Circulating small extracellular vesicle-based miRNA classifier for follicular thyroid carcinoma: a diagnostic study.

BACKGROUND: The diagnosis of follicular thyroid carcinoma (FTC) prior to surgery remains a major challenge in the clinic. METHODS: This multicentre diagnostic study involved 41 and 150 age- and sex-matched patients in the training cohort and validation cohort, respectively. The diagnostic properties of circulating small extracellular vesicle (sEV)-associated and cell-free RNAs were compared by RNA sequencing in the training cohort. Subsequently, using a quantitative real-time polymerase chain reaction (qRT‒PCR) assay, high-quality candidates were identified to construct an RNA classifier for FTC and verified in the validation cohort. The parallel expression, stability and influence of the RNA classifier on surgical strategy were also investigated. RESULTS: The diagnostic properties of sEV long RNAs, cell-free long RNAs and sEV microRNAs (miRNAs) were comparable and superior to those of cell-free miRNAs in RNA sequencing. Given the clinical application, the circulating sEV miRNA (CirsEV-miR) classifier was developed from five miRNAs based on qRT‒PCR data, which could well identify FTC patients (area under curve [AUC] of 0.924 in the training cohort and 0.844 in the multicentre validation cohort). Further tests revealed that the CirsEV-miR score was significantly correlated with the tumour burden, and the levels of sEV miRNAs were also higher in sEVs from the FTC cell line, organoid and tissue. Additionally, circulating sEV miRNAs remained constant after different treatments, and the addition of the CirsEV-miR classifier as a biomarker improves the current surgical strategy. CONCLUSIONS: The CirsEV-miR classifier could serve as a noninvasive, convenient, specific and stable auxiliary test to help diagnose FTC following ultrasonography.

Trends, Influence Factors, and Doctor-Patient Perspectives of Web-Based Visits for Thyroid Surgery Clinical Care: Cross-Sectional Study.

BACKGROUND: In recent years, the new generation of telecommunication technologies has profoundly changed the traditional medical industry. To alleviate the medical difficulties faced by patients with thyroid diseases, hospitals have opened web-based visits and actively combined online-to-offline outpatient services. OBJECTIVE: This study aims to explore differences between office and web-based outpatient services from doctors' and patients' perspectives, illustrate the effect of the COVID-19 pandemic on outpatient services, and provide clues for improving the online-to-offline mode of care for patients with thyroid diseases. METHODS: We collected the complete web-based and office outpatient records of the Thyroid Surgery Center of West China Hospital. A total of 300,884 completed patient encounters occurred (201,840 office visits and 99,044 web-based visits) from January 1, 2019, to May 31, 2022. We performed logistic regression to evaluate the association between the chosen visit type and patients' sociodemographic characteristics. RESULTS: The number of web-based visits rapidly increased since March 2020 and reached 45.1% (4752/10,531) of all encounters in December 2021. The COVID-19 pandemic dramatically accelerated the development of web-based visits. Web-based visits were preferred by patients 18-45 years old (odds ratio [OR] 2.043, 95% CI 1.635-2.552, P<.001), patients with relatively high-paying jobs (technical staff: OR 1.278, 95% CI 1.088-1.479, P=.003; office clerk: OR 1.25, 95% CI 1.07-1.461, P=.005; national public servant: OR:1.248, 95% CI 1.042-1.494, P=.02), and patients living in Sichuan Province (excluding Chengdu; OR 1.167, 95% CI 1.107-1.23, P<.001). The medicine cost (P<.001) and examination cost (P<.001) of office visits were significantly higher than those of web-based visits. CONCLUSIONS: Web-based outpatient visits have increased rapidly in recent years, and the COVID-19 pandemic has boosted their development. The preference for web-based visits was influenced by the socioeconomic and demographic characteristics of both patients and doctors.

Distant metastasis in medullary thyroid carcinoma: Clinical outcomes and implications of T stage.

