The Predictive Factors of Combined Implant Application for Breast Cancer Patients Receiving Immediate Breast Reconstruction with a Pedicled Omental Flap.

BACKGROUND: Whether a laparoscopically harvested omental flap is adequate for total breast reconstruction could not be determined preoperativaly due to lack of reliable assessment methods. This study aimed to establish a statistical model to predict the probability of omental flap insufficiency. METHODS: In this study, 200 female patients with breast cancer receiving immediate breast reconstruction with pure pedicled omental flaps or pedicled omental flaps combined with implants after nipple-areolar complex-sparing mastectomy were divided into two groups depending on whether implants were needed or not. The clinical characteristics of these two groups were compared. Correlation of body mass index (BMI) and omental volume was analyzed. Binary logistic regression was performed to predict the probability of implant requirement based on clinical parameters, showing significant differences between the two groups. RESULTS: The patients who needed implants in adjunct treatment were younger. In addition, they had larger breast specimens and smaller omental volumes than the others whose omental flaps were sufficient for total breast reconstruction. Body mass index and omental volume showed a moderately positive correlation. Age, specimen volume, and BMI all were entered into the logistic regression equation. For the patients with a BMI lower than 24.0 kg/m2, the probability of requiring implants was 5.467 times that of comparable patients with a BMI of 24.0 kg/m2 or higher. At the cutoff of 0.61, the regression equation yielded a sensitivity of 84.2% and a specificity of 72.1% in recognizing subjects with the necessity of implant application. CONCLUSION: The combination of BMI, age, and volume of breast specimen could predict with high accuracy whether implants are required for breast cancer patients receiving pedicled omental flap-based breast reconstruction.

Hypoxic papillary thyroid carcinoma cells-secreted exosomes deliver miR-221-3p to normoxic tumor cells to elicit a pro-tumoral effect by regulating the ZFAND5.

Papillary thyroid cancer (PTC) has seen a worldwide expansion in incidence in the past three decades. Tumor-derived exosomes have been associated with the metastasis of cancer cells and are present within the local hypoxic tumor microenvironment, where they mediate intercellular communication by transferring molecules including microRNAs (miRNAs) between cells. Although miRNAs have been shown to serve as non-invasive biomarkers for cancer diagnosis, the role of hypoxia-induced tumor-derived exosomes in PTC progression remains unclear. Herein, we investigated the differentially expressed miRNA expression profiles from GEO datasets (GSE191117 and GSE151180) by using the DESeq package in R and identified a novel role for miR-221-3p as an oncogene in PTC development. In vivo and in vitro loss and gain assays were used to clarify the mechanism of hypoxic PTC cells derived exosomal-miR-221-3p in PTC. miR-221-3p was upregulated in human PTC plasma exosomes, tissues and cell lines. We found that hypoxic PTC cells derived exosomal-miR-221-3p promoted normoxic PTC cells proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in vitro, while inhibition of miR-221-3p limited PTC tumor growth in our PTC xenograft model in nude mice. We finally identified ZFAND5, to be a miR-221-3p target. Mechanistically, hypoxic PTC cell lines-derived exosomes carrying miR-221-3p promoted PTC tumorigenesis by regulating ZFAND5. Our findings further the understanding of the underlying mechanisms associated with PTC progression and identify exosomal-miR-221-3p as a potential biomarker for the diagnosis and prognosis of PTC patients. Our study also suggests that miR-221-3p inhibitors could be a potential treatment strategy for PTC.

Clinical characteristics and long-term outcomes for parapharyngeal metastases of well-differentiated thyroid cancer during 131 I therapy and follow-up.

