Exclusive Endoscopic Resection of Nasopharyngeal Papillary Adenocarcinoma via Combined Transnasal and Transoral Approach

Low grade nasopharyngeal papillary adenocarcinoma (LGNPPA) is an extremely rare variant of nasopharyngeal cancer, which exhibits distinct clinicopathological characteristics. Surgical resection has been regarded as the principal treatment. For this, transpalatal or transfacial approach has been classically used for exposure of the field. Up for now, there has been no report on applying endoscopic approach for this disease, which could be an effective alternative to minimize possible morbidities of palatotomy or maxillotomy. Endoscopic approach can be justified considering narrow extent and indolent behavior of LGNPPA. We report a patient with LGNPPA, which was successfully resected exclusively by endoscopic visualization. Our case exhibited narrow-based exophytic features with compatible immunopathologic profiles of LGNPPA. Exclusive endoscopic resection can be effective and less-morbid modality for this rare disease as in this case

Anti-proliferative activity of A. Oxyphylla and its bioactive constituent nootkatone in colorectal cancer cells

Background A. oxyphylla extract is known to possess a wide range of pharmacological activites. However, the molecular mechanism of A. oxyphylla and its bioactive compound nootkatone in colorectal cancer is unknown. Methods Our study aims to examine the role of A. oxyphylla and its bioactive compound nootkatone, in tumor suppression using several in vitro assays. Results Both A. oxyphylla extract and nootkatone exhibited antiproliferative activity in colorectal cancer cells. A. oxyphylla displayed antioxidant activity in colorectal cancer cells, likely mediated via induction of HO-1. Furthermore, expression of pro-apoptotic protein NAG-1 and cell proliferative protein cyclin D1 were increased and decreased respectively in the presence of A. oxyphylla. When examined for anticancer activity, nootkatone treatment resulted in the reduction of colony and spheroid formation. Correspondingly, nootkatone also led to increased NAG-1 expression and decreased cyclin D1 expression. The mechanism by which nootkatone suppresses cyclin D1 involves protein level regulation, whereas nootkatone increases NAG-1 expression at the transcriptional level. In addition to having PPARγ binding activity, nootkatone also increases EGR-1 expression which ultimately results in enhanced NAG-1 promoter activity. Conclusion In summary, our findings suggest that nootkatone is an anti-tumorigenic compound harboring antiproliferative and pro-apoptotic activity.This work was supported by the Research Institute for Veterinary Science, and BK21 PLUS Program for Creative Veterinary Science Research Center, Seoul National University, and by a National Research Foundation of Korea (NRF) grant funded by the Korean government (2018R1A2B2002923) to S.J.B. This work was also partially supported by a clinical research grant (NCC1810150) provided by the National Cancer Center to J.R. and S.J.B. The Fig. 7 Nootkatone controls the NAG-1 expression at the transcriptional level. a Nootkatone increases NAG-1 promoter activity. HCT-116 cells were transfected with pNAG-1 − 1086/+ 41 luciferase and pRL-null plasmid. The cells were treated with EtOH or various concentrations of nootkatone for 24 h, and luciferase activity was measured. The y-axis refers to the ratio of firefly luciferase over renillar luciferase activity. The EtOH-treated cells were set as 1.0. Statistical significance was displayed as *p < 0.05, ***p < 0.001 versus EtOH-treated cells. The data represent mean ± SD from three independent experiments. b Three deletion NAG-1 promoter constructs were co-transfected with pRL-null vector into HCT-116 cells. The cells were treated with EtOH or 100 μM of nootkatone for 24 h, and luciferase activity was measured. Fold induction refers to the ratio of luciferase activity in nootkatone-treated cells versus EtOH-treated cells. Statistical significance was displayed as **p < 0.01 and ***p < 0.001 versus EtOH-treated cells. The data represent mean ± SD from three independent experiments. c HCT-116 cells were co-transfected with wild type pNAG-1 − 133/+ 41 in the presence of empty or EGR-1 expression vector. Cells were subsequently treated with 100 μM nootkatone for 24 h. The results are presented as means ± S.D. of three independent transfections. d Western blot of EGR-1 protein in the presence of nootkatone. β-actin was used as loading control. e Luciferase activity of EGR-1 promoter-luciferase construct (pEGR-1260-LUC). The cells were treated with EtOH or nootkatone for 24 h prior to measurement of luciferase activity. Fold induction refers to the ratio of luciferase activity in nootkatone-treated cells compared to EtOH-treated cells. Statistical significance represented as *p < 0.05, ***p < 0.001 versus EtOH-treated cells. n.s. represents not significant. The data represent mean ± SD from four independent experiments Yoo et al. BMC Cancer (2020) 20:881 Page 10 of 12 funding agency did not have any influence in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript

