Publications by authors named "Jin Hee Kim"

691 Publications

Efficacy and safety of elagolix with add-back therapy in women with uterine fibroids and coexisting adenomyosis.

F S Rep 2021 Sep 26;2(3):338-346. Epub 2021 May 26.

Departments of Obstetrics & Gynecology & Surgery, Mayo Clinic and Mayo Medical School, Rochester, Minnesota.

Objective: To determine if coexisting adenomyosis limits the efficacy of elagolix, an oral gonadotropin-releasing hormone antagonist, with hormonal add-back therapy in reducing heavy menstrual bleeding in women with uterine fibroids.

Design: Pooled analysis of two identical, double-blind, randomized, placebo-controlled, 6-month phase 3 trials (Elaris Uterine Fibroids [UF]-1 and UF-2).

Setting: A total of 153 gynecological clinical care settings in the United States and Canada.

Patients: Premenopausal women (18-51 years) with >80 mL of menstrual blood loss (MBL)/cycle and uterine fibroids with and without coexisting adenomyosis diagnosed by ultrasound and/or magnetic resonance imaging at baseline.

Interventions: Participants were randomized 1:1:2 to placebo, elagolix 300 mg twice daily alone, or elagolix 300 mg twice daily with estradiol 1 mg/norethindrone acetate 0.5 mg once daily.

Main Outcome Measures: The primary endpoint was the proportion of women who had <80 mL of MBL during the final month and ≥50% reduction in MBL from baseline to the final month. Adverse events were monitored.

Results: Of 786 women treated across the two trials, 16% (126 women) had coexisting adenomyosis. Among this subset, a significantly greater proportion of women who received elagolix with add-back therapy (77.1% [95% confidence interval, 66.2, 88.0]) met both primary endpoint criteria compared with women who received placebo (12.2% [95% confidence interval, 1.0, 23.4]). Adverse events most frequently reported in the elagolix with add-back adenomyosis subset were hot flushes (18.3%), nausea (11.7%), and night sweats (8.3%).

Conclusions: Elagolix with add-back therapy significantly reduced heavy menstrual bleeding in women with uterine fibroids and coexisting adenomyosis, suggesting that elagolix efficacy was not adversely affected by the presence of adenomyosis (Elaris UF-1 and UF-2 Clinical-Trials.gov numbers, NCT02654054 and NCT02691494).
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http://dx.doi.org/10.1016/j.xfre.2021.05.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441572PMC
September 2021

Role of adjuvant radiotherapy in extrahepatic bile duct cancer: A multicenter retrospective study (Korean Radiation Oncology Group 18-14).

Eur J Cancer 2021 Aug 30;157:31-39. Epub 2021 Aug 30.

Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, South Korea. Electronic address:

Purpose: To evaluate the role of adjuvant radiotherapy (RT) after curative resection in patients with extrahepatic bile duct (EHBD) cancer.

Methods: Between January 2000 and December 2015, 1475 patients with EHBD cancer who underwent curative resection were accrued from 14 institutions in Korea. Among these, 959 patients did not receive any adjuvant therapy (RT(-) group), while 516 underwent postoperative RT with or without chemotherapy (RT(+) group).

Results: The median age was 67 years. Nodal involvement was present in 482 patients (32.7%), and resection margin was involved in 293 patients (19.9%). RT(+) group had more patients with proximal tumours, advanced tumours, nodal involvement, perineural invasion, and involved resection margin than RT(-) group (all p < 0.001). With a median follow-up of 36 months, there were 211 locoregional recurrences, 307 distant metastases and 322 combined locoregional and distant failures. On multivariate analysis incorporating age, tumour location, differentiation, pT classification, pN classification, perineural invasion and resection margin, adjuvant RT was associated with improved overall survival (hazard ratio, 0.74; 95% confidence interval, 0.63-0.86; p < 0.001). When RT(+) group was separated into RT alone, concurrent chemoradiotherapy (CCRT) and CCRT followed by chemotherapy, the greatest benefit was observed in patients treated with CCRT followed by chemotherapy (hazard ratio, 0.52; 95% confidence interval, 0.41-0.68).

Conclusions: Adjuvant RT combined with chemotherapy improved survival outcomes of resected EHBD cancer patients. Considering the greatest benefit observed in patients receiving CCRT followed by chemotherapy, a randomised controlled trial comparing chemotherapy alone and CCRT followed by chemotherapy is urgently needed.
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http://dx.doi.org/10.1016/j.ejca.2021.07.045DOI Listing
August 2021

Postmastectomy Radiation Therapy for Node-Negative Breast Cancer of 5cm or Larger Tumors: A Multicenter Retrospective Analysis (KROG 20-03).

Cancer Res Treat 2021 Aug 25. Epub 2021 Aug 25.

Proton Therapy Center, National Cancer Center, Goyang, Korea.

Purpose: To evaluate the role of postmastectomy radiation therapy (PMRT) in patients with node-negative breast cancer of 5cm or larger tumors undergoing mastectomy.

Materials And Methods: Medical records of 274 patients from 18 institutions treated with mastectomy between Jan 2000 and Dec 2016 were retrospectively reviewed. Among these, 202 patients underwent PMRT, while 72 did not. Two hundred and forty-one patients (88.0%) received systemic chemotherapy, and 172 (62.8%) received hormonal therapy. Patients receiving PMRT were younger, more likely to have progesterone receptor-positive tumors, and received adjuvant chemotherapy more frequently compared with those without PMRT (p <0.001, 0.018, and <0.001, respectively). Other characteristics were not significantly different between the two groups.

Results: With a median follow-up of 95 months (range, 1-249), there were 9 locoregional recurrences, and 20 distant metastases. The 8-year locoregional recurrence-free survival rates were 98.0% with PMRT and 91.3% without PMRT (p=0.133), and the 8-year disease-free survival (DFS) rates were 91.8% with PMRT and 73.9% without PMRT (p=0.008). On multivariate analysis incorporating age, histologic grade, lymphovascular invasion, hormonal therapy, chemotherapy, and PMRT, the absence of lymphovascular invasion and the receipt of PMRT were associated with improved DFS (p=0.025 and 0.009, respectively).

