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Circular RNAs (circRNAs) are broad and diverse endogenous non-coding RNAs. Emerging evidence has revealed that circRNAs play pivotal roles in cancers, regulating the gene expression by acting as a microRNA (miRNA) sponge. However, the biological functions of circRNAs in bladder cancer (BCa) remain largely unknown. In this study, we identified an altered circRNA, termed circFUT8, by screening RNA sequencing data generated from three BCa tissues and matched adjacent normal bladder tissues. Quantitative real-time PCR analysis demonstrated that circFUT8 was downregulated in BCa tissues and correlated with patients’ prognosis, histological grade, and lymph node (LN) metastasis. Functionally, gain- and loss-of-function assays indicated that circFUT8 inhibited the migration and invasion of BCa cell lines in vitro and LN metastasis in vivo. Mechanistically, circFUT8 directly bound to miR-570-3p and partially abrogated its oncogenic role, and miR-570-3p could suppress the expression of tumor suppressor gene Krüpple-like factor 10 (KLF10) by binding its 3′ untranslated region (3′ UTR). Moreover, we found that circFUT8 promoted the expression of KLF10 by competitively sponging miR-570-3p. In conclusion, circFUT8 functions as a tumor suppressor in BCa cells by targeting the miR-570-3p/KLF10 axis and may serve as a potential biomarker and therapeutic target for the management of BCa patients with LN metastasis. Keywords: circFUT8, bladder cancer, lymph node metastasis, miR-570-3p, KLF10, Slug

Patients with breast cancer and breast cancer survivors are frequent users of botanicals and their bioactive phytochemicals. In China, active ingredients in Sophora flavescens like matrine (MT), oxymatrine (OMT), other Sophora flavescens alkaloids and Compound Kushen Injection (CKI) are extensively used for multiple malignant tumors. In vivo and in vitro studies have confirmed that these activities or injection have significant effects on relieving symptoms, alleviating side effects after chemotherapy and improving the quality of life of breast cancer patients, where there is evidence for efficacy. A large number of experimental studies have also revealed that they can inhibit the proliferation, invasion and migration of breast cancer cells according to different mechanisms. This provides promising valuable supportive therapies for prevention, treatment and postoperative recovery of breast cancer. Rigorous clinical research and experimental studies reflect integrative care as it is used in hospital is needed to responsibly move this field forward. This review summarizes an up to date knowledge of the available bioactive phytochemicals, their discovery, current clinical and experimental status.

Growing evidence suggests that circular RNAs (circRNAs) play pivotal roles in cancer progression. In this study, bioinformatic analysis identified a dysregulated circRNA termed circPTPRA in bladder cancer (BC). By using qRT-PCR analysis, we verified that circPTPRA is down-regulated in clinical BC specimens compared with the matched non-tumor samples, while correlation analyses showed that low circPTPRA expression is associated with poor prognosis, advanced tumor stage and larger tumor size. Based on these findings, we conducted functional assays and revealed that circPTPRA inhibits BC cell proliferation in vitro and tumor growth in vivo. In addition, RNA pull-down, miRNA capture, FISH, and luciferase reporter assays demonstrated that circPTPRA can directly sponge miR-636. Cell transfection experiments showed that miR-636 promotes the proliferation of BC cells by decreasing the expression of Krüppel Like Factor 9 (KLF9) upon binding to the 3’UTR of its mRNA. Further analysis confirmed that circPTPRA competitively sponges miR-636 to upregulate the KLF9 expression, leading to decreased proliferation of BC cells. Our investigation indicates that circPTPRA acts as a tumor suppressor in BC, and suggests that this circRNA may be a novel prognostic biomarker and therapeutic target in BC.

Background Metastasis is a major obstacle in the treatment of bladder cancer (BC). Circular RNAs exert various functions in the aggressive biological behaviour of cancers. In this study, we aimed to elucidate how circPICALM influences BC metastasis. Methods The expression of circPICALM was analysed by real-time PCR. The tumourigenic properties of BC cells were evaluated using in vitro migration, invasion, and wound healing assays and an in vivo footpad model. The interaction between circPICALM and miR-1265 was confirmed by pull-down and dual-luciferase reporter assays and biotin-labelled miRNA capture. The interaction of STEAP4 and focal adhesion kinase (FAK) was confirmed by co-immunoprecipitation. Findings CircPICALM was downregulated in BC tissues, and low circPICALM expression was related to advanced T stage, high grade, lymph node positivity and poor overall survival. Overexpression of circPICALM inhibited the metastasis of BC cells, and DHX9 negatively regulated circPICALM levels. CircPICALM colocalized with miR-1265 and acted as a sponge for this miRNA, and the pro-invasion effect of miR-1265 was abolished by circPICALM overexpression. STEAP4, a target of miR-1265, suppressed metastasis; it bound to FAK to prevent autophosphorylation at Y397 and influenced EMT in BC cells. Interpretation CircPICALM can inhibit BC metastasis and bind to miR-1265 to block its pro-invasion activity. STEAP4 is a target of miR-1265 and is related to FAK phosphorylation and EMT. Fund This research was supported by National Natural Science Foundation of China, No.81772728, National Natural Science Foundation of China, No.81772719, National Natural Science Foundation of China No.81572514.

