Deep learning for real-time detection of breast cancer presenting pathological nipple discharge by ductoscopy.

Objective: As a common breast cancer-related complaint, pathological nipple discharge (PND) detected by ductoscopy is often missed diagnosed. Deep learning techniques have enabled great advances in clinical imaging but are rarely applied in breast cancer with PND. This study aimed to design and validate an Intelligent Ductoscopy for Breast Cancer Diagnostic System (IDBCS) for breast cancer diagnosis by analyzing real-time imaging data acquired by ductoscopy. Materials and methods: The present multicenter, case-control trial was carried out in 6 hospitals in China. Images for consecutive patients, aged ≥18 years, with no previous ductoscopy, were obtained from the involved hospitals. All individuals with PND confirmed from breast lesions by ductoscopy were eligible. Images from Beijing Chao-Yang Hospital were randomly assigned (8:2) to the training (IDBCS development) and internal validation (performance evaluation of the IDBCS) datasets. Diagnostic performance was further assessed with internal and prospective validation datasets from Beijing Chao-Yang Hospital; further external validation was carried out with datasets from 5 primary care hospitals. Diagnostic accuracies, sensitivities, specificities, and positive and negative predictive values for IDBCS and endoscopists (expert, competent, or trainee) in the detection of malignant lesions were obtained by the Clopper-Pearson method. Results: Totally 11305 ductoscopy images in 1072 patients were utilized for developing and testing the IDBCS. Area under the curves (AUCs) in breast cancer detection were 0·975 (95%CI 0·899-0·998) and 0·954 (95%CI 0·925-0·975) in the internal validation and prospective datasets, respectively, and ranged between 0·922 (95%CI 0·866-0·960) and 0·965 (95%CI 0·892-0·994) in the 5 external validation datasets. The IDBCS had superior diagnostic accuracy compared with expert (0.912 [95%CI 0.839-0.959] vs 0.726 [0.672-0.775]; p<0.001), competent (0.699 [95%CI 0.645-0.750], p<0.001), and trainee (0.703 [95%CI 0.648-0.753], p<0.001) endoscopists. Conclusions: IDBCS outperforms clinical oncologists, achieving high accuracy in diagnosing breast cancer with PND. The novel system could help endoscopists improve their diagnostic efficacy in breast cancer diagnosis.

Randomized controlled trial of an alternative drainage strategy vs routine chest tube insertion for postoperative pain after thoracoscopic wedge resection.

BACKGROUND: Thoracoscopic surgery has greatly alleviated the postoperative pain of patients, but postsurgical acute and chronic pain still exists and needs to be addressed. Indwelling drainage tubes are one of the leading causes of postoperative pain after thoracic surgery. Therefore, the aim of this study was to explore the effects of alternative drainage on acute and chronic pain after video-assisted thoracoscopic surgery (VATS). METHODS: Ninety-two patients undergoing lung wedge resection were selected and randomly assigned to the conventional chest tube (CT) group and the 7-Fr central venous catheter (VC) group. Next, the numeric rating scale (NRS) and pain DETECT questionnaire were applied to evaluate the level and characteristics of postoperative pain. RESULTS: NRS scores of the VC group during hospitalization were significantly lower than those of the CT group 6 h after surgery, at postoperative day 1, at postoperative day 2, and at the moment of drainage tube removal. Moreover, the number of postoperative salvage analgesics (such as nonsteroidal anti-inflammatory drugs [(NSAIDs]) and postoperative hospitalization days were notably reduced in the VC group compared with the CT group. However, no significant difference was observed in terms of NRS pain scores between the two groups of patients during the follow-up for chronic pain at 3 months and 6 months. CONCLUSION: In conclusion, a drainage strategy using a 7-Fr central VC can effectively relieve perioperative pain in selected patients undergoing VATS wedge resection, and this may promote the rapid recovery of such patients after surgery. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03230019. Registered July 23, 2017.

Demethylation of the Cosmc Promoter Alleviates the Progression of Breast Cancer Through Downregulation of the Tn and Sialyl-Tn Antigens.