Conclusion: Locoregional recurrence rate was very low in node-negative breast cancer of 5cm or larger tumors treated with mastectomy regardless of the receipt of PMRT. However, PMRT was significantly associated with improved DFS. Further investigation is needed to confirm these findings.
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http://dx.doi.org/10.4143/crt.2021.933DOI Listing
August 2021

Childhood Obesity-Related Mechanisms: MicroRNome and Transcriptome Changes in a Nested Case-Control Study.

Biomedicines 2021 Jul 23;9(8). Epub 2021 Jul 23.

Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul 03080, Korea.

Childhood obesity could contribute to adulthood obesity, leading to adverse health outcomes in adults. However, the mechanisms for how obesity is developed are still unclear. To determine the epigenome-wide and genome-wide expression changes related with childhood obesity, we compared microRNome and transcriptome levels as well as leptin protein levels in whole bloods of 12 obese and 24 normal children aged 6 years. miR-328-3p, miR-1301-3p, miR-4685-3p, and miR-6803-3p were negatively associated with all obesity indicators. The four miRNAs were also associated with 3948 mRNAs, and separate 475 mRNAs (185 among 3948 mRNAs) were associated with all obesity indicators. The 2533 mRNAs (64.2%) among the 3948 mRNAs and 286 mRNAs (60.2%) among the 475 mRNAs were confirmed as targets of the four miRNAs in public databases through miRWalk 2.0. Leptin protein was associated with miR-6803-3p negatively and all obesity indicators positively. Using DAVID bioinformatics resources 6.8, top three pathways for obesity-related gene set were metabolic pathways, pathways in cancer, and PI3K-Akt signaling pathway. The top three obesity-related disease classes were metabolic, cardiovascular, and chemdependency. Our results support that childhood obesity could be developed through miRNAs-related epigenetic mechanism and, further, these obesity-related epigenetic changes could control the pathways related with the development of various diseases.
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http://dx.doi.org/10.3390/biomedicines9080878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389653PMC
July 2021

Effect of Postoperative Radiotherapy after Primary Tumor Resection in De Novo Stage IV Breast Cancer: A Multicenter Retrospective Study (KROG 19-02).

Cancer Res Treat 2021 Jul 13. Epub 2021 Jul 13.

Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Purpose: To investigate the impact of postoperative radiotherapy (PORT) in de novo metastatic breast cancer (dnMBC) patients undergoing planned primary tumor resection (PTR) and to identify the subgroup of patients who would most benefit from PORT.

Materials And Methods: This study enrolled 426 patients with dnMBC administered PTR alone or with PORT. The primary and secondary outcomes were overall and progression-free survival (OS and PFS), respectively.

Results: The median follow-up time was 53.7 months (range, 3.1-194.4). The 5-year OS and PFS rates were 73.2% and 32.0%, respectively. For OS, clinical T3/4 stage, triple-negative breast cancer (TNBC), postoperative chemotherapy alone were significantly poor prognostic factors, and administration of PORT failed to show its significance. Regarding PFS, PORT was a favorable prognostic factor (hazard ratio [HR]: 0.64, 95% confidence interval [CI]: 0.50-0.82, p <0.001), in addition to T1/2 stage, ≤5 metastases, and non-TNBC. According to the multivariate analyses of OS in the PORT group, we divided the patients into three groups [Group 1, T1/2 and non-TNBC (n=193); Group 2, T3/4 and non-TNBC (n=171); and Group 3, TNBC (n=49)], and evaluated the effect of PORT. Although PORT had no significance for OS in all subgroups, it was a significant factor for good prognosis regardingPFS in Group 1 and 2, not in Group 3.

Conclusion: PORT was associated with a significantly better PFS in patients with dnMBC who underwent PTR. Patients with clinical T1/2 stage and non-TNBC benefited most from PORT, while those with TNBC showed little benefit.
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http://dx.doi.org/10.4143/crt.2021.632DOI Listing
July 2021

Influence of Concurrent and Adjuvant Temozolomide on Health-Related Quality of Life of Patients with Grade III Gliomas: A Secondary Analysis of a Randomized Clinical Trial (KNOG-1101 Study).

Cancer Res Treat 2021 Jul 6. Epub 2021 Jul 6.

Department of Neurosurgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

Purpose: The KNOG-1101 study showed improved 2-year PFS with temozolomide during and after radiotherapy compared to radiotherapy alone for patients with anaplastic gliomas. This trial investigates the effect of concurrent and adjuvant temozolomide on health-related quality of life (HRQoL).

Materials And Methods: In this randomized, open-label, phase II trial, 90 patients with WHO grade III glioma were enrolled across multiple centers in South Korea between March 2012 to February 2015 and followed up through 2017. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) and 20-item EORTC QLQ-Brain Neoplasm (QLQ-BN20) were used to compare HRQoL between patients assigned to CCRT with temozolomide followed by 6 cycles of adjuvant temozolomide (Arm A) and radiotherapy (RT) alone (Arm B).

Results: Of the 90 patients in the study, 84 patients (93.3%) completed the baseline HRQoL questionnaire. Emotional functioning, fatigue, nausea and vomiting, dyspnea, constipation, appetite loss, diarrhea, seizures, itchy skin, drowsiness, hair loss, and bladder control were not affected by the addition of temozolomide. All other items did not differ significantly between Arm A and Arm B throughout treatment. Global health status particularly stayed consistent at the end of adjuvant temozolomide (p=0.47) and at the end of RT (p=0.33).

Conclusion: The addition of concurrent and adjuvant temozolomide did not show negative influence on HRQoL with improvement of progression-free survival for patients with anaplastic gliomas. The absence of systematic and clinically relevant changes in HRQoL suggests that an overall long-term net clinical benefit exists for concurrent and adjuvant temozolomide.
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http://dx.doi.org/10.4143/crt.2021.393DOI Listing
July 2021

Infectious Respiratory Diseases Decreased during the COVID-19 Pandemic in South Korea.

Int J Environ Res Public Health 2021 06 3;18(11). Epub 2021 Jun 3.

Department of Integrative Bioscience & Biotechnology, Sejong University, 209 Neungdong-ro, Gwangjin-gu, Seoul 05006, Korea.