Robotic and Endoscopic Thyroid Surgery: Evolution and Advances

To minimize surgical morbidity and neck scarring, minimally invasive thyroidectomy and robotic/endoscopic thyroidectomy via cervical, axillary, anterior chest, breast, postauricular or transoral approaches have been developed over the past 20 years. In this article, we review the evolution of robotic and endoscopic thyroid surgery and recent advances. Among remote access approaches, the gasless transaxillary approach, bilateral axillo-breast approach, postauricular facelift approach, and transoral vestibular approach are in common use today. Each procedure has its own advantages and disadvantages. Therefore, we need to understand these advantages and limitations, and to select the appropriate method for each patient. The most significant advantage of remote access thyroidectomy is its excellent cosmesis. The complication rate is similar in patients undergoing a remote access approach and those undergoing conventional surgery if the former is performed by experienced surgeons. Operative time is significantly longer in remote access thyroidectomy. In conclusion, remote access thyroidectomy is feasible and its outcomes are comparable to those of conventional transcervical thyroidectomy in highly selected patients

Quercetin Induces Anticancer Activity by Upregulating Pro-NAG-1/GDF15 in Differentiated Thyroid Cancer Cells

Simple Summary Thyroid cancer is one of the most common cancers worldwide, and its incidence has increased over the last few decades. It is difficult to diagnose different types of thyroid cancer. Tumor tissues from papillary thyroid cancer patient showed higher expression of mature NAG-1, whereas adjacent normal tissues showed higher expression of pro-NAG-1. Several anti-cancer compounds increased pro-NAG-1 expression in thyroid cancer cell line. Quercetin (3,3&apos;,4&apos;,5,7-pentahydroxyflavone) is a flavonoid that is a major component of various plants, including raspberries, grapes, and onions. Quercetin induced apoptosis by inducing only pro-NAG-1 expression, but not mature NAG-1, mediated by the transcription factor C/EBP. This study indicates that pro-NAG-1 could be used as a useful biomarker for thyroid cancer and also provides a potential therapeutic target for the treatment of thyroid cancer with quercetin. Although the treatment of thyroid cancer has improved, unnecessary surgeries are performed due to a lack of specific diagnostic and prognostic markers. Therefore, the identification of novel biomarkers should be considered in the diagnosis and treatment of thyroid cancer. In this study, antibody arrays were performed using tumor and adjacent normal tissues of patients with papillary thyroid cancer, and several potential biomarkers were identified. Among the candidate proteins chosen based on the antibody array data, mature NAG-1 exhibited increased expression in tumor tissues compared to adjacent normal tissues. In contrast, pro-NAG-1 expression increased in normal tissues, as assessed by western blot analysis. Furthermore, pro-NAG-1 expression was increased when the thyroid cancer cells were treated with phytochemicals and nonsteroidal anti-inflammatory drugs in a dose-dependent manner. In particular, quercetin highly induced the expression of pro-NAG-1 but not that of mature NAG-1, with enhanced anticancer activity, including apoptosis induction and cell cycle arrest. Examination of the NAG-1 promoter activity showed that p53, C/EBP alpha, or C/EBP delta played a role in quercetin-induced NAG-1 expression. Overall, our study indicated that NAG-1 may serve as a novel biomarker for thyroid cancer prognosis and may be used as a therapeutic target for thyroid cancers.Y

Metachronous Second Primary Malignancies after Head and Neck Cancer in a Korean Cohort (1993-2010).