OBJECTIVE: Parapharyngeal metastases (PPM) are rarely observed in patients with well-differentiated thyroid cancer (WDTC). Radioiodine (131 I) therapy has been the main treatment for metastatic and recurrent DTC after thyroidectomy. This study was performed to evaluate the clinicopathological features and long-term outcomes associated with survival of patients with PPM at the end of follow-up. DESIGN: In total, 14,984 consecutive patients with DTC who underwent 131 I therapy after total or near-total thyroidectomy from 2004 to 2021 were retrospectively reviewed. Therapeutic efficacy was evaluated using the Response Evaluation Criteria in Solid Tumours v1.1 and logistic regression analysis. The disease status was determined using dynamic risk stratification. Disease-specific survival (DSS) was assessed using the Kaplan-Meier method and a Cox proportional hazards model. PATIENTS: Seventy-five patients with PPM from WDTC were enroled in this study. Their median age at the initial diagnosis of PPM was 40.2 ± 14.1 years, and the patients comprised 32 men and 43 women (male:female ratio, 1.00:1.34). Of the 75 patients, 43 (57.33%) presented with combined distant metastases. Fifty-seven (76.00%) patients had 131 I avidity and 18 had non-131 I avidity. At the end of follow-up, 22 (29.33%) patients showed progressive disease. Sixteen of the 75 patients died; of the remaining 59 patients, 6 (8.00%) had an excellent response, 6 (8.00%) had an indeterminate response, 10 (13.33%) had an biochemical incomplete response, and 37 (49.33%) had a structural incomplete response. Multivariate analysis confirmed that age at initial PPM diagnosis, the maximal size of PPM, and 131 I avidity had significant effects on progressive disease of PPM lesions (p = .03, p= .02, and p < .01, respectively). The 5- and 10-year DSS rates were 98.49% and 62.10%, respectively. Age of ≥55 years at initial diagnosis of PPM and the presence of concomitant distant metastasis were independently associated with a poor prognosis (p = .03 and p = .04, respectively). CONCLUSION: The therapeutic effect for PPM was closely associated with 131 I avidity, age at initial PPM diagnosis, and maximal size of PPM at the end of follow-up. Age of ≥55 years at initial diagnosis of PPM and the presence of concomitant distant metastasis were independently associated with poor survival.

Transoral endoscopic selective lateral neck dissection for papillary thyroid carcinoma: a pilot study.

BACKGROUND: Transoral endoscopic thyroid surgery via the vestibular approach (TOETVA) has been gradually accepted worldwide due to its scar-free effect on the neck. Even central cervical lymphadenectomy has been performed in some cases of papillary thyroid carcinoma (PTC). However, there are few reports involving lateral neck dissection with TOETVA. In this study, we attempted to perform selective lateral neck dissection (SLND) for PTC via a transoral vestibular approach. METHODS: This prospective study was conducted from January 2016 to December 2018 in twenty PTC patients with unilateral T1 tumors without capsular invasion and patients with abnormal level III and IV lymph nodes who underwent SLND via a transoral vestibular approach. RESULTS: Endoscopic surgery was successfully accomplished in all 20 PTC patients. The mean age was 29.2 ± 5.5 (20-41) years. The mean operation time was 146.0 ± 18.7 (114-193) min. The average postoperative hospital stay was 6.8 ± 1.3 (5-10) days. The mean number of removed nodes was 7.4 ± 2.5 (4-12) in the central neck and 10.9 ± 2.8 (6-16) in the lateral neck, and the positive yield amounts were 2.0 ± 1.2 (0-4) and 2.7 ± 1.9 (0-6), respectively. No major complications occurred except for 1 case of transient unilateral recurrent laryngeal nerve palsy and two cases of effusion in the operative area. No evidence of persistent or recurrent disease was observed in these patients during a mean follow-up of 24.3 ± 9.1 (6-36) months. The cosmetic results and protection of personal privacy of this procedure were excellent. CONCLUSION: Endoscopic SLND via the transoral vestibular approach is feasible, safe, and effective for selected PTCs. A multicenter large comparative study is necessary.

Network meta-analysis of surgical treatment for secondary hyperparathyroidism.

