Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demon-strated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain unknown.In this study,we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis.Additionally,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,respectively.Computational simulation and BioLayer interferometry were used to confirm their binding affinity.Our results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)pathway.In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways.Moreover,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel anti-angiogenic therapy for endometriosis.

Background and Objectives: For T1–T2 early glottic cancer, single modality treatment with radiation therapy (RT) or transoral laser microsurgery is the standard therapeutic option. However, the choice between surgery and RT has been debated for decades. Even though patient selection bias for each modality inherently exists in the retrospective study, this study aimed to compare the oncologic outcomes of the actual treatment of these patients between surgery-based treatment and RT.Materials and Method The medical records of 417 patients with T1–T2N0 glottic squamous cell carcinoma were reviewed who were treated at our institution between 1995 and 2014. The patients were divided into two groups; primarily surgery-based treatment (OP, n=209) or RT (n=208). Results: In the T1 stage, local failure, overall survival (OS), and disease-free survival (DFS) rates were not different between the OP and RT groups. However, in the T2 stage, the local failure rate was higher in the RT group (p<0.01). OS and DFS were higher in the OP group (p=0.019 and p=0.004, respectively). Larynx-preservation rate was similar in both groups (97.1% and 96.2%, p=0.576). Multivariate analysis showed that age (>65), presence of multiple primary cancer, and treatment modality were significant variables influencing OS and DFS. Conclusion Surgery-based treatment provided better local control rates, DFS, and OS in patients with T1–T2N0 glottic SCC. In the T1 stage, treatment outcomes were similar between OP and RT groups. In the T2 stage, OP showed better results than RT, suggesting that refined strategies are required to improve the oncologic outcomes of RT for T2 glottic cancer.

Purpose: This study aimed to investigate the oncologic outcomes and prognostic factors of salvage treatments in patients with recurrent oropharyngeal squamous cell carcinoma (OPSCC) after radiotherapy (RT)-based treatment. Materials and Methods: A cancer registry was used to retrieve the records of 337 patients treated with definitive RT or concurrent chemoradiotherapy (CRT) from 2008 to 2018 at a single institution. The poor-responder group (PRG) was defined as patients with residual or recurrent disease after primary treatment, and the oncologic outcomes for each salvage treatment method were analyzed. In addition, prognostic indicators of recurrence-free survival (RFS) and overall survival (OS) were identified in patients who underwent salvage treatment. Results: After initial (C)RT, the PRG comprised 71 of the 337 patients (21.1%): 18 patients had residual disease, and 53 had recurrence after primary treatment (mean time to recurrence 19.5 months). Of these, 63 patients received salvage treatment (surgery 57.2%, re-(C)RT 23.8%, and chemotherapy 19.0%), and the salvage success rate was 47.6% at the last follow-up. The overall 2-year OS for salvage treatments was 56.4% (60.8% for the salvage surgery group and 46.2% for the salvage re-(C)RT). Salvage surgery patients with negative resection margins had better oncologic outcomes than those with close/positive resection margins. Using multivariate analyses, locoregional recurrence and residual disease after primary surgery were associated with poor outcome after salvage treatment. In Kaplan-Meier analyses, p16 status was significantly associated with OS in the initial treatment setting but not in the salvage setting. Conclusion In recurrent OPSCC after RT-based treatment, successful salvage was achieved in 56.4% patients who had undergone salvage surgery and radiation treatment. Salvage treatment methods should be selected carefully, given recurrence site as a prognostic factor for RFS.