Infectious respiratory diseases are highly contagious and very common, and thus can be considered as one of the leading causes of morbidity and mortality worldwide. We followed up the incidence rates (IRs) of eight infectious respiratory diseases, including chickenpox, measles, pertussis, mumps, invasive pneumococcal disease, scarlet fever, rubella, and meningococcal disease, after COVID-19 mitigation measures were implemented in South Korea, and then compared those with the IRs in the corresponding periods in the previous 3 years. Overall, the IRs of these diseases before and after age- or sex-standardization significantly decreased in the intervention period compared with the pre-intervention periods ( < 0.05 for all eight diseases). However, the difference in the IRs of all eight diseases between the IRs before and after age-standardization was significant ( < 0.05 for all periods), while it was not significant with regard to sex-standardization. The incidence rate ratios for eight diseases in the pre-intervention period compared with the intervention period ranged from 3.1 to 4.1. These results showed the positive effects of the mitigation measures on preventing the development of respiratory infectious diseases, regardless of age or sex, but we need to consider the age-structure of the population to calculate the effect size. In the future, some of these measures could be applied nationwide to prevent the occurrence or to reduce the transmission during outbreaks of these infections. This study provides evidence for strengthening the infectious disease management policies in South Korea.
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http://dx.doi.org/10.3390/ijerph18116008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199908PMC
June 2021

Metabolite and Elastase Activity Changes in Beach Rose () Fruit and Seeds at Various Stages of Ripeness.

Plants (Basel) 2021 Jun 24;10(7). Epub 2021 Jun 24.

BK21 Interdisciplinary Program in IT-Bio Convergence System, Chonnam National University, Gwangju 61186, Korea.

Rose hips are the fruits of the beach rose ( To determine the optimal harvest time and to obtain the maximum functional compounds, rose hips at various stages of ripeness (immature, early, mid, and late) were harvested, and the flesh tissue and seeds were separated. The rose hip flesh showed the highest total phenolic content at the mid-ripeness stage (8.45 ± 0.62 mg/g gallic acid equivalent concentration (dry weight)). The early-, mid-, and late-ripeness stages of rose hip flesh did not show significantly different 2,2-diphenyl-1-picrylhydrazyl antioxidant capacities. The elastase inhibitory activity of the 95% ethanol extract from the rose hip seeds was highest at the mid-ripeness stage; however, the elastase inhibitory activity of the rose hip tissue was not significantly different from that of the seeds. Pathway analysis using MetaboAnalyst showed that sucrose, fructose, and glucose gradually increased as the fruit ripened. Ursolic acid was detected in the seeds but not in the flesh. Of the fatty acids, linoleic acid concentrations were highest in rose hip seeds, followed by linolenic acid, oleic acid, and palmitic acid. Fatty acids and ursolic acid might be the active compounds responsible for elastase inhibitory activity and can be utilized as a functional cosmetic material.
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http://dx.doi.org/10.3390/plants10071283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8309187PMC
June 2021

Thymoma-Associated Paraneoplastic Myositis, Presenting with Rapidly Progressive Muscle Contractures.

J Clin Neurol 2021 Jul;17(3):496-498

Department of Neurology, Neuroscience Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

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http://dx.doi.org/10.3988/jcn.2021.17.3.496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242300PMC
July 2021

Surgical site infections in gynecology: the latest evidence for prevention and management.

Curr Opin Obstet Gynecol 2021 08;33(4):296-304

Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, USA.

Purpose Of Review: Surgical site infection (SSI) remains one of the most common postoperative surgical complications. Prevention and appropriate treatment remain paramount.

Recent Findings: Evidence-based recommendations include recognition and reduction of preoperative risks including hyperglycemia and smoking, treatment of preexisting infections, skin preparation with chlorhexidine gluconate, proper use of preoperative antibiotics, and implementation of prevention bundles. Consideration should be given to the use of dual antibiotic preoperative treatment with cephazolin and metronidazole for all hysterectomies.

Summary: Despite advancements, SSI in gynecologic surgery remains a major cause of perioperative morbidity and healthcare cost. Modifiable risk factors should be evaluated and patients optimized to the best extent possible prior to surgery. Preoperative risks include obesity, hyperglycemia, smoking, and untreated preexisting infections. Intraoperative risk-reducing strategies include appropriate perioperative antibiotics, correct topical preparation, maintaining normothermia, and minimizing blood loss. Additionally, early recognition and prompt treatment of SSI remain crucial.
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http://dx.doi.org/10.1097/GCO.0000000000000717DOI Listing
August 2021

Inter-institutional Variation in Intensity-modulated Radiotherapy for Breast Cancer in Korea (KROG 19-01).

Anticancer Res 2021 Jun;41(6):3145-3152

Department of Radiation Oncology, Chonnam National University Medical School, Gwangju, Republic of Korea.

Background/aim: To present the variations in the target delineation and the planning results of intensity-modulated radiation therapy (IMRT) for breast cancers.

Patients And Methods: We requested the target volumes and organs at risk delineation for two cases of left breast cancers, and evaluated the IMRT plans including the supraclavicular and internal mammary node irradiation.

Results: Twenty-one institutions participated in this study. Differences in the planning target volume among institutions reached up to three-times for breast-conserving surgery (BCS) case and five-times for mastectomy case. Mean heart doses ranged from 3.3 to 24.1 Gy for BCS case and from 5.0 to 26.5 Gy for mastectomy case. Ipsilateral lung volumes receiving more than 20 Gy ranged from 4.7 to 57.4% for BCS case and from 16.4 to 55.5% for mastectomy case.

Conclusion: There were large variations in the target delineation and planning results of IMRT for breast cancers among institutions. Considering the increased use of breast IMRT, more standardized protocols are needed.
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http://dx.doi.org/10.21873/anticanres.15100DOI Listing
June 2021

Optimizing External Beam Radiotherapy as per the Risk Group of Localized Prostate Cancer: A Nationwide Multi-Institutional Study (KROG 18-15).

Cancers (Basel) 2021 May 31;13(11). Epub 2021 May 31.

Yonsei Cancer Center, Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 03722, Korea.

Purpose: This nationwide multi-institutional study analyzed the patterns of care and outcomes of external beam radiotherapy (EBRT) in localized prostate cancer patients. We compared various risk classification tools and assessed the need for refinements in current radiotherapy (RT) schemes.