Second primary malignancy (SPM) is the major long-term cause of patient mortality with head and neck squamous cell carcinoma (HNSCC). As the incidence of high-risk human papillomavirus (HPV)-related HNSCC is increasing globally, we analyzed the patterns of SPM occurrence, the effect of the index tumor site along with attributes to HPV, and the effect of SPM on survival in South Korean patients with head and neck cancer (HNC). Data were retrieved from the Korea Central Cancer Registry, a nationwide population-based cancer registry, from 1993 to 2010. Standardized incidence ratios were analyzed and compared between index tumor sites, particularly oropharyngeal vs. non-oropharyngeal sites. After adjustment for competing risks, 3- and 5-year SPM rates were calculated using the cumulative incidence function. The effects of SPM occurrence on overall survival (OS) were then analyzed. SPM rates were significantly lower for HPV-attributable oropharyngeal sites than for non-oropharyngeal sites, such as the larynx and hypopharynx (p<0.001). SPM rates were also lower for oral cavity first primary sites than for non-oropharyngeal first primary sites (p<0.001). SPMs typically occurred in the esophagus, lungs and the head and neck. Uterine cervical cancers occurred significantly more frequently after index oropharyngeal cancer in women. The 5-year and 10-year OS rates were 57.8 and 45.7% in all HNC patients, respectively. The OS after SPM occurrence was poor (5-year, 31.8%; 10-year, 20.8%) compared to after index HNC occurrence (5-year, 68.4%; 10-year, 41.2%). SPM occurrence in the esophagus and lung/bronchus showed a worse OS than SPM localized to the head and neck. South Korean HNC patient, the first primary cancer site affected SPM risk and distribution. The 5- and 10-year OS rates deteriorated after SPM occurrence, particularly in the esophagus and lungs. Further optimization of follow-up strategies for effective surveillance of SPM, particularly in the esophagus and lungs, is warranted

Long-term survival of patients with thyroid cancer according to the methods of tumor detection: A nationwide cohort study in Korea.

In this retrospective cohort study, we compared the survival of patients detected by screening with those detected based on symptoms, according to their tumor stages. After propensity score matching, 2,130 patients with papillary or follicular thyroid cancer, identified by screening detection (SD) and clinical detection (CD), were included. We compared the survival rates of patients identified by SD and CD in the early and advanced stages of thyroid cancer. Cox proportional hazard models were used to compare the hazard ratios (HRs) for mortality between the two groups. Of the 1,065 patients in each group, 12 (1.1%) died in the SD group, compared to 44 (4.1%) in the CD group, during an average 9.4 years (p<0.001). For early stage, there was no significant difference in all-cause and thyroid cancer-specific mortality between the two groups (p = 0.08, p = 0.0502). However, for advanced stage, the survival rates in the SD group were significantly higher than in the CD group (p<0.001, p = 0.004). Moreover, after adjusting for covariates, the HRs of all-cause mortality of the SD group was significantly lower than that of the CD group for the advanced stage patients (HRs: 0.37 [95% CIs: 0.17-0.80]), while no significant difference was observed in the early stage. While screening for thyroid cancer was not beneficial for early stage patients, our findings suggest that detection via screening is associated with better survival for patients with advanced stage cancer. However, the effects of selection bias and lead time bias could not be entirely excluded

Spade-Shaped Anastomosis after Laparoscopic Proximal Gastrectomy Using Double Suture Anchoring between the Posterior Wall of the Esophagus and the Anterior Wall of the Stomach (SPADE Operation): A Case Series

We introduced SPADE operation, a novel anastomotic method after laparoscopic proximal gastrectomy (PG). Technical modifications were performed and settled. This report aimed to demonstrate the short-term clinical outcomes after settlement. Data from 34 consecutive patients who underwent laparoscopic PG with SPADE between June 2017 and March 2020 were retrospectively reviewed. Reflux was evaluated based on the patients’ symptoms and follow-up endoscopy using Los Angeles (LA) classification and RGB Classification (Residue, Gastritis, Bile). Other complications were classified using the Clavien–Dindo method. The incidence of reflux esophagitis was 2.9% (1/34). Bile reflux was observed in six patients (17.6%), and residual food was observed in 16 patients (47.1%) in the endoscopy. Twenty-eight patients had no reflux symptoms (82.4%), while five patients (14.7%) and one patient (2.9%) had mild and moderate reflux symptoms, respectively. The rates of anastomotic stricture and ileus were 14.7% (5/34) and 11.8% (4/34), respectively. No anastomotic leakage was observed. The incidence of major complications (Clavien-Dindo grade III or higher) was 14.7%. The SPADE operation following laparoscopic PG is effective in reducing gastroesophageal reflux. Its clinical usefulness should be validated using prospective clinical trials