Publications by authors named "Sang Wook Kang"

240 Publications

Feasibility and safety of the posterior retroperitoneoscopic approach in the resection of aortocaval and infrarenal paraganglioma: a single-center experience.

Surg Endosc 2021 Aug 2. Epub 2021 Aug 2.

Department of Surgery, Yonsei Cancer Center, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.

Background: The posterior retroperitoneoscopic approach (PRA) has been under attention as a method for resection of paraganglioma (PGL) for the past few years. However, only a few studies have explored the effectiveness and safety of the PRA for aortocaval and infrarenal PGL resection.

Methods: We designed this retrospective study to investigate the safety and effectiveness of the PRA for aortocaval and infrarenal PGL resection in a single center. We retrospectively reviewed the medical records of patients who underwent PRA for PGL resection at our medical center from January 2006 to March 2021. Eight patients were enrolled, of whom six had aortocaval PGL. We investigated the surgical outcomes of enrolled patients.

Results: The locations of the tumors in relation to the renal vein were: suprarenal in two (25.0%) patients, at the renal vein level in three (37.5%) patients, and infrarenal in three (37.5%) patients. The mean operative time of the enrolled patients was 101.5 ± 39.1 min. The mean postoperative stay was 3.5 ± 1.5 days, and the estimated blood loss was 31.3 ± 51.4 ml. There was one minor complication (chyle leakage), and two hypotensive events occurred during the surgery. Focusing on the results of the renal vein level and infrarenal PGL resection, the mean operative time, mean postoperative stay, and estimated blood loss of the patients were 109.2 ± 41.3 min, 3.5 ± 1.8 days, and 41.7 ± 56.4 ml, respectively.

Conclusion: The PRA for aortocaval and infrarenal PGL resection is feasible and safe. Additional data analysis and long-term follow-up are needed in the future.
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http://dx.doi.org/10.1007/s00464-021-08662-0DOI Listing
August 2021

Unexpected remission of hyperparathyroidism caused by hemorrhage due to the use of fine-needle aspiration biopsy: two cases report.

Gland Surg 2021 Jun;10(6):2047-2053

Department of Surgery, Severance Hospital, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.

Hyperparathyroidism is not a rare disease; if a parathyroid adenoma is confirmed, the treatment of choice is the surgical resection. Diagnostic use of fine-needle aspiration biopsy (FNAB) for histological confirmation in patients with hyperparathyroidism is controversial. And spontaneous remission of hyperparathyroidism caused by bleeding or infarction of the adenoma rarely occurs. Here we have reported two cases of hyperparathyroidism in which spontaneous remission occurred due to the use of FNAB for diagnosis. The remission was confirmed after surgical removal and pathological review of the adenoma. The first patient diagnosed with primary hyperparathyroidism (PHPT) had neck pain and severe swelling 4 days after FNAB, and spontaneous remission due to intracapsular hemorrhage was confirmed after surgery. In the second patient receiving hemodialysis treatment for end-stage renal disease, hyperparathyroidism spontaneously resolved after FNAB and the parathyroid hormone (PTH) levels normalized after surgery. The first patient maintained a normal level of PTH for 6 years, and the second patient received kidney transplantation 6 years after surgery, and the normal level of PTH was confirmed for 13 years. Caution is needed while performing FNAB for diagnosis of hyperparathyroidism and during decision making regarding whether to observe the patient or perform surgery after spontaneous remission due to bleeding or infarction.
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http://dx.doi.org/10.21037/gs-21-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258889PMC
June 2021

Comparison of Surgical Outcomes between Robotic Transaxillary and Conventional Open Thyroidectomy in Pediatric Thyroid Cancer.

Cancers (Basel) 2021 Jun 30;13(13). Epub 2021 Jun 30.

Department of Surgery, Yonsei University College of Medicine, Severance Hospital, Seoul 03722, Korea.

Thyroid cancer in children is very uncommon. For pediatric thyroid cancer, robotic surgery has served as a minimally invasive surgical alternative to conventional open surgery. Our study aimed to evaluate the results of robotic versus open surgical treatment for patients with thyroid cancer younger than 20 years of age at the time of diagnosis. This retrospective review included 161 pediatric patients who underwent robotic transaxillary or conventional open thyroidectomy at our institution from 2008 to 2019. Of these patients, 99 comprised the robotic group and 62 the open group. Patient demographics, surgical outcomes, and disease-free survival rates were compared between the two groups. Patients in the open group were more likely to have advanced stage diseases with a larger tumor size and higher tumor-node-metastasis stage than those in the robotic group. Operation time and follow-up period were similar in both groups. Patients in the robotic group had a lower rate of postoperative complications and a shorter length of hospital stay, but they also had a lower average number of retrieved central lymph nodes. However, there were no significant between group differences in recurrence rates and disease-free survival. In the hands of an experienced surgeon, robotic thyroidectomy is a feasible and safe option for pediatric patients.
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http://dx.doi.org/10.3390/cancers13133293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269192PMC
June 2021

Robotic transaxillary lateral neck dissection for thyroid cancer: learning experience from 500 cases.

Surg Endosc 2021 May 27. Epub 2021 May 27.

Department of Surgery, Severance Hospital, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, South Korea.

Background: Differentiated thyroid carcinoma with lateral neck lymph node metastasis requires aggressive operative intervention, including lateral neck dissection. Although several robotic approaches have made precise surgery for thyroid cancer possible, few centers have expanded the technique for application to lateral neck dissections. This study aimed to demonstrate the technical feasibility, cosmetic effectiveness, and safety of robotic transaxillary lateral neck dissection (RTLND) using the da Vinci system.

Methods: From January 2008 to July 2019, 500 patients diagnosed with thyroid cancer with lateral neck node metastasis underwent RTLND. The clinicopathologic characteristics and surgical outcomes were retrospectively reviewed.

Results: All operations were performed successfully without open conversion. As the primary operation for thyroid cancer, 476 (95.2%) patients underwent unilateral or bilateral RTLND, including robotic total thyroidectomy. The remaining 24 patients (4.8%), all of whom had a recurrence, also underwent RTLND with additional procedures, if needed. The mean operation time for the 500 operations was 293.71 ± 67.22 min. Only five cases had recurrence and required further treatment.