Background Circular RNAs (circRNAs) represent a subclass of regulatory RNAs that have been shown to have significant regulatory roles in cancer progression. However, the biological functions of circRNAs in bladder cancer (BCa) are largely unknown. Methods Cell invasion models were established, and invasion-related circRNAs were detected by qPCR. Using above method, circ-ZKSCAN1 was picked out for further study. Circ-ZKSCAN1 expression and survival analyses were performed through qPCR. The survival curves were generated by the Kaplan-Meier method, and the log-rank test was used to assess the significance. Cell proliferation, migration and invasion were examined to investigate the function of circ-ZKSCAN1. Tumorigenesis in nude mice was assessed to determine the effect of circ-ZKSCAN1 in bladder cancer. Biotin-coupled probe pull-down assays, FISH and luciferase reporter assays were conducted to confirm the relationship between circ-ZKSCAN1 and microRNA. RNA-seq revealed different molecular changes in downstream genes. Results Here, we found that circ-ZKSCAN1 was downregulated in BCa tissues and cell lines. Circ-ZKSCAN1 levels were associated with survival, tumor grade, pathological T stage and tumor recurrence. Overexpressed circ-ZKSCAN1 inhibits cell proliferation, migration, invasion and metastasis in vitro and in vivo. Mechanistically, we demonstrated that circ-ZKSCAN1 upregulated p21 expression by sponging miR-1178-3p, which suppressed the aggressive biological behaviors in bladder cancer. Conclusions These results reveal that Circ-ZKSCAN1 acts as a tumor suppressor via a novel circ-ZKSCAN1/miR-1178-3p/p21 axis, which have the important role in the proliferation, migration and invasion ablitities of BCa cells and provide a novel perspective on circRNAs in BCa progression.

Background Circular RNAs (circRNAs) have been considered to mediate occurrence and development of human cancers, generally acting as microRNA (miRNA) sponges to regulate downstream genes expression. However, the aberrant expression profile and dysfunction of circRNAs in human bladder cancer remain to be investigated. The present study aims to elucidate the potential role and molecular mechanism of circACVR2A in regulating the proliferation and metastasis of bladder cancer. Methods circACVR2A (hsa_circ_0001073) was identified by RNA-sequencing and validated by quantitative real-time polymerase chain reaction and agarose gel electrophoresis. The role of circACVR2A in bladder cancer was assessed both in vitro and in vivo. Biotin-coupled probe pull down assay, biotin-coupled microRNA capture, dual-luciferase reporter assay, and fluorescence in situ hybridization were conducted to evaluate the interaction between circACVR2A and microRNAs. Results The expression of circACVR2A was lower in bladder cancer tissues and cell lines. The down-regulation of circACVR2A was positively correlated with aggressive clinicopathological characteristics, and circACVR2A served as an independent risk factor for overall survival in bladder cancer patients after cystectomy. Our in vivo and in vitro data indicated that circACVR2A suppressed the proliferation, migration and invasion of bladder cancer cells. Mechanistically, we found that circACVR2A could directly interact with miR-626 and act as a miRNA sponge to regulate EYA4 expression. Conclusions circACVR2A functions as a tumor suppressor to inhibit bladder cancer cell proliferation and metastasis through miR-626/EYA4 axis, suggesting that circACVR2A is a potential prognostic biomarker and therapeutic target for bladder cancer. Electronic supplementary material The online version of this article (10.1186/s12943-019-1025-z) contains supplementary material, which is available to authorized users.

Thrombus related diseases seriously threaten human's health and life. The drawbacks of thrombolytic drugs, such as poor targeting ability and unexpected bleeding complications limit their clinical application. Thus, targeted delivery and controlled release of drugs at local thrombus sites to achieve efficient thrombolysis is an urgent event to be resolved. Herein, we developed an intelligent system MnO2/uPA@pep-Fuco for precise thrombolysis and thrombus inflammatory microenvironment remodeling. MnO2/uPA@pep-Fuco exhibited an excellent thrombus targeting ability via the high affinity of fucoidan (Fuco) for P-selectin overexpressed by activated platelets. And then pep-Fuco modified onto the surface of mesopore could be removed to release urokinase (uPA) locally under the high level of thrombin microenvironment in thrombus site. Meanwhile, due to the catalase-like activity of MnO2 nanoplatform, MnO2/uPA@pep-Fuco could regulate the inflammatory thrombus microenvironment by eliminating hydrogen peroxide (H2O2), so as to achieve a collaborative thrombolysis therapy. In ferric chloride (FeCl3)-induced carotid thrombus models, MnO2/uPA@pep-Fuco specifically targeted to the obstructive artery (3.43 times that of the normal artery) and significantly decreased the percentage of thrombus closure (5.99 ± 5.07%), demonstrating the superior thrombolysis ability. In addition, the significantly reduced tail bleeding time suggested MnO2/uPA@pep-Fuco might possess a low risk of bleeding complications.

