Multimodal predictive factors of metastasis in lymph nodes posterior to the right recurrent laryngeal nerve in papillary thyroid carcinoma.

Objective: The lymph node posterior to the right recurrent laryngeal nerve (LN-prRLN) is a crucial component of the central lymph nodes (LNs). We aimed to evaluate multimodal predictive factors of LN-prRLN metastasis in patients with papillary thyroid carcinomas (PTCs), including the clinical data, pathologic data, and preoperative sonographic characteristics of PTCs. Methods: A total of 403 diagnosed PTC patients who underwent unilateral, sub-total, or total thyroidectomy with central neck dissection were enrolled in this retrospective study. The clinical data, pathologic data, conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) characteristics of PTCs were collected and evaluated for predicting LN-prRLN metastasis. Results: In this study, 96 PTC patients with LN-prRLN metastasis and 307 PTC patients without LN-prRLN metastasis were included. Univariate analysis demonstrated that PTC patients with LN-prRLN metastasis more often had younger age, larger size, multifocal cancers, A/T < 1, well-margins, microcalcification, petal-like calcification, internal vascularity, centripetal perfusion pattern and surrounding ring enhancement. Multivariate logistic regression analysis revealed that the CEUS centripetal perfusion pattern, central LN detected by ultrasound and LN-arRLN metastasis were independent characteristics for predicting LN-prRLN metastasis in PTC patients. Conclusion: According to our research, it is essential for clinicians to thoroughly dissect central LNs, particularly LN-prRLNs.

Contrast-enhanced ultrasound characteristics of preoperative central cervical lymph node metastasis in papillary thyroid carcinoma.

This study evaluated the preoperative diagnostic value of lymph node ultrasonography in distinguishing between benign and malignant central cervical lymph nodes (CCLNs) in patients with papillary thyroid carcinoma (PTC). A total of 176 patients who had PTC with 216 CCLNs (49 benign and 155 malignant) were enrolled in this study and preoperatively imaged by ultrasonography, including conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS). We evaluated the ultrasonography parameters for each lymph node. Binary logistic regression analysis indicated that multifocality of PTC and the absence of Hashimoto's thyroiditis are independent clinical features related to patients with PTC who also have malignant CCLNs. For preoperative ultrasonography features, heterogeneous enhancement and centripetal perfusion are independent ultrasonographic features to identify malignant and benign CCLNs. This study demonstrated that preoperative CEUS characteristics help to distinguish malignant CCLNs from benign CCLNs.

Value of Contrast-Enhanced Ultrasound for Evaluation of Cervical Lymph Node Metastasis in Papillary Thyroid Carcinoma.

The aim of the study was to evaluate the diagnostic value of contrast-enhanced ultrasound (CEUS) in distinguishing between benign and malignant cervical lymph nodes (LNs) in patients with papillary thyroid carcinoma (PTC). Two hundred and one cervical LNs (157 metastatic from PTC and 44 benign) were evaluated using conventional ultrasonography (US) and CEUS before biopsy or surgery. Histopathology was used as the gold standard. We evaluated the size, long axis/short axis ratio (L/S), fatty hilum, hyper-echogenicity, calcification, cystic change, peripheral vascularity and CEUS parameters for each lymph nodule. The CEUS parameters included enhancement type, homogeneity, perfusion type, ring enhancement, peak intensity (PI) index and area under the curve (AUC) index. Univariate analysis demonstrated that compared with benign LNs, malignant LNs more frequently had L/S < 2, absence of a fatty hilum, presence of hyper-echogenicity, presence of calcification, peripheral vascularity, hyper-enhancement, heterogeneous enhancement, centripetal perfusion, ring enhancement, PI index > 1 and AUC index > 1 on preoperative US and CEUS. Binary logistic regression analysis demonstrated that hyper-enhancement, centripetal perfusion, and ring enhancement are independent CEUS characteristics related to malignant LNs for their differentiation from benign LNs (all p < 0.05). Our study indicated that preoperative CEUS characteristics may serve as a useful tool to identify malignant cervical LNs from benign cervical LNs.