BACKGROUND: Aberrant gene methylation in breast cancer is associated with an unfavorable prognosis. Besides, abnormal Cosmc can induce the expression of Tn and STn antigens. The present study aimed to investigate the roles of Cosmc promoter methylation in breast cancer through the regulation of Tn and STn antigens. METHODS: The expression patterns of Cosmc and the Tn and STn antigens in breast cancer cell lines were determined. Cosmc was overexpressed to explore the effects of Cosmc on cell behavior, including the growth, migration, invasion, and apoptosis of breast cancer cells and tumor growth with in vitro and in vivo experiments. Afterwards, a methyltransferase and a methyltransferase inhibitor were used to alter the methylation status of Cosmc to explore the mechanisms related to Cosmc promoter methylation. RESULTS: Cosmc was poorly expressed in breast cancer cells. Cosmc overexpression inhibited cell growth, migration, and invasion while promoting apoptosis in breast cancer cells in vitro and restraining tumor growth in vivo. Cosmc promoter methylation was found to decrease the levels of Cosmc and increased the expression of the Tn and STn antigens in breast cancer. CONCLUSION: In conclusion, the demethylation of Cosmc mitigates breast cancer progression through the repression of the Tn and STn antigens, which provides evidence for therapeutic considerations for a novel target against breast cancer.

Prediction of postoperative survival of triple-negative breast cancer based on nomogram model combined with expression of HIF-1α and c-myc.

The aims of this study were to explore the expression of hypoxia inducible factor-1α (HIF-1α) and c-myc protein in triple-negative breast cancer (TNBC) and its clinical prognostic significance, and to establish a prediction model for postoperative survival of TNBC based on nomogram.A total of 87 patients with TNBC at the Department of Breast Surgery, Beijing Chaoyang Hospital, Capital Medical University from January 2012 to December 2015 were enrolled in this study. Immunohistochemistry was performed to detect the expression of HIF-1α and c-myc protein in breast cancer tissues. Cox regression analyses were performed to explore the correlation between HIF-1α/c-myc expression and clinical pathological parameters as well as prognosis. Receiver-operating characteristic curve was generated for cox multivariate analysis. A nomogram was generated based on the cox multivariate analysis, and a calibration curve was prepared for the nomogram to evaluate the consistency between the predicted probability of the nomogram and the actual observed probability. The stability of nomogram model was validated with an external cohort including 39 TNBC patients.The positive expression rates of HIF-1α and c-myc protein in breast cancer tissues were 41.4% (36/87) and 55.2% (48/87), respectively. HIF-1α expression was significantly correlated with age, tumor diameter, histological grade, lymph node status, and tumor TNM stage; c-myc expression was significantly associated with tumor diameter, histological grade, lymph node status, and tumor TNM stage. Cox univariate and multivariate analyses showed that HIF-1α and c-myc protein expression, histological grade, lymph node status, and tumor TNM stage were the independent risk factors for postoperative survival in TNBC patients. The AUC of prediction model was 0.843 (0.809-0.887). The nomogram could predict the probability of 3-year disease-free survival according to each patient's condition. The calibration curve displayed good agreement of the predicted probability with the actual observed probability, indicating that the nomogram model had great value of prediction. The external validation indicated the prediction model had good stability.HIF-1α-positive expression, c-myc positive expression, histological grade III, lymph node positive, and TNM stage III tumors suggested that TNBC patients had a poor prognosis. This prediction model can be used to predict postoperative survival of TNBC.

A comparison between laryngeal mask airway and endotracheal intubation for anaesthesia in adult patients undergoing NUSS procedure.

BACKGROUND: This study evaluates and compares the feasibility and safety of application of laryngeal mask airway (LMA) and endotracheal intubation (ETT) for anaesthesia in adult patients undergoing thoracoscopic surgery. METHODS: Sixty adult patients with pectus excavatum (PE) undergoing video-assisted thoracoscopic surgery for the NUSS procedure (VATS-NUSS) between September 2016 and March 2017 were selected and randomly separated into two groups with different methods of airway management. In one group, LMA was applied for general anaesthesia, and in the other group, ETT was used. The clinical parameters before, during and after the surgery in patients from both groups were collected from multiple data resources in a hospital. SPSS software was used for the analysis. RESULTS: Of all the selected patients, the physiological parameters showed similarity between the LMA and ETT groups, indicating consistency in the clinical characteristics of the study sample. Additionally, no significant differences were discovered between the two groups in terms of the anaesthesia and surgical time, peak PetCO2 during operation, anaesthetic satisfaction score, and amount of blood loss as well as inpatient time for recovery. However, with a similar level of anaesthesia effects and suitable parameters for mechanical ventilation, patients in the LMA group showed much more stability in the physiological indicators for inflammation and haemodynamics, including white blood cell count (ΔWBC) and percentage of neutrophil granulocytes (ΔNEU%) in the blood as well as heart rate (ΔHR) and mean arterial pressure (ΔMAP). Moreover, the LMA patients had a significantly shorter time for recovery of consciousness and food/water intake. Finally, compared to the ETT group, patients in the LMA group also had a significantly lower incidence of side effects induced by the anaesthesia procedure after surgery, such as gastrointestinal reactions, throat discomfort and hoarseness. CONCLUSIONS: Compared with ETT, the application of LMA for general anaesthesia may demonstrate promising advantages in airway management for the VATS-NUSS procedure.