Rationale Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy that is almost always fatal and lacks effective systemic treatment options. Current treatments of ATC include surgery, radiation, and chemotherapy, used in combination when possible. In the aspect of immunotherapy, the biomarker of TMB-H and MSI-H may suggest that patients benefit from pembrolizumab. Programmed cell death-ligand 1 (PD-L1) is highly expressed in ATC but has not been written into the guidelines or approved by the FDA as a biomarker for thyroid cancer immunotherapy. Patient concerns A 55-year-old woman was admitted to our hospital because of a slight right-sided neck enlargement in November 2019. Diagnoses The clinical diagnosis was ATC, pT3bN0M0, and stage IVB. Interventions Oral administration of apatinib (250 mg 3 times daily) was initiated after surgery, but some unpleasant side effects emerged after 1 month of treatment. Next-generation sequencing revealed that the tumor harbored 2 mutations, HRAS p.Q61R and TP53 p.P278S, and PD-L1 staining was positive with a high expression. Thus, camrelizumab (programmed cell death protein 1 inhibitor) was combined with apatinib, and apatinib was changed to 250 mg once a day from March 2020. Outcomes No adverse reactions were observed after the treatment immunotherapy combined with antiangiogenic drugs. Currently, the survival time of patients is more than 11 months, and the quality of life is not affected. Conclusion This case suggests that immunotherapy in patients with ATC based upon PD-L1 evaluation provides a therapeutic option. Targeting programmed cell death protein 1/PD-L1 may provide a much-needed treatment option for patients with advanced ATC.

Thrombolytic treatment is the primary method for thrombotic diseases. However, uncontrollable bleeding and secondary vascular embolism are prone. Based on the thrombus microenvironment, this project constructed an "on-off " drug depot that can accurately identify thrombus and respond to changes of shear force to solve above problems. The fucoidan (Fuc)-based core-shell NPs were prepared by β-CD host-guest inclusion interaction. The thrombolytic drug urokinase (UK) and antiplatelet drug tirofiban (TI) were loaded into outer shell and inner core, respectively. In vitro and in vivo results proved that UK@Fuc-TI/PPCD was closed under low blood shear force to reduce bleeding risk. Once arriving at thrombus site, UK@Fuc-TI/PPCD can realize precise “homing” by recognizing P-selectin overexpressed by thrombus. Then sharply increased shear force at targeted thrombus broke the core-shell structure to release UK rapidly, realizing site-specific thrombolysis. Subsequently, TI loaded in PPCD core was slowly released at thrombolysis site, preventing re-embolization of blood vessels. Thrombolysis results demonstrated the in vitro thrombolysis rate of UK@Fuc-TI/PPCD pre-treated with 1000 dyne/cm2 shear force was 91.59%. And in vivo, the percentage of residual thrombus in UK@Fuc-TI/PPCD treatment group was only 9.37% with relatively low bleeding risk, suggested this shear fore-responsive detachable system with thrombus targeting ability and sequential drug release profile can realize the efficient recanalization of embolized vessels.

Resistance to thyroid hormone (RTH) is a rare autosomal hereditary disorder characterized by increased serum thyroid hormone (TH) levels with unsuppressed or increased thyrotropin concentration. It remains unknown whether the coexistence of RTH with papillary thyroid carcinoma (PTC) and Hashimoto thyroiditis (HT) is incidental or whether it possesses a genetic or pathophysiological association. In the present study, a case of RTH with PTC and HT in an 11-year-old Chinese patient was examined and the clinical presentation of RTH with PTC was discussed. In addition, the possible associations between RTH, PTC and HT were determined. HT was confirmed in the patient using an autoimmune assay and thyroid ultrasound. RTH was diagnosed on the basis of clinical manifestations, laboratory information and gene analysis, and PTC was diagnosed according to histological results. Results of BRAFV600E mutation analysis were positive. A literature review of 14 cases of RTH with PTC was included for comparison. The present case report indicates an association of RTH with PTC and HT coexistence in the patient. Close follow-up, histological evaluation and BRAFV600E mutation detection should be performed in each RTH case with HT, since a persistent increase in TSH may be a risk factor for the development of thyroid neoplasm.