BACKGROUND: The eighth edition of the American Joint Committee on Cancer tumour, node, and metastasis staging system did not take T stage into consideration when evaluating Stage IV C medullary thyroid carcinoma (MTC) patients. The aim of this study is to investigate the clinical outcomes and implications of T stage in this population. METHODS: Eligible patients from the Surveillance, Epidemiology, and End Results database and the Department of Thyroid Surgery in West China Hospital of Sichuan University and who were diagnosed with Stage IV C MTC were included in this study. The overall survival (OS), the cancer-specific survival (CSS), and the precise cause of MTC-induced death were analysed. The potential risk factors, including the T stage, in the OS and CSS were evaluated by univariate and multivariate Cox regression models. RESULTS: This retrospective study enroled 204 Stage IV C MTC patients. The 5- and 10-year OS rates were 31.8% and 17.1%, respectively, and the 5- and 10-year CSS rates were 40.4% and 22.5%, respectively. More importantly, the rates of MTC-induced death between primary or distant metastatic lesions in Stage IV C MTC patients were comparable in our institution. Additionally, the univariate and multivariate analyses demonstrated that the presence of an advanced T stage was an independent prognostic factor for both the OS (T4 vs. T1-T3, hazard ratio [HR]: 1.714, 95% confidence interval [CI]: 1.175-2.500, p = .005) and the CSS (T4 vs. T1-T3, HR: 1.848, 95% CI: 1.229-2.780, p = .003). CONCLUSION: To achieve a better risk stratification, further classification of Stage IV C MTC patients by the T stage may be preferable.

A Nomogram to Predict Hungry Bone Syndrome After Parathyroidectomy in Patients With Secondary Hyperparathyroidism.

BACKGROUND: Parathyroidectomy (PTX) has been demonstrated as an effective treatment for patients with secondary hyperparathyroidism (SHPT) of renal origin. However, severe hypocalcemia, called hungry bone syndrome (HBS), is a common complication following PTX in these patients and can lead to poor clinical outcomes, even death. Therefore, exploring risk factors for HBS and establishing a prediction nomogram allow intensive monitoring and prompt treating this postoperative complication, which is the main purpose of this study. METHODS: From October 2016 to October 2018, PTX with autotransplantation (PTX + AT) procedures were performed in 131 patients with SHPT of renal origin by a surgeon and his team in the Thyroid and Parathyroid Surgery Center, West China Hospital, Sichuan University, China. After applying the inclusion and exclusion criteria, a total of 114 patients were enrolled for analyses in this study. Comprehensive data including preoperative, intraoperative, and postoperative variables were prospectively collected and retrospectively analyzed. The univariate and multivariate logistic regression analyses with internal validation by bootstrapping were used to confirm independent risk factors for postoperative HBS. The nomogram was developed based on the statistical analysis results. Receiver operator characteristic (ROC) curves were drawn to compare the prediction performance among different predictors. RESULTS: The occurrence of postoperative HBS was 76.3% (87 out of 114 patients) in this study. Univariate analysis showed that preoperative intact parathyroid hormone (iPTH), serum alkaline phosphatase, bone-specific alkaline phosphatase (bone-ALP) were significantly higher in HBS group than those in non-HBS group, while preoperative corrected serum calcium and albumin were significantly lower in HBS group than those in non-HBS group. Total weight of resected parathyroid glands was significantly heavier in HBS group versus non-HBS group. Multivariate logistic regression analysis with internal validation by bootstrapping demonstrated preoperative iPTH, bone-ALP, preoperative corrected serum calcium, and total weight of resected parathyroid glands were independently associated with postoperative HBS. The nomogram including the abovementioned four independent predictors was constructed and showed better prediction performance than the other four predictors in terms of postoperative HBS. CONCLUSIONS: On the basis of this study, we found higher preoperative iPTH level, higher bone-ALP level, heavier total weight of resected parathyroid glands, and lower preoperative corrected serum calcium level were independent predictors of postoperative HBS in patients with SHPT of renal origin. The nomogram can expediently, accurately, and objectively predict the risk of postoperative HBS in individual patient with SHPT of renal origin.

Diagnostic and prognostic value of preoperative systemic inflammatory markers in anaplastic thyroid cancer.

