Delphian lymph node metastasis predicts occult contralateral carcinoma for unilateral papillary thyroid carcinoma patients with contralateral benign nodules.

BACKGROUND: For unilateral PTC patients with benign nodules in the contralateral lobe evaluated preoperatively, the necessity of total thyroidectomy remains controversial. This study aimed to investigate the predictive factors for occult contralateral carcinoma and whether DLN metastasis could predict it. METHODS: A total of 148 patients with unilateral PTC and contralateral benign nodules who were treated with a near-total thyroidectomy or TT at a single institution between August 2018 and April 2020 were enrolled. Clinicopathological features such as age, sex, TgAb or TPOAb level, primary tumor location, nodule number in contralateral lobe, carcinoma number in primary lobe, tumor size, capsular invasion, central lymph node metastasis, DLN metastasis were analyzed to investigate the rate and predictive factors of occult contralateral carcinoma. RESULTS: 44.6% patients were diagnosed with occult contralateral thyroid carcinoma. Univariate analysis showed that sex (P = 0.008), mulifocality of primary carcinoma (P < 0.001), tumor size (P = 0.033), capsular invasion (P = 0.042), CLN metastasis (P = 0.004), DLN metastasis (P = 0.001) were associated with occult contralateral carcinoma. Multivariate analysis showed that multifocality of primary carcinoma (p = 0.000, OR = 9.729), DLN metastasis (p = 0.042, OR = 4.701), capsular invasion (p = 0.022, OR = 2.909), and male patients (p = 0.006, OR = 3.926) were all independent predictive factors. CONCLUSION: For unilateral PTC patients with benign nodules in the contralateral lobe evaluated preoperatively, multifocality of primary carcinoma, DLN metastasis, capsular invasion, and male patients are independent predictors of occult contralateral carcinoma. We suggest separate excision and frozen section of DLN intraoperatively, if DLNs were confirmed metastasized, a TT was highly recommended.

The utility of sentinel Lymph node biopsy in the lateral neck in papillary thyroid carcinoma.

Background: Regional lymph node metastases (LNMs) are very common in papillary thyroid carcinoma (PTC) and associate with locoregional recurrence. The appropriate management of cervical lymph nodes is very important. Therefore, this study evaluated the application of sentinel lymph node biopsy (SLNB) in the lateral neck in PTC patients. Methods: This prospective study was conducted from 1 November 2015 to 31 December 2017 and recruited 78 PTC patients treated with SLNB in the lateral neck and prophylactic lateral neck dissection (compartments II-IV) followed by thyroidectomy or lobectomy and central neck dissection. Results: There were 78 PTC patients enrolled and sentinel lymph nodes (SLNs) were detected among 77 patients. A total of 30 patients were diagnosed with SLN metastases (SLNMs). The remaining 47 patients were pathologically negative of SLN, whereas 4 patients were found with metastases in the non-SLN samples. The detection rate, sensitivity, specificity, and accuracy rate of SLNB in the lateral neck were 98.7%, 87.1%, 98.7%, and 93.6%, respectively. However, the values varied greatly in each specific compartment of the lateral neck, and all of them were no more than 80%. These 34 PTC patients diagnosed with lateral compartment LNM (LLNM) were more likely to be younger (41.38 vs. 48.95 years old, p = 0.002) and exhibit extrathyroidal extension (56.8% vs. 31.7%, p = 0.026) and central compartment LNM (66.7% vs. 12.1%, p < 0.001). Tumors located in the upper third of the thyroid lobe also had a significantly higher probability of LLNM compared with those in middle or inferior location (66.7% vs. 35.3% vs. 34.8%, p = 0.044). At last, age (OR=0.912, p = 0.026), tumor location (upper vs inferior, OR=17.478, p = 0.011), and central compartment LNM (OR=25.364, p < 0.001) were independently predictive of LLNM. Conclusions: SLNB can help surgeons to identify some PTC patients who may benefit from therapeutic lateral neck dissection and protect some patients from prophylactic lateral neck dissection. However, it cannot accurately indicate specific lateral compartment-oriented neck dissection. Meanwhile, LLNM is more likely to occur in PTC patients with younger age or upper pole tumors or central compartment LNM.