Mother-to-child transmission (MTCT) is responsible for the majority of chronic hepatitis B virus (HBV) infections worldwide. Despite timely HBV immunoprophylaxis of neonates, MTCT can occur in infants born to mothers with high levels of HBV viremia. We performed a retrospective cross-sectional analysis of Asian American women with chronic HBV evaluated with HBV DNA during prenatal care at two community health sites in New York City from 2007 to 2017. We described patient's demographic and clinical characteristics, categorized their HBV disease phase and analysed for variables associated with high MTCT risk (defined by HBV DNA level >200 000 IU/mL) using multivariable logistic regression. A total of 1298 pregnancies among 1012 mostly China-born (97.6%) women with chronic HBV were included in the study. Of the 1241 pregnancies among women not on antiviral treatment, 22.4% were considered high risk for MTCT and, of these, 255 (91.7%) were HBV e antigen (HBeAg)-positive and 19 (6.8%) were HBeAg-negative. HBeAg-positive status and ALT levels between 26 and 50 U/L were associated with higher likelihood for being high risk for MTCT. Only 0.8% of pregnancies low risk for MTCT were in the immune active phase while the majority (58.4%) were in the inactive chronic HBV phase of infection. Approximately one in five (22.4%) pregnancies among Asian American women with chronic HBV was considered high risk for MTCT and met criteria for antiviral therapy. Full assessment of HBV pregnant women and early coordinated care is needed to deliver interventions to prevent MTCT during critical windows of time.

Metastasis is a major obstacle in the treatment of bladder cancer (BC). Circular RNAs exert various functions in the aggressive biological behaviour of cancers. In this study, we aimed to elucidate how circPICALM influences BC metastasis.The expression of circPICALM was analysed by real-time PCR. The tumourigenic properties of BC cells were evaluated using in vitro migration, invasion, and wound healing assays and an in vivo footpad model. The interaction between circPICALM and miR-1265 was confirmed by pull-down and dual-luciferase reporter assays and biotin-labelled miRNA capture. The interaction of STEAP4 and focal adhesion kinase (FAK) was confirmed by co-immunoprecipitation.CircPICALM was downregulated in BC tissues, and low circPICALM expression was related to advanced T stage, high grade, lymph node positivity and poor overall survival. Overexpression of circPICALM inhibited the metastasis of BC cells, and DHX9 negatively regulated circPICALM levels. CircPICALM colocalized with miR-1265 and acted as a sponge for this miRNA, and the pro-invasion effect of miR-1265 was abolished by circPICALM overexpression. STEAP4, a target of miR-1265, suppressed metastasis; it bound to FAK to prevent autophosphorylation at Y397 and influenced EMT in BC cells.CircPICALM can inhibit BC metastasis and bind to miR-1265 to block its pro-invasion activity. STEAP4 is a target of miR-1265 and is related to FAK phosphorylation and EMT. FUND: This research was supported by National Natural Science Foundation of China, No.81772728, National Natural Science Foundation of China, No.81772719, National Natural Science Foundation of China No.81572514.

Background: A large proportion of the patients with papillary thyroid microcarcinoma are young women. Therefore, minimally invasive endoscopic thyroidectomy with central neck dissection (CND) emerged and showed well-accepted results with improved cosmetic outcome, accelerated healing, and comforting the patients. This study aimed to evaluate the safety and effectiveness of robotic total thyroidectomy with CND via bilateral axillo-breast approach (BABA), compared with conventional open procedure in papillary thyroid microcarcinoma. Methods: One-hundred patients with papillary thyroid microcarcinoma from March 2014 to January 2015 in Jinan Military General Hospital of People's Liberation Army (PLA) were randomly assigned to robotic group or conventional open approach group (n = 50 in each group). The total operative time, estimated intraoperative blood loss, numbers of lymph node removed, visual analog scale (VAS), postoperative hospital stay time, complications, and numerical scoring system (NSS, used to assess cosmetic effect) were analyzed. Results: The robotic total thyroidectomy with CND via BABA was successfully performed in robotic group. There were no conversion from the robotic surgeries to open or endoscopic surgery. The subclinical central lymph node metastasis rate was 35%. The mean operative time of the robotic group was longer than that of the conventional open approach group (118.8 ± 16.5 min vs. 90.7 ± 10.3 min, P < 0.05). The study showed significant differences between the two groups in terms of the VASs (2.1 ± 1.0 vs. 3.8 ± 1.2, P < 0.05) and NSS (8.9 ± 0.8 vs. 4.8 ± 1.7, P < 0.05). The differences between the two groups in the estimated intraoperative blood loss, postoperative hospital stay time, numbers of lymph node removed, postoperative thyroglobulin levels, and complications were not statistically significant (all P > 0.05). Neither iatrogenic implantation nor metastasis occurred in punctured porous channel or chest wall in both groups. Postoperative cosmetic results were very satisfactory in the robotic group. Conclusions: Robotic total thyroidectomy with CND via BABA is safe and effective for Chinese patients with papillary thyroid microcarcinoma who worry about the neck scars.