Conclusions: RTLND is technically feasible and safe through the precise manipulation of robotic instruments. While this method is thorough and provides safe and effective surgical outcomes, it also offers the additional advantage of being minimally invasive.
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http://dx.doi.org/10.1007/s00464-021-08526-7DOI Listing
May 2021

Cellulose acetate containing CaO coated on polypropylene for enhanced thermal stability of separator.

Chem Commun (Camb) 2021 May;57(36):4388-4391

Department of Chemistry, Sangmyung University, Seoul 03016, Republic of Korea. and Department of Chemistry and Energy Engineering, Sangmyung University, Seoul 03016, Republic of Korea.

In this study, cellulose acetate (CA) and calcium oxide was used to manufacture an CA-CaO separator with high thermal stability and was then coated on polypropylene (PP). The high melting point of CaO and the complexation of CaO and carbonyl groups in CA increased the thermal stability of CA. Because PP is known to have a higher mechanical stability than CA, the CA-CaO separator was coated twice on the PP support, increasing the stability of the entire separator. Adhesion was imparted between the CA film and the PP film without a separate adhesive due to the swelling effect of the solvent and the water pressure treatment, and pores were even formed by the pressure. Water flux data showed that cellulose acetate containing CaO coated on polypropylene (CA-CaO on PP) obtained a relatively high flux value of 71.67 L m-2 h-1 (LMH) at a pressure of 8 bar. Through thermogravimetric analysis and Fourier transform infrared data, it was confirmed that the surfaces of two polymers were bonded and the stability was improved.
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http://dx.doi.org/10.1039/d1cc00926eDOI Listing
May 2021

Diagnosis for Pheochromocytoma and Paraganglioma: A Joint Position Statement of the Korean Pheochromocytoma and Paraganglioma Task Force.

Endocrinol Metab (Seoul) 2021 Apr 6;36(2):322-338. Epub 2021 Apr 6.

Department of Internal Medicine, Severance Hospital, Endocrine Research Institute, Yonsei University College of Medicine, Seoul, Korea.

Pheochromocytoma and paraganglioma (PPGLs) are rare catecholamine-secreting neuroendocrine tumors but can be life-threatening. Although most PPGLs are benign, approximately 10% have metastatic potential. Approximately 40% cases are reported as harboring germline mutations. Therefore, timely and accurate diagnosis of PPGLs is crucial. For more than 130 years, clinical, molecular, biochemical, radiological, and pathological investigations have been rapidly advanced in the field of PPGLs. However, performing diagnostic studies to localize lesions and detect metastatic potential can be still challenging and complicated. Furthermore, great progress on genetics has shifted the paradigm of genetic testing of PPGLs. The Korean PPGL task force team consisting of the Korean Endocrine Society, the Korean Surgical Society, the Korean Society of Nuclear Medicine, the Korean Society of Pathologists, and the Korean Society of Laboratory Medicine has developed this position statement focusing on the comprehensive and updated diagnosis for PPGLs.
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http://dx.doi.org/10.3803/EnM.2020.908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8090459PMC
April 2021

Lactate Dehydrogenase A as a Potential New Biomarker for Thyroid Cancer.

Endocrinol Metab (Seoul) 2021 Feb 24;36(1):96-105. Epub 2021 Feb 24.

Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Korea.

Background: Several cancers show increased levels of lactate dehydrogenase A (LDHA), which are associated with cancer progression. However, it remains unclear whether LDHA levels are associated with papillary thyroid cancer (PTC) aggressiveness or with the presence of the PTC prognostic marker, the BRAFV600E mutation. This study aimed to evaluate the potential of LDHA as a PTC prognostic marker.

Methods: LDHA expression was examined in 83 PTC tissue specimens by immunohistochemistry. Human thyroid cell lines were genetically manipulated to overexpress BRAFV600E or were treated with a BRAF-specific short hairpin RNA (shBRAF), whose effects on LDHA expression were evaluated by Western blotting. Data from 465 PTC patients were obtained from The Cancer Genome Atlas (TCGA) database and analyzed to validate the in vitro results.

Results: LDHA was aberrantly overexpressed in PTC. Intense immunostaining for LDHA was observed in PTC specimens carrying mutated BRAF, whereas the intensity was less in wild-type BRAF samples. Overexpression of BRAFV600E resulted in LDHA upregulation, whereas treatment with shBRAF downregulated LDHA in human thyroid cell lines. Furthermore, LDHA mRNA expression was significantly elevated and associated with BRAFV600E expression in thyroid cancer tissues from TCGA database. Additionally, LDHA overexpression was found to be correlated with aggressive clinical features of PTC, such as lymph node metastases and advanced tumor stages.

Conclusion: LDHA overexpression is associated with the BRAFV600E mutation and an aggressive PTC behavior. Therefore, LDHA may serve as a biomarker and therapeutic target in PTC.
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http://dx.doi.org/10.3803/EnM.2020.819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937852PMC
February 2021

Clinical Utility of Preoperative Vitamin D3 Injection for Preventing Transient Hypocalcemia after Total Thyroidectomy.

Int J Endocrinol 2021 13;2021:6683089. Epub 2021 Feb 13.

Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea.

Background: Postoperative transient hypocalcemia (TH) is a common complication of total thyroidectomy. This retrospective study evaluated the clinical utility of preoperative vitamin D3 injection for the prevention of TH after total thyroidectomy.

Methods: We included 2294 patients who underwent total thyroidectomy from January 2015 until October 2018 and retrospectively analyzed their data by complete chart review at our hospital. The patients were divided into two groups: vitamin D3 injection (VDI;  = 342) and vitamin D3 noninjection (VDN;  = 1952). TH was defined as serum calcium <8.2 mg/dL and signs or symptoms of hypocalcemia.

Results: The mean preoperative serum 25-hydroxyvitamin D (25-OHD) levels of the VDI group were significantly lower than those of the VDN group (16.5 ± 6.9 ng/mL vs 19.4 ± 8.7 ng/mL,  < 0.001). Multivariate analysis indicated that the significant risk factors of TH include vitamin D noninjection (hazard ratio (HR): 1.717, 95% confidence interval (CI): 1.282-2.300,  < 0.001), male gender (HR: 1.427, 95% CI: 1.117-1.822,  = 0.004), and capsular extension (HR: 1.273, 95% CI: 1.011-1.603,  = 0.040).

