Publications by authors named "Si Hyung Lee"

139 Publications

The long-term risk of lymphoma and skin cancer was not increased after topical calcineurin inhibitor use and phototherapy in a cohort of 25,694 patients with vitiligo.

J Am Acad Dermatol 2021 Jan 25. Epub 2021 Jan 25.

Department of Dermatology, College of Medicine, The Catholic University of Korea, Seoul, Korea. Electronic address:

Background: Topical calcineurin inhibitors have been used to treat vitiligo, either alone or in combination with phototherapy; however, the long-term safety of these agents remains controversial.

Objective: To investigate the risk of lymphoma and skin cancer in vitiligo patients who received TCIs or phototherapy.

Methods: A multicenter retrospective cohort study of 25,694 vitiligo patients who received TCIs or phototherapy for 6 weeks or more between 2001 and 2019 was performed. Cumulative doses of TCIs and total phototherapy sessions were determined. Outcomes were the development of lymphoma or skin cancer after enrollment, confirmed through chart review and pathology reports.

Results: Over 95,203 person-years, 13 cases of lymphoma, 22 actinic keratosis, 15 nonmelanoma skin cancer, and 5 melanoma were observed. The risk of lymphoma and skin cancer was not significantly increased by TCI dose or phototherapy sessions. The interaction between the TCIs and phototherapy was not associated with an increased risk of skin cancer.

Limitations: Retrospective study, individual follow-up duration less than 4 years, no adjustment for comorbidities and medication history. Not generalizable to other races.

Conclusion: The long-term risk of skin cancer or lymphoma was not associated with the use of TCIs, phototherapy, and both treatments in combination in patients with vitiligo.
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http://dx.doi.org/10.1016/j.jaad.2021.01.067DOI Listing
January 2021

Clinical practice guideline for endoscopic resection of early gastrointestinal cancer.

Intest Res 2020 Oct 13. Epub 2020 Oct 13.

Department of Gastroenterology, Korea University Anam Hospital, Seoul, Korea.

Although surgery was the standard treatment for early gastrointestinal cancers, endoscopic resection is now a standard treatment for early gastrointestinal cancers without regional lymph node metastasis. High-definition white light endoscopy, chromoendoscopy, and image-enhanced endoscopy such as narrow band imaging are performed to assess the edge and depth of early gastrointestinal cancers for delineation of resection boundaries and prediction of the possibility of lymph node metastasis before the decision of endoscopic resection. Endoscopic mucosal resection and/or endoscopic submucosal dissection can be performed to remove early gastrointestinal cancers completely by en bloc fashion. Histopathological evaluation should be carefully made to investigate the presence of risk factors for lymph node metastasis such as depth of cancer invasion and lymphovascular invasion. Additional treatment such as radical surgery with regional lymphadenectomy should be considered if the endoscopically resected specimen shows risk factors for lymph node metastasis. This is the first Korean clinical practice guideline for endoscopic resection of early gastrointestinal cancer. This guideline was developed by using mainly de novo methods and encompasses endoscopic management of superficial esophageal squamous cell carcinoma, early gastric cancer, and early colorectal cancer. This guideline will be revised as new data on early gastrointestinal cancer are collected.
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http://dx.doi.org/10.5217/ir.2020.00020DOI Listing
October 2020

Dedicated Cold Snare vs. Traditional Snare for Polypectomy of Diminutive and Small Lesions in a Porcine Model: A Research Group for Endoscopic Instruments and Stents (REIS) Study.

Clin Endosc 2020 Sep 10. Epub 2020 Sep 10.

Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea.

Background/aims: The aim of this in vivo animal study was to evaluate the effectiveness and safety of dedicated cold snare (DCS) compared with those of traditional snare (TS) for cold snare polypectomy (CSP).

Methods: A total of 36 diminutive (5 mm) and 36 small (9 mm) pseudolesions were made by electrocoagulation in the colons of mini-pigs.

Results: For the diminutive lesions, there were no significant differences in technical success rate, procedure time, or complete resection rate between the DCS and TS groups; the rate of uneven resection margin in the DCS group was significantly lower than that of the TS group. For small lesions, technical success rate and complete resection rate were significantly higher in the DCS group than in the TS group (100% [18/18] vs. 55.6% [10/18], p=0.003; 94.4% [17/18] vs. 40% [4/10], p=0.006). In addition, the procedure duration was significantly shorter, and the rate of uneven resection margin was significantly lower in the DCS group (28.5 sec vs. 66.0 sec, p=0.006; 11.1% [2/18] vs. 100% [10/10], p<0.001). Two cases of perforation occurred in the DCS group. Multivariate analysis revealed that DCS use was independently associated with complete resection.

Conclusions: DCS is superior to TS in terms of technical success, complete resection, and reducing the duration of the procedure for CSP of small polyps.
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http://dx.doi.org/10.5946/ce.2020.096DOI Listing
September 2020

Clinical Outcomes of Endoscopic Resection for Low-Grade Dysplasia and High-Grade Dysplasia on Gastric Pretreatment Biopsy: Korea ESD Study Group.

Gut Liver 2020 Aug 10. Epub 2020 Aug 10.

Department of Internal Medicine, Hallym University College of Medicine, Chuncheon Sacred Heart Hospital, Chuncheon, Korea.