Methods And Materials: We included non-metastatic prostate cancer patients treated with primary EBRT from 2001 to 2015 in this study. Data of 1573 patients from 17 institutions were analyzed and re-grouped using a risk stratification tool with the highest predictive power for biochemical failure-free survival (BCFFS). We evaluated BCFFS, overall survival (OS), and toxicity rates.

Results: With a median follow-up of 75 months, 5- and 10-year BCFFS rates were 82% and 60%, and 5- and 10-year OS rates were 95% and 83%, respectively. NCCN risk classification revealed the highest predictive power (AUC = 0.556, 95% CI 0.524-0.588; < 0.001). Gleason score, iPSA < 12 ng/mL, intensity-modulated RT (IMRT), and ≥179 Gy (EQD2, 77 Gy) were independently significant for BCFFS (all < 0.05). IMRT and ≥179 Gy were significant factors in the high-risk group, whereas ≥170 Gy (EQD2, 72 Gy) was significant in the intermediate-risk group and no significant impact of dose was observed in the low-risk group. Both BCFFS and OS improved significantly when ≥179 Gy was delivered using IMRT and hypofractionation in the high-risk group without increasing toxicities.

Conclusions: With NCCN risk classification, dose escalation with modern high-precision techniques might increase survivals in the high-risk group, but not in the low-risk group, although mature results of prospective studies are awaited.
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http://dx.doi.org/10.3390/cancers13112732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198120PMC
May 2021

Reply to Lorenzo et al.

Endoscopy 2021 06 26;53(6):667. Epub 2021 May 26.

Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.

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http://dx.doi.org/10.1055/a-1345-8614DOI Listing
June 2021

COVID-19 Workplace Outbreaks by Industry Sector and Their Associated Household Transmission, Ontario, Canada, January to June, 2020.

J Occup Environ Med 2021 07;63(7):574-580

Public Health Ontario, Toronto, Ontario, Canada (Dr Murti, Ms Achonu, Dr Smith, Dr Brown, Dr Kim, Mr Johnson, Ms Ravindran, and Dr Buchan); Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada (Dr Murti, Dr Smith, Dr Kim, and Dr Buchan).

Objective: To analyze workplace outbreaks by industry sector in the first wave of the pandemic, and associated household cases.

Methods: Number, size, and duration of outbreaks were described by sector, and outbreak cases were compared to sporadic cases in the same time frame. Address matching identified household cases with onset ≥2 days before, ≥2 days after, or within 1 day of the workplace outbreak case.

Results: There were 199 outbreaks with 1245 cases, and 68% of outbreaks and 80% of cases belonged to (1) Manufacturing, (2) Agriculture, Forestry, Fishing, Hunting, (3) Transportation and Warehousing. There were 608 household cases associated with 339 (31%) outbreak cases, increasing the burden of illness by 56%.

Conclusions: Workplace outbreaks primarily occurred in three sectors. Prevention measures should target industry sectors at risk to prevent spread in and out of the workplace.
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http://dx.doi.org/10.1097/JOM.0000000000002201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247533PMC
July 2021

Synergistic Enhancement of Thermoelectric Performances by Cl-Doping and Pb-Excess in (Pb,Sn)Se Topological Crystal Insulator.

Materials (Basel) 2021 Apr 12;14(8). Epub 2021 Apr 12.

Department of Applied Physics, Integrated Education Institute for Frontier Science and Technology (BK21 Four) and Institute of Natural Sciences, Kyung Hee University, Yongin 17104, Korea.

We investigated the thermoelectric properties of the PbSnSe and PbSnSeCl (x = 0.0, 0.2, 0.3, 0.5, 1.0, 2.0 mol.%) compounds, synthesized by hot-press sintering. The electrical transport properties showed that low concentration doping of Cl (below 0.3 mol.%) in the Pb-excess (Pb,Sn)Se samples increased the carrier concentration and the Hall mobility by the increase of carriers' mean free path. The effective mass of the carrier was also enhanced from the measurements of the Seebeck coefficient. The enhanced effective masses of the carrier by the Cl-doping can be understood by the enhanced electron-phonon interaction, caused by the crystalline mirror symmetry breaking. The significantly decreased lattice thermal conductivities showed that the crystalline mirror symmetry breaking decreased the lattice thermal conductivity of the Pb-excess (Pb,Sn)Se. By the Cl-doping and the Pb-excess's synergistic effect, which can suppress the bipolar effect, the values of x = 0.2 and 0.3 mol.% reached 0.8 at 773 K. Therefore, we suggest that Pb-excess and the crystalline mirror symmetry breaking by Cl-doping are effective for high thermoelectric performance in the (Pb,Sn)Se.
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http://dx.doi.org/10.3390/ma14081920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069562PMC
April 2021

Nordihydroguaiaretic Acid as a Novel Substrate and Inhibitor of Catechol Methyltransferase Modulates 4-Hydroxyestradiol-Induced Cyto- and Genotoxicity in MCF-7 Cells.

Molecules 2021 Apr 3;26(7). Epub 2021 Apr 3.

Department of Biological Sciences, Sookmyung Women's University, Seoul 04310, Korea.

Nordihydroguaiaretic acid (NDGA) is a major lignan metabolite found in spp., which are widely used in South America to treat various diseases. In breast tissue, estradiol is metabolized to the catechol estrogens such as 4-hydroxyestradiol (4-OHE), which have been proposed to be cancer initiators potentially involved in mammary carcinogenesis. Catechol--methyltransferase (COMT) catalyzes the methylation of catechol estrogens to their less toxic methoxy derivatives, such as 4--methylestradiol (4-MeOE). The present study investigated the novel biological activities of NDGA in relation to COMT and the effects of COMT inhibition by NDGA on 4-OHE-induced cyto- and genotoxicity in MCF-7 human breast cancer cells. Two methoxylated metabolites of NDGA, 3--methylNDGA (3-MNDGA) and 4-methyl NDGA (4-MNDGA), were identified in the reaction mixture containing human recombinant COMT, NDGA, and cofactors. values for the COMT-catalyzed metabolism of NDGA were 2.6 µM and 2.2 µM for 3-MNDGA and 4-MNDGA, respectively. The COMT-catalyzed methylation of 4-OHE was inhibited by NDGA at an IC of 22.4 µM in a mixed-type mode of inhibition by double reciprocal plot analysis. Molecular docking studies predicted that NDGA would adopt a stable conformation at the COMT active site, mainly owing to the hydrogen bond network. NDGA is likely both a substrate for and an inhibitor of COMT. Comet and apurinic/apyrimidinic site quantitation assays, cell death, and apoptosis in MCF-7 cells showed that NDGA decreased COMT-mediated formation of 4-MeOE and increased 4-OHE-induced DNA damage and cytotoxicity. Thus, NDGA has the potential to reduce COMT activity in mammary tissues and prevent the inactivation of mutagenic estradiol metabolites, thereby increasing catechol estrogen-induced genotoxicities.
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http://dx.doi.org/10.3390/molecules26072060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038350PMC
April 2021

Physical Exercise and Health-Related Quality of Life in Office Workers: A Systematic Review and Meta-Analysis.