Conclusions: Preoperative vitamin D3 injection significantly contributed to the prevention of TH after total thyroidectomy. Further prospective or multicenter studies must be conducted to determine the effect of vitamin D3 injection.
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http://dx.doi.org/10.1155/2021/6683089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896842PMC
February 2021

Implications of US radiomics signature for predicting malignancy in thyroid nodules with indeterminate cytology.

Eur Radiol 2021 Jul 18;31(7):5059-5067. Epub 2021 Jan 18.

Department of Radiology, Research Institute of Radiological Science, and Center for Clinical Imaging Data Science, Yonsei University College of Medicine, Seoul, South Korea.

Objectives: The purpose of this study was to evaluate the role of the radiomics score using US images to predict malignancy in AUS/FLUS and FN/SFN nodules.

Methods: One hundred fifty-five indeterminate thyroid nodules in 154 patients who received initial US-guided FNA for diagnostic purposes were included in this retrospective study. A representative US image of each tumor was acquired, and square ROIs covering the whole nodule were drawn using the Paint program of Windows 7. Texture features were extracted by in-house texture analysis algorithms implemented in MATLAB 2019b. The LASSO logistic regression model was used to choose the most useful predictive features, and ten-fold cross-validation was performed. Two prediction models were constructed using multivariable logistic regression analysis: one based on clinical variables, and the other based on clinical variables with the radiomics score. Predictability of the two models was assessed with the AUC of the ROC curves.

Results: Clinical characteristics did not significantly differ between malignant and benign nodules, except for mean nodule size. Among 730 candidate texture features generated from a single US image, 15 features were selected. Radiomics signatures were constructed with a radiomics score, using selected features. In multivariable logistic regression analysis, higher radiomics score was associated with malignancy (OR = 10.923; p < 0.001). The AUC of the malignancy prediction model composed of clinical variables with the radiomics score was significantly higher than the model composed of clinical variables alone (0.839 vs 0.583).

Conclusions: Quantitative US radiomics features can help predict malignancy in thyroid nodules with indeterminate cytology.
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http://dx.doi.org/10.1007/s00330-020-07670-3DOI Listing
July 2021

Genetic Analysis and Clinical Characteristics of Hereditary Pheochromocytoma and Paraganglioma Syndrome in Korean Population.

Endocrinol Metab (Seoul) 2020 12 23;35(4):858-872. Epub 2020 Dec 23.

Department of Internal Medicine, Severance Hospital, Endocrine Research Institute, Yonsei University College of Medicine, Seoul, Korea.

Background: Pheochromocytoma and paragangliomas (PPGL) are hereditary in approximately 30% to 40% cases. With the advancement of genetic analysis techniques, including next-generation sequencing (NGS), there were attempts to classify PPGL into molecular clusters. With NGS being applied to clinical settings recently, we aimed to review the results of genetic analysis, including NGS, and investigate the association with clinical characteristics in Korean PPGL patients.

Methods: We reviewed the medical records of PPGL patients who visited Severance hospital from 2006 to 2019. We documented the clinical phenotype of those who underwent targeted NGS or had known germline mutations of related genes.

Results: Among 57 PPGL patients, we found 28 pathogenic germline mutations of susceptibility genes. Before the targeted NGS was implemented, only obvious syndromic feature lead to the Sanger sequencing for the specific genes. Therefore, for the exact prevalence, only patients after the year 2017, when targeted NGS was added, were included (n=43). The positive germline mutations were found in 14 patients; thus, the incidence rate is 32.6%. Patients with germline mutations had a higher likelihood of family history. There were significant differences in the type of PPGLs, percentage of family history, metastasis rate, presence of other tumors, and biochemical profile among three molecular clusters: pseudohypoxic tricarboxylic acid cycle-related, pseudohypoxic von Hippel-Lindau (VHL)/endothelial PAS domain-containing protein 1-related, and kinase-signaling group. Germline mutations were identified in seven PPGL-related genes (SDHB, RET, VHL, NF1, MAX, SDHA, and SDHD).

Conclusion: We report the expected prevalence of germline mutations in Korean PPGL patients. NGS is a useful and accessible tool for genetic analysis in patients with PPGLs, and further research on molecular classification is needed for precise management.
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http://dx.doi.org/10.3803/EnM.2020.683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803615PMC
December 2020

Effects of PIN on Osteoblast Differentiation and Matrix Mineralization through Runt-Related Transcription Factor.

Int J Mol Sci 2020 Dec 16;21(24). Epub 2020 Dec 16.

Department of Oral and Maxillofacial Pathology, School of Dentistry, Kyung Hee University, Seoul 02447, Korea.

Sieb. et Zucc. has been used as traditional medicine in inflammatory diseases, and isolated compounds have shown pharmacological activities. Pinoresinol glucoside (PIN) belonging to lignins was isolated from the stem bark of This study aimed to investigate the biological function and mechanisms of PIN on cell migration, osteoblast differentiation, and matrix mineralization. Herein, we investigated the effects of PIN in MC3T3-E1 pre-osteoblasts, which are widely used for studying osteoblast behavior in in vitro cell systems. At concentrations ranging from 0.1 to 100 μM, PIN had no cell toxicity in pre-osteoblasts. Pre-osteoblasts induced osteoblast differentiation, and the treatment of PIN (10 and 30 μM) promoted the cell migration rate in a dose-dependent manner. At concentrations of 10 and 30 μM, PIN elevated early osteoblast differentiation in a dose-dependent manner, as indicated by increases in alkaline phosphatase (ALP) staining and activity. Subsequently, PIN also increased the formation of mineralized nodules in a dose-dependent manner, as indicated by alizarin red S (ARS) staining, demonstrating positive effects of PIN on late osteoblast differentiation. In addition, PIN induced the mRNA level of BMP2, ALP, and osteocalcin (OCN). PIN also upregulated the protein level of BMP2 and increased canonical BMP2 signaling molecules, the phosphorylation of Smad1/5/8, and the protein level of Runt-related transcription factor 2 (RUNX2). Furthermore, PIN activated non-canonical BMP2 signaling molecules, activated MAP kinases, and increased β-catenin signaling. The findings of this study indicate that PIN has biological roles in osteoblast differentiation and matrix mineralization, and suggest that PIN might have anabolic effects in bone diseases such as osteoporosis and periodontitis.
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http://dx.doi.org/10.3390/ijms21249579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765567PMC
December 2020

Long-term outcomes of abdominal paraganglioma.