Background/aims: Some cases of gastric low-grade dysplasia (LGD) and high-grade dysplasia (HGD) on forceps biopsy (FB) are diagnosed as gastric cancer (GC) after endoscopic resection (ER). This study aims to evaluate the clinical outcomes of ER for gastric LGD and HGD on pretreatment FB and to identify the factors that predict pathologic upstaging to GC.

Methods: Patients who underwent ER for LGD and HGD on pretreatment FB from March 2005 to February 2018 in 14 hospitals in South Korea were enrolled, and the patients' medical records were reviewed retrospectively.

Results: This study included 2,150 cases of LGD and 1,534 cases of HGD diagnosed by pretreatment FB. In total, 589 of 2,150 LGDs (27.4%) were diagnosed as GC after ER. infection, smoking history, tumor location in the lower third of the stomach, tumor size >10 mm, depressed lesion, and ulceration significantly predicted GC. A total of 1,115 out of 1,534 HGDs (72.7%) were diagnosed with GC after ER. Previous history of GC, infection, smoking history, tumor location in the lower third of the stomach, tumor size >10 mm, depressed lesion, and ulceration were significantly associated with GC. As the number of risk factors predicting GC increased in both LGD and HGD on pretreatment FB, the rate of upstaging to GC after ER increased.

Conclusions: A substantial proportion of LGDs and HGDs on pretreatment FB were diagnosed as GC after ER. Accurate ER procedures such as endoscopic submucosal dissection should be recommended in cases of LGD and HGD with factors predicting pathologic upstaging to GC.
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http://dx.doi.org/10.5009/gnl19275DOI Listing
August 2020

Effects of Forest Therapy on Health Promotion among Middle-Aged Women: Focusing on Physiological Indicators.

Int J Environ Res Public Health 2020 06 17;17(12). Epub 2020 Jun 17.

National Center for Forest Therapy, Gimcheon, Gyeongbuk 39695, Korea.

Women experience more stress in middle age than in other life stages, and health in middle age is vital, because it influences the quality of life in old age. In this study, the effects of a forest therapy program on physiological changes in 53 middle-aged women (divided into two groups) who lived in the city were examined. One group participated in a three-day program in the forest, followed by three days in the city; the other group participated in a three-day program in the city, followed by three days in the forest. Forest experiments were conducted in a "healing forest," and urban experiments were conducted near a university campus. Blood tests were performed to evaluate the physiological effects of forest therapy. Differences in serotonin levels and vitamin D levels were verified before and after the forest (experimental group) and urban (control group) programs through paired -tests. Statistically significant increases in serotonin levels were noted for participants in the forest program; vitamin D levels also increased, but not by statistically significant values. The findings of this study verify that forest therapy programs promote health among middle-aged women, and may prevent disease and improve quality of life.
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http://dx.doi.org/10.3390/ijerph17124348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344639PMC
June 2020

[Clinical Practice Guideline for Endoscopic Resection of Early Gastrointestinal Cancer].

Korean J Gastroenterol 2020 05;75(5):264-291

Department of Gastroenterology, Korea University Anam Hospital, Seoul, Korea.

Although surgery was the standard treatment for early gastrointestinal cancers, endoscopic resection is now a standard treatment for early gastrointestinal cancers without regional lymph node metastasis. High-definition white light endoscopy, chromoendoscopy, and image-enhanced endoscopy such as narrow band imaging are performed to assess the edge and depth of early gastrointestinal cancers for delineation of resection boundaries and prediction of the possibility of lymph node metastasis before the decision of endoscopic resection. Endoscopic mucosal resection and/or endoscopic submucosal dissection can be performed to remove early gastrointestinal cancers completely by fashion. Histopathological evaluation should be carefully made to investigate the presence of risk factors for lymph node metastasis such as depth of cancer invasion and lymphovascular invasion. Additional treatment such as radical surgery with regional lymphadenectomy should be considered if the endoscopically resected specimen shows risk factors for lymph node metastasis. This is the first Korean clinical practice guideline for endoscopic resection of early gastrointestinal cancer. This guideline was developed by using mainly methods and encompasses endoscopic management of superficial esophageal squamous cell carcinoma, early gastric cancer, and early colorectal cancer. This guideline will be revised as new data on early gastrointestinal cancer are collected.
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http://dx.doi.org/10.4166/kjg.2020.75.5.264DOI Listing
May 2020

Adiponectin-Based Peptide (ADP355) Inhibits Transforming Growth Factor-β1-Induced Fibrosis in Keloids.

Int J Mol Sci 2020 Apr 18;21(8). Epub 2020 Apr 18.

Department of Dermatology, Seoul National University College of Medicine, Seoul 03080, Korea.

