Irradiation stent with 125 I plus TACE versus sorafenib plus TACE for hepatocellular carcinoma with major portal vein tumor thrombosis: a multicenter randomized trial.

BACKGROUND AND AIM: Treatment strategy for hepatocellular carcinoma (HCC) and Vp4 [main trunk] portal vein tumor thrombosis (PVTT) remains limited due to posttreatment liver failure. We aimed to assess the efficacy of irradiation stent placement with 125 I plus transcatheter arterial chemoembolization (TACE) (ISP-TACE) compared to sorafenib plus TACE (Sora-TACE) in these patients. METHODS: In this multicenter randomized controlled trial, participants with HCC and Vp4 PVTT without extrahepatic metastases were enrolled from November 2018 to July 2021 at 16 medical centers. The primary endpoint was overall survival (OS). The secondary endpoints were hepatic function, time to symptomatic progression, patency of portal vein, disease control rate, and treatment safety. RESULTS: Of 105 randomized participants, 51 were assigned to the ISP-TACE group, and 54 were assigned to the Sora-TACE group. The median OS was 9.9 months versus 6.3 months (95% CI: 0.27-0.82; P =0.01). Incidence of acute hepatic decompensation was 16% (8 of 51) versus 33% (18 of 54) ( P =0.036). The time to symptomatic progression was 6.6 months versus 4.2 months (95% CI: 0.38-0.93; P =0.037). The median stent patency was 7.2 months (interquartile range, 4.7-9.3) in the ISP-TACE group. The disease control rate was 86% (44 of 51) versus 67% (36 of 54) ( P =0.018). Incidences of adverse events at least grade 3 were comparable between the safety populations of the two groups: 16 of 49 (33%) versus 18 of 50 (36%) ( P =0.73). CONCLUSION: Irradiation stent placement plus TACE showed superior results compared with sorafenib plus TACE in prolonging OS in patients with HCC and Vp4 PVTT.

The role of bile acid subtypes in the diagnosis of cholangiocarcinoma.

OBJECTIVES: To find the potential biomarkers of cholangiocarcinoma, form a biomarker package, evaluate its efficiency, and validate it. METHODS: R software was used to analyze the differential expression of mRNAs between cholangiocarcinoma and adjacent nontumorous tissues, obtained from The Cancer Genome Atlas (TCGA), and enrich the KEGG pathway. Metabo-Profile Inc. performed the comprehensive bile acid profiling and quantitation. The training set concluded 20 cholangiocarcinoma and 20 nontumorous volunteers. Receiver operating characteristic (ROC) curve and accompanying area under the curve (AUC) was calculated. The top four bile acids formed a new biomarker package. The validation set included 15 cholangiocarcinoma and 15 nontumorous, and the sensitivity and specificity of the new biomarker package were tested. RESULTS: Gene expression of 36 cholangiocarcinoma and nine adjacent nontumorous tissues was obtained in January 2020. Totally 9887 differential genes were eligible (logFC ≥ 1 or ≤ -1, P < 0.05, and adjust P < 0.01). GO analysis showed that 20 KEGG pathways were enriched, including primary bile acid biosynthesis and bile secretion. Comprehensive bile acid profiling and quantitation showed 15 differential bile acid types, and the ROC-AUC was between 0.953 and 0.750. HDCA, isoLCA, bCDCA, and DCA were selected to form a biomarker package. The Logit (p = cholangiocarcinoma) = 7.898 - 3.70*(1isoLCA) - 0.444*(bCDCA) + 0.415*(HDCA) + 0.041*DCA. Its ROC-AUC was 0.944. In the validation set, the sensitivity was 0.933 and the specificity was 0.867. CONCLUSION: Bile acid types package was efficient to distinguish nontumorous population and cholangiocarcinoma. The difference might be associated to the downregulation of primary bile acid biosynthesis and bile secretion pathway of cholangiocarcinoma.

Scutellarin improves the radiosensitivity of non-small cell lung cancer cells to iodine-125 seeds via downregulating the AKT/mTOR pathway.