The bifunctional effect of propofol on thromboxane agonist (U46619)-induced vasoconstriction in isolated human pulmonary artery.

Propofol is known to cause vasorelaxation of several systemic vascular beds. However, its effect on the pulmonary vasculature remains controversial. In the present study, we investigated the effects of propofol on human pulmonary arteries obtained from patients who had undergone surgery. Arterial rings were mounted in a Multi-Myograph system for measurement of isometric forces. U46619 was used to induce sustained contraction of the intrapulmonary arteries, and propofol was then applied (in increments from 10-300 µM). Arteries denuded of endothelium, preincubated or not with indomethacin, were used to investigate the effects of propofol on isolated arteries. Propofol exhibited a bifunctional effect on isolated human pulmonary arteries contracted by U46619, evoking constriction at low concentrations (10-100 µM) followed by secondary relaxation (at 100-300 µM). The extent of constriction induced by propofol was higher in an endothelium-denuded group than in an endothelium-intact group. Preincubation with indomethacin abolished constriction and potentiated relaxation. The maximal relaxation was greater in the endothelium-intact than the endothelium-denuded group. Propofol also suppressed CaCl2-induced constriction in the 60 mM K+-containing Ca2+-free solution in a dose-dependent manner. Fluorescent imaging of Ca2+ using fluo-4 showed that a 10 min incubation with propofol (10-300 µM) inhibited the Ca2+ influx into human pulmonary arterial smooth muscle cells induced by a 60 mM K+-containing Ca2+-free solution. In conclusion, propofol-induced arterial constriction appears to involve prostaglandin production by cyclooxygenase in pulmonary artery smooth muscle cells and the relaxation depends in part on endothelial function, principally on the inhibition of calcium influx through L-type voltage-operated calcium channels.

The prognostic value and potential drug target of phosphatase and tensin homolog in breast cancer patients: A meta-analysis.

BACKGROUND: The prognostic significance of phosphatase and tensin homolog (PTEN) in patients with breast cancer (BC) remains controversial. The aims of our meta-analysis are to evaluate its association with clinicopathological characteristics and prognostic value in patients with breast cancer. METHODS: PubMed, EMBASE, Web of Science, and China National Knowledge Infrastructure (CNKI) were systematically searched up to December 2016. The meta-analysis was performed using hazard ratio (HR), odds ratio (OR), and 95% confidence intervals (CI) as effect measures. A fixed or random effect model was used depending on the heterogeneity analysis. Statistical analysis was performed using Review manager software version 5.3. RESULTS: Seventeen studies including 4343 patients with breast cancer were analyzed. The meta-analysis indicated that breast cancers with PTEN loss were significantly associated with the tumor size ≥2 cm group (ORFEM = 1.68, 95%CIFEM [1.34, 2.10]), negative expression of estrogen receptor (ORREM = 1.95, 95%CIREM [1.09, 3.49]), negative expression of progesterone receptor (ORFEM = 1.72, 95%CIFEM [1.43, 2.08]), the advanced stage (ORREM = 1.94, 95%CIREM [1.35, 2.80]), positive axillary lymph node metastasis (ORREM = 1.80, 95%CIREM [1.30, 2.50]), and the local recurrence (ORFEM = 1.70, 95%CIFEM [1.26, 2.28]). None of other clinicopathological parameters such as the HER2 status and distant metastasis were associated with PTEN loss. The decreased PTEN expression was significantly correlated with the overall survival (OS) of patients (HRREM = 1.83, 95%CIREM [1.32, 2.53]) and the disease-free survival (DFS) of patients (HRREM = 2.43, 95%CIREM [1.31, 4.53]). CONCLUSION: Our meta-analysis demonstrates that PTEN loss is of particular importance for predicting breast cancer aggressiveness and poor prognosis. PTEN is a potential drug target for the development of individualized treatment in BC patients.

