Diagnostic Performance of Preoperative Calcitonin and Procalcitonin Tests for Differential Diagnosis of Medullary Thyroid Cancer.

Medullary thyroid cancer (MTC) shows a relatively poor prognosis among thyroid cancers. Though calcitonin has been used as a diagnostic marker for MTC, it has disadvantages including poor sample stability and discrepancies among results by assay. This study aimed to compare the usefulness of preoperative calcitonin and procalcitonin (PCT) in the diagnosis of MTC. Serum calcitonin and PCT levels were measured before thyroidectomy from MTC (n = 23) and other types of thyroid cancers in patients (n = 1308). Diagnostic performances of calcitonin and PCT for discerning MTC were estimated. In a multivariate analysis, preoperative calcitonin level was independently associated with the diagnosis of MTC, whereas PCT was not. Calcitonin and PCT, respectively, exhibited area under the curve values of 0.997 and 0.979 for the diagnosis of MTC, without significant differences. For calcitonin, the sensitivity, specificity, and positive and negative predictive values were 0.957, 0.992, 0.688, and 0.999, respectively, at a cut-off of 7.2 pg/mL. The corresponding values for PCT were 0.913, 0.995, 0.778, and 0.998 at a cut-off of 0.19 ng/mL. Preoperative calcitonin and PCT showed similar diagnostic utility for MTC. Depending on the patient's clinical status and laboratory environment, these tests can be used as complementary methods for detecting MTC.

Preoperative Ultrasonography Predicts Level II Lymph Node Metastasis in N1b Papillary Thyroid Carcinoma: Implications for Surgical Planning.

PURPOSE: To investigate whether preoperative ultrasonographic (US) features of the index cancer and metastatic lymph nodes (LNs) are associated with level II LN metastasis in N1b papillary rmfthyroid carcinoma (PTC) patients. MATERIALS AND METHODS: We enrolled 517 patients (mean age, 42 [range, 6-80] years) who underwent total thyroidectomy and lateral compartment LN dissection between January 2009 and December 2015. We reviewed the clinicopathologic and US features of the index cancer and metastatic LNs in the lateral neck. Logistic regression analysis was performed to analyze features associated with level II LN metastasis. RESULTS: Among the patients, 196 (37.9%) had level II metastasis on final pathology. In the preoperative model, larger tumor size (odds ratios [ORs], 1.031; 95% confidence interval [CI]: 1.011-1.051, p = 0.002), nonparallel tumor shape (OR, 1.963; 95% CI: 1.322-2.915, p = 0.001), multilevel LN involvement (OR, 1.906; 95% CI: 1.242-2.925, p = 0.003), and level III involvement (OR, 1.867; 95% CI: 1.223-2.850, p = 0.004), were independently associated with level II LN metastasis. In the postoperative model, non-conventional pathology remained a significant predictor for level II LN metastasis (OR, 1.951; 95% CI: 1.121-3.396; p = 0.018), alongside the presence of extrathyroidal extension (OR, 1.867; 95% CI: 1.060-3.331; p = 0.031), and higher LN ratio (OR, 1.057; 95% CI: 1.039-1.076; p < 0.001). CONCLUSIONS: Preoperative US features of the index tumor and LN may be helpful in guiding surgery in N1b PTC. These findings could enhance preoperative planning and decision-making, potentially reducing surgical morbidities by identifying those at higher risk of level II LN metastasis and tailoring surgical approaches accordingly.

Prediction of final pathology depending on preoperative myometrial invasion and grade assessment in low-risk endometrial cancer patients: A Korean Gynecologic Oncology Group ancillary study.