Prophylactic Central Neck Dissection for cN1b Papillary Thyroid Carcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND: The value of prophylactic central neck dissection (PCND) for papillary thyroid carcinoma (PTC) with clinically evident lateral cervical lymph node metastases (cN1b) remains unclear. Therefore, a systematic review and meta-analysis was conducted to assess the efficacy and safety of PCND. METHODS: A comprehensive systematic search was conducted on PubMed, Web of Science, Cochrane library and Embase databases up to September 2021 to identify eligible studies. Controlled clinical trials assessing therapeutic effects and safety of PCND for cN1b PTC patients were included. The risk of bias for each cohort study was assessed using the Newcastle-Ottawa Scale (NOS). The primary outcomes were indexes related to the locoregional recurrence (LRR) and surgical complications. Review Manager software V5.4.0 was used for statistical analysis. A fixed effects model was adopted for the data without heterogeneity, otherwise a random effects model was used. RESULTS: We included 4 retrospective cohort studies, which comprised 483 PTC patients. There was no statistically significant difference in the central neck recurrence (CNR) (10.2% vs. 3.8%, relative risk (RR) = 1.82; 95%CI 0.90-3.67; P = 0.09), lateral neck recurrence (LNR) (5.1% vs. 7.7%, RR = 0.47; 95% CI 0.13-1.74; P = 0.26), and overall recurrence (OR) (18.9% vs. 16.9%, RR = 0.77; 95%CI 0.34-1.76; P = 0.54), between LND + PCND group and LND group. Simultaneously, PCND increased the risk of permanent hypoparathyroidism (11.4% vs. 4.5%, RR = 2.70, 95%CI 1.05-6.94; P = 0.04) and overall complications (17.0% vs. 5.3%, RR = 3.28; 95%CI 1.37-7.86; P = 0.008). CONCLUSIONS: This meta-analysis showed that PCND did not have any advantage in preventing LRR for cN1b PTC. Meanwhile, PCND may result in the increased rate of surgical complications. However, the current evidence is limited and more clinical trials are still needed to further clarify the true role of PCND. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, CRD42021281825.

Low-Grade Adenosquamous Carcinoma of the Axilla of Breast Origin in a Male: A Case Report and Literature Review.

Low-grade adenosquamous carcinoma (LGASC) is a rare invasive tumor that occurs in breast parenchyma. It has previously only been reported in females. Herein, we describe the case of a 52-year-old male who presented with a palpable mass in his right axilla that he reported had been present for 20-years. This is the first report of a male patient with LGASC. Core needle biopsy pathology revealed a benign mass of mammary origin, but its type was initially misdiagnosed. It was only correctly identified via postoperative pathology after local excision, which indicated that the mass exhibited the typical pathological characteristics of LGASC. Immunohistochemical analysis revealed positive expression of estrogen receptor, which was inconsistent with the typical "triple-negative" immunophenotype of LGASC. After resection of the mass the patient was advised to participate in regular outpatient follow-up. In conclusion, LGASC should be considered in male patients with a mass lesion in their breast or axilla, even when core needle biopsy indicates a benign mass of breast origin. One-stage local resection is recommended for the treatment of male patients with LGASC, but it is crucial to ensure that the margins are negative and postoperative adjuvant radiotherapy is not recommended.

Retroperitoneal metastasis synchronous with brain and mediastinal lymph nodes metastasis from breast invasive ductal carcinoma as the first site of distant metastasis: a case report and review of literature.

Breast carcinoma retroperitoneal metastasis is rare. The clinical symptoms of this disease are always non-specific. Laboratory tests are not always helpful for diagnosis and evaluation. We reported a case of a 52 year old Chinese patient who was diagnosed with retroperitoneal metastasis from breast invasive ductal carcinoma as the first site of distant metastasis synchronous with brain and mediastinal lymph nodes metastasis 4 years after modified radical mastectomy. Second-line chemotherapy of docetaxel and capecitabine was recommended. The response evaluation every two to three months was good. Unfortunately, the metastasis in the brain advanced. The patient was transferred to a radiotherapy department to receive radiotherapy and died 10 months later. We also review the related literature.