[Effects of propofol combined with indomethacin on contraction of isolated human pulmonary arteries].

OBJECTIVE: To investigate the effects of propofol combined with indomethacin on the contractile function of isolated human pulmonary arteries. METHODS: Human pulmonary artery preparations were obtained from patients undergoing surgery for lung carcinoma. The intrapulmonary arteries were dissected and cut into rings under microscope for treatment with propofol or propofol combined with indomethacin. In each group, the rings were divided into endothelium-intact and endothelium-denuded groups and mounted in a Multi Myograph system. In propofol group, the rings were preconstricted by U46619 to induce a sustained contraction, and propofol (10-300 mmol/L) was then applied cumulatively. In the combined treatment group, the rings were pretreated with indomethacin (100 µmol/L) for 30 min before application of U46619 to induce sustained contraction, and propofol (10-300 µmol/L) was added cumulatively after the tension became stable. RESULTS: Propofol (10-100 µmol/L) induced constrictions at low concentrations and caused relaxations at higher concentrations (100-300 µmol/L) in the pulmonary artery rings with prior U46619-induced contraction. Propofol caused stronger constrictions in endothelium-intact rings [EC50=4.525∓0.37, Emax=(30.44∓2.92)%] than in endothelium-denuded rings [EC50=4.699∓0.12, Emax=(31.19∓5.10)%, P<0.05]. Pretreatment of the rings with indomethacin abolished constrictions, and the relaxation was more obvious in endothelium-intact group [pD2=3.713∓0.11, Emax=(98.72∓0.34)%] than in endothelium- denuded group [pD2=3.54∓0.03, Emax=(94.56∓0.53)%, P<0.05]. CONCLUSION: Propofol induces constriction at low concentrations and relaxation at high concentrations in human intrapulmonary arteries with U46619-induced contraction. Indomethacin abolishes the constriction induced by propofol in isolated intrapulmonary arteries, suggesting that propofol potentiates U46619-mediated pulmonary vasoconstriction by promoting the concomitant production of prostaglandin by cyclooxygenase in pulmonary artery smooth muscle cells, and the mechanism for its relaxation effect may partly depend on the endothelium.

Clinicopathological and prognostic significance of COX-2 immunohistochemical expression in breast cancer: a meta-analysis.

The prognostic significance of COX-2 in patients with breast cancer remains controversial. The aims of our meta-analysis are to evaluate its association with clinicopathological characteristics and prognostic value in patients with breast cancer. PubMed, EMBASE, Web of Science, the Ovid Database and Grey literature were systematically searched up to May 2016. Twenty-one studies including 6739 patients with breast cancer were analyzed. The meta-analysis indicated that the incidence difference of COX-2 expression was significant when comparing the lymph node positive group to negative group (OR = 1.76, 95% CI [1.30, 2.39]) and the tumor size ≥ 2cm group to the tumor size < 2cm group (OR = 1.71, 95% CI [1.22, 2.39]). None of other clinicopathological parameters such as the ER status, PR status, HER2 status and the vascular invasion status were associated with COX-2 overexpression. The detection of COX-2 was significantly correlated with the disease-free survival (DFS) of patients (HR = 1.58, 95% CI [1.23, 2.03]) and the overall survival (OS) of patients (HR = 1.51, 95% CI [1.31, 1.72]). Our meta-analysis demonstrates that the presence of high levels of COX-2 is associated with poor prognosis for breast cancer patients and predicts bigger tumor size and lymph node metastasis.

Use of laryngeal mask airway for non-endotracheal intubated anesthesia for patients with pectus excavatum undergoing thoracoscopic Nuss procedure.

