Comparative Analysis of Driver Mutations and Transcriptomes in Papillary Thyroid Cancer by Region of Residence in South Korea.

BACKGRUOUND: Radiation exposure is a well-known risk factor for papillary thyroid cancer (PTC). South Korea has 24 nuclear reactors in operation; however, no molecular biological analysis has been performed on patients with PTC living near nuclear power plants. METHODS: We retrospectively included patients with PTC (n=512) divided into three groups according to their place of residence at the time of operation: inland areas (n=300), coastal areas far from nuclear power plants (n=134), and nuclear power plant areas (n=78). After propensity score matching (1:1:1) by age, sex, and surgical procedure, the frequency of representative driver mutations and gene expression profiles were compared (n=50 per group). Epithelial-mesenchymal transition (EMT), BRAF, thyroid differentiation, and radiation scores were calculated and compared. RESULTS: No significant difference was observed in clinicopathological characteristics, including radiation exposure history and the frequency of incidentally discovered thyroid cancer, among the three groups. BRAFV600E mutation was most frequently detected in the groups, with no difference among the three groups. Furthermore, gene expression profiles showed no statistically significant difference. EMT and BRAF scores were higher in our cohort than in cohorts from Chernobyl tissue bank and The Cancer Genome Atlas Thyroid Cancer; however, there was no difference according to the place of residence. Radiation scores were highest in the Chernobyl tissue bank but exhibited no difference according to the place of residence. CONCLUSION: Differences in clinicopathological characteristics, frequency of representative driver mutations, and gene expression profiles were not observed according to patients' region of residence in South Korea.

Immune response and mesenchymal transition of papillary thyroid carcinoma reflected in ultrasonography features assessed by radiologists and deep learning.

INTRODUCTION: Ultrasonography (US) features of papillary thyroid cancers (PTCs) are used to select nodules for biopsy due to their association with tumor behavior. However, the molecular biological mechanisms that lead to the characteristic US features of PTCs are largely unknown. OBJECTIVES: This study aimed to investigate the molecular biological mechanisms behind US features assessed by radiologists and three convolutional neural networks (CNN) through transcriptome analysis. METHODS: Transcriptome data from 273 PTC tissue samples were generated and differentially expressed genes (DEGs) were identified according to US feature. Pathway enrichment analyses were also conducted by gene set enrichment analysis (GSEA) and ClusterProfiler according to assessments made by radiologists and three CNNs - CNN1 (ResNet50), CNN2 (ResNet101) and CNN3 (VGG16). Signature gene scores for PTCs were calculated by single-sample GSEA (ssGSEA). RESULTS: Individual suspicious US features consistently suggested an upregulation of genes related to immune response and epithelial-mesenchymal transition (EMT). Likewise, PTCs assessed as positive by radiologists and three CNNs showed the coordinate enrichment of similar gene sets with abundant immune and stromal components. However, PTCs assessed as positive by radiologists had the highest number of DEGs, and those assessed as positive by CNN3 had more diverse DEGs and gene sets compared to CNN1 or CNN2. The percentage of PTCs assessed as positive or negative concordantly by radiologists and three CNNs was 85.6% (231/273) and 7.1% (3/273), respectively. CONCLUSION: US features assessed by radiologists and CNNs revealed molecular biologic features and tumor microenvironment in PTCs.

Impact of thyroid hormone replacement on the risk of second cancer after thyroidectomy: a Korean National Cohort Study.