Value of Contrast-Enhanced Ultrasound in Partially Cystic Papillary Thyroid Carcinomas.

Partially cystic papillary thyroid carcinomas (PCPTCs) are rarely reported papillary thyroid carcinomas (PTCs) and are usually misdiagnosed as benign nodules. The objective of this study was to provide the various sonographic characteristics of partially cystic thyroid nodules for differentiation between malignant and benign nodules, including those for conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS). Twenty-three PCPTC patients and 37 nodular goiter patients were enrolled in this study. We evaluated the size, cystic percentage, solid echogenicity, calcification, vascularity, and CEUS parameters for each nodule. The final diagnosis of all patients was confirmed via surgery. Univariate analysis demonstrated that compared with benign nodular goiters, PCPTCs more frequently presented with calcification, hypoechogenicity of the solid part, hypoenhancement, heterogeneous enhancement, centrifugal perfusion, peak intensity index <1, time to peak index ≥1, and area under the curve index <1 on preoperative US and CEUS. Binary logistic regression analysis demonstrated that heterogeneous enhancement, centrifugal perfusion, and peak intensity index <1 are independent CEUS characteristics related to malignant PCPTCs and can be used for their differentiation from benign nodular goiters (all p < 0.05). Our study indicated that preoperative CEUS characteristics may serve as a useful tool to distinguish malignant PCPTCs from benign thyroid nodules.

LINC01133 hampers the development of gastric cancer through increasing somatostatin via binding to microRNA-576-5p.

Aim: Our study aimed at investigating how LINC01133 functions in gastric cancer (GC) progression. Materials & methods: Gain-of-function and loss-of-function approaches were applied to analyze the effects of LINC01133, microRNA-576-5p (miR-576-5p) and somatostatin (SST) on the biological behaviors of GC cells and in tumor-bearing nude mice. Results: GC tissues and cells showed low expression of LINC01133, and LINC01133 overexpression decreased malignant phenotypes of GC cells. Moreover, LINC01133 upregulated SST through binding to miR-576-5p. Overexpressing miR-576-5p or suppressing SST reversed the functions of LINC01133 in biological potentials of GC cells and tumor growth. Conclusion: LINC01133 overexpression may inhibit GC development by downregulation of miR-576-5p and upregulation of SST, which suggests new therapeutic targets for GC.

Long noncoding RNA TPT1-AS1 promotes the progression and metastasis of colorectal cancer by upregulating the TPT1-mediated FAK and JAK-STAT3 signalling pathways.

Tumour protein translationally controlled 1 (TPT1) antisense RNA 1 (TPT1-AS1) is known to be involved in the development and metastasis of cervical and ovarian cancers; however, its biological role in colorectal cancer (CRC) remains unknown. This study aimed to determine the function and mechanism of action of TPT1-AS1 in the progression and metastasis of CRC. Elevated TPT1-AS1 levels were observed in CRC tissues. Furthermore, the high expression levels were found to be correlated with unfavourable clinicopathological characteristics in CRC. Cell function experiments demonstrated that TPT1-AS1 depletion impeded cell proliferation, migration and invasion and enhanced cell adhesion; it also attenuated tumorigenesis and metastasis in vivo. Additionally, TPT1-AS1 was predominately located in the nuclei of the cells and could upregulate the expression of TPT1 by recruiting mixed lineage leukaemia protein-1 (MLL1), which increased the trimethylation of H3K4 me3 in the TPT1 promoter region and subsequently activated FAK and JAK-STAT3 signalling cascades. The inhibition of FAK activation by PF573228 significantly attenuated the oncogenic effect of TPT1-AS1. These findings indicated that TPT1-AS1 promoted tumour progression and metastasis in CRC by upregulating TPT1 levels and activating the FAK and JAK-STAT3 signalling pathways. Thus, TPT1-AS1 may be considered as a potential therapeutic target for CRC.

Long non-coding RNA DIO3OS/let-7d/NF-κB2 axis regulates cells proliferation and metastasis of thyroid cancer cells.

