits and review the characteristics of patients, emergency severity index (ESI) level at visits, cause of revisit, diagnosis, and crowding degree of the pediatric ED at the patient's first visit. RESULTS: A total of 16,688 patients visited the pediatric ED and 13,716 patients were discharged from the PED during the period. Of these discharged patients, 534 patients revisited inevitably within 48 hours. The most common cause of revisit was relapse or worsened symptoms (70.0%). There was no significant difference in sex, severity of patient, and crowding degree of the pediatric ED at the first visit, however, patients who revisited were younger than those who did not (p=0.005). The ESI level at the return visit was significantly higher irrespective of admission after revisit (p<0.001). In diagnosis grouping, patients with gastrointestinal diseases, respiratory diseases, and neoplastic diseases showed a higher rate of revisit. CONCLUSION: Approximately 4% of our pediatric ED visits were for children returning within 48 hours. Patients who revisited were younger and patients with gastrointestinal diseases, neoplastic diseases, and respiratory diseases were more likely to revisit. Careful explanation of the possibility of worsened symptoms is necessary for these patients.
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Child , Humans , Crowding , Diagnosis , Emergencies , Emergency Medical Services , Emergency Service, Hospital , Gastrointestinal Diseases , Recurrence , Retrospective StudiesABSTRACT
OBJECTIVE: The purpose of this study was to evaluate displacement of the mandibular condyle after orthognathic surgery using a condylar-repositioning device. METHODS: The patient group comprised 20 adults who underwent bimaxillary surgery between August 2008 and July 2011. The degree of condylar displacement was measured by pre- and postoperative tomographic analysis using centric relation bite and a wire during surgery. A survey assessing temporomandibular joint (TMJ) sound, pain, and locking was performed. The 20 tomographs and surveys were analyzed using the Wilcoxon signed-rank test and McNemar's test, respectively. RESULTS: No significant changes were observed in the anterior, superior, or posterior joint space of the TMJ (p > 0.05). In addition, no significant change was observed in TMJ sound (p > 0.05). However, TMJ pain and locking both decreased significantly after surgery (p < 0.05). CONCLUSIONS: Due to its simplicity, this method may be feasible and useful for repositioning condyles.
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Adult , Humans , Bites and Stings , Centric Relation , Displacement, Psychological , Joints , Mandibular Condyle , Orthognathic Surgery , Temporomandibular JointABSTRACT
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Humans , Analgesics , Blood Pressure , Conscious Sedation , Dentistry , Fentanyl , Heart , Heart Rate , Ketorolac , Memory , Midazolam , Surveys and Questionnaires , Reference Values , Surgery, Oral , Vital SignsABSTRACT
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Aged , Humans , Male , Carcinoma , Carcinoma, Squamous Cell , Gingiva , Head , Lymph Nodes , Neck , Neck Dissection , Neoplasm Metastasis , Thyroid Gland , Thyroid Neoplasms , ThyroidectomyABSTRACT