Keloids, benign cutaneous overgrowths of dermal fibroblasts, are caused by pathologic scarring of wounds during healing. Current surgical and therapeutic modalities are unsatisfactory. Although adiponectin has shown an antifibrotic effect, its large size and insolubility limit its potential use in keloid treatment. We investigated the effect of a smaller and more stable adiponectin-based peptide (ADP355) on transforming growth factor β1 (TGF-β1)-induced fibrosis in a primary culture of keloid fibroblasts prepared from clinically obtained keloid samples. Xenograft of keloid tissues on athymic nude mice was used to investigate the effect of intralesional injection of ADP355. ADP355 significantly attenuated the TGF-β1-induced expression of procollagen type 1 in keloid fibroblasts ( < 0.05). Moreover, it inhibited the TGF-β1-induced phosphorylation of SMAD3 and ERK, while amplifying the phosphorylation of AMP-activated protein kinase ( < 0.05). Knockdown of adiponectin receptor 1 reversed the attenuation of procollagen expression in ADP355-treated TGF-β1-induced fibrosis (). ADP355 also significantly reduced the gross weight and procollagen expression of keloid tissues in xenograft mice compared to control animals. These results demonstrate the therapeutic potential of the adiponectin peptide ADP355 for keloids.
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http://dx.doi.org/10.3390/ijms21082833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215791PMC
April 2020

Incidence of Keratoconus and Its Association with Systemic Comorbid Conditions: A Nationwide Cohort Study from South Korea.

J Ophthalmol 2020 25;2020:3493614. Epub 2020 Mar 25.

Department of Ophthalmology, Soonchunhyang University Hospital Bucheon, Bucheon, Republic of Korea.

Purpose: To determine the incidence of keratoconus and to determine its possible association with common systemic diseases using a nationwide cohort.

Methods: This retrospective nationwide cohort study included 1,025,340 subjects from the Korean National Health Insurance Service-National Sample Cohort database from 2004 to 2013. Estimates for incidence rates of keratoconus were identified. After 1 : 5 matching using propensity scores, associations between keratoconus and certain systemic comorbidities were determined using multivariate logistic regression analysis.

Results: The incidence during the same period was 15.1 cases per 100,000 person-years. Adjusted logistic regression analysis after propensity score matching revealed significant associations between keratoconus and allergic rhinitis (odds ratio (OR): 1.86; 95% confidence interval (CI): 1.63-2.13; < 0.001), asthma (OR: 1.20; 95% CI: 1.06-1.36; < 0.001), atopic dermatitis (OR: 1.33; 95% CI: 1.13-1.56; < 0.001), and diabetes mellitus (DM) (OR: 1.35; 95% CI: 1.15-1.58; < 0.001).

Conclusion: Estimates of the incidence of keratoconus may help in the planning of eye-care policies, and the results of this study determined the associations between allergic diseases and keratoconus. Conflicting results regarding the association between keratoconus and DM should be further evaluated.
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http://dx.doi.org/10.1155/2020/3493614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7152955PMC
March 2020

Increased risk of Alzheimer's disease in patients with psoriasis: a nationwide population-based cohort study.

Sci Rep 2020 04 15;10(1):6454. Epub 2020 Apr 15.

Department of Dermatology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, #222 Banpo-daero, Seocho-gu, 06591, Seoul, Korea.

Although the pathogenesis of Alzheimer's disease (AD) is unclear, neuroinflammation appears to play a role in its development. Psoriasis is a chronic inflammatory skin disease that has recently been found to genetically overlap with AD. We aimed to investigate the risk of AD in patients with psoriasis. Subjects with psoriasis (n = 535,927) and age- and sex-matched controls without psoriasis (at a 5:1 ratio; n = 2,679,635) who underwent ≥3 health examinations between 2008 and 2014 were included, drawn from the Korean National Health Insurance System database. There were 50,209 cases of AD (1.87%) in controls without psoriasis and 11,311 cases (2.11%) in patients with psoriasis, and the median follow-up was 3.35 years. In a multivariable-adjusted model, patients with psoriasis showed a significantly increased risk of AD (hazard ratio, 1.09; 95% CI, 1.07-1.12, p < 0.0001) compared to controls without psoriasis. Among patients with psoriasis, the risk of AD was significantly increased in psoriasis patients not receiving systemic therapy compared to those receiving systemic therapy (hazard ratio, 1.10; 95% CI, 1.08-1.12 vs. hazard ratio, 0.99; 95% CI: 0.90-1.09, p < 0.0001). The incidence of AD was significantly increased in patients with psoriasis compared to control subjects without psoriasis. Of note, systemic treatment for psoriasis was associated with a reduced risk of AD.
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http://dx.doi.org/10.1038/s41598-020-63550-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160134PMC
April 2020

Clinical Practice Guideline for Endoscopic Resection of Early Gastrointestinal Cancer.

Clin Endosc 2020 Mar 30;53(2):142-166. Epub 2020 Mar 30.

Department of Gastroenterology, Korea University Anam Hospital, Seoul, Korea.

Although surgery was the standard treatment for early gastrointestinal cancers, endoscopic resection is now a standard treatment for early gastrointestinal cancers without regional lymph node metastasis. High-definition white light endoscopy, chromoendoscopy, and image-enhanced endoscopy such as narrow band imaging are performed to assess the edge and depth of early gastrointestinal cancers for delineation of resection boundaries and prediction of the possibility of lymph node metastasis before the decision of endoscopic resection. Endoscopic mucosal resection and/or endoscopic submucosal dissection can be performed to remove early gastrointestinal cancers completely by en bloc fashion. Histopathological evaluation should be carefully made to investigate the presence of risk factors for lymph node metastasis such as depth of cancer invasion and lymphovascular invasion. Additional treatment such as radical surgery with regional lymphadenectomy should be considered if the endoscopically resected specimen shows risk factors for lymph node metastasis. This is the first Korean clinical practice guideline for endoscopic resection of early gastrointestinal cancer. This guideline was developed by using mainly de novo methods and encompasses endoscopic management of superficial esophageal squamous cell carcinoma, early gastric cancer, and early colorectal cancer. This guideline will be revised as new data on early gastrointestinal cancer are collected.
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http://dx.doi.org/10.5946/ce.2020.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7137564PMC
March 2020

Autophagy induction can regulate skin pigmentation by causing melanosome degradation in keratinocytes and melanocytes.