BACKGROUND: Main surgical treatments for secondary hyperparathyroidism (SHPT) include subtotal parathyroidectomy (sPTX), total parathyroidectomy with autotransplantation (tPTX+AT), and total parathyroidectomy (tPTX); however, determining the best treatment is debatable. We conducted a network meta-analysis (NMA) comparing three treatments in terms of postoperative hypocalcemia (or hypoparathyroidism), postoperative recurrence, and reoperation. METHODS: We searched PubMed, Medline, the Cochrane Library, and Embase for relevant research from inception to July 30, 2019. We performed our Bayesian NMA using R 3.51 software to assess odds ratios (OR) and 95% confidence intervals (CI). Network and forest plots displayed study outputs. Potential publication bias was assessed with funnel plots using software Stata/MP 13.0. RESULTS: Twenty-six articles comprising 5063 patients were included in our NMA, which showed that postoperative hypocalcemia (or hypoparathyroidism) occurred more frequently in tPTX than in sPTX (OR = 3.50, 95% CI 1.10-11.0) or tPTX+AT patients (OR = 1.80, 95% CI 0.66-5.20). Regarding postoperative hypocalcemia (or hypoparathyroidism), there was no significant difference between sPTX and tPTX+AT (OR = 0.53, 95% CI 0.24-1.10). As for recurrence rates, statistically significant differences were observed between sPTX and tPTX (OR = 25.0, 95% CI 5.1-260), tPTX+AT and tPTX (OR = 20.0, 95% CI 4.2-200), and sPTX and tPTX+AT (OR = 1.30, 95% CI 0.65-2.50). Regarding reoperation rates, sPTX experienced higher incidence compared with tPTX+AT (OR = 1.20, 95% CI 0.53-2.70) or tPTX patients (OR = 2.70, 95% CI 1.20-14.00). CONCLUSIONS: TPTX+AT is recommended as the most efficient and safe surgical SHPT treatment with minimal adverse effects. Large-scale randomized controlled trials are recommended to confirm the NMA results.

PPM1D exerts its oncogenic properties in human pancreatic cancer through multiple mechanisms.

Protein phosphatase, Mg(2+)/Mn(2+) dependent, 1D (PPM1D) is emerging as an oncogene by virtue of its negative control on several tumor suppressor pathways. However, the clinical significance of PPM1D in pancreatic cancer (PC) has not been defined. In this study, we determined PPM1D expression in human PC tissues and cell lines and their irrespective noncancerous controls. We subsequently investigated the functional role of PPM1D in the migration, invasion, and apoptosis of MIA PaCa-2 and PANC-1 PC cells in vitro and explored the signaling pathways involved. Furthermore, we examined the role of PPM1D in PC tumorigenesis in vivo. Our results showed that PPM1D is overexpressed in human PC tissues and cell lines and significantly correlated with tumor growth and metastasis. PPM1D promotes PC cell migration and invasion via potentiation of the Wnt/ß-catenin pathway through downregulation of apoptosis-stimulating of p53 protein 2 (ASPP2). In contrast to PPM1D, our results showed that ASPP2 is downregulated in PC tissues. Additionally, PPM1D suppresses PC cell apoptosis via inhibition of the p38 MAPK/p53 pathway through both dephosphorylation of p38 MAPK and downregulation of ASPP2. Furthermore, PPM1D promotes PC tumor growth in vivo. Our results demonstrated that PPM1D is an oncogene in PC.

Downregulation of Smurf2 ubiquitin ligase in pancreatic cancer cells reversed TGF-ß-induced tumor formation.

Smad ubiquitin regulatory factor 2 (Smurf2) is an E3 ubiquitin ligase that regulates transforming growth factor ß (TGF-ß)/Smad signaling and is implicated in a wide range of cellular responses. However, the exact mechanism whereby Smurf2 controls TGF-ß-induced signaling pathways remains unknown. Here, we identified the relationship between the alternate TGF-ß signaling pathways: TGF-ß/PI3K/Akt/ß-catenin and TGF-ß/Smad2/3/FoxO1/PUMA and Smurf2. The results showed that TGF-ß promoted proliferation, invasion, and migration of human pancreatic carcinoma (PANC-1) cells through the PI3K/Akt/ß-catenin pathway. Inhibiting the PI3K/Akt signal transformed the TGF-ß-induced cell response from promoting proliferation to Smad2/3/FoxO1/PUMA-mediated apoptosis. The activation of Akt inhibited the phosphorylation/activation of Smad3 and promoted the phosphorylation/inactivation of FoxO1, inhibiting the nuclear translocation of both Smad3 and FoxO1 and inhibiting the expression of PUMA, a key apoptotic mediator. However, downregulation of Smurf2 in PANC-1 cells removed Akt-mediated suppression of Smad3 and FoxO1, allowing TGF-ß-induced phosphorylation/activation of Smad2/3, dephosphorylation/activation of FoxO1, nuclear translocation of both factors, and activation of PUMA-mediated apoptosis. Downregulation of Smurf2 also decreased invasion and migration in TGF-ß-induced PANC-1 cells. The in vivo experiments also revealed that downregulation of Smurf2 delayed the growth of xenograft tumors originating from PANC-1 cells especially when treated with TGF-ß. Taken together, these results indicate that expression of Smurf2 plays a central role in the determination and activation/inhibition of particular cellular pathways and the ultimate fate of cells induced by TGF-ß. An increased understanding of the intricacies of the TGF-ß signaling pathway may provide a new anti-cancer therapeutic target.