BACKGROUND: In our previous study, we indicated that scutellarin (SCU) induced an anticancer effect in A549 cells. However, whether SCU regulates the radiosensitivity of non-small cell lung cancer (NSCLC) and its related mechanism is still unclear. METHODS: In this study, we explored the anticancer effect induced by iodine-125 (125 I) and SCU at a sensitizing concentration in A549 and H1975 cells. Cellular apoptosis and proliferation were detected by flow cytometry, Bcl-2/Bax expression level, cell cycle, CCK-8, and EdU staining. A tumor model using nude mice was also carried out to investigate the combined effect of 125 I and SCU in vivo. In addition, the expression level of AKT/mTOR pathway was detected to investigate whether it is linked to the anticancer effect of 125 I and SCU. RESULTS: SCU at a sensitizing concentration promoted the 125 I-induced apoptosis and antiproliferative effect in A549 and H1975 cells. Moreover, the same results were obtained in vivo. Based on our findings, the AKT/mTOR pathway was significantly downregulated after combined treatment with 125 I and SCU. CONCLUSIONS: The results of our study suggested that SCU promotes the anticancer effects induced by 125 I in NSCLC cells by downregulating the AKT/mTOR pathway and lays a foundation for future application of this combined treatment.

Endovascular stenting and coil embolization for management of radiation-induced pseudoaneurysms of the peripheral arteries.

OBJECTIVE: This study was performed to evaluate the safety and efficacy of endovascular stenting and embolization for the management of radiation-induced peripheral arterial pseudoaneurysms. METHODS: Twelve consecutive patients with radiation-induced peripheral arterial pseudoaneurysms (diameter of 10-30 mm and mean size of 20.42 mm) were admitted to our hospital from 1 January 2015 to 31 October 2019. The patients' baseline characteristics, perioperative parameters, device characteristics, and curative effects were systematically recorded and analyzed. RESULTS: The 12 patients comprised 3 men and 9 women with a mean age of 62.90 ± 13.97 years. The iliac artery was the most commonly involved artery, followed by the subclavian artery. In all patients, the pseudoaneurysms were detected by enhanced computed tomography. Twelve covered stents were deployed (7 or 8 mm in diameter and 50 mm in length). Additional coil embolization was performed in three patients (Patients 8, 9, and 10). The primary and secondary technical success rate was 91.7% and 100%, respectively. Apart from one death caused by rebleeding, no patients developed rebleeding during follow-up. CONCLUSION: Endovascular stenting and coil embolization are feasible and effective for the management of radiation-induced peripheral arterial pseudoaneurysms in highly selected patients.

Lobaplatin Enhances Radioactive 125I Seed-Induced Apoptosis and Anti-Proliferative Effect in Non-Small Cell Lung Cancer by Suppressing the AKT/mTOR Pathway.

INTRODUCTION: In recent years, radioactive 125I seed implantation combined with chemotherapy has been regarded as a safe and effective treatment for advanced non-small cell lung cancer (NSCLC). However, the mechanism underlying this success is still unclear. METHODS: In this study, we investigated the apoptosis and anti-proliferative effect induced by 125I in A549, H1975, and H157 cells and determined whether a sensitizing concentration of lobaplatin (LBP) could enhance these effects. We performed in vitro experiments on A549, H1975, and H157 cells; we investigated the effects of 125I or lobaplatin (LBP) alone, or in combination, on cellular apoptosis and proliferation by performing flow cytometry, Bax/Bcl2 ratio, TUNEL, cell viability assay, cell cycle, and EdU. To further verify our findings, a subcutaneous tumor mouse model was established. Moreover, AKT/mTOR pathway was detected to determine whether this pathway was involved in the anti-cancer effect of 125I and LBP by up-regulating or down-regulating the expression of mTOR. RESULTS: Based on our results, the sensitizing concentration of LBP could enhance the 125I-induced apoptosis and anti-proliferation effect. Furthermore, the subcutaneous tumor mouse model obtained the consistent results. More importantly, the AKT/mTOR pathway was down-regulated after the treatment of 125I and LBP, and the anti-cancer effect of 125I and LBP could be compromised by up-regulating the mTOR expression. CONCLUSION: Our study proved that LBP promotes the apoptotic and anti-proliferative effects of 125I in NSCLC cells by inhibiting the AKT/mTOR pathway and provides a foundation for future studies and enhanced combinatorial approaches for NSCLC in the clinical setting.

Feasibility and efficacy study of microwave ablation of recurrent small HCC guided by enhanced liver-specific magnetic resonance imaging contrast agent.