Purpose: Larynx-preserving surgery (LPS) have recently gained popularity and achieved comparable oncologic outcomes to conventional radical surgery for localized hypopharyngeal cancer (HPC). In the current study, the role of LPS has been assessed thoroughly in comparison with upfront radiation therapy (RT). Materials and Methods: We retrospectively reviewed 185 candidates for LPS with cT1-2 disease; 59 patients underwent upfront LPS while 126 patients received upfront RT, respectively. Oncological and functional outcomes were investigated and compared. Results: Following LPS, safe margin (≥ 5 mm) was achieved in 37.3% of patients. Overall, better clinical outcomes at 5 years were achieved following upfront LPS than those following upfront RT: overall survival (OS) (72.7% vs. 59.0%, p=0.045), disease-free survival (DFS) (59.8% vs. 45.0%, p=0.039), and functional laryngeal preservation (100% vs. 89.7%, p=0.010). Although similar outcomes were observed in patients with cT1 disease, better 5-year DFS was achieved following upfront LPS in patients with cT2 disease (57.0% vs. 36.4%, p=0.023) by virtue of better local control. Despite frequent cN2-3 disease in upfront LPS group, comparable outcomes were observed between upfront RT and LPS group. However, multivariable analyses revealed that performance status and double primary cancer diagnosed within 6 months of HPC diagnosis affected OS significantly, while treatment modality per se did not. Conclusion Although upfront LPS could provide better local control than upfront RT in patients with cT2 disease, overall outcomes were comparable following either modality. Treatment selection of larynx-preserving approach for HPC should be individualized based on tumor and patient factors.

COVID-19 ; Humans ; Kidney Transplantation ; Retrospective Studies ; SARS-CoV-2 ; Transplant Recipients

Clinical trials have not consistently supported the use of induction chemotherapy (IC) for locally advanced head and neck squamous cell cancer. Hypopharynx and base of tongue (BOT) cancer has shown relatively poor survival. We investigated the role of IC in improving outcome over current chemoradiotherapy (CRT) in patients with hypopharynx and BOT cancer. Methods: Treatment-naïve patients with stage III/IV (M0) hypopharynx or BOT cancer were randomly assigned to receive CRT alone (CRT arm: cisplatin 100 mg/m2 on D1 3-weekly, two times plus radiotherapy 68.4 Gy/30 fractions on weekdays) versus two 21-day cycles of IC with TPF (docetaxel & cisplatin 75 mg/m2 on D1, and fluorouracil 75 mg/m2 on D1-4) followed by the same CRT regimen (IC arm). The primary endpoint was progression-free survival (PFS). Results: This study closed early after enrollment of 36 patients (19 in the CRT arm, 17 in the IC arm). After a median follow-up of 47.2 months, there was no significant difference in PFS: the median PFS was 26.8 months for the CRT arm and was not reached for the IC arm (p = 0.13). However, the survival curves were widely separated with a plateau after 3 years, suggesting a potential survival benefit from IC: 3-year PFS rates were 45% and 68%, and 3-year overall survival rates were 56% and 86%, in the CRT and IC arms, respectively. Conclusions: This study failed to demonstrate that induction TPF chemotherapy improves survival in patients with BOT and hypopharynx cancer. However, it suggested a favorable outcome with IC to this population.

Background: Conventional diagnostic approaches for adrenal tumors require multi-step processes, including imaging studies and dynamic hormone tests. Therefore, this study aimed to discriminate adrenal tumors from a single blood sample based on the combination of liquid chromatography-mass spectrometry (LC-MS) and machine learning algorithms in serum profiling of adrenal steroids. Methods: The LC-MS-based steroid profiling was applied to serum samples obtained from patients with nonfunctioning adenoma (NFA, n=73), Cushing’s syndrome (CS, n=30), and primary aldosteronism (PA, n=40) in a prospective multicenter study of adrenal disease. The decision tree (DT), random forest (RF), and extreme gradient boost (XGBoost) were performed to categorize the subtypes of adrenal tumors. Results: The CS group showed higher serum levels of 11-deoxycortisol than the NFA group, and increased levels of tetrahydrocortisone (THE), 20α-dihydrocortisol, and 6β-hydroxycortisol were found in the PA group. However, the CS group showed lower levels of dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEA-S) than both the NFA and PA groups. Patients with PA expressed higher serum 18-hydroxycortisol and DHEA but lower THE than NFA patients. The balanced accuracies of DT, RF, and XGBoost for classifying each type were 78%, 96%, and 97%, respectively. In receiver operating characteristics (ROC) analysis for CS, XGBoost, and RF showed a significantly greater diagnostic power than the DT. However, in ROC analysis for PA, only RF exhibited better diagnostic performance than DT. Conclusion The combination of LC-MS-based steroid profiling with machine learning algorithms could be a promising one-step diagnostic approach for the classification of adrenal tumor subtypes.