OBJECTIVES: Fertility-sparing treatment (FST) might be considered an option for reproductive patients with low-risk endometrial cancer (EC). On the other hand, the matching rates between preoperative assessment and postoperative pathology in low-risk EC patients are not high enough. We aimed to predict the postoperative pathology depending on preoperative myometrial invasion (MI) and grade in low-risk EC patients to help extend the current criteria for FST. METHODS/MATERIALS: This ancillary study (KGOG 2015S) of Korean Gynecologic Oncology Group 2015, a prospective, multicenter study included patients with no MI or MI <1/2 on preoperative MRI and endometrioid adenocarcinoma and grade 1 or 2 on endometrial biopsy. Among the eligible patients, Groups 1-4 were defined with no MI and grade 1, no MI and grade 2, MI <1/2 and grade 1, and MI <1/2 and grade 2, respectively. New prediction models using machine learning were developed. RESULTS: Among 251 eligible patients, Groups 1-4 included 106, 41, 74, and 30 patients, respectively. The new prediction models showed superior prediction values to those from conventional analysis. In the new prediction models, the best NPV, sensitivity, and AUC of preoperative each group to predict postoperative each group were as follows: 87.2%, 71.6%, and 0.732 (Group 1); 97.6%, 78.6%, and 0.656 (Group 2); 71.3%, 78.6% and 0.588 (Group 3); 91.8%, 64.9%, and 0.676% (Group 4). CONCLUSIONS: In low-risk EC patients, the prediction of postoperative pathology was ineffective, but the new prediction models provided a better prediction.

No Change in Complications Following Thyroidectomy Despite Increase in Thyroid Cancer Surgeries: A Meta-Regression Analysis.

PURPOSE: The increase in thyroid cancer incidence has inevitably led to an increase in thyroid cancer surgeries. This meta-regression analysis aimed to determine if the rate of post-thyroidectomy complications changes by year. MATERIALS AND METHODS: PubMed and Embase databases were used to perform a systematic literature search of studies published from January 1, 2005, using the keywords "thyroidectomy" and "complication." A meta-regression was performed for post-thyroidectomy hypocalcemia and bleeding. RESULTS: This meta-analysis included 25 studies involving 927751 individuals. Through the years of publications in this study, there was no significant difference in the proportion of post-thyroidectomy hypocalcemia and bleeding (p=0.9978, 0.6393). CONCLUSION: Although the number of thyroid surgeries has recently increased, the incidence of post-thyroidectomy hypocalcemia and bleeding did not significantly increase.

Development of immature ovarian teratoma after mature teratoma in a girl with familial ovarian teratoma: A case report.

BACKGROUND: Immature ovarian teratoma is a rare and aggressive neoplasm that affects young women. This report is the first to describe the development of immature teratoma after ovarian cystectomy for mature teratoma of the ovary in an adolescent female with a family history of ovarian teratoma. CASE SUMMARY: A 16-year-old girl who had undergone bilateral ovarian cystectomy for mature teratomas 3 years ago showed bilateral adnexal tumors during her regular ultrasonography follow-up every 6 months. She received laparoscopic bilateral ovarian cystectomy, and final histopathology showed grade-1 immature teratoma of the left ovary and mature teratoma of the right ovary. Laparoscopic left salpingo-oophorectomy and staging procedures were performed again. Her mother, maternal aunt, and maternal grandmother had also received surgeries for mature ovarian teratomas. CONCLUSION: It is important to have guidance on management of patient and family members with familial ovarian teratomas.

Therapeutic effects of surgical debulking of metastatic lymph nodes in cervical cancer IIICr: a trial protocol for a phase III, multicenter, randomized controlled study (KGOG1047/DEBULK trial).

BACKGROUND: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, well-planned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. METHODS: The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m²), 4-6 times administered intravenously. The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05421650; Clinical Research Information Service Identifier: KCT0007137.

Complication and conversion outcomes in transoral endoscopic thyroidectomy vestibular approach (TOETVA): a retrospective multicenter propensity score-matched cohort study.