We aimed to investigate the effect of thyroid hormone administration on the risk of second primary cancer in patients who underwent thyroidectomy for differentiated thyroid cancer. Data were extracted from the medical billing data of the Health Insurance Review and Assessment Service in South Korea. Patients between 19 and 80 years old who underwent thyroid surgery at least once between January 2009 and June 2020 were included. Data of patients with second primary cancer and control patients with matched age, sex, operation date, and follow-up duration were extracted at a ratio of 1:4. A nested case-control analysis was performed to exclude length bias to confirm the correlation between the duration of thyroid hormone administration, dose, and incidence of second primary cancer. Of the 261,598 patients who underwent surgery for thyroid cancer included in the study, 11,790 with second primary cancer and 47,160 without second primary cancer were matched. The average dose of thyroid hormone increased the adjusted odds ratio (OR) for both low (≤ 50 µg, OR 1.29, confidence interval (CI) 1.12-1.48) and high (< 100 µg, OR 1.24, CI 1.12-1.37) doses. Analyzing over time, the adjusted OR of second primary cancer increased, especially in short (≤ 1 year) (OR 1.19; CI 1.06-1.34) and long (> 5 years) duration (OR 1.25; CI 1.10-1.41). In conclusion, insufficient and excessive thyroid hormone replacement might be linked to increased second primary cancer in patients who underwent thyroidectomy for differentiated thyroid cancer.

Do large thyroid nodules (≥4 cm) without suspicious cytology need surgery?

Background: Fine-needle aspiration biopsy (FNAB) is a good diagnostic tool for thyroid nodules; however, its high false-negative rate for giant nodules remains controversial. Many clinicians recommend surgical resection for nodules >4 cm owing to an increased risk of malignancy and an increased false-negative rate. This study aimed to examine the feasibility of this approach and investigate the incidence of malignancy in thyroid nodules >4 cm without suspicious cytology based on medical records in our center. Methods: This was a retrospective analysis of 453 patients that underwent preoperative FNAB for nodules measuring >4 cm between January 2017 and August 2022 at Severance Hospital, Seoul. Results: Among the 453 patients, 140 nodules were benign and 119 were indeterminate. Among 259 patients, the final pathology results were divided into benign (149) and cancerous (110) groups, and the prevalence of malignancy was 38.9% in the benign group and 55.5% in the indeterminate group. Among the malignancies, follicular carcinoma and follicular variants of papillary carcinoma were observed in 83% of the cytologically benign group and 62.8% of the indeterminate group. Conclusion: Preoperative FNAB had high false-negative rates and low diagnostic accuracy in patients with thyroid nodules >4 cm without suspicious cytologic features; therefore, diagnostic surgery may be considered a treatment option.

Impact of thyroid cancer on the cancer risk in patients with non-alcoholic fatty liver disease or dyslipidemia.

The raised prevalence of obesity has increased the incidence of obesity-related metabolic diseases such as dyslipidemia (DL) and non-alcoholic fatty liver disease (NAFLD), along with the development and progression of various types of cancer, including thyroid cancer. In this study, we investigated whether thyroid cancer in patients with DL and NAFLD could be a risk factor for other cancers. To achieve our goal, we generated two independent cohorts from our institution and from the National Health Insurance System in South Korea. Based on the ICD-10 code, we conducted exact matching (1:5 matching) and estimated the overall risk of thyroid cancer for other cancers in patients with DL or NAFLD. Univariate and multivariate analyses showed that the hazard ratio (HR) of thyroid cancer was 2.007 (95% Confidence Interval [CI], 1.597-2.522) and 2.092 (95% CI, 1.546-2.829), respectively in the institutional cohort and 1.329 (95% CI, 1.153-1.533) and 1.301 (95% CI, 1.115-1.517), respectively in the nationwide cohort. Risk analysis revealed a significant increase in the HR in lip, tongue, mouth, lung, bone, joint, soft tissue, skin, brain, male cancers and lymphoma after thyroid cancer occurred. Thyroid cancer in patients with DL or NAFLD might be a valuable factor for predicting the development of other cancers.

Fine Needle Aspiration Cytology vs. Core Needle Biopsy for Thyroid Nodules: A Prospective, Experimental Study Using Surgical Specimen.