MiR-146b-5p promotes metastasis and induces epithelial-mesenchymal transition in thyroid cancer by targeting ZNRF3.

BACKGROUND/AIMS: Micro-RNA (miR)-146b-5p is overexpressed in papillary thyroid carcinoma (PTC) and associated with extrathyroidal invasion and advanced tumor stage. In the present study, we showed that miR-146b-5p is upregulated in PTC with lymph node metastasis. METHODS: A computational search and luciferase assay identified zinc RING finger 3 (ZNRF3), a negative regulator of Wnt/ß-catenin signaling, as a direct target of miR-146b-5p in PTC. RESULTS: MiR-146b-5p promoted migration and invasiveness and induced epithelial-mesenchymal transition (EMT) of PTC cells, whereas ZNRF3 overexpression reversed this effect. MiR-146b-5p increased the cell surface levels of the Wnt receptors Frizzled-6 and LRP6 and enhanced Wnt/ß-catenin signaling by downregulating ZNRF3, whereas an inhibitor of Wnt/ß-catenin suppressed the effect of miR-146b-5p on migration, invasiveness and EMT of PTC cells. CONCLUSION: These results indicate that miR-146b-5p induces EMT and may promote PTC metastasis through the regulation of Wnt/ß-catenin signaling, and suggest novel potential therapeutic targets for the treatment of PTC.

Relationships of FOXE1 and ATM genetic polymorphisms with papillary thyroid carcinoma risk: a meta-analysis.

We conducted the meta-analysis of all relevant case-control studies aiming to evaluate the relationships of common polymorphisms in forkhead box E1 (FOXE1) and ataxia telangiectasia mutated (ATM) genes to the risk of papillary thyroid carcinoma (PTC). A range of electronic databases were searched without language restrictions: Web of Science (1945 ~ 2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966 ~ 2013), EMBASE (1980 ~ 2013), CINAHL (1982 ~ 2013), and the Chinese Biomedical Database (CBM) (1982 ~ 2013). This meta-analysis was conducted using the STATA 12.0 software. Crude odds ratio (OR) with their 95 % confidence interval (CI) were calculated. Eight case-control studies with 2,085 PTC patients and 10,341 healthy controls were included. Fourteen common polymorphisms were evaluated, including rs3758249 A > G, rs907577 G > A, rs1867277 G > A, rs3021526 C > T, rs1443434 G > T, rs907580 G > A, rs965513 A > G, rs944289 C > T, and rs189037 G > A polymorphisms in the FOXE1 gene and rs373759 G > A, rs4988099 A > G, rs1801516 G > A, rs664677 T > C, and rs609429 G > C polymorphisms in the ATM gene. Our results demonstrated that the FOXE genetic polymorphisms might be closely related to an increased risk of developing PTC under five genetic models (all P < 0.005), especially for rs3758249, rs907577, rs1867277, rs3021526, rs1443434, rs907580, rs704839, rs894673, and rs10119760 polymorphisms. Nevertheless, no positive associations were found between the ATM genetic polymorphisms and the development of PTC (all P > 0.05). The current meta-analysis provided evidence that FOXE1 genetic polymorphisms may contribute to increased PTC risk, especially for rs3758249, rs907577, rs1867277, rs3021526, rs1443434, rs907580, rs704839, rs894673, and rs10119760 polymorphisms. However, the ATM genetic polymorphisms may not be important dominants of susceptibility to PTC.

Subgroup analysis of steadily increased trends in medullary thyroid carcinoma incidence and mortality in the USA, 2000-2020: a population-based retrospective cohort study.