BACKGROUND: Easily accessible, generalized, and inexpensive methods are expected to differentiate anaplastic thyroid carcinoma (ATC) from advanced differentiated thyroid cancer (aDTC). We aimed to explore potential diagnostic and prognostic value of systematic inflammatory markers (SIMs) in ATC and aDTC. METHODS: About 22 ATC, 101 aDTC, and 100 matched early DTC patients were analyzed retrospectively. SIMs included the comprehensive index, neutrophil-monocyte-platelet-to-lymphocyte ratio (NMPLR) and the previously reported ones. Receiver operating characteristic, Kaplan-Meier, and COX regression analyses were mainly conducted. RESULTS: NMPLR exhibited the highest area under the curve value 0.806 (P < .0001) to diagnose ATC from aDTC. NMPLR was identified as an independent risk factor for overall survival (OS) (hazard ratio [HR]: 47.821, 95% confidence interval [CI], 2.863-798.765, P = .007) in ATC, as well as for OS (HR: 7.360, 95% CI, 1.620-33.430, P = .010) and recurrence-free survival (HR: 4.172, 95% CI, 1.139-15.286, P = .031) in aDTC. Taken both refractory types (ATC and aDTC) together, NMPLR could independently predict OS (HR: 6.470; 95% CI, 2.134-19.616; P = .001). CONCLUSION: NMPLR is a generalized index. It showed excellent potential in differential diagnosis and survival prediction in refractory thyroid cancer. However, it needs to be validated in larger cohort and clinical practice.

Comparison of the prognostic values of selected inflammation based scores in patients with medullary thyroid carcinoma: A pilot study.

BACKGROUND: The significance of inflammation based scores including the neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index (PNI), and plasma fibrinogen remains unclear in medullary thyroid carcinoma (MTC). We aimed to compare the prognostic value of these scores. METHODS: Seventy-eight patients newly diagnosed as MTC with operation in our institution from May 2009 to September 2016 were retrospectively evaluated. Receiver operating characteristic (ROC) curves and Kaplan-Meier analyses were calculated to compare the prognostic value of these scores. RESULTS: Increased PLR was predictive of lymph node metastasis (AUC = 0.644, P = 0.022), capsule invasion (AUC = 0.666, P = 0.007), advanced tumor stages (AUC = 0.657, P = 0.011), and recurrence (AUC = 0.655, P = 0.049). Increased fibrinogen was predictive of lymph node metastasis (AUC = 0.669, P = 0.006) and capsule invasion (AUC = 0.631, P = 0.038). Reduced PNI was predictive of recurrence (AUC = 0.655, P = 0.049). Kaplan-Meier analyses and Cox regression analysis revealed that PLR was a significant predictor for recurrence. CONCLUSIONS: PLR, fibrinogen, and PNI are all predictive. Specially, PLR is superior to other inflammation based scores in terms of prognostic ability.

[The Risk Factors of Contralateral Central Lymph Node Metastasis in Solitary Thyroid Papillary Micro-carcinoma].

OBJECTIVE: To explore the possible risk factors of contralateral central lymph node metastasis (CLNM) in solitary thyroid papillary micro-carcinoma (PTMC). METHODS: Clinicopathologic data of 318 patients with confirmed solitary PTMC by final histological who underwent bilateral centeral lymph node dissection (CLND) from April 2012 to May 2015 in our hospital were retrospectively reviewed. Univariate Χ2 test and multivariate logistic regression analysis were used to determine the risk factors of contralateral CLNM in solitary PTMC. RESULTS: The incidence of ipsilateral CLNM and contralateral CLNM in solitary PTMC patients were 40.57% (129/318), 9.75% (31/318), respectively. Univariate analyses revealed that contralateral CLNM had a correlation with tumor located in lower pole, capsular invasionand underlying ipsilateral CLNM (P < 0.05), and had a correlation with underlying nodular goiter (P < 0.05). Multivariate logistic regression analysis showed that tumor located in lower pole and ipsilateral CLNM were independent risk factors for contralateral CLNM (P < 0.05). CONCLUSIONS: Solitary PTMC patients had a low tendency to contralateral CLNM, it shouldn't undergo contralateral CLND commonly, if the tumor located in lower pole or combine withipsilateral CLNM, it should be consider to undergo bilateral CLND.