To evaluate the feasibility and safety of robotic lateral cervical lymph node dissection via BABA, 260 thyroid cancer patients with suspected level II, III, IV, and Vb lymph node metastasis were selected. The lateral cervical compartment was exposed by splitting the sternocleidomastoid muscle longitudinally, and separating between the strap muscles and the anterior margin of the sternocleidomastoid muscle. The procedure was completed in 260 patients. Mean time for robotic lateral node dissection took 80 ± 21 min. The wound catheter was removed 6.3 days. Postoperative transient symptomatic hypocalcemia was observed in 51 patients, transient hoarseness in three, seroma in three, chyle leakage in two, and tracheal injury in one. 124 patients were confirmed to have lymph node metastasis on final pathological report. Average postoperative hospital stay was 6.5 days. Robotic lateral neck dissection by BABA is the acceptable operative alternative for thyroid cancer patients who wished to keep their surgical history private.

ARHGEF6 belongs to the family of guanine nucleotide exchange factors (GEFs) for Rho GTPases, and it specifically activates Rho GTPases CDC42 and RAC1. Arhgef6 is the X-linked intellectual disability gene also known as XLID46, and clinical features of patients carrying Arhgef6 mutations include intellectual disability and, in some cases, sensorineural hearing loss. Rho GTPases act as molecular switches in many cellular processes. Their activities are regulated by binding or hydrolysis of GTP, which is facilitated by guanine nucleotide exchange factors and GTPase-activating proteins, respectively. RAC1 and CDC42 have been shown to play important roles in hair cell (HC) stereocilia development. However, the role of ARHGEF6 in inner ear development and hearing function has not yet been investigated. Here, we found that ARHGEF6 is expressed in mouse cochlear HCs, including the HC stereocilia. We established Arhgef6 knockdown mice using the clustered regularly interspaced short palindromic repeat-associated Cas9 nuclease (CRISPR-Cas9) genome editing technique. We showed that ARHGEF6 was indispensable for the maintenance of outer hair cell (OHC) stereocilia, and loss of ARHGEF6 in mice caused HC stereocilia deficits that eventually led to progressive HC loss and hearing loss. However, the loss of ARHGEF6 did not affect the synapse density and did not affect the mechanoelectrical transduction currents in OHCs at postnatal day 3. At the molecular level, the levels of active CDC42 and RAC1 were dramatically decreased in the Arhgef6 knockdown mice, suggesting that ARHGEF6 regulates stereocilia maintenance through RAC1/CDC42.

Background The molecular classification of breast cancer mainly focuses on estrogen receptor (ER), Progesterone receptor (PgR), and Human Epidermal Growth Factor Receptor 2(HER2/Neu) status detected by immunohistochemistry (IHC) analysis. The β -tubulin isotype III (TUBB3) gene was thought to be a marker of taxane resistance or cancer aggressiveness. Methods To evaluate the clinicopathological significance of TUBB3 expression in breast cancer patients, we measured TUBB3 mRNA levels in 92 breast cancer patients by Quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and examined their correlation with ER, PgR, and HER2 status detected by IHC. Results We observed a significant positive correlation between the TUBB3 mRNA expression and the immunohistochemical positivity of both PgR (p= 0.000) and HER2 (p= 0.001). In addition, TUBB3 mRNA expression was associated with lymph nodes status (P= 0.008) and tumor stages (0.029), but no correlation was found with other clinicopathological features, such as age, pathohistological grades and tumor size. Conclusions In conclusion, TUBB3 expression correlated significantly with molecular markers of breast cancer, such as PgR and HER2, suggesting that TUBB3 mRNA level facilitate the identification of a subset of patients who respond to Taxane treatment in addition to hormonal therapy and trastuzumab.

This report presents the case of a 54-year-old woman with a collision tumour of malignant melanoma and medullary thyroid carcinoma in the thyroid. Twenty four of 25 neck lymph nodes contained metastatic melanoma, with the rest having both metastatic melanoma and medullary carcinoma. Systemic chemotherapy was administered for the malignant melanoma, and a complete response was thus obtained. However, just after having the chemotherapy, multiple lung and brain metastases emerged. The simultaneous occurrence of malignant melanoma and medullary carcinoma in the same thyroid has not been previously reported in the literature. Collision tumour of malignant melanoma and medullary carcinoma of the thyroid might imply bad prognosis.