The incidence rate of medullary thyroid carcinoma (MTC) continues to grow, along with its mortality rate in the USA. However, the subgroup trends in MTC have not yet been established. This population-based retrospective cohort study was based on the Surveillance, Epidemiology, and End Results (SEER) 17/12 registry database. Subgroup analysis was performed through clinicopathological and treatment-related characteristics. Annual average percentage change (AAPC) was calculated using joinpoint regression analysis. A total of 3833 MTC patients and 536 death cases were diagnosed in the SEER database. Between 2000 and 2019, the incidence (AAPC = 1.64) and mortality (AAPC = 3.46) rates of MTC continued to rise. Subgroup analysis showed the proportion of elderly patients (65-84 years) gradually increased in incidence between 2000 and 2020. Patients with early-stage tumors, such as tumors ≤20 mm, showed the same trends. Aspects of treatment, the implementation rate of total thyroidectomy (AAPC = 0.38) and lymph node dissection (AAPC = 1.06) also increased persistently in almost all of the age subgroups. The incidence and mortality of MTC consistently increased from 2000 to 2019. Subgroup analysis indicated a significant increase in elderly patients and early-stage patients, and more attention should be paid to the management of these increased subgroups.

Thyroidectomy without lymph node dissection should be considered for stage T1 medullary thyroid carcinoma: a population-based cohort study.

Background: The necessity and therapeutic value of lymph node dissection (LND) in early stage T1 MTC patients remain controversial. Methods: Patients with T1MTC were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Poisson regression analysis was utilized to investigate promotive factors for lymph node metastasis in T1MTC patients. Fisher's exact test was employed to calculate baseline differences between non-LND and LND groups. Propensity score match (PSM) was used to control baseline bias. Survival outcomes were calculated by Kaplan-Meier method and log-rank test. Multivariable Cox regression assessed the prognostic impact of LND across subgroups. Results: Of 3298 MTC cases, 50.4% were T1MTC. The lymph node metastasis rate increased along with the T stage (from 22.2% to 90.5%). Among 1231 T1MTC patients included after exclusion criteria, 72.0% underwent LND and 22.0% had lymph node metastasis. Patients aged younger than 44 years (RR=1.700, p<0.001), male (RR=1.832, p<0.001), and with tumor larger than 10mm (RR=2.361, p<0.001) were more likely to have lymph node metastasis, while elderly patients (p<0.001) and those with microcarcinoma (p<0.001) were more likely to undergo non-LND procedures. LND provided no OS or DSS benefit over non-LND before and after propensity score match (matched 10-year OS/DSS: LND 83.8/96.2% vs non-LND 81.9/99.3%, p>0.05). Subgroup analyses revealed no prognostic gain with LND in any subgroup (p>0.05). Conclusion: Nearly half of MTC patients were diagnosed at T1 stage and had low lymph node risk. Different from ATA guidelines, avoiding routine LND conferred similar prognosis to standard procedures while potentially improving quality of life. Large-scale prospective multi-center studies should be conducted to further validate these findings.

Improved survival after primary tumor resection in distant metastasis medullary thyroid carcinoma: a population-based cohort study with propensity score matching.

Few studies have investigated the impact of primary tumor resection (PTR) on patients with distant metastasis medullary thyroid carcinoma (DMMTC). This population-based study aims to assess the application of PTR in DMMTC patients, ascertain its benefits, and identify optimal surgical indications. DMMTC Patients diagnosed between 2010 and 2020 were included through the Surveillance, Epidemiology, and End Results (SEER) program. Logistic regression analysis identified driving factors of surgical decision-making. Propensity score matching (PSM), Kaplan-Meier method, and Cox regression were utilized to compare overall survival (OS) and disease-specific survival (DSS) between surgical and non-surgical groups. Subgroup analyses were performed to determine optimal surgical indications. Of 238 DMMTC patients included, 122 (51.3%) patients underwent PTR. Extrathyroidal extension and N1 stage emerged as independent factors promoting the surgical decision. PSM-adjusted survival analyses revealed significant advantages in both OS and DSS for the surgical group. Moreover, subgroup analyses indicated that except for patients aged ≥ 65 years, tumors ≤ 20 mm, or with multiple metastasized sites (> 1), the others significantly benefit from PTR. PTR significantly improves prognosis in selected DMMTC patients. The decision to undergo PTR in other patients should be based on a comprehensive assessment of the disease, surgeon's experience, and family discussions for potential survival benefits.