Ann Surg Treat Res 2020 Dec 26;99(6):315-319. Epub 2020 Nov 26.

Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.

Purpose: Paragangliomas (PGL) are rare neuroendocrine tumors derived from chromaffin cells of the autonomic nervous system. We aim to describe our experience and the long-term outcome of abdominal PGL over the last decade.

Methods: A retrospective review of patients diagnosed with PGL in our hospital between November 2005 and June 2017 was conducted. All nonabdominal PGL were excluded and the clinicopathological features and long-term outcomes of the patients were analyzed.

Results: A total of 46 patients were diagnosed with abdominal PGL. The average age of diagnosis was 55.4 years and there was no sex predilection. The average tumor size was 5.85 cm and they were predominantly located in the infrarenal position (50%). The mean follow-up period was 42 months (range, 1.8-252 months). All patients with metastases had Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) of ≥4. One patient presented with synchronous metastases while 2 developed local recurrence and distant metastases. One presented with only local recurrence. One patient died 5 years after diagnosis.

Conclusion: Abdominal PGL is a rare tumor with excellent long-term prognosis. Recurrence although uncommon, can occur decades after initial diagnosis. Long-term follow-up is therefore recommended for all patients with PGL, especially in patients with PASS of ≥4.
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http://dx.doi.org/10.4174/astr.2020.99.6.315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704273PMC
December 2020

Medicolegal lessons learned from thyroidectomy-related lawsuits: an analysis of judicial precedents in South Korea from 1998 to 2019.

Gland Surg 2020 Oct;9(5):1286-1297

Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.

Background: Thyroid cancer is one of the most common cancers in South Korea, and thyroidectomy is still frequently performed. As new diagnostic methods have led to a significant increase in the early detection of thyroid cancer worldwide, medical disputes related to thyroid surgery are also likely to increase. The purpose of this study was to investigate the causes of medical disputes related to thyroidectomy and to identify ways to prevent unnecessary disputes and malpractice.

Methods: We analyzed 35 judicial decisions involving thyroidectomy in South Korea from January 1998 to July 2019.

Results: The most common cause of lawsuits was "performance error during surgery" (n=19), especially "recurrent laryngeal nerve (RLN) injury" (n=7), of which five cases were ruled medical malpractice. For lawsuits involving misdiagnosis (n=14), five regarding fine needle aspiration cytology (FNAC) and frozen section examination were ruled malpractice. The most common malpractice related to informed consent was "lack of explanation about surgery complications" (n=10).

Conclusions: Surgeons should follow guidelines to protect themselves from diagnostic error dispute; performing FNAC more often might also prevent lawsuits. When the courts judge the surgeon's negligence in cases of RLN injuries, whether bilateral or unilateral, it is necessary to consider fully the surgeon's efforts to prevent RLN injuries. Providing information and building trust through sufficient patient-doctor communication is crucial.
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http://dx.doi.org/10.21037/gs-20-398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667072PMC
October 2020

Surgical outcomes of minimally invasive thyroidectomy in thyroid cancer: comparison with conventional open thyroidectomy.

Gland Surg 2020 Oct;9(5):1172-1181

Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.

Background: Minimally invasive thyroidectomy (MIT) is a safe method of performing thyroidectomy with notable benefits, such as improved cosmesis and reduced postoperative pain. The objective of this retrospective study was to report our experience with the technical feasibility of MIT, and compare its early surgical outcomes with those of conventional open thyroidectomy (COT) in patients with differentiated thyroid carcinoma (DTC).

Methods: A total of 617 patients who underwent MIT and 2,674 patients who underwent COT were reviewed between March 2006 and November 2017 at Yonsei University (Seoul, Korea). The mean follow-up duration was 41.2±19.7 months.

Results: The mean age of patients with DTC was 46.1±11.2 years. The mean operation time in the MIT group was significantly shorter than that of the COT group (63.5±26.2 85.3±36.8 minutes, P<0.001). The mean hospital stay was significantly shorter in the MIT group than it was in the COT group as well (2.7±0.6 3.1±0.8 days, P<0.001). There were significantly fewer painkillers used after surgery in the MIT group than in the COT group (1.2±0.5 2.7±1.6, P<0.001). The mean number of harvested LNs in the MIT group was significantly lower than that of the COT group (3.1±2.6 5.5±4.0, P<0.001).

Conclusions: This study demonstrated that MIT is technically feasible in patients with DTC. MIT is a valuable alternative operative technique to COT with good surgical outcomes and outstanding cosmetic results.
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http://dx.doi.org/10.21037/gs-20-512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667120PMC
October 2020

Preparation of a Cellulose Column for Enhancing the Sensing Efficiency of the Biocide 2-n-Octyl-4-Isothiazolin-3-One.

Polymers (Basel) 2020 Nov 16;12(11). Epub 2020 Nov 16.

Department of Chemistry, Sangmyung University, Seoul 03016, Korea.

In this study, a cellulose acetate (CA) membrane with pores generated by a water pressure treatment was investigated for its ability to serve as a pretreatment filter device for the detection of 2-n-octyl-4-isothiazolin-3-one (OIT). Pores were generated by applying a water pressure of 8 bar to a membrane manufactured using a CA-based polymer solution. The CA used for the manufacturing was an environment-friendly, low-cost and highly energy-efficient material. Furthermore, since the fabricated porous CA polymeric film possessed many hydrophilic functional groups, it could strongly bind hydrophilic substances while avoiding interaction with hydrophobic substances. OIT, which comprises a hydrophobic bond that forms weak bonds over time, can break down more easily than hydrophilic impurities. The different extents of interaction occurring between either the toxic fungicide OIT or the hydrophilic impurities and the CA film were determined by Fourier-transform infrared (FT-IR) spectroscopy. The physicochemical changes in the resulting membrane, which occurred when the pores were generated, were investigated through scanning electron microscopy (SEM) and thermogravimetric analysis (TGA).
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http://dx.doi.org/10.3390/polym12112712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696371PMC
November 2020

Differential Gene Expression Changes in Human Primary Dental Pulp Cells Treated with Biodentine and TheraCal LC Compared to MTA.

Biomedicines 2020 Oct 22;8(11). Epub 2020 Oct 22.

Department of Oral Pathology, School of Dentistry, Chonnam National University, Gwangju 61186, Korea.