Due to the steadily rising morbidity and mortality, thyroid cancer remains the most commonly seen endocrine cancer. The present study attempted to investigate the mechanism from the perspective of long non-coding RNA (lncRNA) regulation. We identified 53 markedly increased lncRNAs in thyroid cancer samples according to TCGA data. Among them, high lncRNA DIO3OS expression was a risk factor for thyroid cancer patients' poorer overall survival. DIO3OS showed to be considerably increased within thyroid cancer tissue samples and cells. Knocking down DIO3OS within thyroid carcinoma cells suppressed cancer cell viability, the capacity of DNA synthesis, cell invasion, as well as cell migration; besides, proliferating markers, ki-67 and PCNA, were decreased by DIO3OS knockdown. Cancer bioinformatics analysis suggested that NF-κB2 might be related to DIO3OS function in thyroid cancer carcinogenesis. NF-κB2 was positively correlated with DIO3OS, and DIO3OS knockdown decreased NF-κB2 protein levels. Knocking down NF-κB2 within thyroid carcinoma cells suppressed cancer cell viability, the capacity of DNA synthesis, cell invasion, cell migration, and the protein levels of proliferating markers. Let-7d directly targeted DIO3OS and NF-κB2; DIO3OS knockdown upregulated let-7d expression. The overexpression of let-7d suppressed cancer cell viability, the capacity of DNA synthesis, cell invasion, cell migration, as well as the protein levels of proliferating markers. Let-7d inhibition remarkably attenuated the functions of DIO3OS knockdown in NF-κB2 expression and thyroid cancer cell phenotype. In conclusion, DIO3OS/let-7d/NF-κB2 axis regulates the viability, DNA synthesis capacity, invasion, and migration of thyroid cancer cells. The clinical application of this axis needs further in vivo and clinical investigation.

Identification of CircRNA-miRNA-mRNA Regulatory Network in Gastrointestinal Stromal Tumor.

Circular RNA (circRNA) abnormal expression and regulation are involved in the occurrence and development of a variety of tumors. However, the role of circRNAs still remains unknown in gastrointestinal stromal tumors (GISTs). In the present study, the differential circRNA expression profile of GISTs was screened by human circRNAs chip and verified by qRT-PCR. The circRNA-miRNA-mRNA regulatory network was constructed using the cytoHubba plugin based on the Cytoscape software. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to explore circRNA functions. Six significantly differential circRNAs were also verified in 20 pairs of GISTs and adjacent tissues by qRT-PCR. The result showed that a total of 543 differentially expressed circRNAs were identified in GISTs, of which 242 were up-regulated and 301 were down-regulated. Additionally, the circRNA-miRNA-mRNA network contained six circRNAs, 30 miRNAs, and 308 mRNAs, and the targeted mRNAs were associated with "regulation of biological process," "intracellular organelle," "protein binding," and enriched in Wnt signaling pathway. Furthermore, qRT-PCR demonstrated that hsa_circRNA_061346, hsa_circRNA_103114, and hsa_circRNA_103870 were significantly up-regulated in GISTs (n = 20), and hsa_ circRNA_405324, hsa_circRNA_406821, and hsa_circRNA_000361 were dramatically down-regulated in GISTs (n = 20). In addition, all of these circRNAs were shown to have high diagnostic values, and most of them were significantly associated with tumor size, mitotic figure, and malignant degrees in GISTs (P < 0.05). Therefore, we concluded that circRNAs were abnormally expressed in GISTs, and the circRNA-miRNA-mRNA regulatory network plays an important role in the occurrence and development of GISTs. Also, the identified six candidate circRNAs might be critical circRNAs and may present as potential diagnostic biomarkers for GISTs.

[Clinical experience and efficacy of endoscopic surgery for papillary thyroid microcarcinoma through total areola approach].