Purpose: To evaluate and compare the diagnostic outcomes of ultrasonography (US)-guided fine needle aspiration (FNA) and core needle biopsy (CNB) performed on the same thyroid nodule using a surgical specimen for direct comparison. Materials and Methods: We included 89 thyroid nodules from 88 patients from February 2015 to January 2016. The inclusion criterion was thyroid nodules measuring ≥ 20 mm (mean size: 40.0 ± 15.3 mm). Immediately after surgical resection, FNA and subsequent CNB were performed on the surgical specimen under US guidance. FNA and CNB cytopathologic results on the specimen were compared with the surgical diagnosis. Results: Among the 89 nodules, 30 were malignant and 59 were benign. Significantly higher inconclusive rates were seen in FNA for malignant than benign nodules (80.0% vs. 39.0%, p < 0.001). For CNB, conclusive and inconclusive rates did not differ between benign and malignant nodules (p = 0.796). Higher inconclusive rates were seen for FNA among cancers regardless of US features, and in the subgroup of size ≥ 40 mm (62.5% vs. 22.9%, p = 0.028). Eleven cancers were diagnosed with CNB (36.7%, 11/30), while none was diagnosed using FNA. Conclusion: In this experimental study using surgical specimens, CNB showed a potential to provide improved diagnostic sensitivity for thyroid cancer, especially when a conclusive diagnosis is limited with FNA.

Thyroid lobectomy is sufficient for differentiated thyroid cancer with upgraded risk after surgery.

Background: It is difficult to reliably distinguish between American Thyroid Association (ATA) low-risk and intermediate-risk differentiated thyroid cancer (DTC) before surgery. Therefore, physicians are faced with a dilemma regarding the necessity and timing of completion total thyroidectomy (CT) after thyroid lobectomy (TL). We evaluated proper surgical methods by analyzing oncologic outcomes of TL in patients with DTC whose risk had been upgraded after surgery. Methods: We retrospectively reviewed the medical records of 1,702 patients with DTC who underwent TL and ipsilateral central lymph node (LN) dissection between January 2006 and December 2011. The patients were classified into Group A (n=1,159; low risk; ≤5 central LN metastases or the absence of pathologic microscopic capsular invasion) and Group B (n=543; upgraded intermediate risk after surgery; >5 central LN metastases or the presence of pathologic microscopic capsular invasion). We analyzed their clinicopathological characteristics and recurrence-free survival. Results: All 32 patients who experienced recurrence underwent CT. After the first operation, the duration until reoperation in Groups A and B were 8.00±2.74 (range, 3.42-12.17) and 5.10±3.09 (range, 1.25-11.67) years, respectively. There was no significant difference in recurrence rates, disease-related mortality rates, or 10-year recurrence-free survival rates between the two groups. The mean follow-up durations in Groups A and B were 10.22±1.58 and 10.13±1.47 years, respectively. Univariate analysis showed that sex, age, tumor size, multifocality, extrathyroidal extension (ETE), and number of central LN metastases were not associated with recurrence after TL, although the rate of central LN metastases was. Multivariate analysis showed that sex, age, tumor size, multifocality, ETE, central LN metastases, and the number of central LN metastases were not associated with recurrence after TL, although multifocality was. Conclusions: TL with prophylactic central compartment neck dissection (CCND) is sufficient for patients with DTC whose risk is upgraded after surgery because they have a good prognosis at long-term follow-up. Larger-scale randomized clinical trials are required to confirm our findings.

Non-genomic activation of the AKT-mTOR pathway by the mitochondrial stress response in thyroid cancer.

Cancer progression is associated with metabolic reprogramming and causes significant intracellular stress; however, the mechanisms that link cellular stress and growth signalling are not fully understood. Here, we identified a mechanism that couples the mitochondrial stress response (MSR) with tumour progression. We demonstrated that the MSR is activated in a significant proportion of human thyroid cancers via the upregulation of heat shock protein D family members and the mitokine, growth differentiation factor 15. Our study also revealed that MSR triggered AKT/S6K signalling by activating mTORC2 via activating transcription factor 4/sestrin 2 activation whilst promoting leucine transporter and nutrient-induced mTORC1 activation. Importantly, we found that an increase in mtDNA played an essential role in MSR-induced mTOR activation and that crosstalk between MYC and MSR potentiated mTOR activation. Together, these findings suggest that the MSR could be a predictive marker for aggressive human thyroid cancer as well as a useful therapeutic target.