Prediction of nonrecurrent laryngeal nerve before thyroid surgery--experience with 1825 cases.

BACKGROUND: Nonrecurrent laryngeal nerve (NRLN) is a rare anatomic anomaly, which often co-occurs with aberrant right subclavian artery (ARSA). With this large case series, we present our experience of predicting the presence of NRLN by the means of chest X-ray film, thoracic computed tomography (CT), and ultrasonography. MATERIALS AND METHODS: A prospective, nonrandomized study has been carried out. A total of 1825 patients with various thyroid disorders scheduled for surgery were recruited between January 2006 and July 2012. All patients underwent preoperative chest X-ray examination. Those suspected with ARSA further underwent thoracic CT scan. Unsuspected patients who had NRLN revealed by surgery were analyzed with ultrasonography postoperatively. RESULTS: A total of 41 patients (2.25%) were suspected to have ARSA by X-ray, of those 19 (46.3%) were confirmed by thoracic CT and proven to have NRLN upon subsequent surgery. No NRLN injury was inflicted. For the remaining 22 cases, CT scan suggested a normal right subclavian artery and none had NRLN upon surgery. For the 1784 unsuspected patients, 4 (0.22%) were discovered to have NRLN upon surgery, of those one was injured. For the 19 predicted NRLN, the time used for identifying the nerve was significantly shorter than the four cases with unsuspected NRLN (t = -15.978; P = 0.000). After the operation, all these unsuspected NRLN were confirmed to have ARSA by ultrasonography. CONCLUSIONS: Patients scheduled for thyroid surgery should be screened for ARSA upon routine chest X-ray and thyroid ultrasonography before surgery. Detection of ARSA can accurately predict the existence of NRLN; hence prevent NRLN injury during subsequent surgery.

The prognostic value of lymph node dissection in patients with parathyroid carcinoma.

Background: Surgery is the only curative treatment strategy for parathyroid carcinoma (PC). However, the optimal extent of surgery remains uncertain, particularly regarding whether routine central lymph node dissection (LND) confers a survival advantage to patients with PC. This study aimed to evaluate the prognostic value of LND in PC patients. Methods: Patients diagnosed with PC between 2004 and 2018 were identified in the Surveillance, Epidemiology, and End Results (SEER)-18 registries. With inclusion and exclusion criteria, a total of 338 patients were included as cohort 1 to describe the characteristics of PC, while 215 patients were selected as cohort 2 to assess the effect of LND on cancer-specific survival (CSS). Univariate and multivariate Cox proportional hazards regression models were used to identify independent risk factors associated with CSS. Propensity score matching (PSM) was performed to adjust for potential confounding variables. The prognostic value of LND was further analyzed in subgroups stratified by predictors associated with CSS. Results: The 5- and 10-year CSS were 94.4% and 87.9% respectively in cohort 1. LND failed to significantly improve CSS in the entire cohort 2 and the PSM cohort 2. Large tumor size (>40 mm) and distant metastasis were independently associated with poor CSS. Subgroup analyses revealed that LND was not significantly associated with improved CSS in patients with aggressive PC, such as those with a tumor size greater than 40 mm. Unexpectedly, LND may compromise CSS in patients with distant disease (P=0.03). Conclusions: PC is a rare and indolent endocrine malignancy. The presence of large tumors and distant metastases are independent predictors of poor CSS. Routine central LND as part of initial surgery does not significantly improve CSS in PC patients, even for those with large tumors, lymph node metastasis, or distant disease.

Impact of different categories of intermediate risk factors on the recurrence of papillary thyroid carcinoma: a retrospective cohort study.