Int J Environ Res Public Health 2021 04 5;18(7). Epub 2021 Apr 5.

Department of Integrative Bioscience & Biotechnology, Sejong University, 209 Neungdong-ro, Gwangjin-gu, Seoul 05006, Korea.

Office workers are at high risk for many chronic diseases, lowering their health-related quality of life (HRQOL). This systematic review and meta-analysis aimed to summarize the effects of physical exercise on HRQOL in office workers with and without health problems using data obtained from randomized controlled trials (RCTs), quasi-experimental, and observational studies. We searched PubMed, Web of Science, Scopus, Cochrane Library, and several grey literature databases, and identified 26 relevant studies for the synthesis. Overall, physical exercise significantly improved general (standardized mean difference (SMD) = 1.05; 95% confidence interval (CI): 0.66 to 1.44) and mental (SMD = 0.42; 95% CI: 0.19 to 0.66) HRQOL in office workers. Compared with healthy office workers, unhealthy office workers experienced greater improvements in general (unhealthy, SMD = 2.76; 95% CI: 1.63 to 3.89; healthy, SMD = 0.23; 95% CI: -0.09 to 0.56) and physical (unhealthy, SMD = 0.38; 95% CI: 0.17 to 0.58; healthy, SMD = -0.20; 95% CI: -0.51 to 0.11) HRQOL. Unsupervised physical exercise significantly improved general and mental HRQOL, while directly supervised physical exercise significantly improved only general HRQOL. Although physical exercise, especially unsupervised physical exercise, should be encouraged to improve HRQOL in office workers, detailed recommendations could not be made because of the diverse exercise types with different intensities. Therefore, further studies are needed to determine the optimal exercise for office workers with different health conditions.
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http://dx.doi.org/10.3390/ijerph18073791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038562PMC
April 2021

Safety and Effectiveness of an In-Hospital Screening Station for Coronavirus Disease 2019 in Response to the Massive Community Outbreak.

Risk Manag Healthc Policy 2021 19;14:1637-1647. Epub 2021 Apr 19.

Department of Family Medicine, Kyungpook National University Hospital, Kyungpook National University Chilgok Hospital, Daegu, Korea.

Purpose: To evaluate the results of operating an in-hospital coronavirus disease 2019 screening station on an outpatient basis and to identify the effectiveness and necessity of such a screening station.

Patients And Methods: This cross-sectional study included 1345 individuals who were tested for COVID-19 using real-time reverse transcription polymerase chain reaction (RT-PCR) at an in-hospital screening station on an outpatient basis. The subjects were healthcare workers (HCWs) with suspected COVID-19 symptoms or exposure to patients with confirmed COVID-19, caregivers at the hospital for complete enumeration, and patients who were scheduled to be admitted to a nonrestricted area in the hospital or to visit for outpatient treatment, but had suspected COVID-19 symptoms. The subjects were divided and compared as follows: HCW versus non-HCW groups and RT-PCR positive versus negative groups.

Results: A total of 140 had symptoms, 291 wanted to be tested, and 664 were asymptomatic but were screened. Seven subjects had positive results for COVID-19. Compared with the non-HCWs, the HCWs were younger and had a lower rate of underlying medical conditions. In addition, there were more women, individuals with exposure to confirmed cases, and individuals with symptoms or those who just wanted to be tested. The frequency of all symptoms was high among the HCWs. The results of the logistic regression analysis showed that the HCWs were significantly associated with the presence of symptoms, having an odds ratio of 23.317 (confidence interval, 15.142-35.907L; < 0.001). The positive group had a high rate of exposure to patients with confirmed COVID-19 and had more subjects with symptoms or those who wanted to be tested.

Conclusion: In-hospital screening stations are a relatively safe way to protect and support HCWs and to reduce and manage the spread of infection within the hospital effectively during an outbreak in the community.
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http://dx.doi.org/10.2147/RMHP.S287213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064719PMC
April 2021

Genotyping by Sequencing-Based Discovery of SNP Markers and Construction of Linkage Map from F Population of Pepper with Contrasting Powdery Mildew Resistance Trait.

Biomed Res Int 2021 15;2021:6673010. Epub 2021 Mar 15.

Department of Vegetable Crops, Korea National College of Agriculture and Fisheries, Jeonju 54874, Republic of Korea.

Powdery mildew (PM) is a common fungal disease infecting pepper plants worldwide. Molecular breeding of pepper cultivars with powdery mildew resistance is desirable for the economic improvement of pepper cultivation. In the present study, 188 F population derived from AR1 (PM resistant) and TF68 (PM sensitive) parents were subjected to high-throughput genotyping by sequencing (GBS) for the identification of single nucleotide polymorphism (SNP) markers. Further, the identified SNP markers were utilized for the construction of genetic linkage map and QTL analysis. Overall read mapping percentage of 87.29% was achieved in this study with the total length of mapped region ranging from 2,956,730 to 25,537,525 bp. A total of 41,111 polymorphic SNPs were identified, and a final of 1,841 SNPs were filtered for the construction of a linkage map. A total of 12 linkage groups were constructed corresponding to each chromosome with 1,308 SNP markers with the map length of 2506.8 cM. Further, two QTLs such as and were identified in chromosomes 2 and 5, respectively, for the PM resistance. Overall, the outcomes of the present endeavor can be utilized for the marker-assisted selection of pepper with powdery mildew-resistant trait.
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http://dx.doi.org/10.1155/2021/6673010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987414PMC
May 2021

The Development of the Postpartum Depression Self-Management Mobile Application "Happy Mother".