TERT Promoter and BRAF V600E Mutations in Papillary Thyroid Cancer: A Single-Institution Experience in Korea.

Telomerase reverse transcriptase (TERT) promoter mutation has been investigated for its clinical and prognostic significance in aggressive papillary thyroid cancer (PTC). In this study, we aimed to assess the prevalence, clinicopathologic features, and treatment outcomes of TERT mutation-positive PTCs along with the common BRAF V600E mutation. We performed mutational analyses for BRAF and the TERT promoter in thyroid cancer patients who had undergone surgery at our institution since 2019. We reviewed and analyzed 7797 patients with PTC in this study. The prevalence of BRAF V600E and TERT promoter mutations was 84.0% and 1.1%, respectively. Multifocal gene mutations in bilateral PTCs were identified. TERT promoter mutations were associated with older age, larger tumor size, tumor multifocality, tumor variants, advanced stages, more adjuvant radioactive iodine treatment (RAI), higher stimulated serum thyroglobulin level before RAI, and more uptakes in the regions outside the surgical field on a post-RAI whole-body scan. The coexistence of BRAF V600E and TERT promoter mutations exacerbated all clinicopathologic characteristics. The frequency of TERT promoter mutations was the lowest in this study, compared to previous studies. TERT promoter mutations consistently correlated with aggressive PTCs, and the synergistic effect of both mutations was evident. Specific clinical settings in our institution and in Korea may have led to these distinctive results. Prospective multicenter studies with longer follow-up periods are required to establish valuable oncologic outcomes.

Cell non-autonomous effect of hepatic growth differentiation factor 15 on the thyroid gland.

The thyroid gland plays an essential role in the regulation of body energy expenditure to maintain metabolic homeostasis. However, to date, there are no studies investigating the morphological and functional changes of the thyroid gland due to mitochondrial stress in metabolic organs such as the liver. We used data from the Genotype-Tissue Expression portal to investigate RNA expression patterns of the thyroid gland according to the expression of growth differentiation factor 15 (GDF15) such as the muscles and liver. To verify the effect of hepatic GDF15 on the thyroid gland, we compared the morphological findings of the thyroid gland from liver-specific GDF15 transgenic mice to that of wild type mice. High GDF15 expression in the muscles and liver was associated with the upregulation of genes related to hypoxia, inflammation (TGF-α via NFκB), apoptosis, and p53 pathway in thyroid glands. In addition, high hepatic GDF15 was related to epithelial mesenchymal transition and mTORC1 signaling. Electron microscopy for liver-specific GDF15 transgenic mice revealed short mitochondrial cristae length and small mitochondrial area, indicating reduced mitochondrial function. However, serum thyroid stimulating hormone (TSH) level was not significantly different. In our human cohort, those with a high serum GDF15 level showed high fasting glucose, alanine transaminase, and alkaline phosphatase but no difference in TSH, similar to the data from our mice model. Additionally, high serum GDF15 increased the risk of lymph node metastasis to lateral neck. The hepatic GDF15 affected thyroid morphogenesis via a TSH-independent mechanism, affecting aggressive features of thyroid cancers.

Re-do Operation Using a Robotic System due to Locoregional Recurrence after Initial Thyroidectomy for Thyroid Cancer.