Pigment Cell Melanoma Res 2020 05 11;33(3):403-415. Epub 2019 Nov 11.

Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

Autophagy regulates cellular turnover by disassembling unnecessary or dysfunctional constituents. Recent studies demonstrated that autophagy and its regulators play a wide variety of roles in melanocyte biology. Activation of autophagy is known to induce melanogenesis and regulate melanosome biogenesis in melanocytes. Also, autophagy induction was reported to regulate physiologic skin color via melanosome degradation, although the downstream effectors are not yet clarified. To determine the role of autophagy as a melanosome degradation machinery, we administered several autophagy inducers in human keratinocytes and melanocytes. Our results showed that the synthetic autophagy inducer PTPD-12 stimulated autophagic flux in human melanocytes and in keratinocytes containing transferred melanosomes. Increased autophagic flux led to melanosome degradation without affecting the expression of MITF. Furthermore, the color of cell pellets of both melanocytes and keratinocytes was visibly lightened. Inhibition of autophagic flux by chloroquine resulted in marked attenuation of PTPD-12-induced melanosome degradation, whereas the expression of melanogenesis pathway genes and proteins remained unaffected. Taken together, our results suggest that the modulation of autophagy can contribute to the regulation of melanocyte biology and skin pigmentation.
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http://dx.doi.org/10.1111/pcmr.12838DOI Listing
May 2020

Risk Factors and Clinical Outcomes of Non-Curative Resection in Patients with Early Gastric Cancer Treated with Endoscopic Submucosal Dissection: A Retrospective Multicenter Study in Korea.

Clin Endosc 2020 Mar 25;53(2):196-205. Epub 2019 Oct 25.

Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Korea.

Background/aims: The purpose of this study was to investigate the risk factors and long-term clinical outcomes of non-curative resection (NCR) in a large-scale patient population.

Methods: We retrospectively analyzed the clinical data of 3,094 patients who underwent endoscopic submucosal dissection (ESD) of early gastric cancer from March 2005 to March 2018 at 13 institutions in Korea. We analyzed the risk factors for NCR and the survival between patients with curative resection and those with NCR with no additional treatment.

Results: The NCR rate was 21.4% (661/3,094). In multivariate regression analysis, the risk factors affecting NCR with ESD were old age, undifferentiated tumor, tumor location in the upper body, tumor size ≥2 cm, and presence of an ulcer. In Cox proportional hazard regression analysis, tumor size ≥2 cm, submucosal invasion, positive horizontal margin, and lymphovascular invasion were risk factors for local recurrence. In Kaplan-Meier analysis, there was no statistically significant difference in the overall survival between the two groups (log-rank p=0.788). However, disease-specific survival was significantly lower in the NCR group (log-rank p=0.038).

Conclusion: Clinicians should be aware of the risk factors for NCR and local recurrence after ESD for early gastric cancer, and should consider providing additional treatment after NCR.
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http://dx.doi.org/10.5946/ce.2019.123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7137576PMC
March 2020

Endoscopic features aiding the diagnosis of gastric mucosa-associated lymphoid tissue lymphoma.

Yeungnam Univ J Med 2019 05 26;36(2):85-91. Epub 2019 Feb 26.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea.

The incidence of gastric mucosa-associated lymphoid tissue (MALT) lymphoma is increasing worldwide, but the diagnosis is difficult. Most patients are asymptomatic or complain of nonspecific gastrointestinal symptoms. As the endoscopic features of gastric MALT lymphoma are variable and nonspecific, the possibility of this condition may be overlooked during esophagogastroduodenoscopy, and it remain undiagnosed. Therefore, this condition needs to be considered when an abnormal mucosa is observed during this procedure. Biopsy performed during endoscopy is the primary diagnostic test, but false negative results are possible; large numbers of samples should be collected from both normal and abnormal mucosae. Endoscopic ultrasonography is useful to assess the depth of invasion and to predict the treatment response. After treatment, follow-up tests are required every 3 months until complete remission is achieved, and annually thereafter. Early diagnosis of gastric MALT lymphoma is difficult, and its diagnosis and follow-up require wide experience and competent endoscopic technique.
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http://dx.doi.org/10.12701/yujm.2019.00136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784630PMC
May 2019

Transduction Pattern of AAVs in the Trabecular Meshwork and Anterior-Segment Structures in a Rat Model of Ocular Hypertension.

Mol Ther Methods Clin Dev 2019 Sep 10;14:197-205. Epub 2019 Jul 10.

Department of Ophthalmology, College of Medicine, Soonchunhyang University, Cheonan 31151, Republic of Korea.