An automatic parathyroid recognition and segmentation model based on deep learning of near-infrared autofluorescence imaging.

INTRODUCTION: Near-infrared autofluorescence imaging (NIFI) can be used to identify parathyroid gland (PG) during surgery. The purpose of the study is to establish a new model, help surgeons better identify, and protect PGs. METHODS: Five hundred and twenty three NIFI images were selected. The PGs were recorded by NIFI and marked with artificial intelligence (AI) model. The recognition rate for PGs was calculated. Analyze the differences between surgeons of different years of experience and AI recognition, and evaluate the diagnostic and therapeutic efficacy of AI model. RESULTS: Our model achieved 83.5% precision and 57.8% recall in the internal validation set. The visual recognition rate of AI model was 85.2% and 82.4% on internal and external sets. The PG recognition rate of AI model is higher than that of junior surgeons (p < 0.05). CONCLUSIONS: This AI model will help surgeons identify PGs, and develop their learning ability and self-confidence.

Video-assisted selective lateral neck dissection for papillary thyroid carcinoma.

BACKGROUND: The minimally invasive video-assisted thyroidectomy (MIVAT) for thyroid benign nodules and central neck dissection (CND) for papillary thyroid microcarcinoma (PTMC) have been applied, presently, we attempted to perform video-assisted selective lateral neck dissection (VASLND) for papillary thyroid carcinoma (PTC). METHODS: Twenty-six consecutive PTC patients with unilateral tumor (size <4.0 cm) and suspected lymph node metastasis at level III, IV, or IIa were included from March 2009 to January 2012. RESULTS: VASLND was successfully performed in all 26 PTC patients. The mean operative time was 46 min (range 26-75 min) on VASLND. No major complications occurred. Average postoperative hospital stay was 3.6 days (range 2-8 days). The mean number of removed nodes was 7.3 (range 4-12) in central neck and 8.3 (range 3-21) in lateral compartment. Positive yield amounted to a mean value of 2.6 (range 0-5) and 3 (range 0-6), respectively. No persistent or recurrent disease was observed in any patient during a follow-up period. The cosmetic result was excellent. CONCLUSIONS: Our initial experience demonstrates that VASLND is feasible and safe for selected PTCs, with superior appearance and less pain. Nevertheless, larger series and comparative studies with longer follow-up could be necessary to confirm its oncological effectiveness.

A meta-analysis comparing lightweight meshes with heavyweight meshes in Lichtenstein inguinal hernia repair.

BACKGROUND: To evaluate the influence of lightweight and heavyweight mesh on postoperative recovery in Lichtenstein inguinal hernia repair. METHODS: PubMed, EMBASE, and the Cochrane library were used to search for published clinical randomized controlled trials (RCTs), which compared lightweight meshes with heavyweight meshes in Lichtenstein inguinal hernia repair. Two independent reviewers assessed the trials for eligibility and quality, and all the related data matching our standards were abstracted for meta-analysis by RevMan 5.0 software. The evaluation criteria included recurrence, pain, seroma, hematoma, the sensation of a foreign body, wound infection, urine retention, and testicular atrophy. RESULTS: A total of 2231 hernias from 11 RCTs were included. Compared with a heavyweight polypropylene mesh, the lightweight mesh led to less postoperative chronic pain (odds ratio [OR] = 0.64, 95% confidence interval (CI) = 0.51-0.82; P < .05) and less sensation of a foreign body (OR = 0.56; 95% CI = 0.40-0.78; P < .05), regardless of whether the mesh was made of partially absorbable or nonabsorbable material. There was no significant difference in postoperative recurrence, seroma, hematoma, wound infection, urine retention, and testicular atrophy. CONCLUSION: Current evidence suggests that the use of a lightweight mesh is associated with less postoperative pain and less sensation of a foreign body, without increasing the incidence of recurrence. Further high-quality, long-term follow-up RCTs are needed to provide more reliable evidence.

Clinical efficacy and inflammatory reaction of submental endoscopic thyroidectomy versus conventional thyroidectomy: A prospective randomized study.