Korean Society of Thyroid-Head and Neck Surgery appointed a Task Force to provide guidance on the implementation of a surgical treatment of oral cancer. MEDLINE databases were searched for articles on subjects related to “surgical management of oral cancer” published in English. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. The quality of evidence was rated with use RoBANS (Risk of Bias Assessment Tool for Nonrandomized Studies) and AMSTAR (A Measurement Tool to Assess the Methodological Quality of Systematic Reviews). Evidence-based recommendations for practice were ranked according to the American College of Physicians grading system. Additional directives are provided as expert opinions and Delphi questionnaire when insufficient evidence existed. The Committee developed 68 evidence-based recommendations in 34 categories intended to assist clinicians and patients and counselors, and health policy-makers. Proper surgical treatment selection for oral cancer, which is directed by patient- and subsite-specific factors, remains the greatest predictor of successful treatment outcomes. These guidelines are intended for use in conjunction with the individual patient's treatment goals.
Advisory Committees ; Bias (Epidemiology) ; Carcinoma, Squamous Cell ; Counseling ; Expert Testimony ; Humans ; Mouth Neoplasms ; Neck ; Republic of Korea

BACKGROUND/AIMS: This nationwide, multicenter prospective randomized controlled trial aimed to compare the efficacy and safety of 10-day concomitant therapy (CT) and 10-day sequential therapy (ST) with 7-day clarithromycin-containing triple therapy (TT) as first-line treatment for Helicobacter pylori infection in the Korean population. METHODS: Patients with H. pylori infection were assigned randomly to 7d-TT (lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg twice daily for 7 days), 10d-ST (lansoprazole 30 mg and amoxicillin 1 g twice daily for the first 5 days, followed by lansoprazole 30 mg, clarithromycin 500 mg, and metronidazole 500 mg twice daily for the remaining 5 days), or 10d-CT (lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg twice daily for 10 days). The primary endpoint was eradication rate by intention-to-treat (ITT) and per-protocol (PP) analyses. RESULTS: A total of 1,141 patients were included. The 10d-CT protocol achieved a markedly higher eradication rate than the 7d-TT protocol in both the ITT (81.2% vs 63.9%) and PP analyses (90.6% vs 71.4%). The eradication rate of the 10d-ST protocol was superior to that of the 7d-TT protocol (76.3% vs 63.9%, ITT analysis; 85.0% vs 71.4%, PP analysis). No significant differences in adherence or serious side effects were found among the three treatment arms. CONCLUSIONS: The 10d-CT and 10d-ST regimens were superior to the 7d-TT regimen as standard first-line treatment in Korea.
Amoxicillin ; Arm ; Clarithromycin ; Disease Eradication ; Helicobacter pylori ; Helicobacter ; Humans ; Korea ; Lansoprazole ; Metronidazole ; Prospective Studies

PURPOSE: We designed a modified technique to perform an advanced procedure using conventional instruments and did not employ specialized single-incision laparoscopic surgery (SILS) port equipment. We compared postoperative results for transumbilical, single-port laparoscopic appendectomy (TUSPLA) and single-incision, 2-port laparoscopic appendectomy (SITPLA). METHODS: This retrospective study enrolled 77 patients who underwent TUSPLA or SITPLA to provide more minimally invasive surgery between May 2017 and April 2018. TUSPLA was performed in 39 patients and 38 underwent SITPLA. In the SITPLA group, two 5-mm trocars were inserted through the umbilicus and an extra puncture site was used for a left-handed instrument. Demographic characteristics, operative data, and postoperative outcomes were collected and compared between the groups. RESULTS: The mean total operative time in the SITPLA group was shorter than in the TUSPLA group (p=0.003). The mean laparoscopic instrumental time was also shorter (p<0.001) in the SITPLA. The number of postoperative analgesics in the SITPLA group was less than in the TUSPLA group (p=0.002). The length of hospital day after surgery was shorter in the SITPLA group than in the TUSPLA group (p=0.008). There were no other significant differences between the groups. CONCLUSION: SITPLA had a shorter operative time, required less pain management, and had a similar cosmetic outcome when compared with TUSPLA.
Analgesics ; Appendectomy ; Humans ; Laparoscopy ; Minimally Invasive Surgical Procedures ; Operative Time ; Pain Management ; Punctures ; Retrospective Studies ; Surgical Instruments ; Umbilicus