Adeno-associated viruses (AAVs) are the vector of choice for gene therapy in the eye, and self-complementary AAVs (scAAVs), which do not require second-strand DNA synthesis, can be transduced into cells of the trabecular meshwork (TM). The scAAV transduction patterns in the anterior segment of normotensive eyes have been investigated previously, but those in ocular hypertensive (OHT) eyes have not. We assessed the transduction efficiencies of AAV serotypes 2, 5, and 8 in the anterior-segment structures of the eyes of Sprague-Dawley rats with OHT by circumlimbal suturing, followed 3 days later by intracameral injection of scAAV serotype 2 (scAAV2), scAAV5, or scAAV8 packaged with EGFP. The transduction of scAAV2 and scAAV5 in the TM of OHT rats was markedly enhanced after 1 month, and transduction of scAAV5 was more efficient than that of scAAV2; transduction of scAAV8 into the TM did not occur. The transduction of scAAV2, scAAV5, and scAAV8 was enhanced in the ciliary body, iris, and corneal endothelium of the OHT eyes for 3 months. The expression levels of receptors for scAAV2 and scAAV5 were significantly increased in the OHT compared with control eyes. The results demonstrated that scAAV2 and scAAV5 target the ciliary body and TM in OHT eyes, and that the OHT-related changes in anterior-segment structures enhance scAAV transduction.
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http://dx.doi.org/10.1016/j.omtm.2019.06.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685643PMC
September 2019

Nationwide antibiotic resistance mapping of Helicobacter pylori in Korea: A prospective multicenter study.

Helicobacter 2019 Aug 20;24(4):e12592. Epub 2019 May 20.

Department of Internal Medicine, Ansan Hospital, Korea University College of Medicine, Ansan, Korea.

Introduction: The eradication rates for Helicobacter pylori have decreased in Korea although the prevalence of this bacterium has also decreased. Antibiotic resistance is likely to be a crucial factor in H. pylori eradication success, and we therefore mapped these resistance patterns nationwide in Korea.

Materials And Methods: Five hundred and ninety adult subjects were prospectively enrolled from 2017 to 2018 from 15 centers across six geographic areas of Korea. A total of 580 biopsy tissues had been sampled from these patients during an upper endoscopy and were frozen at -80°C and delivered to a central laboratory. The agar dilution method was used to determine the minimum inhibitory concentration of amoxicillin, clarithromycin, metronidazole, tetracycline, ciprofloxacin, and levofloxacin for each H. pylori isolate.

Results: The culture success rate was 60.2% (349/580). Resistance rates against clarithromycin, metronidazole, amoxicillin, tetracycline, levofloxacin, and ciprofloxacin were 17.8%, 29.5%, 9.5%, 0%, 37.0%, and 37.0%, respectively. The geographic distribution of metronidazole and quinolone resistance was highly variable. Some subjects had multiple H. pylori strains in the antrum and body of the stomach and showed a heterogeneous resistance profile between these anatomic areas. The H. pylori multidrug resistance (MDR) rate was 25.2% (88/349) among amoxicillin, clarithromycin, metronidazole, tetracycline, and quinolone and 11.2% (39/349) among four of these major antibiotics except for quinolone. The Seoul and Chungcheong areas showed a relatively lower MDR rate.

Conclusion: The antibiotic resistance of H. pylori differs by drug and geographic area in Korea. Detailed nationwide antibiotic resistance mapping is needed to develop an effective H. pylori eradication strategy.
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http://dx.doi.org/10.1111/hel.12592DOI Listing
August 2019

Critical Role of ATP-P2X7 Axis in UV-Induced Melanogenesis.

J Invest Dermatol 2019 07 26;139(7):1554-1563.e6. Epub 2019 Mar 26.

Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. Electronic address:

Purinergic signaling participates in skin physiology and pathology, such as hair growth, wound healing, inflammation, pain, and skin cancer. However, few studies have investigated the involvement of purinergic signaling in skin pigmentation. This study demonstrated that extracellular adenosine 5'-triphosphate (ATP) released from keratinocytes by UVB radiation promotes melanin production in primary human epidermal melanocytes and ex vivo skin cultures. Intracellular calcium ion and protein kinase C/CREB signaling contributed to ATP-mediated melanogenesis. Also, P2X7 receptor was proven to play a pivotal role in ATP-mediated melanogenesis because P2X7 receptor blockade abrogated ATP-induced melanin production. In addition, MNT1 cells with P2X7 receptor knockout using CRISPR/Cas9 system did not show any increase in MITF expression when co-cultured with UV-irradiated keratinocytes compared to MNT1 cells with intact P2X7 receptor, which showed increased expression of MITF. In conclusion, our results indicate that the extracellular ATP-P2X7 signaling axis is an adjunctive mechanism in UV-induced melanogenesis. Furthermore, ATP-induced purinergic signaling in melanocytes may alter skin pigmentation.
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http://dx.doi.org/10.1016/j.jid.2019.02.031DOI Listing
July 2019

Vergleich (split-lesion) von langer und kurzer Pulsdauer bei der Narbentherapie mit dem gepulsten Farbstofflaser.

J Dtsch Dermatol Ges 2019 03;17(3):324-326

Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.

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http://dx.doi.org/10.1111/ddg.13767_gDOI Listing
March 2019

A Somatic p.Phe29del Mutation of Connexin 26 (GJB2) Manifesting as Acantholytic Dyskeratotic Epidermal Nevus.

JAMA Dermatol 2019 05;155(5):633-635

Cutaneous Biology Research Institute, Department of Dermatology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.