Comput Inform Nurs 2021 Apr 2;39(8):439-449. Epub 2021 Apr 2.

Author Affiliations: College of Nursing, Pusan National University, Yangsan (Dr Seo, Ms Kim, and Ms Lee); College of Nursing, The Catholic University of Korea, Seoul (Dr Na), South Korea.

Postpartum depression is the most common mood disorder that occurs after childbirth, rendering it a significant public health problem. Information and communication technologies hold tremendous promise for expanding the reach of quality mental healthcare and closing the treatment gap for depression. In particular, given that mobile applications are inexpensive and provide information systematically, they are suitable as a method of health management that does not require visiting a medical center. The purposes of this study were to document the process of developing a mobile application for the self-management of postpartum depression and to share usability test results. The mobile application "Happy Mother" was developed based on the first five of seven stages in the mobile application development lifecycle model. Components of cognitive behavioral therapy were adopted to guide content development for "Happy Mother." The usability of the completed mobile application was tested in the following three steps: it increased awareness of mood, promoted self-management, and implemented specific methods a mother can use in her daily life to improve mood, including modifications made based on the results of the usability test.
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http://dx.doi.org/10.1097/CIN.0000000000000738DOI Listing
April 2021

Scattering Mechanisms and Suppression of Bipolar Diffusion Effect in BiTeSeI Compounds.

Materials (Basel) 2021 Mar 22;14(6). Epub 2021 Mar 22.

Department of Applied Physics, Integrated Education Institute for Frontier Science and Technology (BK21 Four) and Institute of Natural Sciences, Kyung Hee University, Yongin 17104, Korea.

We investigated the anisotropic thermoelectric properties of the BiTeSeI (x = 0.0, 0.1, 0.3, 0.5 mol.%) compounds, synthesized by ball-milling and hot-press sintering. The electrical conductivities of the BiTeSeI were significantly improved by the increase of carrier concentration. The dominant electronic scattering mechanism was changed from the mixed (T ≤ 400 K) and ionization scattering (T ≥ 420 K) for pristine compound (x = 0.0) to the acoustic phonon scattering by the iodine doping. The Hall mobility was also enhanced with the increasing carrier concentration. The enhancement of Hall mobility was caused by the increase of the mean free path of the carrier from 10.8 to 17.7 nm by iodine doping, which was attributed to the reduction of point defects without the meaningful change of bandgap energy. From the electron diffraction patterns, a lattice distortion was observed in the iodine doped compounds. The modulation vector due to lattice distortion increased with increasing iodine concentration, indicating the shorter range lattice distortion in real space for the higher iodine concentration. The bipolar thermal conductivity was suppressed, and the effective masses were increased by iodine doping. It suggests that the iodine doping minimizes the ionization scattering giving rise to the suppression of the bipolar diffusion effect, due to the prohibition of the Bi antisite defect, and induces the lattice distortion which decreases lattice thermal conductivity, resulting in the enhancement of thermoelectric performance.
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http://dx.doi.org/10.3390/ma14061564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004870PMC
March 2021

Simultaneous selective removal of cesium and cobalt from water using calcium alginate-zinc ferrocyanide-Cyanex 272 composite beads.

Environ Sci Pollut Res Int 2021 Aug 1;28(31):42014-42023. Epub 2021 Apr 1.

School of Architectural, Civil, Environmental, and Energy Engineering, Kyungpook National University, 80 Daehak-Ro, Buk-Gu, Daegu, 41566, Republic of Korea.

Composite beads consisting of Ca alginate mixed with zinc ferrocyanide (ZnFC) and Cyanex 272 were synthesized in order to selectively adsorb Cs and Co from water. Their physicochemical properties of the synthesized composite beads were characterized using various techniques, including FESEM, EDX, FTIR, and TGA. The ZnFC/Cyanex 272/alginate (ZCA) composite beads were then tested as an adsorbent for the selective removal of Cs and Co from an aqueous solution. The adsorption capacity increased with increasing ZnFC and Cyanex 272 contents. The adsorption process followed the Langmuir model and pseudo-second-order kinetics. The ZCA composite beads exhibited excellent selectivity toward Cs and Co even in the presence of competitive cations (K, Na, Fe, and Ni). The adsorption capacity of the ZCA composite beads for Cs and Co was almost maintained after three times of adsorption-desorption process.
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http://dx.doi.org/10.1007/s11356-021-13342-6DOI Listing
August 2021

The Role of Postoperative Radiotherapy in Intracranial Solitary Fibrous Tumor/Hemangiopericytoma: A Multi-Institutional Retrospective Study (KROG 18-11).

Cancer Res Treat 2021 Mar 24. Epub 2021 Mar 24.

Department of Radiation Oncology, Seoul National University Hospital, Seoul National University, College of Medicine, Seoul, Korea.

Purpose: To evaluate the role of postoperative radiotherapy (PORT) in intracranial solitary fibrous tumor/hemangiopericytoma (SFT/HPC).

Methods And Materials: A total of 133 patients with histologically confirmed HPC were included from 8 institutions. Gross total resection (GTR) and subtotal resection (STR) were performed in 86 and 47 patients, respectively. PORT was performed in 85 (64%) patients. The prognostic effects of sex, age, performance, WHO grade, location, size, Ki-67, surgical extent, and PORT on local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) were estimated by univariate and multivariate analyses.

Results: The 10-year PFS, and OS rates were 45%, and 71%, respectively. The multivariate analysis suggested that PORT significantly improved LC (p<0.001) and PFS (p<0.001). The PFS benefit of PORT was maintained in the subgroup of GTR (p=0.001), WHO grade II (p=0.001) , or STR (p<0.001). In the favorable subgroup of GTR and WHO grade II, PORT was also significantly related to better PFS (p=0.028). WHO grade III was significantly associated with poor DMFS (p=0.029). In the PORT subgroup, the 0-0.5 cm margin of the target volume showed an inferior LC to a large margin with 1.0-2.0 cm (p=0.021). Time-dependent Cox proportion analysis showed that distant failures were significantly associated with poor OS (p=0.003).

