These guidelines aim to establish the standard practice for diagnosing and treating patients with differentiated thyroid cancer (DTC). Based on the Korean Thyroid Association (KTA) Guidelines on DTC management, the “Treatment of Advanced DTC” section was revised in 2024 and has been provided through this chapter. Especially, this chapter covers surgical and nonsurgical treatments for the local (previous surgery site) or regional (cervical lymph node metastasis) recurrences. After drafting the guidelines, it was finalized by collecting opinions from KTA members and related societies. Surgical resection is the preferred treatment for local or regional recurrence of advanced DTC. If surgical resection is not possible, nonsurgical resection treatment under ultrasonography guidance may be considered as an alternative treatment for local or regional recurrence of DTC. Furthermore, if residual lesions are suspected even after surgical resection or respiratory-digestive organ invasion, additional radioactive iodine and external radiation treatments are considered.

Pediatric differentiated thyroid cancers (DTCs), mostly papillary thyroid cancer (PTC, 80-90%), are diagnosed at more advanced stages with larger tumor sizes and higher rates of locoregional and/or lung metastasis. Despite the higher recurrence rates of pediatric cancers than of adult thyroid cancers, pediatric patients demonstrate a lower mortality rate and more favorable prognosis. Considering the more advanced stage at diagnosis in pediatric patients, preoperative evaluation is crucial to determine the extent of surgery required. Furthermore, if hereditary tumor syndrome is suspected, genetic testing is required. Recommendations for pediatric DTCs focus on the surgical principles, radioiodine therapy according to the postoperative risk level, treatment and follow-up of recurrent or persistent diseases, and treatment of patients with radioiodine-refractory PTCs on the basis of genetic drivers that are unique to pediatric patients.

Differentiated thyroid cancer demonstrates a wide range of clinical presentations, from very indolent cases to those with an aggressive prognosis. Therefore, diagnosing and treating each cancer appropriately based on its risk status is important. The Korean Thyroid Association (KTA) has provided and amended the clinical guidelines for thyroid cancer management since 2007. The main changes in this revised 2024 guideline include 1) individualization of surgical extent according to pathological tests and clinical findings, 2) application of active surveillance in low-risk papillary thyroid microcarcinoma, 3) indications for minimally invasive surgery, 4) adoption of World Health Organization pathological diagnostic criteria and definition of terminology in Korean, 5) update on literature evidence of recurrence risk for initial risk stratification, 6) addition of the role of molecular testing, 7) addition of definition of initial risk stratification and targeting thyroid stimulating hormone (TSH) concentrations according to ongoing risk stratification (ORS), 8) addition of treatment of perioperative hypoparathyroidism, 9) update on systemic chemotherapy, and 10) addition of treatment for pediatric patients with thyroid cancer.

The primary objective of initial treatment for thyroid cancer is minimizing treatment-related side effects and unnecessary interventions while improving patients’ overall and disease-specific survival rates, reducing the risk of disease persistence or recurrence, and conducting accurate staging and recurrence risk analysis. Appropriate surgical treatment is the most important requirement for this purpose, and additional treatments including radioactive iodine therapy and thyroid-stimulating hormone suppression therapy are performed depending on the patients’ staging and recurrence risk. Diagnostic surgery may be considered when repeated pathologic tests yield nondiagnostic results (Bethesda category 1) or atypia of unknown significance (Bethesda category 3), depending on clinical risk factors, nodule size, ultrasound findings, and patient preference. If a follicular neoplasm (Bethesda category 4) is diagnosed pathologically, surgery is the preferred option. For suspicious papillary carcinoma (suspicious for malignancy, Bethesda category 5), surgery is considered similar to a diagnosis of malignancy (Bethesda category 6). As for the extent of surgery, if the cancer is ≤1 cm in size and clinically free of extrathyroidal extension (ETE) (cT1a), without evidence of cervical lymph node (LN) metastasis (cN0), and without obvious reason to resect the contralateral lobe, a lobectomy can be performed. If the cancer is 1-2 cm in size, clinically free of ETE (cT1b), and without evidence of cervical LN metastasis (cN0), lobectomy is the preferred option. For patients with clinically evident ETE to major organs (cT4) or with cervical LN metastasis (cN1) or distant metastasis (M1), regardless of the cancer size, total thyroidectomy and complete cancer removal should be performed at the time of initial surgery. Active surveillance may be considered for adult patients diagnosed with low-risk thyroid papillary microcarcinoma. Endoscopic and robotic thyroidectomy may be performed for low-risk differentiated thyroid cancer when indicated, based on patient preference.