This study aimed to analyze the effects of pulp capping materials on gene expression changes in primary tooth-derived dental pulp cells using next-generation sequencing. Dental pulp cells were extracted and treated with mineral trioxide aggregate (MTA), Biodentine (BD), or TheraCal LC (TC). Cell viability assays were performed. Total RNA was extracted and analyzed through mRNA sequencing. Bioinformatic analysis of differential gene expression in dental pulp cells exposed to BD or TC versus MTA was performed. MTA, BD, and TC exposure had no significant effect on pulp cell viability ( > 0.05). Gene sets associated with inflammatory response ( = 2.94 × 10) and tumor necrosis factor alpha (TNF-α) signaling via the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway ( = 2.94 × 10) were enriched in all materials. In BD-treated cells, Wnt/β-catenin signaling ( = 3.15 × 10) gene sets were enriched, whereas enrichment of interferon gamma (IFN-γ) response ( = 3 × 10) was observed in TC-treated cells. In gene plot analysis, marked increases in receptor activator of nuclear factor kappa-Β ligand () expression were seen in TC-treated cells over time. Despite the similar cell viabilities exhibited among MTA-, BD-, and TC-treated cells, patterns of gene networks differed, suggesting that diverse functional gene differences may be associated with treatment using these materials.
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http://dx.doi.org/10.3390/biomedicines8110445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690278PMC
October 2020

Completion Total Thyroidectomy Is Not Necessary for Papillary Thyroid Microcarcinoma with Occult Central Lymph Node Metastasis: A Long-Term Serial Follow-Up.

Cancers (Basel) 2020 Oct 18;12(10). Epub 2020 Oct 18.

Department of Surgery, Severance Hospital, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul 03722, Korea.

The necessity of completion total thyroidectomy in patients with papillary thyroid microcarcinoma (PTMC) and pathological central lymph node metastasis (pCLNM) who underwent thyroid lobectomy with central compartment neck dissection (CCND) is unclear. We determined the necessity of completion total thyroidectomy by retrospectively comparing the prognosis according to the presence of pCLNM during a long-term follow-up. We enrolled 876 patients with PTMC who underwent thyroid lobectomy with prophylactic CCND from January 1986 to December 2009. Patients were divided according to central lymph node (CLN) metastasis: 165 (18.8%) and 711 (81.2%) in the CLN-positive and CLN-negative groups, respectively. Medical records were reviewed retrospectively, and clinicopathologic characteristics and recurrence rates were analyzed. The CLN-positive group was associated with male sex ( = 0.001), larger tumor size ( < 0.001), and more microscopic capsular invasion ( < 0.001) compared with the CLN-negative group. There was no significant difference between the two groups' recurrence ( = 0.133) or disease-free ( = 0.065) survival rates. Univariate and multivariate analyses showed no factors associated with tumor recurrence except male sex (hazard ratio = 3.043, confidence interval 1.117-8.288, = 0.030). Patients who were diagnosed with pCLNM after undergoing thyroid lobectomy with prophylactic CCND do not require completion total thyroidectomy; however, frequent follow-up is necessary for patients with PTMC and pCLNM.
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http://dx.doi.org/10.3390/cancers12103032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603084PMC
October 2020

Enhanced Olefin Transport by SiO Particles for Polymer/Ag Metal/Electron Acceptor Composite Membranes.

Authors:
Sang Wook Kang

Polymers (Basel) 2020 Oct 10;12(10). Epub 2020 Oct 10.

Department of Chemistry, Sangmyung University, Seoul 03016, Korea.

We showed the potential of poly(ethylene--propylene) (EPR)/silver metal/-benzoquinone composite membranes for propylene/propane mixtures, i.e., a selectivity of 10 and a mixed gas permeance of 0.5 GPU (1 GPU = 1 × 10 cm (STP)/(cm s cmHg) in a previous study. In this study, we additionally found that the incorporation of fumed silica nanoparticles into EPR/silver metal/-benzoquinone (-BQ) composite membranes exhibited much higher permeance and selectivity for propylene/propane mixtures. The positive polarity of silver metal continuously increased with the increasing silica content up to the 0.1 weight ratio, as revealed by x-ray photoelectron spectroscopy (XPS). This increase in the polarity of silver metal was attributed to the enhanced interaction of -BQ with the surface of Ag nanoparticles by the increased dispersion of -BQ by fumed silica nanoparticles. Differential scanning calorimetry (DSC) also presented that the glass transition temperature (T) of the membranes was almost invariant. Therefore, the improvement of the permeance and selectivity with the silica nanoparticles was attributable to the increased polarity of the silver metal rather than the structural change.
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http://dx.doi.org/10.3390/polym12102316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600099PMC
October 2020

Effects of the amide alkaloid piperyline on apoptosis, autophagy, and differentiation of pre-osteoblasts.

Phytomedicine 2020 Dec 17;79:153347. Epub 2020 Sep 17.

Department of Oral and Maxillofacial Pathology, School of Dentistry, Kyung HeeUniversity,26, Kyungheedae-ro, Dongdaemun-gu,Seoul02453, South Korea. Electronic address:

Background: Amide alkaloidsare typical constituents in plants of the Piperaceae family. Most of the pharmacological properties of Piper nigrum L. are attributed to the major amide alkaloid, piperine. Piperyline (PIPE) is a further amide alkaloid that has been isolated from P. nigrum.

Hypothesis/purpose: This study was performed to examine the biological effects of PIPE on pre-osteoblasts and elucidate the underlying mechanisms.

Study Design: We investigated the effects of PIPE in MC3T3E-1 cells, which are widely used for studying osteoblast behavior in in vitro cell systems.

Methods: We evaluated cell viability based on the MTT assay, apoptosis by TUNEL staining, adhesion and migration by cell adhesion and migration assays, and osteoblast differentiation by alkaline phosphatase activity and staining. Western blot and immunocytochemical analyses were used to investigate cell signaling pathways.