OBJECTIVES: To investigate the feasibility and efficacy of liver-specific magnetic resonance imaging (MRI) with gadolinium-containing contrast agent guidance for microwave ablation (MWA) of recurrent small hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The Ethics Committee of the First Affiliated Hospital of Fujian Medical University approved this study. Eighteen patients presented with 30 recurrent small HCCs, at least one lesion per patient was undetectable on unenhanced MRI, but this was clearly demonstrated in the hepatobiliary phase after liver-specific MRI contrast agent administration. Gd-BOPTA (16 cases) or Gd-EOB-DTPA (2 cases) were injected half an hour before the procedure, and MWA was performed by percutaneous puncture of the target lesion with a magnetic resonance-compatible microwave antenna under 1.5 T MRI guidance. RESULTS: The technical success rate was 100%. The mean maximum diameter of the lesions was 9.7 ± 2.8 mm (5.0-15.4 mm). The mean follow-up time was 11.6 ± 4.7 months (range, 4-19 months), and no local recurrence was observed. CONCLUSIONS: MWA of small HCCs guided by enhanced liver-specific MRI contrast agent is a safe and effective technique.

Advances in Doped ZnO Nanostructures for Gas Sensor.

Gas sensors based on metal oxides semiconductor (MOS) have attracted extensive attention from both academic and industry. ZnO, as a typical MOS, exhibits potential applications in toxic gas detection, owning to its wide band gap, n-type transport characteristic and excellent electrical performance. Meanwhile, doping is an effective way to improve the sensing performance of ZnO materials. In this review, the effects of different types of doping on morphology, crystal structure, band gap and depletion layer of ZnO materials are comprehensively discussed. Theoretical analysis on the strategies for enhancing the sensing properties of ZnO is also provided. This review puts forward the reasonable insight for designing efficient n-type ZnO-based semiconductor oxide sensing materials.

Modified percutaneous transhepatic papillary balloon dilation for patients with refractory hepatolithiasis.

BACKGROUND: Some patients with hepatolithiasis cannot tolerate surgery due to severe cardiac or pulmonary comorbidities, or cannot be endoscopically treated because of altered gastrointestinal anatomies. AIM: To propose a modified percutaneous transhepatic papillary balloon dilation procedure, and evaluate the clinical efficacy and safety of this modality. METHODS: Data from 21 consecutive patients who underwent modified percutaneous transhepatic papillary balloon dilation with hepatolithiasis were retrospectively analyzed. Using auxiliary devices, intrahepatic bile duct stones were pushed into the common bile duct and expelled into the duodenum with an inflated balloon catheter. The outcomes recorded included success rate, procedure time, hospital stay, causes of failure, and procedure-related complications. Patients with possible long-term complications were followed up for 2 years. RESULTS: Intrahepatic bile duct stones were successfully removed in 20 (95.23%) patients. Mean procedure time was 65.8 ± 5.3 min. Mean hospital stay was 10.7 ± 1.5 d. No pancreatitis, gastrointestinal, or biliary duct perforation was observed. All patients were followed up for 2 years, and there was no evidence of reflux cholangitis or calculi recurrence. CONCLUSION: Modified percutaneous transhepatic papillary balloon dilation was feasible and safe with a small number of patients with hepatolithiasis, and may be a treatment option in patients with severe comorbidities or in patients in whom endoscopic procedure was not successful.

Association of Hepatitis B Virus DNA Level and Follow-up Interval With Hepatocellular Carcinoma Recurrence.

Importance: Antiviral treatment is important in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) comprehensive therapy. A high HBV DNA level is an independent risk factor for HBV-related HCC, but no quantifiable clinical index is available to date. Objective: To evaluate the feasibility and availability of the novel HBV DNA quantitation-time index (HDQTI), which includes HBV DNA quantitation and follow-up, to predict HBV-related HCC prognosis. Design, Setting, and Participants: This retrospective prognostic study of patients with HCC from multiple centers in China was performed from January 1, 2002, to December 31, 2016. The median follow-up time was 18 months, and the longest follow-up time was 147 months. Data analysis was performed from January 1, 2017, to December 31, 2018. Main Outcomes and Measures: Clinical characteristics, antitumor management, antiviral treatment, HDQTI scores, follow-up information, and overall survival were recorded and analyzed. A receiver operating characteristic curve and accompanying area under the curve were calculated for HDQTI. Results: A total of 842 patients (mean [SD] age, 61.80 [9.85] years; 513 [60.9%] male) were included in the study. Of all included patients, 734 received no antiviral therapy before diagnosis (no previous diagnosis of HBV infection), 43 underwent nonstandard antiviral therapy, and 65 received regular antiviral therapy. Compared with the group without antiviral treatment, the Barcelona Clinic Liver Cancer (BCLC) stage was earlier (A:B:C, 73.8%:26.2%:0% to 5.7%:65.5%:28.8%, P < .001), the mean (SD) tumor size was smaller (2.89 [1.26] to 7.56 [3.28] cm, P < .001), the ratio of baseline HBV DNA level of more than 105 copies/mL was lower (10.8% to 40.6%, P < .001), and the ratio of the α1-fetoprotein level more than 400 ng/mL was less (21.5% to 78.2%, P < .001) in the standard antiviral treatment group, whereas the nonstandard treatment group was between the 2 groups. Recurrence occurred in 39 of 109 BCLC stage A cases. Patients with HDQTI scores higher than 34 had high risk of recurrence; at this cutoff level, the sensitivity of the HDQTI was 76.9% and the specificity was 92.9%, with an area under curve of 0.928. Patients in various BCLC stages had similar trends in overall survival and HDQTI scores (BCLC stage A: HDQTI score <34, not applicable; HDQTI score ≥34, 44.0 months; 95% CI, 38.3-49.7 months; BCLC stage B: HDQTI score <34, 35.0 months; 95% CI, 33.3-36.7 months; HDQTI score ≥34, 17.0 months; 95% CI, 14.5-19.5 months; P = .002; BCLC stage C: HDQTI score <34, 18.0 months; 95% CI, 16.5-19.6 months; HDQTI scores ≥34, 10.0 months; 95% CI, 8.5-11.5 months; P = .005). Conclusions and Relevance: The findings suggest that the HDQTI can be used as an independent prognostic indicator of recurrence in HBV-related HCC. Shorter follow-up intervals and accurate imaging evaluation are recommended in patients with HDQTI scores of 34 or higher.