Rhabdomyosarcoma (RMS) comprises of heterogeneous group of neoplasms that occasionally express epithelial markers on immunohistochemistry (IHC). We herein report the case of a patient who developed RMS of the skull with EWSR1 fusion and anaplastic lymphoma kinase (ALK) and cytokeratin expression as cytomorphologic features. A 40-year-old man presented with a mass in his forehead. Surgical resection was performed, during which intraoperative frozen specimens were obtained. Squash cytology showed scattered or clustered spindle and epithelioid cells. IHC revealed that the resected tumor cells were positive for desmin, MyoD1, cytokeratin AE1/ AE3, and ALK. Although EWSR1 rearrangement was identified on fluorescence in situ hybridization, ALK, and TFCP2 rearrangement were not noted. Despite providing adjuvant chemoradiation therapy, the patient died of tumor progression 10 months after diagnosis. We emphasize that a subset of RMS can express cytokeratin and show characteristic histomorphology, implying the need for specific molecular examination.

Gastric wall abscess is a rare condition characterized by a purulent inflammatory process resulting in the formation of a pocket of pus in the stomach. As the mucosa is usually intact, it requires various tools such as endoscopic ultrasonography or computed tomography for the differential diagnosis to rule out more common subepithelial tumors. Even after the diagnosis, the treatment for gastric wall abscess was previously restricted to surgical resection in combination with antibiotics. Currently, in order to avoid unnecessary surgery, the alternative method of initial treatment with an endoscopic approach is recommended. It also helps to choose appropriate antibiotics with confirmation of the pathogen by drainage. There are few reports that describe the detailed processing of the endoscopic drainage, and there is no consensus on the treatment. The pathogens that cause gastric wall abscess are usually Streptococci, Staphylococci, and Escherichia coli. There is only one case reported to be caused by Candida albicans. This is the first report of Elizabethkingia anopheles as the pathogen of the gastric wall abscess. Here, we report a case of gastric wall abscess in a 75-year-old man, safely treated by endoscopic drainage and antibiotics, confirmed by isolating the contents of the abscess.

Purpose: The relationship between microsatellite instability (MSI) and tumor response after neoadjuvant chemoradiotherapy (nCRT) in rectal cancer remains unclear. The present study aimed to evaluate the association between MSI and tumor response to nCRT in rectal cancer treatment. Methods: Patients with rectal cancer from 2 tertiary hospitals who underwent nCRT, followed by radical surgery, were included. The microsatellite status was determined using a PCR-based Bethesda panel. Tumors with a Dworak’s tumor regression grade of 3 or 4 were considered to have a good response. Predictive factors for a good response to nCRT were analyzed. Results: Of the 1,401 patients included, 910 (65.0%) had MSI results and 1.5% (14 of 910) showed MSI-H. Among all the patients, 519 (37.0%) showed a good response to nCRT. A univariate analysis showed that MSI-H tended to be negatively associated with a good response to nCRT, but no statistical significance was observed (7.1% vs. 24.1%, P = 0.208).Multivariate analysis showed that well-differentiated tumors were the only predictive factor for good response to nCRT (odds ratio [OR], 2.241; 95% confidence interval [CI], 1.492–3.364; P < 0.001). MSI status tended to be associated with the response to nCRT (OR, 0.215; 95% CI, 0.027–1.681; P = 0.143). Conclusion MSI-H was not associated with response to nCRT in patients with rectal cancer.