OBJECTIVE: To investigate the experience and efficacy of endoscopic thyroidectomy for papillary thyroid microcarcinoma (PTMC) through total areola approach.
 Methods: A total of 117 PTMC patients, who were diagnosed pathologically in Minimally Invasive Surgical Center, Second Xiangya Hospital, Central South University from June 2016 to December 2017, were divided into a endoscopic surgery group (n=72) and an open surgery group (n=45). The number of dissected central lymph nodes, blood loss, amount of drainage, occurrence of postoperative complication and recurrence were collected and compared.
 Results: Compared with the open surgery group, the blood loss was less and the operative time was longer in the endoscopic surgery group (P<0.05). There were no significant differences between the 2 groups in the number of dissected central lymph nodes, amount of drainage and occurrence of postoperative complication (all P>0.05). The mean follow-up time was more than 20 months, and there was no recurrence in the 2 groups. 
 Conclusion: Endoscopic thyroidectomy with central compartment neck dissection through total areola approach is safe and feasible in patients with PTMC. It has many advantages, such as no scar on neck, less blood loss, shorter hospital stay and more acceptable to young patients.

MicroRNA-153 inhibits cell proliferation, migration, invasion and epithelial-mesenchymal transition in breast cancer via direct targeting of RUNX2.

A number of microRNAs (miRNAs) are involved in the development and malignant progression of numerous types of human cancer including breast cancer. The underlying regulatory mechanism of miRNA-153 (miR-153) in breast cancer progression remains largely unknown. The present study demonstrated that miR-153 expression levels were significantly reduced in breast cancer tissue samples and cell lines, compared with adjacent healthy tissue samples and normal human breast cell line MCF-10A. In addition, low miR-153 expression was associated with advanced clinical staging and metastasis in patients with breast cancer. However, no association with age, subtype or differentiation was identified. Furthermore, patients with breast cancer with low miR-153 expression had poor prognosis, compared with patients with breast cancer with high miR-153 expression. Overexpression of miR-153 reduced proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in breast cancer SK-BR-3 and BT-549 cells. Runt-related transcription factor 2 (RUNX2), which was revealed to be significantly upregulated in breast cancer, was verified as a target gene of miR-153 in SK-BR-3 and BT-549 cells by luciferase reporter gene assay. High RUNX2 expression was associated with advanced clinical staging as well as distant and lymph node metastasis in patients with breast cancer. However, no association with age, subtype or differentiation was identified. Additionally, an inverse correlation between miR-153 and RUNX2 mRNA expression levels was observed in breast cancer tissues. RUNX2 overexpression reduced the suppressive effects of miR-153 on the proliferation, migration, invasion and EMT of SK-BR-3 and BT-549 cells. The present study indicated that miR-153 may serve a role in breast tumor growth and metastasis via direct targeting of RUNX2. The miR-153/RUNX2 axis may be used as a potential therapeutic target in breast cancer treatment.

Analysis of Clinical Efficiency and Safety of Laparoscopic Anus-Conserving Operation for Ultralow Rectal Cancer.

To explore the efficiency and safety of laparoscopic anus-conserving operation for ultralow rectal cancer, we retrospectively reviewed 236 patients with ultralow rectal cancer who underwent laparoscopic anus-conserving operation (experimental group, n = 124) or conventional open surgery (control group, n = 112). Operation-related indexes, pathological results of mesentery, incidence rates of postoperative complications, anus preservation rates, anal sphincter controllability after surgery, and survival rates of the first, second, and third years after operation were compared between the two groups. The amount of intraoperative bleeding, first postoperative exhaust time, abdominal drainage, pain score, and hospital stay in the experimental group were significantly less than those in the control group (P < 0.05). There were no significant differences in the postoperative circumferential resection margin, distal resection margin, number of dissected lymph nodes, successful resection rate, and quality of mesorectum between the two groups (P > 0.05). The total incidence rate of postoperative complications, anal sphincter controllability, and survival rates after surgery were similar between the two groups (P > 0.05). The anus preservation rate of the experimental group (84.7%) was significantly higher than that of the control group (69.6%) (P < 0.05). Laparoscopic anus-conserving operation is effective and safe in treatment of patients with ultralow rectal cancer, which has advantages such as small trauma, less intraoperative bleeding, short hospital stay, rapid recovery, a low incidence rate of postoperative complications, and a high anus-preserving rate, so it is worthy of clinical application.

Portable detection of colorectal cancer SW620 cells by using a personal glucose meter.