Locoregional recurrent thyroid cancer is commonly treated with re-do operation. This study aimed to investigate the feasibility of using robotic system for re-do operation in locoregional recurrent thyroid cancer. Sixty-five patients who underwent re-do robotic operation using trans-axillary approach for locoregional recurrent thyroid cancer from October 2007 to April 2021 at Yonsei University Hospital were analyzed. Completion total thyroidectomy (CTT) was performed in 26 cases, CTT and modified radical neck node dissection (mRND) in 16, and mRND in 23. Most of the re-do robotic operations were performed at site of previous incision. All patients were diagnosed with papillary thyroid carcinoma (PTC). CTT with central compartment neck dissection (CCND) took 117.6 ± 26.3 min, CTT with mRND 255.6 ± 38.6 min, and mRND, 211.7 ± 52.9 min. Transient hypocalcemia occurred in 17 (26.2%) patients and permanent hypocalcemia occurred in 3 (4.6%). There was one case of recurrent laryngeal nerve(RLN) injury. One patient was diagnosed with structural recurrence after re-do robotic operation. Median follow-up duration was 50.7 ± 37.1 months. Re-do robotic operation can be an alternative for patients who are diagnosed with locoregional recurrent thyroid cancer after thyroidectomy, with no increase in morbidity, similar oncologic outcomes, and superior cosmetic satisfaction.

Comparisons Between Normocalcemic Primary Hyperparathyroidism and Typical Primary Hyperparathyroidism.

BACKGROUND: Normocalcemic primary hyperparathyroidism (NPHPT) was first described in 2008. It is defined as consistently elevated serum parathyroid hormone (PTH) levels with normal serum calcium (sCa) concentration, after excluding secondary causes of PTH elevation. However, the exact definition and management strategy for NPHPT remain controversial. We retrospectively investigated the clinicopathological features and short-term outcomes of NPHPT patients. METHODS: A total of 280 patients who were surgically indicated for primary hyperparathyroidism (PHPT) at the Yonsei Severance Medical Center between 2015 and 2019 were included. Patients were classified according to preoperative PTH, corrected sCa, and ionized calcium (iCa) levels as follows: typical primary hyperparathyroidism (TPHPT, elevated PTH, sCa, and iCa, n = 158) and NPHPT (elevated PTH, normal sCa, n = 122). RESULTS: NPHPT was commonly seen in younger individuals (aged < 50 years, P = 0.025); nephrolithiasis and bone fractures were common. Preoperative PTH level was higher in the TPHPT group (P < 0.001). The NPHPT group had higher numbers of multiple parathyroid lesions (P = 0.004) that were smaller (P = 0.011). NPHPT patients were further divided into two subgroups according to iCa levels: the elevated (n = 95) and normal iCa (n = 27) groups. There was no significant difference between the two subgroups regarding symptoms and multiplicity of lesions. CONCLUSION: We found that NPHPT may be a heterogeneous disease entity of PHPT with high rates of multi-gland disease, which appears to be biochemically milder but symptomatic. Intraoperative PTH monitoring might help increase the surgery success rate. Moreover, the short-term outcomes of NPHPT after surgery did not differ from that of TPHPT.

Long Non-Coding RNA-Based Functional Prediction Reveals Novel Targets in Notch-Upregulated Ovarian Cancer.

Notch signaling is a druggable target in high-grade serous ovarian cancers; however, its complexity is not clearly understood. Recent revelations of the biological roles of lncRNAs have led to an increased interest in the oncogenic action of lncRNAs in various cancers. In this study, we performed in silico analyses using The Cancer Genome Atlas data to discover novel Notch-related lncRNAs and validated our transcriptome data via NOTCH1/3 silencing in serous ovarian cancer cells. The expression of novel Notch-related lncRNAs was down-regulated by a Notch inhibitor and was upregulated in high-grade serous ovarian cancers, compared to benign or borderline ovarian tumors. Functionally, Notch-related lncRNAs were tightly linked to Notch-related changes in diverse gene expressions. Notably, genes related to DNA repair and spermatogenesis showed specific correlations with Notch-related lncRNAs. Master transcription factors, including EGR1, CTCF, GABPα, and E2F4 might orchestrate the upregulation of Notch-related lncRNAs, along with the associated genes. The discovery of Notch-related lncRNAs significantly contributes to our understanding of the complex crosstalk of Notch signaling with other oncogenic pathways at the transcriptional level.