Transoral endoscopic thyroidectomy with vestibular approach (TOETVA) is a scarless thyroid surgery used as an alternative to open conventional surgery. Our aim was to investigate possible risk factors for complications and conversion during TOETVA. The study was conducted internationally by centres from Turkiye, the Republic of Korea, Italy, and Peru. A total of 406 patients who underwent TOETVA and were ≥ 18 years of age were included in the study. Demographic, pre-, intra-, and postoperative data were collected and compared between the groups with/without complication/conversion to identify possible predictors of complication/conversion. Subsequently, patients with complication/conversion were matched by the hospital, age, sex, and American Society of Anesthesiologists classification score using a propensity score (PSM) of 1:3 to eliminate confounding differences. Results were reported for the un-matched and matched groups. Complications occurred in 11 (2.7%) patients. High body mass index (26.4 ± 3.4 vs. 23.3 ± 3.7, p = 0.007), larger tumor size (1.7 ± 1.3 cm. vs. 1.1 ± 1.0 cm, p = 0.012), larger thyroid volume (20.0 ± 9.2 vs. 12.8 ± 8.5, p = 0.007) and long operation time (127.8 ± 45.0 min. vs. 97.7 ± 38.5 min., p = 0.008) were significantly associated with complications in un-matched analyses. Older age (42.7 ± 8.0 vs. 34.9 ± 9.2, p = 0.023), high BMI (26.7 ± 3.2 vs. 23.3 ± 3.7, p = 0.012), and longer operation time (160.1 ± 54.1 min. vs. 97.4 ± 37.8, p = 0.001) were significantly related to conversion in un-matched analyses. However, significance was lost after PSM for both complication and conversion. The data from this study conducted on TOETVA cases do not suggest a risk factor for complications and conversion with PSM.

Human papillomavirus genotyping for predicting disease progression in women with biopsy-negative or cervical intraepithelial neoplasia grade 1 of low-grade intraepithelial lesion cytology.

OBJECTIVE: Our study used human papillomavirus (HPV) genotyping to assess the disease occurrence probability in women with a low-grade squamous intraepithelial lesion (LSIL) without histologically confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+). METHODS: This study investigated CIN2+ incidence in 1986 women from January 2005 to August 2016, including 1123 with LSIL who were histology-proven negative and 863 with LSIL who were histology-proven CIN1. Baseline high-risk HPV (HR-HPV) status was determined using the hybrid capture II assay (HC2), and HR-HPV genotype was determined using the HPV DNA chip test (HDC). RESULTS: Among 1986 women, the HC2 yielded positive results in 1529 (77.0%), while the HDC identified 1624 (81.8%). Thus, the overall HDC and HC2 agreement was 93.2%. Overall, 169 (8.5%) patients developed CIN2+. The 5-year cumulative CIN2+ incidence rates for HPV-16, HPV-18, HPV-31, and HPV-33 were 11.8%, 9.9%, 16.3%, and 16.1%, respectively. Multivariate analysis revealed that HPV-16 (HR 1.637, 95% CI 1.064 to 2.520, p=0.025), HPV-31 (HR 1.845, 95% CI 1.051 to 3.238, p=0.033), and HPV-33 (HR 2.272, 95% CI 1.235 to 4.183, p=0.008) were significantly associated with CIN2+ development. CONCLUSION: Among women with LSIL, those who test positive for HPV-16, HPV-31, or HPV-33 may require more rigorous follow-up because of a higher CIN2+ risk.

Robotic parathyroidectomy is a feasible technique for primary hyperparathyroidism.

PURPOSE: Focused parathyroidectomy is the gold standard treatment modality for primary hyperparathyroidism, which allows accurate preoperative localization. Robotic parathyroidectomy has emerged as a feasible procedure for focused parathyroidectomy. This study aimed to report the experiences of gasless robotic transaxillary parathyroidectomy for primary hyperparathyroidism in a single center. METHODS: We assessed the data obtained from patients who underwent gasless robotic parathyroidectomy with the transaxillary approach between December 2013 and August 2022 and were diagnosed with primary hyperparathyroidism at our institute. The data included clinical, biochemical, and pathological features and operation time. RESULTS: Of the 12 patients, 11 were women and one was a man. The median age of the patients was 44.5 years (range: 15-65 years). The median preoperative maximum mass diameters on ultrasonography and neck computed tomography were 1.2 ± 0.5 and 1.1 ± 0.6 cm, respectively. The median size of the postoperative maximum mass diameter in gross pathology was 1.3 ± 0.4 cm. The location of the enlarged parathyroid was left superior in five patients, right inferior in four, left inferior in three, and no right superior in one. In the final pathological examination, all cases were parathyroid adenomas. Only one case experienced a postoperative bleeding complication. At six months from surgery, average of an axillary scar length was 5.85 cm, and an average width was 0.21 cm. The mean operative time was 113 ± 48 min. The mean robot docking and console times were 9 ± 5 and 47 ± 52 min, respectively. CONCLUSIONS: Robotic transaxillary parathyroidectomy is a feasible technique in select patients with primary hyperparathyroidism and preoperatively localized disease. The gasless robotic transaxillary approach provides procedural safety as well as superior cosmetic results without a neck scar.