BACKGROUND: Data regarding the long-term recurrence in patients with intermediate-risk papillary thyroid carcinoma (PTC) are limited. The aim of this study was to assess the impact of primary tumor-related risk factors and lymph node (LN)-only risk factors on recurrence-free survival (RFS) in patients with intermediate-risk PTC. MATERIALS AND METHODS: Patients with PTC who received initial treatment at our institution between 2010 and 2016 were retrospectively reviewed. A total of 799 intermediate-risk PTC patients were included and further categorized into subgroups according to the different categories of intermediate risk factors. The RFS rates of these subgroups were investigated and compared. RESULTS: Structural recurrence developed in 11 patients (1.4%) of the whole cohort during a median follow-up duration of 96 months. There were no significant differences in RFS between the primary tumor-only risk group and the LN-only risk group, while the combined group of primary tumor risk factors and LN risk factor (metastatic LNs >5) was associated with a worse RFS rate. In the matched-pair analysis, no significant difference in RFS was found between patients who underwent thyroid lobectomy (TL) and those who underwent total thyroidectomy (TT) (6-year RFS: 99.6% vs. 98.8%, P = 0.316) during a median follow-up duration of 100 months. CONCLUSIONS: Intermediate-risk PTC patients who underwent TL had a comparable RFS to those who underwent TT. The combination of primary tumor risk factors and LN risk factor (metastatic LNs >5) may be a useful tool for predicting the risk of long-term structural recurrence in patients with intermediate-risk PTC.

[Clinical research strategy for cN0 thyroid papillary carcinoma central lymph node dissection].

OBJECTIVE: To discuss the pattern of central lymph node metastasis of cN0 single thyroid papillary carcinoma and provide clinical evidence-supported proof for central lymph node dissection. METHODS: The performed thyroidectomy and bilateral central lymph node dissection for 150 patients with cN0 single papillary thyroid carcinoma. The bilateral central lymph nodes were divided into 4 parts: the cornu inferius cartilaginis thyroideae region of ipsilateral central area, the lower part of ipsilateral central area, the cornu inferius cartilaginis thyroideae region of contralateral central area, the lower part of contralateral central area on the baseline of 1 cm below the cornu inferius cartilaginis thyroideae. We analyzed the differences and influencing factors of lymph node metastasis in these 4 parts. RESULTS: The lymph node metastasis rate in lower part of ipsilateral central area was the highest (56.7%), followed by the lower part of contralateral central area (28.0%), the cornu inferius cartilaginis thyroideae region of ipsilateral central area (17.3%), and the cornu inferius cartilaginis thyroideae region of contralateral central area (0). In the logistic analysis of multiple factors, invaded thyroid capsule was an independent factor for lymph node metastasis in both the cornu inferius cartilaginis thyroideae region of ipsilateral central area (ß = 0.1835, χ(2) = 0.3102, P < 0.05) and lower part of contralateral area (ß = 0.3166, χ(2) = 1.4640, P < 0.05). The patients' age ≥ 45 years (ß = 0.5737, χ(2) = 6.5923) and invaded thyroid capsule (ß = 0.4258, χ(2) = 3.4735) were independent factors for lower part of ipsilateral central area (both P < 0.05). CONCLUSION: The cornu inferius cartilaginis thyroideae region of contralateral central area of cN0 single PTC patients could not be cleared routinely.

Exosome-mediated delivery of miR-519e-5p promotes malignant tumor phenotype and CD8+ T-cell exhaustion in metastatic PTC.

CONTEXT: Distant metastases are the primary cause of therapy failure and mortality in patients with papillary thyroid carcinomas (PTCs). However, the underlying mechanism responsible for the initiation of tumor cell dissemination and metastasis in PTCs has rarely been investigated. OBJECTIVE: The aim of this study was to investigate effects and underlying molecular mechanisms of circulating exosomal microRNAs (miRNAs) in distant metastatic PTCs. METHODS: The most relevant circulating exosomal miRNA to distant metastatic PTCs were verified between distant metastatic PTCs and nondistant metastatic PTCs by miRNA microarray, quantitative real-time polymerase chain reaction (qRT‒PCR) assays and receiver operating characteristic (ROC) curves. The parental and recipient cells of that circulating exosomal miRNA were then explored. In vitro and in vivo experiments were further performed to elucidate the function and potential mechanisms of circulating exosomal miRNAs that contribute to the development of distant metastases. RESULTS: We identified that PTC-derived exosomal miR-519e-5p was significantly upregulated in the circulatory system in distant metastatic PTCs. Further tests demonstrated that PTC cells can acquire a more malignant phenotype via hnRNPA2B1 mediated sorting of tumor suppressor miR-519e-5p into exosomes to activate Wnt signaling pathway via upregulating PLAGL2. Furthermore, miR-519e-5p included in PTC-derived exosomes can be transferred to recipient CD8+ T cells and aid in tumor immune escape in distant organs through inhibiting Notch signaling pathway by downregulating NOTCH2. CONCLUSION: Our findings highlighted the dual role of PTC-derived exosomal miR-519e-5p in distant metastasis, which may improve our understanding of exosome-mediated distant metastatic mechanisms.

