Background: Although metformin, a first-line drug for treating diabetes, may play an important role in inhibition of epithelial ovarian cancer cell growth and cancer stem cells (CSCs), metformin at low dose showed less effect on the proliferation of ovarian cancer cells. In this study, we evaluated the effect of metformin at low dose on ovarian CSCs in order to understand the molecular mechanisms underlying.Methods: The inhibitory effects of metformin at los dose on proliferation and population of ovarian cancer cells including SKOV3 and A2780 were assessed by cell proliferation assay and flow cytometry. Quantitative real-time PCR assay on expression of Bcl-2, Survivin and Bax was performed to determine the effect of metformin at low dose on epithelial-mesenchymal transition (EMT) of cancer cells and CSCs. Tumor sphere formation assay was also performed to evaluate the effect of metformin on spheres forming ability of CSCs. The therapeutic efficacy and the anti-CSC effects of metformin at low dose were investigated by using both SKOV3 cells and primary tumor xenografts. In addition, the CSC frequency and EMT in tumor xenograft models were also assessed by flow cytometry and quantitative real-time PCR.Results: Metformin at low dose did not affect the proliferation of ovarian cancer cells. However, it inhibited population of CD44⁺CD117⁺selectively, neither CD133⁺nor ALDH⁺cells. It suppressed expression of snail2, twist and vimentin significantly in cancer cells and CD44⁺CD117⁺CSCsin vitro. Low dose of metformin reduced survivin expression in CSCs. Low concentrations of metformin inhibited the secondary and the tertiary tumor sphere formation, decreased SKOV3 and primary ovarian tumor xenograft growth, enhanced the anticancer effect of cisplatin, and lowered the proportion of CD44⁺CD117⁺CSCs in the xenograft tissue. Metformin was also associated with a reduction of snail2, twist, and vimentin in CD44⁺CD117⁺ovarian CSCsin vivo.Conclusions: Our results implicate that metformin at low dose inhibits selectively CD44⁺CD117⁺ovarian CSCs through inhibition of EMT and potentiates the effect of cisplatin.

The present study aimed to investigate the clinical outcomes of percutaneous transhepatic biliary drainage in patients with obstructive jaundice and identify potential predictors of patient survival. Clinical data from 102 patients (66 males and 36 females; median age, 63.50 years; range, 29‑84 years) with a mean (± standard deviation) pre‑drainage serum bilirubin level of 285.4 (±136.7 µmol/l), were retrospectively studied. Technical and clinical success, complications and survival time were recorded and their relationship with clinical factors, including age, obstruction level, liver metastases, serum bilirubin level and subsequent treatments following drainage, were analyzed by Fisher's exact test. Patient survival rate and other predictors were analyzed by Kaplan‑Meier survival curves and Cox's proportional hazard model. The technical and clinical success rates were 100 and 76.5%, respectively. The presence of liver metastases was associated with reduced successful drainage. The overall complication rate was 7.8% and the overall median survival time was 185 days [95% confidence interval (CI), 159‑211 days]. A log‑rank test showed that age (χ2, 4.003; P=0.04), bilirubin levels following procedure (χ2, 5.139; P=0.02) and subsequent therapy (χ2, 15.459; P=0.00) affected survival time. However, Cox's regression analysis revealed no administration of additional treatments to be a risk factor of survival (odds ratio, 2.323; 95% CI, 1.465‑3.685; P=0.000). Percutaneous transhepatic biliary drainage for malignant biliary obstruction was found to be a safe and effective method to relieve jaundice caused by progressive neoplasms. Subsequent radical therapy following drainage, including surgery, chemotherapy and other local treatment types, are likely to increase patient survival.

The aim of the present study was to determine the diagnostic accuracy of computed tomography (CT)‑guided core needle biopsy (CNB) and to retrospectively analyze the correlation between the factors and complications of the procedure. Between January 2009 and June 2010, CNB was performed on 345 lung lesions in 343 patients. These patients were then followed up for at least two years. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of the CNB diagnoses were calculated. The correlation between factors, such as smoking, positoin and maximal diameter, and the complications of pneumothorax and hemorrhage was analyzed by χ2 test. The sensitivity, specificity, accuracy, PPV and NPV of the CNB diagnoses were 97.3, 100, 97.7, 100 and 87.7%, respectively. A statistically significant correlation was found between pneumothorax and the factors of smoking (P=0.015) and position (P<0.01) and length of the needle in the normal parenchyma (P=0.011), as well as between hemorrhage and the maximal diameter (P=0.005) and length of the needle in the normal parenchyma (P<0.01) and the frequency of needle adjustments (P<0.01). A CT‑guided core needle biopsy of the lung lesions provides a high diagnostic yield. Smoking, the decubitus position and a longer length of the needle in the normal parenchyma were found to represent risk factors for a pneumothorax. In addition, a small diameter and longer length of the needle in the normal parenchyma and a more frequent adjustment of the needle were poor predictive factors of hemorrhage.