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http://dx.doi.org/10.1001/jamadermatol.2018.5852DOI Listing
May 2019

Split-lesion comparison of long and short pulses for pulsed dye laser treatment of scars.

J Dtsch Dermatol Ges 2019 03 13;17(3):324-326. Epub 2019 Feb 13.

Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.

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http://dx.doi.org/10.1111/ddg.13767DOI Listing
March 2019

Association between Three Heavy Metals and Dry Eye Disease in Korean Adults: Results of the Korean National Health and Nutrition Examination Survey.

Korean J Ophthalmol 2019 Feb;33(1):26-35

Department of Ophthalmology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea.

Purpose: To investigate the associations between blood heavy metal concentrations and dry eye disease using a Korean population-based survey.

Methods: This study included 23,376 participants >40 years of age who participated in the Korean National Health and Nutrition Examination Survey from 2010 to 2012. Blood concentrations of lead, cadmium, and mercury were measured in all participants. The associations between blood heavy metal concentrations and dry eye disease were assessed using multivariate logistic regression analyses.

Results: After adjusting for potential confounders, including age, sex, lifestyle behaviors and sociodemographic factors, the analyses revealed an increased odds ratio (OR) for dry eye disease with higher blood mercury concentrations (tertile 2: OR, 1.22; 95% confidence interval [CI], 0.91 to 1.64; tertile 3: OR, 1.39; 95% CI, 1.02 to 1.89; = 0.039). The prevalence of dry eye disease was not associated with blood lead (tertile 2: OR, 1.15; 95% CI, 0.87 to 1.51; tertile 3: OR, 0.83; 95% CI, 0.59 to 1.16; = 0.283) or cadmium (tertile 2: OR, 1.05; 95% CI, 0.77 to 1.44; tertile 3: OR, 1.15; 95% CI, 0.84 to 1.58; = 0.389) concentrations. There were no significant associations between any of the three heavy metals and dry eye disease in males after adjusting for potential confounding factors, but blood mercury concentrations in females were associated with dry eye disease (tertile 2: OR, 1.18; 95% CI, 0.83 to 1.69; tertile 3: OR, 1.58; 95% CI, 1.12 to 2.24; = 0.009).

Conclusions: Mercury concentrations in blood were associated with dry eye disease. Our results suggested that controlling environmental exposure to mercury may be necessary to reduce the incidence of dry eye disease.
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http://dx.doi.org/10.3341/kjo.2018.0065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372379PMC
February 2019

Is Radical Surgery Necessary for All Patients Diagnosed as Having Non-Curative Endoscopic Submucosal Dissection?

Clin Endosc 2019 Jan 30;52(1):21-29. Epub 2019 Jan 30.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea.

If a lesion does not meet the expanded indication criteria for treatment with endoscopic therapy for early gastric cancer or does not have a positive resection margin, it is regarded as suitable for non-curative resection. Non-curative resection is closely related to the risk of local recurrence, lymph node metastasis, and poor prognosis. If the result is confirmed as non-curative resection, additional treatment should be considered depending on the risks of residual tumor, local recurrence, and lymph node metastasis. As lymphatic invasion is the most important risk factor of recurrence and poor prognosis, surgical treatment should be considered if lymphatic invasion is present. If patients are not suitable for additional surgery owing to old age or coexisting severe disease, close surveillance can be an alternative treatment option.
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http://dx.doi.org/10.5946/ce.2019.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6370927PMC
January 2019

[Clinical Efficacy of Radiotherapy in Negative or Unresponsive to Eradication Therapy Primary Gastric Mucosa-Associated Lymphoid Tissue Lymphoma].

Korean J Gastroenterol 2019 Jan;73(1):19-25

Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea.

Background/aims: The eradication of () is an effective treatment in gastric mucosa-associated lymphoid tissue (MALT) lymphoma associated with infection. However, the treatment strategy in gastric MALT lymphoma patients who are -negative or unresponsive to eradication therapy remains controversial. In this study, we investigated the clinical efficacy of treatments other than eradication therapy in these groups of patients.

Methods: This was a retrospective single-center study based on the medical records of patients diagnosed with gastric MALT lymphoma at Yeungnam University Medical Center between January 2005 and December 2016. Patients were treated with eradication therapy, chemotherapy, or radiotherapy according to their infection status and stage of gastric MALT lymphoma.

Results: Of the 68 eligible patients, 50 were enrolled in the study. Of the 42 patients with -positive gastric MALT lymphoma, 36 (81.7%) were treated with eradication therapy as primary treatment and 25 (69.4%) achieved a complete response (CR). Patients without a CR after eradication therapy (n=11, 30.6%) received radiotherapy as a secondary treatment. Two patients with -positive gastric MALT lymphoma and eight with -negative gastric MALT lymphoma received radiotherapy as the primary treatment. CR was achieved in all 21 patients treated with radiotherapy as primary or secondary treatment. The 5-year progression-free survival rate after radiotherapy was 92.9%.

Conclusions: Radiotherapy may be a worthwhile treatment option in patients with -negative MALT lymphoma or -positive MALT lymphoma that is not responsive to eradication therapy.
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http://dx.doi.org/10.4166/kjg.2019.73.1.19DOI Listing
January 2019

Adeno-Associated Viral Vector 2 and 9 Transduction Is Enhanced in Streptozotocin-Induced Diabetic Mouse Retina.