[Predictors of level V lymphatic metastasis in papillary thyroid carcinoma].

OBJECTIVE: To study the predictors of level V metastasis in papillary thyroid carcinoma (PTC). METHODS: The clinic data of 122 patients with PTC who underwent therapeutic lateral neck dissection between March 2004 and November 2010 was analyzed retrospectively. There were 31 male and 91 female patients. The median age at diagnosis was 38.5 years (ranging from 8 to 87 years). All the patients had undergone unilateral or bilateral lymph node dissection (II-VI or I-VI). Univariate analysis and multivariate analysis were performed using χ(2) test and binary Logistic regression test, respectively. RESULT: The level V metastases was significantly associated with capsular invasion, extrathyroidal extension, preoperative distant metastasis, the size of primary, ipsilateral level IV lymph node metastasis and simultaneous metastases to ipsilateral level II, III and IV (χ(2) = 4.223 - 13.748, P < 0.05). Age, sex, tumor-multifocal, pTNM, central lymph node metastases ipsilateral level II lymph node metastases and ipsilateral level III lymph node metastases were not found to be associated with level V metastases (χ(2) = 0.882 - 3.167, P > 0.05). In multivariate analysis, extrathyroidal extension (OR = 8.32, 95%CI: 2.44 - 28.3, P = 0.001) and simultaneous metastases to ipsilateral level II, III and IV (OR = 7.81, 95%CI: 2.11 - 28.8, P = 0.002) were independent predictors of level V metastasis. CONCLUSIONS: Extrathyroidal extension, simultaneous metastases to ipsilateral level II, III and IV are risk factors for level V lymph nodes metastases in PTC. Dissection of level V lymph nodes should be considered for PTC patients with extrathyroidal extension and simultaneous metastases to ipsilateral level II, III and IV.

Risk stratification in patients with anaplastic thyroid carcinoma: role of age.

BACKGROUND: Thyroid carcinoma is the only cancer that regards age as an important predictor of thyroid cancer-specific survival (CSS). While the 8th American Joint Committee on Cancer (AJCC) staging system raised the age cutoff from 45 to 55 years for differentiated thyroid carcinoma (DTC) to more accurately predict the prognosis, there is no new information regarding the role of age in the prognosis of anaplastic thyroid carcinoma (ATC). The aim of this study was to determine the optimal age cutoff values for mortality risk stratification in ATC patients. Furthermore, a nomogram to predict ATC CSS was developed in each age group. METHODS: Patients diagnosed with ATC between 2004 and 2015 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. After applying inclusion and exclusion criteria, a total of 1140 patients were enrolled as cohort 1 to describe the characteristics of ATC, while a total of 556 patients were included as cohort 2 to determine age cutoff values for risk stratification by X-tile program. Training set and testing set were randomly generated to develop and validate a predictive nomogram of CSS in each age group. RESULTS: The 6-month, 1-year, and 2-year survival was 27.6%, 15.1%, and 6.2%, respectively, in cohort 1. X-tile program results showed that the optimal age cutoff values for mortality risk stratification were 65 and 85 years old (p < 0.001). Distant metastasis was independently associated with CSS in patients younger than 85 years old, and these patients benefited more from complete resection of the tumor and radiotherapy/chemotherapy. However, no predictors of CSS were identified in patients over 85 years old, and interventions (surgery, radiotherapy, and chemotherapy) targeting ATC had little role in disease control in these patients. The nomogram was developed and validated based on the independent CSS predictors in each age group. The C-index values of the training set and testing set were 0.735 [95% CI, 0.696-0.774] and 0.733 [95% CI, 0.663-0.804] for CSS in patients of ≤64 years old, while the values were 0.767 [95% CI, 0.730-0.804] and 0.783 [95% CI, 0.718-0.848] in patients of 65-84 years old. All of the C-index values were larger than 0.7, which showed acceptable prediction performance of the nomograms. CONCLUSIONS: Age can be used as an auxiliary stratification factor of prognosis in ATC patients. The survival may be improved in patients younger than 85 years old if combination therapy (surgery, radiotherapy, and chemotherapy) was indicated and applicable, while no optimal therapeutic strategy was determined in patients older than 85 years old. The established nomograms can provide good prediction of CSS according to age group.