Increased Expression of Exosomal AGAP2-AS1 (AGAP2 Antisense RNA 1) In Breast Cancer Cells Inhibits Trastuzumab-Induced Cell Cytotoxicity.

BACKGROUND Trastuzumab therapy is important for patients with HER2-positive breast cancer, but more and more patients have experienced trastuzumab resistance during recent years. Accumulating evidence from recent studies showed that long non-coding RNAs (lncRNAs) play essential roles in chemoresistance of various cancer types, but the precise role of lncRNAs in trastuzumab resistance is unclear. In the present study, we aimed to identify the biofunction of lncRNA APAP2-AS1 in tranastuzumab resistance and to reveal the underlying regulatory mechanism. MATERIAL AND METHODS By culturing HER2-positive SKBR-3 and BT474 cells with transtuzumab-containing medium, we built trastuzumab-resistant cells. Quantitative real-time PCR was used to test the expression of AGAP2-AS1 in the built trastuzumab-resistant cells. Cell viability assay and TUNEL assay were used to test the cell viability and apoptosis in each group. Exosomes were purified from cells cultured in exosomes-depleted FBS and identified by transmission electron microscopy. RESULTS qRT-PCR assay suggested that AGAP2-AS1 was upregulated in the built trastuzumab-resistant cells when compared with parental sensitive cells. Cell viability assay showed that silencing of AGAP2-AS1 enhanced the cytotoxicity induced by trastuzumab treatment. Mechanistically, we revealed that AGAP2-AS1 was secreted outside cells by incorporation into exosomes in an hnRNPA2B1-dependent manner. More importantly, co-culture AGAP2-AS1-containing exosomes with sensitive cells reduced the trastuzumab-induced cell death, and silencing of AGAP2-AS1 from exosomes reversed this effect. In summary, AGAP2-AS1 promotes trastuzumab resistance of breast cancer cells through packaging into exosomes. CONCLUSIONS Knockdown of AGAP2-AS1 may be helpful for improving the clinical outcome for HER2+ breast cancer patients and could serve as a therapeutic target.

The Utility of Sentinel Lymph Node Biopsy in Papillary Thyroid Carcinoma with Occult Lymph Nodes.

BACKGROUND: The sentinel lymph node (SLN) is defined as the first draining node from the primary lesion, and it has proven to be a good indicator of the metastatic status of regional lymph nodes in solid tumors. The aim of this study was to evaluate the clinical application of SLN biopsy (SLNB) in papillary thyroid carcinoma (PTC) with occult lymph nodes. METHODS: From April 2006 to October 2012, 212 consecutive PTC patients were treated with SLNB using carbon nanoparticle suspension (CNS). Then, the stained nodes defined as SLN were collected, and prophylactic central compartment neck dissection (CCND) followed by total thyroidectomy or subtotal thyroidectomy were performed. All the samples were sent for pathological examination. RESULTS: There were 78 (36.8%) SLN metastasis (SLNM)-positive cases and 134 (63.2%) SLNM-negative cases. The sensitivity, specificity, positive and negative predictive values, and false-positive and false-negative rates of SLNB were 78.8%, 100%, 100%, 84.3%, 0%, and 21.2%, respectively. The PTC patients with SLNM were more likely to be male (48.2% vs. 32.7%, p = 0.039) and exhibited multifocality (52.6% vs. 33.3%, p = 0.025) and extrathyroidal extension (56.7% vs. 33.5%, p = 0.015). A greater incidence of non-SLN metastases in the central compartment was found in patients with SLNM (41/78, 52.6%) than in those without SLNM (21/134, 15.7%; p < 0.05). However, the SLNM-negative PTC patients with non-SLN metastases were more likely to be male (37.9% vs. 9.5%, p < 0.05). CONCLUSIONS: The application of SLNB using CNS is technically feasible, safe, and useful, especially for male patients with co-existing multifocality and extrathyroidal extension. However, the sensitivity of SLNB must be improved and its false-negative rate reduced before it can be a routine procedure and replace prophylactic CCND. More attention should be paid to PTC patients (especially males) without SLNM for signs of non-SLN metastases.