Mol Ther Methods Clin Dev 2019 Jun 1;13:55-66. Epub 2018 Dec 1.

Department of Ophthalmology, College of Medicine, Soonchunhyang University, Cheonan 31151, Republic of Korea.

Adeno-associated viruses (AAVs) are currently the most popular vector platform technology for ocular gene therapy. While transduction efficiency and tropism of intravitreally administered AAV has been fairly well established in various retinal conditions, its transduction pattern in diabetic retinas has not previously been characterized. Here, we describe the transduction efficiencies of four different AAV serotypes, AAV2, 5, 8, and 9, in streptozotocin (STZ)-induced diabetic mouse retinas after intravitreal injections, which differed according to the duration of diabetic induction. STZ was intraperitoneally injected into C57/B6 diabetic mice subjected to unilateral intravitreal injection of AAV2, AAV5, AAV8, and AAV9 packaged with EGFP. Significantly enhanced AAV2 and AAV9 transduction was observed in 2-month-old diabetic mouse retinas compared to the 2-week-old diabetic mouse retinas and nondiabetic, vector uninjected or injected retinas. Intravitreal injection of AAV5 or AAV8 serotype in 2-month- and 2-week-old diabetic mouse retinas did not show any significant vector transduction enhancement compared to the nondiabetic control retinas. The tropism of AAV2 and AAV9 in diabetic mouse retinas differed. AAV2 was transduced into various retinal cells, including Müller cells, microglia, retinal ganglion cells (RGCs), bipolar cells, horizontal cells, and amacrine cells, whereas AAV9 was effectively transduced only into RGC and horizontal cells. The expression levels of receptors and co-receptors for AAV2 and AAV9 were significantly increased in 2-month-old diabetic mouse retinas. The results of our study demonstrated that AAV2 and AAV9 may be the vector of choice in treating diabetic retinopathy (DR) with gene therapy, and DR-related retinal changes may improve AAV vector transduction efficiency.
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http://dx.doi.org/10.1016/j.omtm.2018.11.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6330514PMC
June 2019

Risk for neurodegenerative disorders in Korean patients with vitiligo: A nationwide retrospective cohort study.

J Am Acad Dermatol 2019 08 14;81(2):621-623. Epub 2019 Jan 14.

Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2019.01.007DOI Listing
August 2019

Corrigendum.

J Neurogastroenterol Motil 2019 Jan;25(1):175

Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea.

The original version of this article contains one mistake. The term "protein pump inhibitors (PPIs)" in the Introduction of page 219 should have been written as "proton pump inhibitors (PPIs)."
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http://dx.doi.org/10.5056/jnm25013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326210PMC
January 2019

Esophageal Basaloid Squamous Carcinoma Treated by Endoscopic Resection and Radiation.

Korean J Gastroenterol 2018 Nov;72(5):258-261

Department of Pathology, Yeungnam University College of Medicine, Daegu, Korea.

Esophageal basaloid squamous carcinoma (BSC) is a rare, aggressive variant of squamous cell carcinoma. BSC is usually diagnosed in advanced stage and its prognosis is relatively poor. A 59-year-old male with subepithelial lesion of the esophagus that was incidentally discovered during health promotion examination was referred to our hospital. Esophagogastroduodenoscopy showed a 10-mm bulging mucosa with an intact surface at 34 cm from incisor teeth. Endoscopic ultrasonography revealed a smooth margined homogenous hypoechoic lesion, measuring 11.3×3.9 mm with a submucosal layer of origin. The patient underwent endoscopic mucosal resection of the subepithelial lesion. Pathologic examination of the resected specimen revealed BSC with involvement of vertical margin by tumor. The patient then underwent radiotherapy, and is doing well without recurrence for 35 months. We report a case of esophageal BSC confined to submucosal layer successfully treated with endoscopic resection followed by radiation.
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http://dx.doi.org/10.4166/kjg.2018.72.5.258DOI Listing
November 2018

Efficacy of 0.5-L 1-L polyethylene glycol containing ascorbic acid as additional colon cleansing methods for inadequate bowel preparation as expected by last stool examination before colonoscopy.

World J Clin Cases 2019 Jan;7(1):39-48

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu 42415, South Korea.

Background: No consensus has been reached in patients suspected of having inadequate bowel preparation regarding optimal salvage methods, which negatively affects the efficacy and quality of colonoscopy. The most ideal and reasonable rescue option involves early suspicion and identification of patients with inadequate preparation before sedation, additional oral ingestion of a suitable preparation formulation, and same-day colonoscopy.

Aim: To compare 0.5-L and 1-L polyethylene glycol containing ascorbic acid (PEG + Asc) as additional bowel cleansing methods after a 2-L split-dose PEG + Asc regimen in patients with expected inadequate bowel preparation before colonoscopy.

Methods: Individuals with expected inadequate bowel preparation based on last stool form, such as turbid liquid, particulate liquid, or liquid with small amounts of feces, were randomized to either a 0.5-L PEG + Asc group or a 1-L PEG + Asc group. The primary endpoint was bowel preparation as assessed using the Aronchick bowel preparation scale (ABPS) and Boston bowel preparation scale (BBPS) scores. The secondary endpoints were cecal intubation time, withdrawal time, polyp detection rate (PDR), adenoma detection rate (ADR), individual compliance with additional PEG + Asc, and patient satisfaction.