Clinicopathologic Characteristics and Outcomes of Massive Multinodular Goiter: A Retrospective Cohort Study.

Background: Thyroidectomy for massive goiters is challenging because of the increased risk of tracheomalacia, combined sternotomy, postoperative morbidity, and mortality, whereas studies investigating the clinicopathologic characteristics, postoperative morbidities, and surgical outcomes of massive goiters are limited. Methods: Patients with goiters undergoing thyroid surgery between 2009 and 2019 were retrospectively reviewed. A total of 227 patients were enrolled and divided into massive goiter group and large goiter group according to the weight of the goiter. Clinicopathologic characteristics, postoperative morbidities, and surgical outcomes were compared between the two groups. Results: Seventy-four patients (32.6%) had a goiter weighing more than 250 g and 153 patients (67.4%) were categorized in the large goiter group. Compared to large goiter patients, massive goiter patients had higher rates of retrosternal extension (82.4% vs. 30.7%), combined sternotomy (12.2% vs. 1.3%), intensive care unit admission (25.7% vs. 7.2%), transient hypoparathyroidism (41.9% vs. 25.5%), and transient recurrent laryngeal nerve palsy (10.8% vs. 3.3%) as well as prolonged length of hospital stay (P < 0.05). Conclusions: Massive goiter patients were at increased risk of combined sternotomy, intensive care unit admission, postoperative morbidities as well as prolonged length of hospital stay after thyroidectomy compared to large goiter patients, but most of them can be treated through a cervical approach with a favorable outcome.

Identification of Circulating Exosomal microRNAs Associated with Radioiodine Refractory in Papillary Thyroid Carcinoma.

Papillary thyroid carcinoma (PTC) has a favorable prognosis, but a fraction of cases show progressive behaviors, becoming radioiodine refractory (RAIR) PTC. To explore circulating exosomal microRNAs (miRNAs) associated with RAIR PTC, the miRNA profiles in exosomes from parental and induced RAIR cell lines were firstly identified with a next-generation sequencing technique. The Na+/I- symporter (NIS) related miRNAs were then validated by quantitative real-time PCR (qRT-PCR) in plasma of PTC patients with non-131I-avid metastases and those with 131I-avid metastases. The regulation of exosomal miRNAs on NIS were also verified. We identified that miR-1296-5p, upregulation in exosomes from RAIR cell lines, and the plasma of patients with RAIR PTC achieved the largest areas under the curve (AUC) of 0.911 and that it is an independent risk factor for RAIR PTC. In addition, miR-1296-5p was abundantly detected in the tissue of RAIR PTC and can directly target downstream gene of NIS. Taken together, our findings suggested that circulating exosomal miRNAs, particularly miR-1296-5p, may be involved in the pathogenesis of RAIR PTC by directly targeting NIS.

Case Report: A New Entity: Multiple Differentiated Variant of Papillary Thyroid Carcinoma With Advanced Clinical Behavior.