Results: We found that at concentrations ranging from 1 to 30 μM, PIPE inhibited cell growth and induced apoptosis in pre-osteoblasts, which was accompanied by the upregulation of apoptotic proteins but downregulation of anti-apoptotic proteins. In contrast, PIPE had no appreciable effect on the autophagy pathway. Nevertheless, PIPE reduced cell adhesion and migration via the inactivation of non-receptor tyrosine kinase (Src)/focal adhesion kinase (FAK) and mitogen-activated protein kinases, and also promoted the downregulation of matrix metalloproteinase 2 and 9 levels. Furthermore, at concentrations of 10 and 30 μM, PIPE suppressed osteoblast differentiation, as indicated by reductions in alkaline phosphatase staining and activity. In addition, PIPE reduced the protein levels of phospho-Smad1/5/8 and runt-related transcription factor 2, and the mRNA levels of osteopontin, alkaline phosphatase, and osteocalcin.

Conclusion: The findings of this study indicate that PIPE has biological effects associated with cell adhesion, migration, proliferation, and osteoblast differentiation, and suggest a potential role for this alkaloid in the treatment of bone diseases.
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http://dx.doi.org/10.1016/j.phymed.2020.153347DOI Listing
December 2020

Correction to: Clinical Assessment of Pediatric Patients with Differentiated Thyroid Carcinoma: A 30-Year Experience at a Single Institution.

World J Surg 2020 Dec;44(12):4276

Department of Surgery, Yonsei University College of Medicine, Seoul, 03722, Korea.

The article "Clinical Assessment of Pediatric Patients with Differentiated Thyroid Carcinoma: A 30-Year Experience at a Single Institution", written by Kim et al., was originally published electronically on the publisher's internet portal (currently SpringerLink) on May 21, 2020, with open access. With the authors' decision to step back from Open Choice, the copyright of the article changed on September 14, 2020 to © Société Internationale de Chirurgie 2020 and the article is forthwith distributed under the terms of copyright. The original article has been corrected.
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http://dx.doi.org/10.1007/s00268-020-05783-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853027PMC
December 2020

Long-Term Stable 1-butyl-3-methylimidazolium Hexafluorophosphate/Ag Metal Composite Membranes for Facilitated Olefin Transport.

Authors:
Sang Wook Kang

Membranes (Basel) 2020 Aug 18;10(8). Epub 2020 Aug 18.

Department of Chemistry, Sangmyung University, Seoul 03016, Korea.

For the preparation of long-term stable ionic liquid/Ag nanoparticles composites, we compared the separation performance of 1-butyl-3-methylimidazolium tetrafluoroborate (BMIMBF)/Ag, and 1-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF)/Ag composite membranes with time. Separation performance showed that the BMIMPF/Ag metal composite membrane was more stable than the BMIMBF/Ag metal composite membrane for more than 160 h. These differences in long-term stability in BMIMPF/Ag and BMIMBF/Ag metal composite membranes was attributable to the phase separation between ionic liquid and nanoparticles. In particular, the phase separation between ionic liquid and silver nanoparticles was not observed with time in hydrophobic ionic liquid BMIMPF, confirmed by X-ray photoelectron spectroscopy.
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http://dx.doi.org/10.3390/membranes10080191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463454PMC
August 2020

TMARg, a Novel Anthraquinone Isolated from Nakai, Increases Osteogenesis and Mineralization through BMP2 and β-Catenin Signaling.

Int J Mol Sci 2020 Jul 27;21(15). Epub 2020 Jul 27.

Department of Oral and Maxillofacial Pathology, School of Dentistry, Kyung Hee University, Seoul 02447, Korea.

Background: Plant extracts have long been regarded as useful medicines in the treatment of human diseases. Nakai has been used as a traditional medicine, as it has pharmacological properties such as antioxidant and anti-inflammatory activity. However, the biological functions of TMARg, isolated from the roots of in osteoblast differentiation remain unknown. This study was performed to investigate the pharmacological effects and intracellular signaling of TMARg in the osteoblast differentiation of pre-osteoblast MC3T3-E1 cells and mesenchymal precursor C2C12 cells.

Methods: Cell viability was evaluated using an MTT assay. Early and late osteoblast differentiation was examined by analyzing the activity of alkaline phosphatase (ALP), and by staining it with Alizarin red S (ARS). Cell migration was determined by using migration assays. Western blot analysis and immunocytochemical analysis were used to examine the intracellular signaling pathways and differentiation proteins.

Results: In the present study, TMARg showed no cytotoxicity and increased the osteoblast differentiation in pre-osteoblasts, as assessed from the alkaline phosphate (ALP) staining and activity and ARS staining. TMARg also induced BMP2 expression and increased the p-smad1/5/8-RUNX2 and β-catenin pathways in both MC3T3-E1 and C2C12 cells. Furthermore, TMARg activated mitogen-activated protein kinases (MAPKs) and increased the cell migration rate. In addition, the TMARg-mediated osteoblast differentiation was suppressed by BMP and Wnt inhibitors with the downregulation of BMP2 expression.

Conclusion: These findings demonstrate that TMARg exerts pharmacological and biological effects on osteoblast differentiation through the activation of BMP2 and β-catenin signaling pathways, and suggest that TMARg might be a potential phytomedicine for the treatment of bone diseases.
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http://dx.doi.org/10.3390/ijms21155332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432489PMC
July 2020

Preparation and Characterization of PEBAX-5513/AgBF/BMIMBF Membranes for Olefin/Paraffin Separation.

Polymers (Basel) 2020 Jul 13;12(7). Epub 2020 Jul 13.

Department of Chemistry, Sangmyung University, Seoul 03016, Korea.

In this study, we investigated a poly(ether-block-amide)-5513 (PEBAX-5513)/AgBF/1-butyl-3-methylimidazolium tetrafluoroborate (BMIMBF) composite membrane, which is expected to have a high stabilizing effect on the Ag ions functioning as olefin carriers in the amide group. Poly(ethylene oxide) (PEO) only consists of ether regions, whereas the PEBAX-5513 copolymer contains both ether and amide regions. However, given the brittle nature of the amide, the penetration of BMIMBF remains challenging. The nanoparticles did not stabilize after their formation in the long-term test, thereby resulting in a poor performance compared to previous experiments using PEO as the polymer (selectivity 3; permeance 12.3 GPU). The properties of the functional groups in the polymers were assessed using Fourier transform infrared spectroscopy, scanning electron microscopy, and thermogravimetric analysis, which confirmed that the properties endowed during the production of the film using the ionic liquid can impact the performance.
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http://dx.doi.org/10.3390/polym12071550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408108PMC
July 2020

Benefit of diverse surgical approach on short-term outcomes of MEN1-related hyperparathyroidism.