Discovery of New Anti-Cancer Agents against Patient-Derived Sorafenib-Resistant Papillary Thyroid Cancer.

Thyroid cancer is the most well-known type of endocrine cancer that is easily treatable and can be completely cured in most cases. Nonetheless, anti-cancer drug-resistant metastasis or recurrence may occur and lead to the failure of cancer therapy, which eventually leads to the death of a patient with cancer. This study aimed to detect novel thyroid cancer target candidates based on validating and identifying one of many anti-cancer drug-resistant targets in patient-derived sorafenib-resistant papillary thyroid cancer (PTC). We focused on targeting the sarco/endoplasmic reticulum calcium ATPase (SERCA) in patient-derived sorafenib-resistant PTC cells compared with patient-derived sorafenib-sensitive PTC cells. We discovered novel SERCA inhibitors (candidates 33 and 36) by virtual screening. These candidates are novel SERCA inhibitors that lead to remarkable tumor shrinkage in a xenograft tumor model of sorafenib-resistant patient-derived PTC cells. These results are clinically valuable for the progression of novel combinatorial strategies that facultatively and efficiently target extremely malignant cancer cells, such as anti-cancer drug-resistant PTC cells.

Comparison of delayed bleeding to immediate bleeding following thyroidectomy.

It is important to identify risk factors for post-thyroidectomy bleeding requiring airway intervention or reoperation. Therefore, we aimed to compare the characteristics of patients with postoperative bleeding after thyroid surgery according to the period until reoperation. We conducted a retrospective study analyzing data between April 2009 and July 2022 and included 126 patients who had postoperative bleeding. The patients were grouped according to the period between thyroidectomy and reoperation due to bleeding (0 day, 1-7 days, > 7 days). We performed among-group comparisons of patient characteristics and surgical aspects, including the extent of surgery. The ratios of male-female and lateral neck dissection were higher in the post-operative bleeding group than in the group without bleeding. In the analysis of patients with postoperative bleeding, grouped according to period between thyroidectomy and reoperation, there was a significant among-group difference in the male-female ratio. The male sex was positively correlated with the reoperation period. Further, the reoperation period was also positively correlated with total thyroidectomy and lateral neck dissection and the operation time showed a significant among-group difference. Our results indicate that the male sex and lateral neck dissection are risk factors for postoperative bleeding after thyroidectomy. Furthermore, male sex, total thyroidectomy, and lateral neck dissection are risk factors for delayed bleeding. Therefore, clinicians should consider these factors for interventions against immediate or delayed bleeding after thyroidectomy.

Integrative analysis of circular RNA regulatory network in papillary thyroid carcinoma.

Papillary thyroid cancer (PTC) is the most common type of endocrine cancer worldwide. Generally, PTC has an excellent prognosis; however, lymph node metastases and recurrences occur frequently. Over the last decade, circular RNAs (circRNAs), a large class of noncoding RNAs (ncRNAs), have emerged as key regulators of various tumor progression pathways. Here, we aimed to identify novel circRNAs as PTC biomarkers. Differentially expressed circRNAs and mRNAs were analyzed using public datasets from the Gene Expression Omnibus and Cancer Genome Atlas. In addition, we screened for target miRNAs using online prediction databases. Based on these results, we established a circRNA-miRNA-mRNA regulatory network associated with PTC, in which protein-protein interaction networks led to the identification of hub genes. Functional enrichment and survival analyses were performed to gain insights into the biological mechanisms of circRNA involvement. As a result, we found that two circRNAs (hsa_circ_0041829 and has_circ_0092299), four miRNAs (miR-369, miR-486, miR-574, and miR-665), and nine hub genes (BBC3, E2F1, FYN, MAG, SDC1, SDC3, SNAP25, TK1, and TYMS) play significant roles in PTC progression. This study provides a novel framework for understanding the roles of circRNA-miRNA-mediated gene regulation in PTC. It also introduces potential therapeutic targets and prognostic biomarkers, which may serve as a basis for developing targeted therapeutic interventions for PTC.