The present study was carried out to investigate the effect of Arctigenin on cell growth and the mechanism of cell death elicited by Arctigenin were examined in FaDu human pharyngeal carcinoma cells. To determine the apoptotic activity of Arctigenin in FaDu human pharyngeal carcinoma cells, cell viability assay, DAPI staining, caspase activation analysis, and immunoblotting were performed. Arctigenin inhibited the growth of cells in a dose-dependent manner and induced nuclear condensation and fragmentation. Arctigenin-treated cells showed caspase-3/7 activation and increased apoptosis versus control cells. FasL, a death ligand associated with extrinsic apoptotic signaling pathways, was up-regulated by Arctigenin treatment. Moreover, caspase-8, a part of the extrinsic apoptotic pathway, was activated by Arctigenin treatments. Expressions of anti-apoptotic factors such as Bcl-2 and Bcl-xL, components of the mitochondria-dependent intrinsic apoptosis pathway, significantly decreased following Arctigenin treatment. The expressions of pro-apoptotic factors such as BAX, BAD and caspase-9, and tumor suppressor -53 increased by Arctigenin treatments. In addition, Arctigenin activated caspase-3 and poly (ADP-ribose) polymerase (PARP) induced cell death. Arctigenin also inhibited the proliferation of FaDu cells by the suppression of p38, NF-κB, and Akt signaling pathways. These results suggest that Arctigenin may inhibit cell proliferation and induce apoptotic cell death in FaDu human pharyngeal carcinoma cells through both the mitochondria-mediated intrinsic pathway and the death receptormediated extrinsic pathway.

The aim of the present study was to investigate the physiological role of nicotinamide phosphoribosyltransferase (NAMPT) associated with odontogenic differentiation during tooth development in mice. Mouse dental papilla cell-23 (MDPC-23) cells cultured in differentiation media were stimulated with the specific NAMPT inhibitor, FK866, and Visfatin (NAMPT) for up to 10 days. The cells were evaluated after 0, 4, 7, and 10 days. Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The mineralization assay was performed by staining MDPC-23 cells with Alizarin Red S solution. After cultivation, MDPC-23 cells were harvested for quantitative PCR or Western blotting. Analysis of variance was performed using StatView 5.0 software (SAS Institute Inc., Cary, NC, USA). Statistical significance was set at p < 0.05. The expression of NAMPT increased during the differentiation of murine odontoblast-like MDPC-23 cells. Furthermore, the up-regulation of NAMPT promoted odontogenic differentiation and accelerated mineralization through an increase in representative odontoblastic biomarkers, such as dentin sialophosphoprotein, dentin matrix protein-1, and alkaline phosphatase in MDPC-23 cells. However, treatment of the cells with the NAMPT inhibitor, FK866, attenuated odontogenic differentiation, as evidenced by the suppression of odontoblastic biomarkers. These data indicate that NAMPT regulated odontoblastic differentiation through the regulation of odontoblastic biomarkers. The increase in NAMPT expression in odontoblasts was closely related to the formation of the extracellular matrix and dentin via the Runx signaling pathway. Therefore, these data suggest that NAMPT is a critical regulator of odontoblast differentiation during tooth development.

Objective: Data pertaining to the prognostic value of the combination of high neutrophilto-lymphocyte ratio (NLR) and anemia on admission in patients with ST-segment elevation myocardial infarction (STEMI) are limited. The objective of this study was to investigate the clinical value of baseline NLR in combination with anemia in predicting clinical outcomes after STEMI. Methods: A total of 5,194 consecutive patients with STEMI within 12 hours of symptom onset from the Korea Acute Myocardial Infarction Registry-National Institute of Health database between 2011 and 2015 were categorized into 4 groups according to their NLR and hemoglobin levels: low NLR (<4) without anemia (n=2,722; reference group); high NLR (≥4) without anemia (n=1,527); low NLR with anemia (n=508); and high NLR with anemia (n=437). The co-primary outcomes were 180-day and 3-year all-cause mortality. Results: Mortality rates significantly increased at the 3-year follow-up across the groups (3.3% vs. 5.4% vs. 16.5% vs. 21.7% for 180-day mortality and 5.3% vs. 9.0% vs. 23.8% vs. 33.4% for 3-year mortality; all p-trends <0.001). After adjusting for baseline covariates, the combination of high NLR and anemia was a significant predictor of 180-day mortality after STEMI with low NLR and no anemia as the reference (adjusted hazard ratio, 2.16; 95% confidence interval, 1.58–2.95; p<0.001). Similar findings were observed for the 3-year mortality. Conclusions This nationwide prospective cohort study showed that the combination of high NLR (≥4) and anemia is a strong predictor of all-cause mortality after STEMI.