There are many histological morphological types of papillary thyroid carcinoma (PTC), but the most frequently seen types are conventional. A single PTC commonly has a conventional and/or a variant morphological pattern. PTC with multiple (more than two) well-differentiated morphological patterns are extremely rare. We herein report the rare case of a 48-year-old male with initial diaphragmatic, pancreatic, and liver tumors from PTC. Then, the PTC was discovered following resection of these tumors, an ultrasound-guided fine-needle aspiration (US-FNA) cytology of a huge mass in the thyroid's left lobe revealed a PTC. After postoperative recovery, physical and ultrasound examinations identified an irregular large nodule in the thyroid's isthmus and left lobe, several swollen lymph nodes in the left neck, a mass in the left gluteus maximus, and several masses in both the bilateral parotid and salivary regions. The US-FNA's pathological examination confirmed metastatic PTCs in the left gluteus maximus and bilaterally in the parotid and salivary glands. An 18-fluorodeoxyglucose positron-emission tomography and computed tomography scan revealed abnormal uptakes in numerous locations (e.g., thyroid's isthmus and left lobe, bilateral parotid gland, and subcutaneous tissues). The patient underwent palliative therapy-including total thyroidectomy, bilateral central neck dissection, left lateral neck dissection, and excision of the bilateral parotid and salivary glands. A whole-body scan post-therapeutic radioactive iodine ablation revealed exclusive thyroid bed uptake. The patient subsequently underwent thyroid stimulating hormone (TSH) repression therapy and chemotherapy with lenvatinib, and thereafter achieved stable clinical conditions. Further histopathological analysis of the PTC revealed multiple differentiated morphological patterns in the single tumor located in the isthmus and left lobe of the thyroid, and in some metastatic lesions. Different metastatic lesions also presented different morphological patterns of PTC. In conclusions, we identified a new entity of PTC as a multiple differentiated variant of PTC (MDV-PTC) with an aggressive clinical nature.

Novel Recurrent Altered Genes in Chinese Patients With Anaplastic Thyroid Cancer.

BACKGROUND: Anaplastic thyroid cancer (ATC) is a rare but lethal malignancy, and few systematic investigations on genomic profiles of ATC have been performed in Chinese patients. METHODS: Fifty-four ATC patients in West China Hospital between 2010 to 2020 were retrospectively analyzed, while 29 patients with available samples were sequenced by whole-exome sequencing (WES). The associations between genomic alterations and clinical characteristics were statistically evaluated. RESULTS: The median overall survival was 3.0 months in the entire cohort, which was impacted by multiple clinical features, including age, tumor size, and different treatment strategies. In the WES cohort, totally 797 nonsilent mutations were detected; the most frequently altered genes were TP53 (48%), BRAF (24%), PIK3CA (24%), and TERT promoter (21%). Although these mutations have been well-reported in previous studies, ethnic specificity was exhibited in terms of mutation frequency. Moreover, several novel significantly mutated genes were identified including RBM15 (17%), NOTCH2NL (14%), CTNNA3 (10%), and KATNAL2 (10%). WES-based copy number alteration analysis also revealed a high frequent gain of NOTCH2NL (41%), which induced its increased expression. Gene mutations and copy number alterations were enriched in phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin (mTOR), NOTCH, and WNT pathways. CONCLUSIONS: This study reveals shared and ethnicity-specific genomic profiles of ATC in Chinese patients and suggests NOTCH2NL may act as a novel candidate driver gene for ATC tumorigenesis.

Surgical procedures for hepatolithiasis.

BACKGROUND/AIMS: The aim of this study is to explore the surgical treatment for hepatolithiasis. METHODOLOGY: Data of 1431 consecutive patients who underwent surgical treatment from January 2000 to December 2006 in West China Hospital were collected retrospectively and analyzed. Surgical procedures included T-tube insertion combined intraoperative cholangioscopic removal of intrahepatic stones, hepatectomy, cholangiojejunostomy and liver transplantation. RESULTS: 1384 patients were performed T-tube insertion combined intraoperative and postoperative cholangioscopic removal of intrahepatic stones and the rate of residual stone was 11.5%. 370 patients were performed hepatectomy and the rate of residual stone was 2.7%. 23 patients were performed cholangiojejunostomy and the rate of residual stone was 26.1%. 15 patients of hepatolithiasis were performed liver transplantation, and they had survived from liver transplantation. CONCLUSIONS: T-tube insertion combined intraoperative cholangioscopic removal of intrahepatic stones and cholangioscopic lithotripsy should be considered for patients of hepatolithiasis above all. Hepatic resection is optimal for patients with liver atrophy, liver abscess and biliary stricture. However, liver transplantation is a possible method for end-stage hepatolithiasis.