OBJECTIVES: This prospective study aimed to explore the clinical efficacy and inflammatory reaction of submental endoscopic thyroidectomy versus conventional thyroidectomy. METHODS: We prospectively recruited 45 patients (total 90 patients) who met the eligibility criteria to undergo conventional open thyroidectomy or submental endoscopic thyroidectomy from January 2021 to July 2022 in the Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. These patients were evaluated using the following indices: number of lymph nodes dissected, complications, pain severity, inflammatory indicators, cosmetic satisfaction, and economic cost. All data were analyzed by the t-test or chi-squared test. RESULTS: Ninety patients were enrolled. The two groups did not significantly differ regarding baseline characteristics. All patients who underwent thyroidectomy had a similar trauma index and increased level of inflammation. There were no significant differences between the open thyroidectomy and submental endoscopic thyroidectomy groups in the total number of lymph nodes dissected, number of positive lymph nodes, drainage volume, and complications. The Vancouver scar score and cosmetic satisfaction score were significantly better in the submental endoscopic thyroidectomy group than the open thyroidectomy group. The submental endoscopic thyroidectomy group had a significantly lower pain scores on postoperative days 1 and 2, less downtime, and cheaper medical and esthetic costs than the open thyroidectomy group. CONCLUSION: Compared with conventional open thyroidectomy, submental endoscopic thyroidectomy did not increase the degree of trauma, had superior clinical efficacy, caused less pain, required a shorter downtime, achieved a better cosmetic effect, and was associated with lower healthcare costs.

Genetic analysis and clinicopathologic features of locally advanced papillary thyroid cancers: a prospective observational study.

PURPOSE: Locally advanced papillary thyroid cancer (LAPTC) has poor prognosis. Large-scale genomic testing has revealed multiple oncogenic drivers which may be essential for understanding tumor progression. However, the accurate identification of high recurrence risk and poor prognosis in thyroid carcinoma remains unclear. The objective of this study was to analyze genetic profile and clinicopathologic features of locally advanced papillary thyroid cancers. METHODS: An observational cohort study was performed to identify molecular characteristics of LAPTC and a prognosis comparison of LAPTC with different genetic mutations. ThyroSeq v2 next-generation sequencing (57-gene panel) was performed on fresh tumor tissue. Then, the clinicopathological features between tumors with different genetic mutations were compared. Additionally, correlations of tumor recurrence and disease free survival with different genetic alterations were analyzed. RESULTS: This study showed that the main mutation is common BRAFV600E (66.2%, 43/65) in LAPTC, followed by the TERT promoter mutations (38.5%, 25/65). Synergetic mutations of BRAFV600E and TERT promoters (B&T) were identified in 26.2% LAPTC (17/65), which is associated with tall-cell variant, extrathyroidal invasion and advanced tumor stage (III/IV). The synergetic mutations of B&T are also significantly associated with higher risk of recurrence (hazard ratio [HR], 6.0; 95% confidence interval, CI 1.26-28.55, P = 0.02) and mortality (17.6%, 3/17). CONCLUSIONS: Synergetic mutations of B&T are common in LAPTC, which is associated with the aggressive clinicopathologic features and an increased risk of recurrence and mortality. This finding may help to predict aggressive behavior of LAPTC and to assist in clinical decision-making.

Single-Cell Transcriptomic Atlas of Parathyroid Adenoma and Parathyroid Carcinoma.

Primary hyperparathyroidism is typically characterized by monoclonal parathyroid tumors that secrete an excessive amount of parathyroid hormone (PTH). However, the underlying pathogenesis of tumorigenesis remains unclear. We performed single-cell transcriptomic analysis on five parathyroid adenoma (PA) and two parathyroid carcinoma (PC) samples. A total of 63,909 cells were divided into 11 different cell categories; endocrine cells accounted for the largest proportion of cells in both PA and PC, and patients with PC had larger populations of endocrine cells. Our results revealed significant heterogeneity in PA and PC. We identified cell cycle regulators that may play a critical role in the tumorigenesis of PC. Furthermore, we found that the tumor microenvironment in PC was immunosuppressive, and endothelial cells had the highest interactions with other cell types, such as fibroblast-musculature cells and endocrine cells. PC development may be stimulated by fibroblast-endothelial cell interactions. Our study clarifies the transcriptional signatures that underlie parathyroid tumors and offer a potential significant contribution in the study of pathogenesis of PC. © 2023 American Society for Bone and Mineral Research (ASBMR).