Conclusion: This multicenter study supports the role of PORT in disease control of intracranial SFT/HPC, irrespective of the surgical extent and grade. For LC, PORT should enclose the tumor bed with sufficient margin.
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http://dx.doi.org/10.4143/crt.2021.142DOI Listing
March 2021

Effects of Glucagon-Like Peptide-1 Analogue and Fibroblast Growth Factor 21 Combination on the Atherosclerosis-Related Process in a Type 2 Diabetes Mouse Model.

Endocrinol Metab (Seoul) 2021 Feb 24;36(1):157-170. Epub 2021 Feb 24.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

Background: Glucagon-like peptide-1 (GLP-1) analogues regulate glucose homeostasis and have anti-inflammatory properties, but cause gastrointestinal side effects. The fibroblast growth factor 21 (FGF21) is a hormonal regulator of lipid and glucose metabolism that has poor pharmacokinetic properties, including a short half-life. To overcome these limitations, we investigated the effect of a low-dose combination of a GLP-1 analogue and FGF21 on atherosclerosis-related molecular pathways.

Methods: C57BL/6J mice were fed a high-fat diet for 30 weeks followed by an atherogenic diet for 10 weeks and were divided into four groups: control (saline), liraglutide (0.3 mg/kg/day), FGF21 (5 mg/kg/day), and low-dose combination treatment with liraglutide (0.1 mg/kg/day) and FGF21 (2.5 mg/kg/day) (n=6/group) for 6 weeks. The effects of each treatment on various atherogenesisrelated pathways were assessed.

Results: Liraglutide, FGF21, and their low-dose combination significantly reduced atheromatous plaque in aorta, decreased weight, glucose, and leptin levels, and increased adiponectin levels. The combination treatment upregulated the hepatic uncoupling protein-1 (UCP1) and Akt1 mRNAs compared with controls. Matric mentalloproteinase-9 (MMP-9), monocyte chemoattractant protein-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) were downregulated and phosphorylated Akt (p-Akt) and phosphorylated extracellular signal-regulated kinase (p-ERK) were upregulated in liver of the liraglutide-alone and combination-treatment groups. The combination therapy also significantly decreased the proliferation of vascular smooth muscle cells. Caspase-3 was increased, whereas MMP-9, ICAM-1, p-Akt, and p-ERK1/2 were downregulated in the liraglutide-alone and combination-treatment groups.

Conclusion: Administration of a low-dose GLP-1 analogue and FGF21 combination exerts beneficial effects on critical pathways related to atherosclerosis, suggesting the synergism of the two compounds.
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http://dx.doi.org/10.3803/EnM.2020.781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937856PMC
February 2021

Neurotoxic Effects of Local Anesthetics on Developing Motor Neurons in a Rat Model.

J Clin Med 2021 Feb 25;10(5). Epub 2021 Feb 25.

Department of Anesthesiology & Pain Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea.

Neurotoxic effects of local anesthetics (LAs) on developing motor neurons have not been documented. We investigated the neurotoxic effects of LAs on developing motor neurons in terms of cell viability, cytotoxicity, reactive oxygen species (ROS), and apoptosis. Embryonic spinal cord motor neurons were isolated from Sprague-Dawley rat fetuses and exposed to one of the three LAs-lidocaine, bupivacaine, or ropivacaine-at concentrations of 1, 10, 100, or 1000 µM. The exposure duration was set to 1 or 24 h. The neurotoxic effects of LAs were determined by evaluating the following: cell viability, cytotoxicity, ROS production, and apoptosis. In the 1-h exposure group, the motor neurons exposed to lidocaine and bupivacaine had reduced cell viability and increased cytotoxicity, ROS, and apoptosis in a concentration-dependent manner. Lidocaine showed the highest toxicity, followed by bupivacaine. In the 24-h exposure group, all three LAs showed significant effects (decreased cell viability and increased cytotoxicity, ROS, and apoptosis) on the motor neurons in a concentration-dependent manner. The neurotoxic effects of lidocaine were greater than those of bupivacaine and ropivacaine. Ropivacaine appeared to have the least effect on motor neurons. This study identified the neurotoxic effects of lidocaine and bupivacaine on developing spinal cord motor neurons.
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http://dx.doi.org/10.3390/jcm10050901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956179PMC
February 2021

Review of multi-species biofilm formation from foodborne pathogens: multi-species biofilms and removal methodology.

Crit Rev Food Sci Nutr 2021 Mar 5:1-11. Epub 2021 Mar 5.

Department of Food and Nutrition, Kookmin University, Seoul, Korea.

Multi-species biofilms are ubiquitous worldwide and are a concern in the food industry. Multi-species biofilms have a higher resistance to antimicrobial therapies than mono-species biofilms. In addition, multi-species biofilms can cause severe foodborne diseases. To remove multi-species biofilms, controlling the formation process of extracellular polymeric substances (EPS) and quorum sensing (QS) effects is essential. EPS disruption, inhibition of QS, and disinfection have been utilized to remove multi-species biofilms. This review presents information on the formation and novel removal methods for multi-species biofilms.
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http://dx.doi.org/10.1080/10408398.2021.1892585DOI Listing
March 2021

Combined Hepatocellular-Cholangiocarcinoma: Magnetic Resonance Imaging Features and Prognosis According to Risk Factors for Hepatocellular Carcinoma.

J Magn Reson Imaging 2021 06 9;53(6):1803-1812. Epub 2021 Feb 9.

Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.

Background: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) can develop in patients with and without risk factors for hepatocellular carcinoma (HCC).

Purpose: To compare the clinical and magnetic resonance imaging (MRI) characteristics of cHCC-CCA in patients with and without risk factors for HCC, and to assess the influence of risk factors on patient prognosis.

Study Type: Retrospective.

Population: A total of 152 patients with surgically confirmed cHCC-CCA.

Field Strength/sequence: 1.5-T and 3-T/T1-weighted dual gradient-echo in- and opposed-phase, T2-weighted turbo-spin-echo, diffusion-weighted single-shot spin-echo echo-planar, and T1-weighted three-dimensional gradient-echo contrast-enhanced sequences.