It is of great value to develop general, low-cost and even household methods for colorectal cancer detection. Here, a portable detection strategy based on a personal glucose meter (PGM) was designed for meeting this purpose. In this strategy, the anti-EpCAM coated magnet beads (MBs) were used as capture probes for enriching cancer cells and the aptamer modified and invertase loaded graphene oxides (GO) were used as report probes for producing glucose signal. This method is sensitive with detection limit as low as 560 cells, and demonstrates excellent detection specificity. Meanwhile, we succeeded in the specific detection of target cells in 20% human serum samples, indicating this method has great prospect in clinical diagnosis. Moreover, this method presents favourable universality for detecting different colorectal cancer cells by just using different recognition aptamers. Importantly, this method can be implemented for the target cell detection at room temperature without any expensive and large-scale instruments but a portable PGM. Therefore, this portable detection method possesses great potential in point-of-care detection of colorectal cancer cells.

Long noncoding AFAP1-antisense RNA 1 is upregulated and promotes tumorigenesis in gastric cancer.

Long noncoding RNA serves important roles in gastric cancer (GC). However, the prognostic significance and tumorigenesis effect of AFAP1-antisense RNA 1 (AS1) in GC remain to be clarified. The present study was conducted in order to determine the expression level of AFAP1-AS1 by reverse transcription-quantitative polymerase chain reaction. It was demonstrated that AFAP1-AS1 expression level was higher in GC tissues in comparison with adjacent tissues. By analyzing 66 GC tissue specimens, AFAP1-AS1 expression level was found to be markedly associated with tumor size, clinical stage and differentiation. By performing multivariate Cox regression test, AFAP1-AS1 expression level was confirmed to be an independent factor for poor prognosis in patients with GC. Furthermore, SGC-7901 and BGC-823 cells were used for further investigation following transfection of an AFAP1-AS1 short hairpin RNA lentiviral vector. Knockdown of AFAP1-AS1 significantly inhibited GC cell proliferation, migration and invasion abilities in vitro. Finally, nude mice experiments confirmed that downregulation of AFAP1-AS1 in GC cells suppressed tumor growth in vivo. In conclusion, the results of the present study suggested that AFAP1-AS1 may serve as a valuable prognostic indicator and therapeutic target for GC.

Effectiveness and safety of total laparoscopic distal gastrectomy versus laparoscopy-assisted distal gastrectomy for gastric cancer: A retrospective cohort study.

AIM: To compare the results of total laparoscopic distal gastrectomy (TLDG) and laparoscopy-assisted distal gastrectomy (LADG) and explore the safety and feasibility of TLDG. METHODS: Data were collected and analyzed from patients underwent TLDG and LADG from January 2009 to December 2011 at our institution. RESULTS: 127 LADG cases and 104 TLDG cases were included and balanced for age, sex, BMI, ASA scores, and CEA level in this study. A decrease in postoperative pain (P < 0.001), wound infection rate (P = 0.013), and hospitalization time after surgery (P < 0.001) was found in the TLDG group. Compared with the LADG group, there was no increase in operative time (P = 0.084), intraoperative blood loss (P = 0.061), or anastomotic fistula rate (P = 0.473). Statistical differences did not exist in recurrence and (or) metastasis (P = 0.204), 5-years disease-free survival (DFS) rate and overall survival (OS) (P = 0.570 and 0.560, respectively). CONCLUSION: As long as it follows the surgical principles of malignant tumor, TLDG can achieve the same therapeutic effect as LADG does. TLDG is safe and feasible for gastric cancer patients though further studies are needed.