Genetic variants of interleukin-4 gene in autoimmune thyroid diseases: an updated meta-analysis.

Autoimmune thyroid diseases (AITDs) including Graves' disease (GD) and Hashimoto's thyroiditis (HT) are common autoimmune endocrine disorders. Interleukin-4 (IL-4), a cytokine secreted by T cells, plays a critical role in antigen-specific Th2 responses. The IL-4 gene is highly polymorphic and it has been reported that the polymorphism at -590 (T/C, rs2243250) in the promoter region of IL-4 may contribute to the development of AITDs. Recently, several case-control studies have examined the association of genetic variants of IL-4 with AITDs. However, the results of these studies remain conflicting. To systematically study the role of IL-4 in the pathogenesis of AITDs, we conducted a meta-analysis including 11 eligible studies (1847 cases and 2068 healthy controls). Fixed-effect or random-effect models were used to calculate pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Our results revealed a significant association between the IL-4 genetic variant (-590, T/C, rs2243250) and the risk of developing AITDs (TC + TT versus TT genotype: OR = 1.83, 95% CI = 1.083-3.091, p = 0.024). These findings demonstrate that the IL-4 rs2243250 genetic variant might play a key role in the development of AITDs.

Metastasis of distal esophageal carcinoma to the thyroid with presentation simulating primary thyroid carcinoma: a case report and review of the literature.

Metastasis to the thyroid is extremely rare. There is a lack of awareness of and adequate preparation for this situation, especially in an individual without a past history of malignancy. We describe a rare case of a 61-year-old man in whom a primary distal esophageal carcinoma gave rise to a metastatic palpable mass in the thyroid gland. Palliative bilateral near-total thyroidectomy was performed with pathology showing squamous cell carcinoma and tracheostomy was carried out simultaneously due to airway compression with related symptoms. A review of the literature only reveals 4 similar cases. Secondary neoplasm of the thyroid mimicking a primary malignant lesion is seldom encountered, however, in order to make appropriate treatment, the most critical problem is to distinguish the difference between the above two and the final diagnosis can only be confirmed on pathologic examination. Although the prognosis of thyroid metastasis is commonly felt to be poor, improvement of living quality and prolongation of survival may be obtained in such patients through correct diagnosis and treatment.

Down-regulation of miRNA-30a in human plasma is a novel marker for breast cancer.

The present study was to evaluate the value of miRNA-30a in plasma as potential tumor marker in detecting breast cancer (BC). Using a novel approach to extract miRNA-30a from the plasma followed by real-time quantitative polymerase chain reaction (RQ-PCR) analysis, levels of miRNA-30a were quantified in plasma specimens of 100 BCs and 64 age-matched and disease-free healthy controls (HC). And we compared the diagnostic value of plasma miRNA-30a with conventional circulating tumor markers CA153 and CEA. The median levels of miRNA-30a were significantly lower in preoperative BC than those in HC (P < 0.001). The levels of CEA and CA153 were all significantly higher in preoperative BC compared with those in HC (P = 0.008 and P = 0.001, respectively), and only the level of CA153 decreased in postoperative BC compared with preoperative BC (P = 0.015). ROC analysis showed the sensitivity and specificity of miRNA-30a for BC diagnosis at 74.0 and 65.6 %, respectively, whereas the sensitivities of CEA and CA153 were 12.0 and 14.0 %, respectively. The status of ER and triple-negative BC was significantly associated with miRNA-30a level (P = 0.007 and P = 0.005, respectively). And no other clinicopathological features were found to had significant difference. Our findings suggest that plasma miRNA-30a decreased in patients with BC and has great potential to use as novel biomarkers for BC diagnosis.