Breast cancer is the most common cancer in women around the world. However, the molecular mechanisms underlying breast cancer pathogenesis are only partially understood. Here, in this study, we found that P2X7R was up-regulated and miR-216b was down-regulated in breast cancer cell lines and tissues. Using bioinformatic analysis and 3′UTR luciferase reporter assay, we determined P2X7R can be directly targeted by miR-216b, which can down-regulate endogenous P2X7R mRNA and protein levels. Ectopic expression of miR-216b mimics leads to inhibited cell growth and apoptosis, while blocking expression of the miR-216b results in increased cell proliferation. Furthermore, our findings demonstrate that knockdown of P2X7R promotes apoptosis in breast cancer cells through down-regulating Bcl-2 and increasing the cleavage caspase-3 protein level. Finally, we confirmed that down-regulation of miR-216b in breast cancer is inversely associated with P2X7R expression level. Together, these findings establish miR-216b as a novel regulator of P2X7R and a potential therapeutic target for breast cancer.

In the present study, we found that three enzymes, MVK, MDD and FPPS, in the mevalonate pathway (MVP) of cholesterol biosynthesis, can be simultaneously inhibited by two green tea polyphenols ((-)-epicatechin-3-gallate, ECG; (-)-epigallocatechin-3-gallate, EGCG). Molecular dynamics simulations and pharmacophore studies were carried out to elucidate the tri-targeted inhibition mechanisms. Our results indicate that similar triangular binding pockets exist in all three enzymes, which is essential for their binding with polyphenols. Two distinct binding poses for ECG and EGCG were observed in our MD simulations. These results shed light on the potential for further selective and multi-targeted inhibitor design for the treatment of hyperlipidemia.

The aim of this study was to evaluate the clinical application and superiority of the da Vinci(®) Si Surgical System (Intuitive Surgical Inc., Sunnyvale, CA) in total parathyroidectomy for secondary hyperparathyroidism.Total parathyroidectomy was performed with the da Vinci Si Surgical System by the four-trocar axillo-bilateral-breast approach. The patients were placed in the supine position, and the operation procedure included creating the workspace, docking, and consoling stages. The camera arm is centered in the working space. Three working arms are then placed adjacent to the camera. The Harmonic(®) scalpel (Ethicon Endo-surgery, Inc., Cincinnati, OH) was used for hemostasis and gland resection, and dissected parathyroid was taken out by a specimen pouch.Total parathyroidectomy with trace amounts of parathyroid tissue autotransplantation in 6 patients was successfully performed with the da Vinci Si Surgical System. There were no operation-related complications and no conversions to open or endoscopic surgery. Mean operation time was 156 minutes. Patients were discharged from the hospital 6 days after surgery. The postoperative cosmetic result was satisfactory, with minimal numbness and tingling on the anterior chest.This initial study shows that robotic total parathyroidectomy via the axillo-bilateral-breast approach is a safe and feasible alternative to selected patients, especially those with esthetic concerns.

Background Electrocautery has been proven to be associated with prolonged serous drainage that might result in several complications in patients requiring axillary lymph node dissection for breast cancer. We proposed that the Harmonic Focus might outperform electrocautery in axillary lymph node dissection, resulting in shorter operative times and reduced postoperative complications. Patients and Methods One hundred twenty-eight women with confirmed T1-3 N1-2 breast cancer were randomly assigned to undergo mastectomy or breast-conserving surgery with axillary dissection by using Harmonic Focus or electrocautery. Sixty-four has surgery with Harmonic Focus (group A) and 64 with electrocautery (group B) by the same surgical team. Operative time, blood loss, total drainage volume and days, incidence of seroma, hematoma, pain score, and flap necrosis were recorded. Results Using Harmonic Focus significantly diminished operative time, blood loss, total drainage volume, days of stay, and visual analogue scale as compared with traditional electrocautery. There was no statistical difference between the 2 groups regarding seroma, hematoma, and flap necrosis. Conclusion Axillary lymph node dissection using Harmonic Focus is feasible, safe, and a more comfortable design for the surgeon.

Gynecomastia is a benign clinical condition that is the unilateral or bilateral enlargement of the male breast, but sometimes it causes serious psychological and physical stress in young men and brings about phobia of malignancy in elderly men. Minimally invasive and functional therapy represents an inevitable trend in breast surgery. We investigated the feasibility and safety of vacuum-assisted biopsy device in treating gynecomastia.From January 2006 to January 2010, 20 male patients with gynecomastia were treated by an 8-gauge vacuum-assisted biopsy device. The average age was 24.7 years (range, 18-47 years).The operation was successfully performed in all 20 patients with a mean operating time of 51 minutes and a hospital stay of 4 days. Postoperative complications included 1 case of hematoma, but no nipple necrosis, local skin necrosis, or skin buttonhole occurred. No other operation-related complications were observed. Satisfactory chest contour was gained in all cases without any abnormality, skin redundancy, or recurrence during the follow-up of 6-48 months.Treatment of gynecomastia by the Mammotome device is distinctive, practicable in manipulation, safe, and can achieve excellent cosmetic results. The Mammotome procedure simply represents another novel treatment option for gynecomastia.