Synergistic antitumor effects of cMet inhibitor in combination with anti-VEGF in colorectal cancer patient-derived xenograft models.

cMet signaling pathway is involved in the resistance to anti-VEGF therapy and cMet overexpression is associated with tumor progression and poor prognosis. In this study, the expression of cMet in 146 Chinese colorectal cancer (CRC) patients was examined by immunohistochemistry staining. Our data demonstrated that cMet overexpression rate was 42.5% (62/146) and cMet overexpression was closely correlated with distant metastasis of CRC. Using CRC patient-derived xenograft (PDX) mouse models we investigated antitumor activity of a novel selective cMet inhibitor volitinib alone or in combination with anti-VEGF inhibitor apatinib in vivo. Our results showed that combination treatment significantly inhibited tumor growth in two PDX models. While volitinib treatment alone induced moderate improvement in tumor growth inhibition, combination treatment synergistically reduced microvessel density, suppressed proliferation, and increased apoptosis in PDX models. Further analysis showed synergistic inhibition of MAPK and PI3K/Akt pathways by volitinib and apatinib. Taken together, our data provide a rationale to targeting both cMet and VEGF in the treatment of cMet overexpressing CRC in clinical trials.

Original endoscopic orbital decompression of lateral wall through hairline approach for Graves' ophthalmopathy: an innovation of balanced orbital decompression.

BACKGROUND: Orbital decompression is an important surgical procedure for treatment of Graves' ophthalmopathy (GO), especially in women. It is reasonable for balanced orbital decompression of the lateral and medial wall. Various surgical approaches, including endoscopic transnasal surgery for medial wall and eye-side skin incision surgery for lateral wall, are being used nowadays, but many of them lack the validity, safety, or cosmetic effect. PATIENTS AND METHODS: Endoscopic orbital decompression of lateral wall through hairline approach and decompression of medial wall via endoscopic transnasal surgery was done to achieve a balanced orbital decompression, aiming to improve the appearance of proptosis and create conditions for possible strabismus and eyelid surgery afterward. From January 29, 2016 to February 14, 2017, this surgery was performed on 41 orbits in 38 patients with GO, all of which were at inactive stage of disease. Just before surgery and at least 3 months after surgery, Hertel's ophthalmostatometer and computed tomography (CT) were used to check proptosis and questionnaires of GO quality of life (QOL) were completed. FINDINGS: The postoperative retroversion of eyeball was 4.18±1.11 mm (Hertel's ophthalmostatometer) and 4.17±1.14 mm (CT method). The patients' QOL was significantly improved, especially the change in appearance without facial scar. The only postoperative complication was local soft tissue depression at temporal region. Obvious depression occurred in four cases (9.76%), which can be repaired by autologous fat filling. INTERPRETATION: This surgery is effective, safe, and cosmetic. Effective balanced orbital decompression can be achieved by using this original and innovative surgery method. The whole manipulation is safe and controllable under endoscope. The postoperative scar of endoscopic surgery through hairline approach is covered by hair and the anatomic structure of anterior orbit is not impacted.

TGFß1-Induced LncRNA UCA1 Upregulation Promotes Gastric Cancer Invasion and Migration.

According to recent studies, long noncoding RNA urothelial carcinoma associated 1 (UCA1) is involved in the development and progression of many malignant tumors, including gastric cancer (GC). We validated the detailed role of UCA1 in human GC cell lines and GC tissues so as to determine its exact function and the underlying mechanism of GC invasion and migration. In our research, lncRNA-UCA1 was specifically upregulated in GC tissues and cell lines, and augmented GC cell proliferation, and invasive and migratory capabilities. High UCA1 expression in GC was related with poorer prognosis (poorer invasion depth, lymph node metastasis, advanced TNM [T is for the original (primary) tumor, N for nearby (regional) lymph nodes that are involved, and M for distant metastasis] stage, and shorter overall survival). Epithelial mesenchymal transition (EMT), associated with malignancy of cancers, was reported to be responsible for invasion and migration of cancer cells. Transforming growth factor ß1 (TGFß1)-induced EMT was well evaluated. UCA1 silence reduced the protein levels of EMT-related factors, vimentin and snail, while promoted E-cadherin and zonula occludens-1 protein levels in GC cells; the effect of UCA1 could be partly restored by TGFß1 treatment. Taken together, UCA1 might regulate the tumor proliferation, invasion, and metastasis under TGFß1 induction. Taken together, UCA1 might present a potential oncogenic factor by promoting GC cell proliferation, invasion, and migration. UCA1 could serve as a novel biomarker for prognosis and a novel therapeutic target of GC treatment.