Background: Three-dimensional conformal radiation therapy (3DCRT)/intensity-modulated radiation therapy (IMRT) combined with or without transcatheter arterial chemoembolization (TACE) for locally advanced hepatocellular carcinoma (HCC) has shown favorable outcomes in local control and survival of locally advanced HCC. However, intra-hepatic spreading and metastasis are still the predominant treatment failure patterns. Sorafenib is a multikinase inhibitor with effects against tumor proliferation and angiogenesis. Maintenance Sorafenib would probably prevent or delay the intrahepatic and extrahepatic spread of HCC after radiotherapy, which provides the rationale for the combination of these treatment modalities. Methods and design: Patients with solitary lesion (bigger than 5 cm in diameter) histologically or cytologically confirmed HCC receive TACE (1-3 cycles) plus 3DCRT/IMRT 4-6 weeks later. Maintenance Sorafenib will be administered only for the patients with non-progression disease 4 to 6 weeks after the completion of radiotherapy. The dose will be 400 mg, p.o., twice a day. Sorafenib will be continuously given for 12 months unless intolerable toxicities and/or tumor progression. If no more than 3 patients discontinue Sorafenib treatment who experience dose-limiting toxicity after necessary dose modification and delay and/or radiation-induced liver disease in the first 15 enrolled patients, the study will recruit second fifteen patients for further evaluating safety and efficacy of treatment. Hypothesis of the current study is that Sorafenib as a maintenance therapy after combined therapy of 3DCRT/IMRT and TACE is safe and superior to radiotherapy combined with TACE alone in terms of time to progression (TTP), progression-free survival (PFS) and overall survival (OS) in comparison to historical data. Discussion: A recent meta-analysis showed TACE in combination with radiotherapy, improved the survival and the tumor response of patients, and was thus more therapeutically beneficial. In this study, local therapy for HCC is the combination of TACE and radiotherapy. Radiation exposure as a kind of stress might induce the compensatory activations of multiple intracellular signaling pathway mediators, such as PI3K, MAPK, JNK and NF-kB. Vascular endothelial growth factor (VEGF) was identified as one factor that was increased in a time- and dose-dependent manner after sublethal irradiation of HCC cells in vitro, translating to enhanced intratumor angiogenesis in vivo. Therefore, Sorafenib-mediated blockade of the Raf/MAPK and VEGFR pathways might enhance the efficacy of radiation, when Sorafenib is followed sequentially as a maintenance modality. (ClinicalTrials.gov number, NCT00999843.)

At present, there is no standardized method for the diagnosis and management of pulmonary nodular lesions (PNLs) smaller than 3 cm. This study investigated the use of computed tomography (CT)‑guided hookwire localization and video‑assisted thoracoscopic surgery (VATS) for PNLs. A total of 103 patients undergoing CT‑guided hookwire localization and VATS were enrolled, and 107 lesions were collected. We assessed the localization achievement ratio, complications rate, conversion thoracotomy rate, intraoperative dislodgement rate, pathological diagnosis rate, duration of surgery and average days of hospitalization. All 107 nodules from 103 patients were successfully localized (100%), the asymptomatic pneumothorax rate was 36.9%, the asymptomatic hemorrhage rate was 40.8% and the simultaneous pneumothorax and hemorrhage rate was 8.7%. A conversion thoracotomy was required in 2 (1.9%) patients and the intraoperative dislodgement rate was 2.9%. The average time for localization was 11±4 min, and the average times for wedge resection and lobectomies were 16±2 and 95±30 min, respectively. The mean hospitalization time following the surgery was 6±3 days. All 107 nodules managed to achieve pathological diagnoses. A combination of CT‑guided hookwire localization and VATS for PNL is a safe and efficient procedure of great clinical value.

Totally implantable access ports (TIAPs) are used for patients with poor peripheral vascular support requiring central venous access. In recent years, TIAPs have been gradually accepted and promoted by patients, doctors, and nurses owing to their advantages of convenient carrying, a long maintenance period, low complications, and a high quality of life for patients. Currently, medical personnel that handle TIAP implantation and management in China are from different areas of healthcare, including surgery, internal medicine, radiology, nurse anesthesia, vascular access, etc., and many only handle TIAP as a part of their duties. Therefore, the operating procedures and steps for the diagnosis and treatment of complications of TIAP vary from person to person, resulting in different incidence and treatment methods for complications in the implantation and use of TIAP in different medical units. Based on this, we have updated the Shanghai expert consensus on TIAPs from 2015 and explored the diagnosis and treatment procedures of related complications while continuing to emphasize standardized implantation and maintenance.