Internal mammary node (IMN) metastasis has a similar prognostic importance as axillary nodal involvement. However, sampling of IMN is not performed routinely.To evaluate a simplified method for internal mammary sentinel node (IMSN) biopsy of breast cancer patients.A combination of simultaneous perilesional and intradermal radiocolloid injections over the lesion was used. All IMSNs were confirmed by lymphoscintigraphy and Carbon Nanoparticles Suspension Injection preoperatively and excised extrapleurally through the intercostal muscles.Twenty-three of the 94 patients were found to have metastatic disease in the IMSNs. Four of 65 patients had metastases in the IMNs but not in the axilla. All 23 patients with positive IMSN were upstaged and received radiation to the internal mammary chain. The time from separating the pectoral major muscle to touch the node was ranged 21-48 min. The detecting sensitivity combined with preoperative lymphoscintigraphy, intraoperative gamma probe detection, and intraoperative black dye methods for IMSN was 100%.The approach used is a reliable surgical technique for removing IMSN. It can improve the nodal staging in breast cancer with IMN metastases.

The axillary reverse mapping (ARM) procedure can distinguish lymphatics draining the arm from those draining the breast. It has been proposed to preserve lymphatic drainage of the upper limbs and reduce the incidence of upper limb lymphedema during breast cancer surgery. The aim of our study was to assess the feasibility of ARM in modified radical mastectomy and to evaluate its effect on prevention of lymphedema.From January 2012 to March 2014, a prospective study was performed in 265 breast cancer patients who underwent modified radical mastectomy. Patients were divided into 2 groups, 127 patients (47.93%, control group) received a traditional axillary lymph node dissection (ALND), and 138 patients (52.07%, experimental group) received ARM preservation of the nodes and lymphatics during ALND. Radioactive tracer and methylene blue were used for ARM of the nodes and lymphatics. All of the identified ARM nodes were diagnosed using fine needle aspiration cytology for assessment of metastatic status. All resected axillary lymph nodes were conducted in a pathology examination to evaluate tumor metastasis. Data were collected on variations in identification of the ARM nodes and lymphatics, the metastasis of ARM nodes, and the occurrence of lymphedema.In the experimental group, the ARM procedure was successfully conducted in 129 cases (93.48%). ARM nodes metastasis occurred in 11 patients (8.53%). The median follow-up time was 20 months, at the last evaluation there were 42 patients who developed upper limb lymphedema in the control group (33.07%), and in the experimental group the incidence of lymphedema was 5.93% (7/118; P .001). None of the patients had nodal relapses during the follow-up time.ARM appears to be a feasible technique with which to identify upper arm nodes and lymphatics during the modified radical mastectomy procedure. The incidence of lymphedema can be decreased in patients with use of the ARM procedure.

Background The aim of the study was to evaluate total parathyroidectomy with trace amounts of parathyroid tissue (30 mg) as a surgical option in secondary hyperparathyroidism (sHPT) treatment. Methods From January 2008 to March 2012, 47 patients underwent parathyroidectomy. Comparisons of demographic data, symptoms, and preoperative or postoperative biochemistry were made between total parathyroidectomy with trace amounts of parathyroid tissue autotransplantation group and total parathyroidectomy group. Results Out of 47 cases, 45 had successful operation. 187 parathyroid glands identified at the initial operation were reported in 47 patients. 43 patients had been diagnosed with parathyroid hyperplasia, and 4 patients had a benign adenoma. After operation, pruritus, bone pain and muscle weakness disappeared, also serum PTH and serum phosphate were declined markedly as well. After discharge, two patients (in total parathyroidectomy group) were readmitted because of postoperative hypoparathyroidism. Graft-dependent recurrence was not observed in an average follow-up of 42 months. Conclusions Total parathyroidectomy with sternocleidomastoid muscle trace amounts of parathyroid tissue autotransplantation is considered to be a feasible, safe and effective surgical option for the patients with sHPT.

The human multidrug resistance 1 gene (MDR1) is an important candidate gene influencing the susceptibility to various diseases, including breast cancer. The object of this study was to investigate on MDR1 gene polymorphisms and its relationship with the susceptibility to breast cancer. A total of 271 patients with breast cancer and 225 healthy controls were enrolled in this study. Data about the risk factors for breast cancer were collected using questionnaires. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing methods were used to investigate the c.3073A > C polymorphisms. We observed no significant differences in the allelic and genotypic frequencies of c.3073A > C polymorphisms between patients and control subjects. Furthermore, there were no significant differences about the distribution of the breast cancer patients' risk factors among AA, AC and CC genotype. Results from this study suggested that c.3073A > C polymorphism was not associated with the susceptibility to breast cancer in the studied population. Future studies evaluating the association between c.3073A > C variant and breast cancer risks are essential to reach to more reliable results on larger populations.