Genomic Profiling Reveals the Variant Landscape of Sporadic Parathyroid Adenomas in Chinese Population.

OBJECTIVE: To define somatic variants of parathyroid adenoma (PA) and to provide novel insights into the underlying molecular mechanism of sporadic PA. METHODS: Basic clinical characteristics and biochemical indices of 73 patients with PA were collected. Whole-exome sequencing was performed on matched tumor-constitutional DNA pairs to detect somatic alterations. Functional annotation was carried out by ingenuity pathway analysis afterward. The protein expression of the variant gene was confirmed by immunohistochemistry, and the relationship between genotype and phenotype was analyzed. RESULTS: Somatic variants were identified in 1549 genes, with an average of 69 variants per tumor (range, 13-2109; total, 9083). Several novel recurrent somatic variants were detected, such as KMT2D (15/73), MUC4 (14/73), POTEH (13/73), CD22 (12/73), HSPA2 (12/73), HCFC1 (11/73), MAGEA1 (11/73), and SLC4A3 (11/73), besides the previously reported PA-related genes, including MEN1 (11/73), CASR (6/73), MTOR (4/73), ASXL3 (3/73), FAT1 (3/73), ZFX (5/73), EZH1 (2/73), POT1 (2/73), and EZH2 (1/73). Among them, KMT2D might be the candidate driver gene of PA. Crucially, 5 patients carried somatic mutations in CDC73, showed an aggressive phenotype similar to that of parathyroid carcinoma (PC), and had a decreased expression of parafibromin. Pathway analysis of recurrent potential PA-associated driver variant genes revealed functional enrichments in the signaling pathway of Notch. CONCLUSION: Our study expanded the pathogenic variant spectrum of PA and indicated that KMT2D might be a novel candidate driver gene and be considered as a diagnostic biomarker for PA. Meanwhile, CDC73 mutations might be an early developmental event from PA to PC. The results provided insights into elucidating the pathogenesis of parathyroid tumorigenesis and a certain basis for clinical diagnosis and treatment.

MiR-153-3p Suppresses Cell Proliferation, Invasion and Glycolysis of Thyroid Cancer Through Inhibiting E3F3 Expression.

PURPOSE: The aim was to research the role of miR-153-3p and E2F3 in the development of thyroid tumors. METHODS: A total of 91 thyroid cancer patients were involved. The role of miR-153-3p in THCA cell lines and Nthy-ori3-1 cell line was researched. qPCR was used to detect miR-153-3p and E2F3 expression. MiR-153-3p mimic, inhibitor, siE2F3 or corresponding controls were transfected in cells. CCK8 was used to verify the proliferation. Cell cycle and apoptosis was detected by flow cytometry. Transwell assay was applied for migration and invasion, and glycolysis was monitored. The binding of miR-153-3p and E2F3 was predicted by targetscan database, and verified by luciferase reporter and RNA-pull down assay. Western blot was used to detect E2F3 expression. Rescue assay was undertaken to verify the effect of siE2F3 on miR-153-3p inhibitor. Moreover, the effect of miR-153-3p mimic on tumor volume and weight was measured. IHC assay was processed to E2F3 and Ki67 expression, and TUNEL assay was used for apoptosis. RESULTS: MiR-153-3p expressed lower in thyroid tumors and cells. The level of miR-153-3p was negatively related with TNM stage. MiR-153-3p inhibited cell proliferation, invasion migration, and induced cycle arrest and apoptosis. Moreover, it negatively regulated E2F3. siE2F3 rescued effects of miR-153-3p inhibitor in all above biological processes in thyroid cancer cells. MiR-153-3p inhibited tumor growth. Moreover, it inhibited E2F3 and Ki67 expression, and also increased apoptosis in vivo. CONCLUSION: MiR-153-3p suppresses cell proliferation, invasion and glycolysis of thyroid cancer through inhibiting E3F3 expression, which may be a biomarker for thyroid cancer diagnose.