Evaluation of public's perception of scar cosmesis after thyroidectomy: results of a survey of Turkish versus South Korean individuals.

Purpose: Visible scars on the neck caused by thyroid surgery give rise to significant aesthetic, functional, and psychosocial problems. The objective of this study is to comparatively investigate the public perception of neck scar cosmesis in Turkish and South Korean populations. Methods: This survey was prepared to collect participants' demographic and socioeconomic data and determine their perception of scar cosmesis on the neck and consisted of 15 questions. One thousand thirty-nine individuals who did not undergo thyroid surgery completed the survey. The P-values of <0.05 were deemed to indicate statistical significance. Results: There were 1,039 respondents, of whom 525 (50.5%) were Turkish and 514 (49.5%) were South Korean. South Korean respondents stated that they would be significantly more uncomfortable with the thought of having a scar due to thyroid surgery, compared to the Turkish respondents (P < 0.001). The South Korean respondents stated that they would be significantly more concerned about the scar's length, thickness, and darkening color, compared to the Turkish respondents (P < 0.001 for all cases). Conclusion: Patients' expectations, which are affected by various sociodemographic factors and cultural characteristics, are as important as the medical condition when deciding on the type of thyroid surgery. The study findings clearly indicated that the South Korean population would be significantly more uncomfortable with having a scar on the neck, compared to the Turkish population. Therefore, in selected cases, a scarless thyroidectomy approach, such as transoral endoscopic thyroidectomy, vestibular approach may be preferable for societies like South Korea.

Co-inhibition of glutaminolysis and one-carbon metabolism promotes ROS accumulation leading to enhancement of chemotherapeutic efficacy in anaplastic thyroid cancer.

Anaplastic thyroid cancer (ATC) is one of the most aggressive tumors with an extremely poor prognosis. Based on the several biological features related to glutamine metabolism in ATC, we hypothesized glutaminolysis inhibition induces cell death in ATC cells. However, glutamine metabolism inhibition triggered cell growth arrest independent of cell death in ATC, suggesting that other signaling pathways avoid glutamine metabolism inhibition-induced stress exist. To investigate the functional mechanism against glutamine metabolism inhibition, we conducted mRNA and ATAC-Sequencing data analysis and found that glutamine deprivation increased ATF4-mediated one-carbon metabolism. When we inhibited PHGDH, the first rate-limiting enzyme for one-carbon metabolism, cell growth arrest was promoted upon glutamine metabolism inhibition by accumulating intracellular ROS. We next observed that the co-inhibition of glutamine and one-carbon metabolism could augment the anticancer effects of drugs used in patients with ATC. Finally, single-cell RNA sequencing analysis revealed that one-carbon metabolism was strengthened through the evolutionary process from PTC to ATC. Collectively, our data demonstrate that one-carbon metabolism has a potential role of modulation of cell fate in metabolic stress and can be a therapeutic target for enhancing antitumor effects in ATC.

Lateral neck dissection for the treatment of synchronous and metachronous lateral neck metastasis of N1b papillary thyroid cancer.

Introduction: Metachronous lateral neck recurrence after thyroidectomy for N1b papillary thyroid cancer is accompanied by high morbidity and increased difficulty of reoperation. From the perspective of recurrence, the objective of this study was to compare patients who underwent metachronous lateral neck dissection (mLND) despite initial thyroidectomy and patients who underwent synchronous lateral neck dissection (sLND) for papillary thyroid cancer and analyze the risk factors for recurrence after mLND. Method: This retrospective study involved 1,760 patients who underwent lateral neck dissection for papillary thyroid cancer at the Gangnam Severance Hospital, a tertiary medical center in Korea, from June 2005 to December 2016. The primary outcome was structural recurrence, and secondary outcome measures were risk factors of recurrence in the mLND group. Result: A total of 1,613 patients underwent thyroidectomy and sLND at diagnosis. In 147 patients, thyroidectomy alone was performed at the time of diagnosis, and mLND was performed when recurrence to the lateral neck lymph node was confirmed. During a median follow-up of 102.1 months, 110 (6.3%) patients experienced a recurrence. There was no significant difference in the recurrence between the sLND and mLND groups (6.1% vs 8.2%, P=.32). The period from lateral neck dissection to recurrence was longer in the mLND group than in the sLND group (113.6 ± 39.4 months vs 87.0 ± 33.8 months, respectively, P<.001). Age ≥50 years (adjusted HR=5.209, 95% CI=1.359-19.964; P=.02), tumor size >1.45 cm (adjusted HR=4.022, 95% CI=1.036-15.611; P=.04), and lymph node ratio in the lateral compartment (adjusted HR=4.043, 95% CI=1.079-15.148; P=.04) were independent variables predictive of recurrence after mLND. Conclusion: mLND is suitable for treating lateral neck recurrence in patients with N1b papillary thyroid cancer who previously underwent thyroidectomy. Lateral neck recurrence after treatment in patients who underwent mLND was predicted by age, tumor size, and lymph node ratio in the lateral compartment.