The aim of this study was to evaluate outcomes for patients with papillary thyroid microcarcinoma (PTMC) treated at a single institution during a 162-month period and to determine which patients need aggressive treatment. Two hundred seventy-three patients with PTMC had subtotal or total thyroidectomy 1 prophylactic or therapeutic lymph node dissection. Clinical and histopathological characteristics of 273 patients were identified and statistically analyzed. The tumors were multifocal in 36.3 per cent of the patients with PTMCs. Fifty-six per cent had neck lymph node metastases at diagnosis. Large-sized tumor (over 5 mm), age older than 45 years, multifocality, bilaterality, and extrathyroidal extension were associated with subclinical central lymph node metastases. Ninety-six patients older than 45 years of age were upgraded from Stage I to III or IVA. Ten patients with lateral node recurrence or local recurrence in the residual thyroid had one or more risk factors. The high rates of multifocality and Level VI area subclinical lymph node metastasis were two important clinical and histopathological characteristics of PTMC. Patients who had one or more risk factors should receive more aggressive surgical management.

The aim of this study was to compare operating time, postoperative outcomes, and surgical complications of total thyroidectomy plus level III-IV and VI dissection between the no-tie technique using the Harmonic Focus and classic suture ligation for hemostasis. Fifty-four patients underwent total thyroidectomy plus level III-IV and VI dissection by classic suture ligation and 51 patients by the Harmonic Focus. There was obvious distinction as to the operating time between the Focus and classic group (102.8 and 150.1 minutes, respectively, P < 0.05). Drainage volume (202.7 ± 187.0 mL vs 299.7 ± 201.4 mL, P < 0.05) were significantly lower in the Focus group. Transient hypoparathyroidism had no statistically significant difference between the groups (17.6% vs 18.5%, P > 0 .05). No patient experienced nerve injury or permanent hypocalcemia. The use of Harmonic Focus for the control of thyroid vessels during thyroid surgery is reliable and safe. The device can offer extraordinary capabilities for delicate tissue grasping and dissection.

Within the last ten years, the development of innovative minimally invasive breast biopsy technologies has made a significant impact on the diagnostic evaluation of impalpable breast lesions. The Mammotome minimally invasive biopsy system is a diagnostic tool used under stereotactic or ultrasound guidance. The minimally invasive biopsies for 143 impalpable breast lesions in 86 patients were performed using the B-ultrasound-guided 8-gauge vacuum-assisted Mammotome system at Jinan Military General Hospital. One hundred and forty-three breast lesions in 86 patients were excised completely using this method. The average biopsy procedure time was 17 min (range, 3-45 min). Clinically, suspicious lesions were satisfactorily confirmed by this system. One hundred and twenty-one lesions were diagnosed as fibroadenoma, nineteen lesions as breast adenosis, one lesion as invasive breast cancer, and two lesions as ductal carcinoma in situ. Skin ecchymosis was found in two patients. One hundred and thirty-two impalpable lesions were completely excised, as demonstrated by the follow-up ultrasound examination. The results suggest that the B-ultrasound-guided Mammotome system may be an efficient tool for the diagnosis and treatment of impalpable breast lesions.

e22089 Background: The aims of this study was to determine the clinical implications of internal mammary node biopsy as staging, treatment with radiotherapy and systemic treatment and a prognostic factor in patients with breast cancer. Methods: Internal mammary node biopsy via intercostal space was performed in 344 cases of breast cancer. Anatomical location of internal mammary nodes were recorded. Pathological status of internal mammary node were detected by H and E stains. Results: Internal mammary node biopsy was successfully finished in 344 patients.There were 162 cases (48.26%) with positive axillary nodes, while the internal mammary nodes were involved in 72 cases (20.93%).53 patients (32.72%) had regional metastases in both the axillary and internal mammary lymph nodes.19 (5.52%) patients had internal mammary node metastasis but no axillary node metastases. PN stage migration was seen in 72 patients with a positive internal mammary node. There was no statistic relation between internal mammary nodes metastases and tumor location (X2 =0.48, P>0.05). There was no complication such as pneumothorax or haemorrhagia. Conclusions: The approach used is a reliable surgical technique for removing lymph node from intercostal space. Without exploring internal mammary nodes status, pN stage was incomplete. Internal mammary node biopsy enables treatment to be better adjusted to the needs of the individual patient. Using internal mammary node biopsy, patients with a negative internal mammary node can be prevented from radiation to internal mammary nodal areas. This leads to optimization of treatment.