Sci Rep 2020 06 30;10(1):10634. Epub 2020 Jun 30.

Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, 03722, Seoul, Republic of Korea.

Surgical excision is the preferred treatment for multiple endocrine neoplasia type 1 (MEN1)-related primary hyperparathyroidism (PHPT), although controversy regarding the surgical strategy exists. We retrospectively investigated the short-term outcomes of PHPT by various surgical extents. Thirty-three patients who underwent parathyroidectomy due to MEN1-related PHPT at Yonsei Severance Hospital between 2005 and 2018 were included (age [mean ± SD], 43.4 ± 14.1 [range, 23-81] years). Total parathyroidectomy with auto-transplantation to the forearm (TPX) was the most common surgical method (17/33), followed by less-than-subtotal parathyroidectomy (LPX; 12/33) and subtotal parathyroidectomy (SPX; 4/33). There was no postoperative persistent hyperparathyroidism. Recurrence was high in the LPX group without significance (1 in TPX, 2 in SPX, and 3 in LPX, p = 0.076). Permanent and transient hypoparathyroidism were more common in TPX (n = 6/17, 35.3%, p = 0.031; n = 4/17, 23.5%, p = 0.154, respectively). Parathyroid venous sampling (PVS) was introduced in 2013 for preoperative localisation of hyperparathyroidism at our hospital; nine among 19 patients operated on after 2013 underwent pre-parathyroidectomy PVS, with various surgical extents, and no permanent hypoparathyroidism (p = 0.033) or post-LPX recurrence was observed. Although TPX with auto-transplantation is the standard surgery for MEN1-related PHPT, surgical extent individualisation is necessary, given the postoperative hypoparathyroidism rate of TPX and feasibility of PVS.
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http://dx.doi.org/10.1038/s41598-020-67424-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326992PMC
June 2020

CO Separation with Polymer/Aniline Composite Membranes.

Polymers (Basel) 2020 Jun 17;12(6). Epub 2020 Jun 17.

Department of Chemistry, Sangmyung University, Seoul 03016, Korea.

Polymer composite membranes containing aniline were prepared for CO/N separation. Aniline was selected for high separation performance as an additive containing both the benzene ring to interfere with gas transport and an amino group that could induce the accelerated transport of CO molecules. As a result, when aniline having both a benzene ring and an amino group was incorporated into polymer membranes, the selectivity was largely enhanced by the role of both gas barriers and CO carriers. Selective layers coated on the polysulfone were identified by scanning electron microscopy (SEM) images and the interaction with aniline in the polymer matrix was confirmed by FT-IR spectroscopy. The binding energy of oxygen in the polymer matrix was investigated by XPS, and the thermal stability of the composite membrane was confirmed by TGA.
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http://dx.doi.org/10.3390/polym12061363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362012PMC
June 2020

Comparison of long-term prognosis for differentiated thyroid cancer according to the 7th and 8th editions of the AJCC/UICC TNM staging system.

Ther Adv Endocrinol Metab 2020 19;11:2042018820921019. Epub 2020 May 19.

Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.

Background: The 8th edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) tumor-node-metastasis (TNM) staging system was released with major revisions. The purpose of this retrospective study was to investigate differences between the 7th and 8th editions of the AJCC/UICC TNM staging system and to compare the predictability of prognosis between the two staging systems with patients who underwent thyroidectomy for differentiated thyroid cancer (DTC) at a single institution.

Methods: A total of 3238 patients underwent thyroid operation from January 2002 to December 2006 at Yonsei University Hospital (Seoul, Korea), of which 2294 with complete clinical data and sustained follow up were enrolled. Clinicopathologic features and TNM staging by applying the 7th and 8th editions of the AJCC/UICC were analyzed retrospectively by the complete review of medical charts and pathology reports of patients. Mean follow-up duration was 132.9 ± 27.9 months.

Results: A significant number of T3 patients were downstaged to T1 (838, 36.5%) and T2 (122, 5.3%). After applying the 8th edition of the AJCC/UICC TNM staging system, the number of stage I patients increased significantly from 1434 (62.5%) to 2058 (89.7%), whereas numbers of stage III and IV patients decreased significantly from 644 (28.1%) to 33 (1.4%) and from 199 (8.7%) to 17 (0.7%), respectively. According to Kaplan-Meier survival analyses and values of the Harrell's c-index and integrated area under the curve (iAUC), the 8th edition has significantly better predictive performance for disease-free survival (DFS) and disease-specific survival (DSS) than the 7th edition.

Conclusions: A significant population was downstaged after applying the 8th edition of the AJCC/UICC TNM staging system, and the 8th edition provided significantly better accuracy in predicting DFS and DSS in patients with DTC.
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http://dx.doi.org/10.1177/2042018820921019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238312PMC
May 2020

Clinical Assessment of Pediatric Patients with Differentiated Thyroid Carcinoma: A 30-Year Experience at a Single Institution.

World J Surg 2020 10;44(10):3383-3392

Department of Surgery, Yonsei University College of Medicine, Seoul, 03722, Korea.

Background: Thyroidectomy is the typical treatment for pediatric thyroid carcinoma; total thyroidectomy is commonly performed. We aimed to report our experience at a single tertiary institution and to evaluate the risk factors for recurrence, especially based on surgical extent, in pediatric patients with differentiated thyroid carcinoma (DTC).

Methods: A data of 94 pediatric patients who underwent thyroid surgery for DTC from January 1982 to December 2012 at Yonsei University Hospital (Seoul, Korea) were reviewed. The clinicopathologic features and surgical outcomes were retrospectively analyzed through complete chart reviews.

Results: The mean age was 16.6 ± 3.0 (range, 5-19) years. Fourteen patients had recurrence. Tumor size >2 cm (hazard ratio [HR], 14.241; p = 0.011) and positive lymph nodes (HR, 1.056; p = 0.039) were significant risk factors for disease-free survival (DFS) in multivariate analysis. In Kaplan-Meier analysis, a statistically significant difference was noted in the DFS according to tumor size 2 cm (p < 0.001). However, the DFS was not significantly different between the bilateral total thyroidectomy (BTT) and less than BTT groups (p = 0.215).