Results: Initially, 98 patients were included, but 8 were later excluded due to withdrawal of consent to participate in the study. Adequate bowel preparation (as assessed by ABPS) was observed in 80.9% (38/47) of subjects in the 0.5-L group and in 88.4% (38/43) of subjects in the 1-L group ( = 0.617). Mean total BBPS was 6.7 points in the 0.5-L group and 7.0 points in the 1-L group ( = 0.458). ADRs and PDRs were similar in the two groups, and cecal intubation and withdrawal times were not significantly different. However, mean patient satisfaction score was significantly higher in the 0.5-L group ( = 0.041).

Conclusion: The bowel cleaning efficacy of additional 0.5-L PEG + Asc was not inferior to that of 1-L PEG + Asc. Additional 0.5-L PEG + Asc is worthwhile when inadequate bowel preparation is expected before colonoscopy.
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http://dx.doi.org/10.12998/wjcc.v7.i1.39DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327135PMC
January 2019

A Homozygous Nonsense Mutation in the DSG3 Gene Causes Acantholytic Blisters in the Oral and Laryngeal Mucosa.

J Invest Dermatol 2019 05 5;139(5):1187-1190. Epub 2018 Dec 5.

Department of Dermatology and Cutaneous Biology Research Institute, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. Electronic address:

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http://dx.doi.org/10.1016/j.jid.2018.09.038DOI Listing
May 2019

Squamous cell carcinoma of the nail unit: a retrospective review of 19 cases in Asia and comparative review of Western literature.

Int J Dermatol 2019 Apr 27;58(4):428-432. Epub 2018 Nov 27.

Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea.

Background: Reports regarding squamous cell carcinoma of the nail unit (SCCnu) are rare in Asia.

Objectives: To investigate the features of SCCnu in the Asian population.

Method: We performed a retrospective review of patients diagnosed with SCCnu at our institution between 2012 and 2017.

Results: Nineteen cases were included. Thirteen patients were male (68.4%). The fingers were most frequently affected (73.7%). Mean delay to diagnosis was 62.4 months. Misdiagnosis rate was high (78.9%). Frequent clinical features were subungual tumor, subungual hyperkeratosis, nail dystrophy, ulcer, and nail loss. The majority of cases were invasive SCC in 15 cases (78.9%), while SCC in situ was found in four cases (21.1%). Local recurrence was detected in two cases (10.5%) following surgical resection. However, distant metastasis was not reported.

Conclusion: This study provides data of 19 SCCnu cases in Asia. Clinical characteristics of SCCnu in this study were similar to those of reports from Western countries. However, we found a higher frequency of more invasive cases and longer delay to diagnosis in our study; this advocates the need for greater attention on nail disorders among healthcare providers, particularly in Asia.
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http://dx.doi.org/10.1111/ijd.14306DOI Listing
April 2019

On-demand versus half-dose continuous therapy with esomeprazole for maintenance treatment of gastroesophageal reflux disease: A randomized comparative study.

Medicine (Baltimore) 2018 Oct;97(43):e12732

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Republic of Korea.

Background And Aims: No consensus has been established regarding optimal long-term maintenance therapy in symptomatic gastroesophageal reflux disease (GERD). The aim of this study was to compare the efficacies of on-demand and continuous therapy with esomeprazole as maintenance treatments for GERD.

Methods: Patients with upper gastrointestinal (GI) endoscopy-proven GERD who received initial proton pump inhibitor (PPI) therapy for 8 weeks were randomized to an on-demand group (esomeprazole 40 mg) or a continuous group (esomeprazole 20 mg). Intensities and frequencies of heartburn and acid regurgitation were assessed using a 6-point Likert scale (0 = no symptoms; 5 = very severe symptoms) and a 6-point frequency scale (0 = none; 5 = symptoms for > 5 days per week) at baseline (start of maintenance treatment) and after 12 weeks of treatment. Alleviation of symptoms was quantified using percentages of patients with a Likert scale or frequency scale of 0 or 1.

Results: Of the 88 patients enrolled, 8 patients were excluded due to follow-up loss in early period of this study, and finally, 39 in the on-demand group and 41 in the continuous group were analyzed. No significant intergroup difference was found between Likert scale or frequency scale of heartburn or regurgitation at baseline. Percentages of symptom alleviations in the on-demand and continuous groups for intensity of heartburn were 56.4%/48.8% at baseline (P = .523) and 82.1%/87.8% at 12 weeks (P = .471), for frequency of heartburn were 61.5%/46.3% at baseline (P = .173) and 76.9%/87.8% at 12 weeks (P = .200), for intensity of regurgitation was 53.8%/43.9% at baseline (P = .374) and 82.1%/87.8% at 12 weeks (P = .471), and for frequency of regurgitation was 61.5%/56.1% at the baseline (P = .621) and 82.1%/82.9% at 12 weeks (P = .918), respectively. Furthermore, no significant intergroup difference was found for convenience of medication or subjective satisfaction.

Conclusions: Intensities and frequencies of heartburn and regurgitation responded well to maintenance treatment in patients in the on-demand and continuous groups. On-demand therapy with esomeprazole 40 mg appears to be sufficient for maintenance treatment in GERD patients.
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http://dx.doi.org/10.1097/MD.0000000000012732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6221682PMC
October 2018