Assessment: MRI features according to the Liver Imaging Reporting and Data System (LI-RADS) and pathologic findings based on revised classification were compared between patients with and without risk factors for HCC. Overall survival (OS) and recurrence-free survival (RFS) were also compared between the two groups, and factors associated with survival were evaluated.

Statistical Tests: The clinico-pathologic and MRI features of the two groups were compared using Student's t-tests, Mann-Whitney U-tests, and chi-square tests. OS and RFS were evaluated by the Kaplan-Meier method, and factors associated with survival were evaluated by Cox proportional hazard model.

Results: cHCC-CCA in patients with risk factors were more frequently classified as LI-RADS category 4 or 5 (LR-4/5; probably or definitely HCC) (48.7%), whereas those without risk factors were more frequently classified as category M (LR-M; probably malignant, not specific for HCC) (63.6%). RFS and OS did not differ significantly according to risk factors (P = 0.63 and 0.83). Multivariable analysis showed that pathologic tumor type (hazard ratio 2.02; P < 0.05) and LI-RADS category (hazard ratio 2.19; P < 0.05) were significantly associated with RFS and OS, respectively.

Data Conclusion: Although MRI features of cHCC-CCA differed significantly between patients with and without risk factors for HCC, postsurgical prognosis did not. LI-RADS category and pathologic tumor type were independently correlated with postsurgical prognosis in patients with cHCC-CCA.

Level Of Evidence: 3 TECHNICAL EFFICACY STAGE: 2.
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http://dx.doi.org/10.1002/jmri.27528DOI Listing
June 2021

A functional genomics screen identifying blood cell development genes in Drosophila by undergraduates participating in a course-based research experience.

G3 (Bethesda) 2021 01;11(1)

Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Undergraduate students participating in the UCLA Undergraduate Research Consortium for Functional Genomics (URCFG) have conducted a two-phased screen using RNA interference (RNAi) in combination with fluorescent reporter proteins to identify genes important for hematopoiesis in Drosophila. This screen disrupted the function of approximately 3500 genes and identified 137 candidate genes for which loss of function leads to observable changes in the hematopoietic development. Targeting RNAi to maturing, progenitor, and regulatory cell types identified key subsets that either limit or promote blood cell maturation. Bioinformatic analysis reveals gene enrichment in several previously uncharacterized areas, including RNA processing and export and vesicular trafficking. Lastly, the participation of students in this course-based undergraduate research experience (CURE) correlated with increased learning gains across several areas, as well as increased STEM retention, indicating that authentic, student-driven research in the form of a CURE represents an impactful and enriching pedagogical approach.
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http://dx.doi.org/10.1093/g3journal/jkaa028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022729PMC
January 2021

Optimal treatment strategies for small cell carcinoma of the uterine cervix: A retrospective multi-center study (KROG 19-03).

Eur J Obstet Gynecol Reprod Biol 2021 Mar 22;258:396-400. Epub 2021 Jan 22.

Department of Radiation Oncology, Chung-Ang University Hospital, Seoul, Republic of Korea.

Objective: This multi-institutional study aimed to identify the optimal treatment strategy for small cell carcinoma of the cervix.

Study Design: We retrospectively collected the medical records of 166 patients diagnosed with small cell carcinoma of the uterine cervix from January 2000 to December 2015 from 13 institutions of the Korean Radiation Oncology Group. After excluding 18 (10.8 %) patients who initially had distant metastasis, the treatment outcomes of 148 patients were analyzed.

Results: After a median 46.4 (1.4-231.9) months of follow-up, the 5-year progression-free survival (PFS) and overall survival (OS) rates of all patients were 45.9 % and 63.5 %, respectively. Distant metastasis was the dominant pattern of failure occurring in 67 patients (45.3 %). We stratified the patients according to the primary local treatment: primary surgery (n = 119), primary radiotherapy (RT) (n = 26), and no local treatment group (n = 3). Although the primary RT group had advanced disease (FIGO stage ≧ IIB) more frequently than the primary surgery group (80.8 % vs. 47.9 %), the PFS and OS did not differ between the groups in multivariate analysis.

Conclusion: Definitive RT is a reasonable local treatment option for small cell cervical cancer, particularly for advanced cases. Given the high rates of distant relapse, an effective systemic therapy protocol is warranted for small cell cervical cancer patients.
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http://dx.doi.org/10.1016/j.ejogrb.2021.01.034DOI Listing
March 2021

Impact of radiation dose on complications among women with breast cancer who underwent breast reconstruction and post-mastectomy radiotherapy: A multi-institutional validation study.

Breast 2021 Apr 20;56:7-13. Epub 2021 Jan 20.

Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address:

Purpose: Emerging data suggest that higher radiation doses in post-mastectomy radiotherapy may be associated with an increased risk of reconstruction complications. This study aimed to validate previous findings regarding the impact of radiation dose on complications among women with breast cancer using a multi-center dataset.

Methods: Fifteen institutions participated, and women with breast cancer who received radiotherapy after either autologous or prosthetic breast reconstruction were included. The primary endpoint was major post-radiation therapy complications requiring re-operation for explantation, flap failure, or bleeding control.

Results: In total, 314 patients were included. Radiotherapy was performed using both conventional fractionation and hypofractionation in various schedules. The range of the radiation therapy dose in Equivalent Dose in 2 Gy fractions (EQD2; α/β = 3.5) varied from 43.4 to 71.0 Gy (median dose: 48.6 Gy). Boost radiation therapy was administered to 49 patients. Major post-radiation therapy complications were observed in 24 (7.6%) patients. In multivariate analysis, an increasing EQD2 per Gy (odds ratio [OR]: 1.58, 95% confidence interval [CI]: 1.26-1.98; p < 0.001), current smoking status (OR: 25.48, 95% CI: 1.56-415.65; p = 0.023), and prosthetic breast reconstruction (OR: 9.28, 95% CI: 1.84-46.70; p = 0.007) were independently associated with an increased risk of major complications.

Conclusion: A dose-response relationship between radiation dose and the risk of complications was validated in this multi-center dataset. In this context, we hypothesize that the use of hypofractionated radiotherapy (40 Gy in 15 fractions) may improve breast reconstruction outcomes. Our multi-center prospective observational study (NCT03523078) is underway to further validate this hypothesis.
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http://dx.doi.org/10.1016/j.breast.2021.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848800PMC
April 2021
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