Clinical Implications of Age in Differentiated Thyroid Cancer: Comparison of Clinical Outcomes between Children and Young Adults.

BACKGROUND: Pediatric patients with differentiated thyroid cancer (DTC) present with unique characteristics compared to adult patients. This study aimed to evaluate clinical presentation and surgical outcomes according to age and to identify the clinical significance of age in DTC. METHODS: In total, 98 pediatric patients, 1261 young adult patients, and 4017 adult patients with DTC who underwent thyroid surgery between January 1982 and December 2012 at Yonsei University Hospital (Seoul, Republic of Korea) were retrospectively reviewed. The mean follow-up duration was 120.4 ± 54.2 months. RESULTS: Mean tumor size was significantly larger in the pediatric group than in the adult groups (p < 0.001). The recurrence rate was significantly higher in the pediatric group (14.3% versus 6.6% versus 3.0%, p=0.004 and p < 0.001). In multivariate analysis, the risk of disease-free survival (DFS) was lower in the adult group (HR, 0.362; p < 0.001). Reanalysis of patients with tumor size of 2-4 cm revealed that the adult group was not a significant risk factor for DFS in multivariate analysis (HR, 0.305; 95% CI, 0.158 to 0.588; p < 0.001). CONCLUSIONS: Our findings suggest that pediatric patients present with more aggressive features and higher recurrence rates compared to adult patients and should be carefully treated from initial evaluation to surgery and postoperative care.

Robotic Adrenalectomy Using the da Vinci SP Robotic System: Technical Feasibility Comparison with Single-Port Access Using the da Vinci Multi-arm Robotic System.

BACKGROUND: Laparoscopic adrenalectomy is the gold standard for adrenal tumor; however, robotic adrenal surgery has gained interest recently. For minimally invasive surgeries, we first reported on robotic adrenalectomy using a single-port access performed using the da Vinci multi-arm robotic system (RA-SA) in 2011. Since its introduction in 2018, we first performed robotic adrenalectomy using the da Vinci SP robotic system in 2020. OBJECTIVE: We aimed to introduce the novel single-port robotic system (RA-SP) for adrenalectomy and evaluate its technical feasibility by comparing it with the surgical outcomes of patients who underwent robotic adrenalectomy using the RA-SA. METHODS: Eight patients who underwent robotic adrenalectomy using the RA-SP from February 2020 to June 2021 were compared with 11 patients who underwent RA-SA from 2011 to 2015 by a single surgeon. RESULTS: The two groups were similar in age, sex, body mass index, type of operation, and final pathologic diagnosis. Despite no significant differences, RA-SP resulted in moderately less mean operation time, estimated blood loss, and length of hospitalization. CONCLUSIONS: The Da Vinci SP robotic system is a novel, safe, and feasible technique to improve the convenience of operation and cosmetic effect for adrenalectomy.

Laparoscopic adrenalectomy: comparison of outcomes between posterior retroperitoneoscopic and transperitoneal adrenalectomy with 10 years' experience.