Using Type I Collagen Gel to Prevent Postoperative Intrauterine Adhesion: A Multicenter Retrospective Study.

We evaluated the clinical outcomes of using type 1 collagen gel after therapeutic resectoscopy; overall, 150 women aged > 20 who planned to undergo therapeutic resectoscopy were enrolled. The patients were randomly assigned to either of the anti-adhesive treatment groups: the type 1 collagen gel (Collabarrier®) (study group; N = 75) or the sodium hyaluronate and sodium carboxymethylcellulose gel group (control group; N = 75) after resectoscopy. One month after applying anti-adhesive materials, postoperative intrauterine adhesions were evaluated using second-look hysteroscopy; the incidence rate of postoperative intrauterine adhesions examined through second-look hysteroscopy showed no significant differences between the groups. There were no statistical differences between the frequency and mean scores of the type and intensity of adhesions in both groups. Finally, no significant differences in adverse events, serious adverse events, adverse device effects, and serious adverse device effects were noted between the two groups; type 1 collagen gel can be effectively and safely used in intrauterine surgery to minimize postoperative adhesions, thereby eventually decreasing the prevalence of infertility, secondary amenorrhea, and recurrent pregnancy loss in reproductive women.

Clinicopathological and Genetic Characteristics of Patients of Different Ages with Diffuse Sclerosing Variant Papillary Thyroid Carcinoma.

Diffuse sclerosing variant papillary thyroid carcinoma (DSVPTC) is commonly observed in young patients, with a median age at diagnosis in the third decade of life. Further, the risk of recurrence is higher for DSVPTC than for classical PTC. Therefore, this study aimed to describe the clinicopathological and genetic characteristics of patients of different ages with DSVPTC. We retrospectively reviewed 397 patients who underwent thyroidectomy for DSVPTC at Gangnam Severance Hospital, Yonsei University, from January 2005 to December 2017. The mean age at diagnosis was 36.7 ± 11.6 years, with most patients (163, 41.1%) aged 31-40 years. DSVPTC was predominant in women (276, 69.5%). We observed recurrence in 46 (11.6%) patients, with regional nodal recurrence being the most common type of recurrence (32 patients, 69.6%). The mean tumour size was larger in younger patients than in older patients. DSVPTC was more aggressive in paediatric patients with a larger-sized tumour, more common multiplicity, and lateral neck metastasis. Through random sampling, we selected 41 patients by age group and examined the mutations in 119 genes using next-generation sequencing. BRAF, KRAS, and TERT displayed relatively higher mutation rates than other genes. DSVPTC displays different clinical, pathological, and molecular profiles than classical PTC. The BRAF, KRAS, and TERT mutations are the most important, with age-specific differences.

PMCA inhibition reverses drug resistance in clinically refractory cancer patient-derived models.