Conclusions: BTT remains the treatment of choice in pediatric patients with DTC. Lobectomy may be considered for patients with limited disease, including those with tumor size <2 cm, no suspicious lymph nodes, intrathyroidal lesion, and no multifocal disease.
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http://dx.doi.org/10.1007/s00268-020-05598-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458901PMC
October 2020

Effect of Ionic Radius in Metal Nitrate on Pore Generation of Cellulose Acetate in Polymer Nanocomposite.

Polymers (Basel) 2020 Apr 23;12(4). Epub 2020 Apr 23.

Department of Chemistry, Sangmyung University, Seoul 03016, Korea.

To prepare a porous cellulose acetate (CA) for application as a battery separator, Cd(NO)·4HO was utilized with water-pressure as an external physical force. When the CA was complexed with Cd(NO)·4HO and exposed to external water-pressure, the water-flux through the CA was observed, indicating the generation of pores in the polymer. Furthermore, as the hydraulic pressure increased, the water-flux increased proportionally, indicating the possibility of control for the porosity and pore size. Surprisingly, the value above 250 LMH (L/mh) observed at the ratio of 1:0.35 (mole ratio of CA: Cd(NO)·4HO) was of higher flux than those of CA/other metal nitrate salts (Ni(NO) and Mg(NO)) complexes. The higher value indicated that the larger and abundant pores were generated in the cellulose acetate at the same water-pressure. Thus, it could be thought that the Cd(NO)·4HO salt played a role as a stronger plasticizer than the other metal nitrate salts such as Ni(NO) and Mg(NO). These results were attributable to the fact that the atomic radius and ionic radius of the Cd were largest among the three elements, resulting in the relatively larger Cd of the Cd(NO) that could easily be dissociated into cations and NO ions. As a result, the free NO ions could be readily hydrated with water molecules, causing the plasticization effect on the chains of cellulose acetate. The coordinative interactions between the CA and Cd(NO)·4HO were investigated by IR spectroscopy. The change of ionic species in Cd(NO)·4HO was analyzed by Raman spectroscopy.
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http://dx.doi.org/10.3390/polym12040981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240385PMC
April 2020

Cystic Lateral Lymph Node Metastases From Papillary Thyroid Cancer Patients.

Laryngoscope 2020 12 10;130(12):E976-E981. Epub 2020 Apr 10.

Department of Surgery, Severance Hospital, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.

Objectives/hypothesis: Papillary thyroid carcinoma (PTC) tends to metastasize rather early to local lymph nodes (LNs). Incidences of cystic LN metastases is relatively rare compared with that of solid LN metastases. Few studies have attempted to assess the characteristics in these patients. This study aimed to compare the clinicopathologic characteristics and surgical outcomes between patients with cystic LN metastases and those with solid LN metastases.

Study Design: Retrospective cohort study.

Methods: We retrospectively reviewed the data of 1,028 patients with N1b PTC who underwent bilateral total thyroidectomy with central compartment neck dissection and modified radical neck dissection between January 2005 and September 2011. Of these, 136 (13.2%) had cystic LN metastases and 892 (86.8%) had solid LN metastases. Clinicopathologic characteristics and surgical outcomes were compared between these two patient groups.

Results: The proportion of patients with thyroid tumor multifocality was relatively higher in the cystic node cohort (19.9% vs. 12.7%, P = .048). The number of total metastatic LNs and positive lateral LNs was slightly higher in the cystic node cohort (11.3 ± 8.9 vs. 9.7 ± 7.5, P = .029 and 6.9 ± 6.3 vs. 5.5 ± 4.6, P = .018, respectively). The proportion of patients with recurrence was higher in the cystic node cohort (14.0% vs. 3.0%, P < .001). Multivariate analysis indicated that cystic nodes were a significant risk factor for recurrence (hazard ratio: 5.265, 95% confidence interval: 2.898-9.563).

Conclusions: This study demonstrates that cystic lateral LN metastases are associated with aggressive tumor behavior in PTC patients. and that their presence is a significant independent prognostic factor for disease-free survival.

Level Of Evidence: 2b Laryngoscope, 2020.
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http://dx.doi.org/10.1002/lary.28631DOI Listing
December 2020

JNK suppresses melanogenesis by interfering with CREB-regulated transcription coactivator 3-dependent MITF expression.

Theranostics 2020 4;10(9):4017-4029. Epub 2020 Mar 4.

Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul 05505, Korea.

Melanogenesis is a critical self-defense mechanism against ultraviolet radiation (UVR)-induced skin damage and carcinogenesis; however, dysregulation of melanin production and distribution causes skin-disfiguring pigmentary disorders. Melanogenesis is initiated by UVR-induced cAMP generation and ensuing activation of transcription factor CREB, which induces expression of the master melanogenic regulator MITF. Recent studies have demonstrated that recruitment of CRTCs to the CREB transcription complex is also required for UVR-stimulated melanogenesis. Therefore, modulation of cAMP-CRTC/CREB-MITF signaling may be a useful therapeutic strategy for UVR-associated skin pigmentary disorders. : We identified the small-molecule Ro31-8220 from CREB/CRTC activity screening and examined its melanogenic activity in cultured mouse and human melanocytes as well as in human skin. Molecular mechanisms were deciphered by immunoblotting, RT-PCR, promoter assays, tyrosinase activity assays, immunofluorescent examination of CRTC3 subcellular localization, and shRNA-based knockdown. : Ro31-8220 suppressed basal and cAMP-stimulated melanin production in melanocytes and human melanocyte co-culture as well as UVR-stimulated melanin accumulation in human skin through downregulation of MITF and tyrosinase expression. Mechanistically, down regulation of MITF expression by Ro31-8220 was due to inhibition of transcriptional activity of CREB, which was resulted from phosphorylation-dependent blockade of nuclear translocation of CRTC3 via JNK activation. The selective JNK activator anisomycin also inhibited melanin production through phosphoinhibition of CRTC3, while JNK inhibition enhanced melanogenesis by stimulating CRTC3 dephosphorylation and nuclear migration. : Melanogenesis can be enhanced or suppressed via pharmacological modulation of a previously unidentified JNK-CRTC/CREB-MITF signaling axis. As Ro31-8220 potently inhibits UVR-stimulated melanin accumulation in human skin, suggesting that small-molecule JNK-CRTC signaling modulators may provide therapeutic benefit for pigmentation disorders.
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http://dx.doi.org/10.7150/thno.41502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086364PMC
May 2021
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