BACKGROUND: The aim of the present study was to determine the safety and feasibility of the use of laryngeal mask airway (LMA) for non-endotracheal intubated anesthesia for patients with pectus excavatum (PE) undergoing thoracoscopic Nuss procedure. METHODS: Between July 2015 and December 2015, 30 selected patients with PE were planned to undergo a thoracoscopic Nuss procedure using LMA for non-endotracheal intubated anesthesia in the Guangdong General Hospital. The clinical data were analyzed to evaluate the safety and feasibility of this technique. RESULTS: Of the 30 selected patients, two were female, the mean age was 16.04±5.09 years and the average Haller index was 3.37±0.88. A total of 27 cases (90%) succeeded at the first attempt, one patient required conversion to an endotracheal tube (ETT) because of continuous air leak. The peripheral O2 saturation (SpO2), end-tidal carbon dioxide (EtCO2) values, heart rate (HR), and mean arterial blood pressure (MAP) remained stable throughout the procedure in all cases. All of the 30 patients were successfully corrected without requiring conversion to an open surgery. Two patients experienced postoperative nausea and one reported a sore throat. Neither gastro-esophageal reflux nor in-hospital mortality occurred. CONCLUSIONS: The use of LMA for non-endotracheal intubated anesthesia for selected patients with PE undergoing thoracoscopic Nuss procedure is clinically safe and technically feasible.

[Dexmedetomidine inhibits 5-HT-induced intrapulmonary artery vasoconstriction].

OBJECTIVE: To investigate the effect of dexmedetomidine on 5-HT-induced constrictions of isolated human intrapulmonary arteries and explore the mechanisms. METHODS: Lung tissue was obtained from patients undergoing surgery for lung carcinoma. Intrapulmonary arteries were dissected and cut into rings, which were mounted in a Multi Myograph system to determine the effect of dexmedetomidine (0.3-3 nmol/L) on 5-HT-induced vasoconstrictions. The influences of the endothelium removal and various drugs including L-NAME, yohimbine and indomethacin were tested on the effects of dexmedetomidine. RESULTS: Dexmedetomidine (0.1-100 nmol/L) did not obviously affect the resting tension of endothelium-intact human intrapulmonary arteries. 5-HT induced concentration-dependent contraction in endothelium-intact intrapulmonary arteries [pD2: 6.11∓0.05, Emax: (102.10∓1.96)%]. In the rings with intact endothelium, dexmedetomidine (0.3-3 nmol/L) significantly attenuated the Emax and pD2 of 5-HT-induced vasoconstriction [pD2: 5.94∓0.03, Emax: (79.96∓1.31)%]. 5-HT also induced concentration-dependent contraction in endothelium-denuded intrapulmonary arteries [pD2: 6.10∓0.07, Emax: (107.40∓3.20)%]. Dexmedetomidine produced no significant effects on the rings with denuded endothelium. The effects of dexmedetomidine on 5-HT-induced vasoconstriction was suppressed by L-NAME and yohimbine, but not by indomethacin. CONCLUSION: Dexmedetomidine can inhibit 5-HT-induced vasoconstriction of isolated human intrapulmonary arteries probably through α2-adrenergic acceptor and NO released from the endothelium.

[Analysis of the association between double-lumen endobronchial tube and inner diameter of the left main bronchus].

OBJECTIVE: To investigate the association of the left double-lumen endobronchial tube (DLT) and the inner diameter of the left main bronchus. METHODS: Totally 100 adult patients who required intubation of a left-sided DLT during anesthesia for elective thoracic surgery were randomly enrolled in this study. All the participants underwent a preoperative chest CT scan by a spiral CT scanner. The diameters of the trachea and left main bronchus were measured with three-dimensional image reconstruction technique. All the measurements were performed using the electronic calipers of the spiral CT scanner and the left-sided DLT (Portex SIMS, USA) of the sizes 41Fr, 39Fr, 37Fr, and 35Fr were selected, being predicted according to the inner diameter of the left main bronchus. The placement of DLT was performed after anesthesia induction, and a DLT of a smaller size was selected if the bronchial end of the DLT failed to enter the left main bronchus after two attempts. The trachea and left main bronchus were examined for injury and other complications with postoperative fibreoptic bronchoscopy (FOB). RESULTS: All the 100 patients were intubated with DLT of appropriate sizes and satisfactory lung isolation was achieved. Postoperative complications of the trachea and bronchus were observed in none of the patients with FOB examination. The appropriate size of DLT is correlated with the left main bronchial diameter (correlation coefficient r=0.7346). CONCLUSION: Clinically, the size of DLT can be determined in accordance with the inner diameter of the left main bronchea.