BACKGROUND: Laparoscopic adrenalectomy is widely used for treating various adrenal tumors. Posterior retroperitoneoscopic adrenalectomy was introduced after transperitoneal laparoscopic adrenalectomy. The comparability and superiority of posterior retroperitoneoscopic adrenalectomy have been widely investigated. We aimed to compare the outcomes of posterior retroperitoneoscopic adrenalectomy and transperitoneal laparoscopic adrenalectomy using 10 years' data. The changes in outcomes over time were also analyzed. METHODS: This was a retrospective observational study. A total of 505 patients who underwent laparoscopic adrenalectomy between 2009 and 2018 were included. The patients were divided into two groups: transperitoneal (n=114) and retroperitoneal (n=391) groups. Patients who underwent posterior retroperitoneoscopic adrenalectomy were further classified into sub-groups (sub-group 1: 2009-2012; sub-group 2: 2013-2015; and sub-group 3: 2016-2018) based on time periods. Clinicopathological factors and postoperative outcomes were retrospectively reviewed and analyzed. RESULTS: The retroperitoneal group showed significantly shorter operation time, diet initiation time, and hospital stay compared to the transperitoneal group (P=0.000, 0.000 and 0.000, respectively). Analgesics were used less frequently in the retroperitoneal group than in the transperitoneal group (P=0.048). In the retroperitoneal group, the time to postoperative diet initiation shortened over time (P=0.000). CONCLUSIONS: Posterior retroperitoneoscopic adrenalectomy is a favorable surgical method that results in patient outcomes that are comparable to those of conventional transperitoneal laparoscopic adrenalectomy, without compromising patient safety.

Efficacy of Immunohistochemistry for SDHB in the Screening of Hereditary Pheochromocytoma-Paraganglioma.

The most common genetic backgrounds of hereditary paraganglioma and pheochromocytoma (PPGL) are SDHx germline mutations. Given the fact that the immunohistochemistry (IHC) result for SDHB is always negative regardless of the type of SDHx mutation, we aimed to evaluate the efficacy of using SDHB IHC for screening SDHx mutations in PPGL cases. In total, 52 patients who underwent surgery for PPGL treatment between 2006 and 2020 and underwent genetic analysis at diagnosis were included. Tissue microarrays (TMAs) were constructed with PPGL tissues and IHC for SDHB was performed on TMA sections. All 10 patients with SDHB-negative IHC contained SDHB or SDHD mutations. The genetic test results of patients with SDHB-weakly positive IHC varied (one SDHB, two RET, one VHL, and three unknown gene mutations). There were no SDHx mutations in the SDHB-positive IHC group. Six patients with weakly positive SDHB IHC with primarily unknown genetic status were re-called and underwent next-generation sequencing. None of them had SDHx mutations. In conclusion, SDHB-negative IHC is a cost-effective and reliable method to predict SDHx mutations. However, in the case of weakly positive SDHB staining, an additional gene study should be considered.

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

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.

Simultaneous Expression of Long Non-Coding RNA FAL1 and Extracellular Matrix Protein 1 Defines Tumour Behaviour in Young Patients with Papillary Thyroid Cancer.

We investigated the regulatory mechanism of FAL1 and unravelled the molecular biological features of FAL1 upregulation in papillary thyroid cancer (PTC). Correlation analyses of FAL1 and neighbouring genes adjacent to chromosome 1q21.3 were performed. Focal amplification was performed using data from copy number alterations in The Cancer Genome Atlas (TCGA) database. To identify putative transcriptional factors, PROMO and the Encyclopaedia of DNA Elements (ENCODE) were used. To validate c-JUN and JUND as master transcription factors for FAL1 and ECM1, gene set enrichment analysis was performed according to FAL1 and ECM1 expression. Statistical analyses of the molecular biological features of FAL1- and ECM1-upregulated PTCs were conducted. FAL1 expression significantly correlated with that of neighbouring genes. Focal amplification of chromosome 1q21.3 was observed in ovarian cancer but not in thyroid carcinoma. However, PROMO suggested 53 transcription factors as putative common transcriptional factors for FAL1 and ECM1 simultaneously. Among them, we selected c-JUN and JUND as the best candidates based on ENCODE results. The expression of target genes of JUND simultaneously increased in FAL1- and ECM1-upregulated PTCs, especially in young patients. The molecular biological features represented RAS-driven PTC and simultaneously enriched immune-related gene sets. FAL1 and ECM1 expression frequently increased simultaneously and could be operated by JUND. The simultaneous upregulation might be a potential diagnostic and therapeutic target for RAS-driven PTC.