BACKGROUND: Cancer cells have developed molecular strategies to cope with evolutionary stressors in the dynamic tumor microenvironment. Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) is a metabolic rheostat that regulates diverse cellular adaptive behaviors, including growth and survival. However, the mechanistic role of PGC1α in regulating cancer cell viability under metabolic and genotoxic stress remains elusive. METHODS: We investigated the PGC1α-mediated survival mechanisms in metabolic stress (i.e., glucose deprivation-induced metabolic stress condition)-resistant cancer cells. We established glucose deprivation-induced metabolic stress-resistant cells (selected cells) from parental tumor cells and silenced or overexpressed PGC1α in selected and parental tumor cells. RESULTS: Several in vitro and in vivo mouse experiments were conducted to elucidate the contribution of PGC1α to cell viability in metabolic stress conditions. Interestingly, in the mouse xenograft model of patient-derived drug-resistant cancer cells, each group treated with an anti-cancer drug alone showed no drastic effects, whereas a group that was co-administered an anti-cancer drug and a specific PMCA inhibitor (caloxin or candidate 13) showed marked tumor shrinkage. CONCLUSIONS: Our results suggest that PGC1α is a key regulator of anti-apoptosis in metabolic and genotoxic stress-resistant cells, inducing PMCA expression and allowing survival in glucose-deprived conditions. We have discovered a novel therapeutic target candidate that could be employed for the treatment of patients with refractory cancers.

Primary thyroid lymphoma: A single-center experience.

Background: Primary thyroid lymphoma (PTL) is a very rare entity accounting for 5% of all thyroid malignancies and less than 2% of lymphomas. PTLs are classified as non-Hodgkin's B-cell lymphomas in the majority of cases, although Hodgkin's lymphoma of the thyroid has also been identified. This study aimed to identify the clinical, biochemical, and pathological features of primary thyroid lymphomas. Methods: From January 2008 to December 2020, data from patients diagnosed with PTL treated at the Gangnam Severance Hospital, including clinical, biochemical, and pathological features of thyroid lymphomas, were assessed. Results: Of 10 patients, nine women and one man, with a median age of 62 (range, 44-82) years were included. Fine needle aspiration biopsy was performed in nine patients and surgical resection was performed in one patient without biopsy. Excisional and surgical biopsies were performed in all patients, including five who underwent excisional biopsy and five who underwent thyroidectomy. Histological analyses revealed that all 10 lymphomas were non-Hodgkin B-cell lymphoma; six patients had diffuse large B-cell lymphoma, three had mucosa-associated lymphoid tissue lymphoma, and one had Burkitt lymphoma. Four patients received chemotherapy, two were treated with chemoradiation therapy, one received radiation therapy only, one did not require more treatment after surgery, one refused treatment, and one was transferred to another hospital. Conclusions: Although PTLs are scarce, clinicians should be aware of this rare entity and evaluate and treat PTLs on an individual basis.

Bioinformatics and Connectivity Map Analysis Suggest Viral Infection as a Critical Causative Factor of Hashimoto's Thyroiditis.

Hashimoto's thyroiditis (HT) is a common autoimmune disease, and its prevalence is rapidly increasing. Both genetic and environmental risk factors contribute to the development of HT. Recently, viral infection has been suggested to act as a trigger of HT by eliciting the host immune response and subsequent autoreactivity. We analyzed the features of HT through bioinformatics analysis so as to identify the markers of HT development. We accessed public microarray data of HT patients from the Gene Expression Omnibus (GEO) and obtained differentially expressed genes (DEGs) under HT. Gene Ontology (GO) and KEGG-pathway-enrichment analyses were performed for functional clustering of our protein-protein interaction (PPI) network. Utilizing ranked gene lists, we performed a Gene Set Enrichment Analysis (GSEA) by using the clusterprofiler R package. By comparing the expression signatures of the huge perturbation database with the queried rank-ordered gene list, a connectivity map (CMap) analysis was performed to screen potential therapeutic targets and agents. The gene expression profile of the HT group was in line with the general characteristics of HT. Biological processes related to the immune response and viral infection pathways were obtained for the upregulated DEGs. The GSEA results revealed activation of autoimmune-disease-related pathways and several viral-infection pathways. Autoimmune-disease and viral-infection pathways were highly interconnected by common genes, while the HLA genes, which are shared by both, were significantly upregulated. The CMap analysis suggested that perturbagens, including SRRM1, NLK, and CCDC92, have the potential to reverse the HT expression profile. Several lines of evidence suggested that viral infection and the host immune response are activated during HT. Viral infection is suspected to act as a key trigger of HT by causing autoimmunity. SRRM1, an alternative splicing factor which responds to viral activity, might serve as potential marker of HT.