Thoracic Endovascular Aortic Repair for Type B Aortic Dissection Associated with Retrograde Type A Intramural Hematoma.

PURPOSE: To evaluate feasibility and efficacy of thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD) associated with retrograde type A intramural hematoma (IMH). MATERIALS AND METHODS: From April 2013 to January 2017, 15 consecutive patients with TBAD associated with retrograde type A IMH who underwent TEVAR were reviewed retrospectively. There was no cardiac tamponade, aortic regurgitation, involvement of coronary artery, or sign of cerebral ischemia in these patients. Enhanced CT was used in 4 patients to diagnose malperfusion of abdominal visceral arteries or lower extremity artery and underwent emergent TEVAR. For the remaining 11 patients, repeated enhanced CT after initial medical treatment within 24 hours from onset of pain showed expansion of IMH in 8 patients or presence of periaortic hematoma in 3 patients. Delayed TEVAR was scheduled for these cases. RESULTS: Successful deployment of the stent graft was achieved in all patients. There were no severe postoperative complications, such as retrograde type A aortic dissection or aortic rupture. Sudden death occurred in 1 patient 3 months after the procedure. Thrombosis of the false lumen, shrinkage of the diameter of the aorta, and complete absorption of the IMH were observed in the remaining patients at a mean follow-up of 19.8 months ± 6.57. CONCLUSIONS: TEVAR for treatment of TBAD with retrograde type A IMH is feasible and effective. It represents a treatment option for patients with TBAD associated with type A IMH with a proximal entry tear located in the descending aorta.

Percutaneous transhepatic cholangiography versus endoscopic retrograde cholangiography for the pathological diagnosis of suspected malignant bile duct strictures.

To compare the diagnostic performance of percutaneous transhepatic cholangiography and endoscopic retrograde cholangiography for the pathological assessment of suspected malignant bile duct stricture, using brush cytology and forceps biopsy.The study group comprised 79 consecutive patients who underwent pathological assessment for suspected malignant biliary stricture, 38 of whom underwent percutaneous transhepatic cholangiography (group A) and the other 41 underwent endoscopic retrograde cholangiography (group B). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated. A subset analysis was performed to determine the effect of location and pathological type of the stricture on diagnostic performance, and complications were analyzed.The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 86.7%, 100%, 100%, 66.7%, and 89.5%, respectively, in group A, and 77.1%, 100%, 100%, 42.9%, and 80.4%, respectively, in group B. For hilar biliary strictures, the sensitivity and accuracy were superior in group A than in group B. Mild complications (transient c and bile leakage) were identified in 7 cases in each group, all resolved spontaneously within 3 to 5 days.Both brush cytology and forceps biopsy performed during percutaneous transhepatic cholangiography and endoscopic retrograde cholangiography provided good diagnostic sensitivity and accuracy. Therefore, both diagnostic approaches can play an important role in planning therapeutic strategy. However, for strictures located at the hilum, pathology sampling via percutaneous transhepatic cholangiography is preferable to endoscopic retrograde cholangiography, as it provides higher sensitivity and accuracy.

The Combination of MK-2206 and WZB117 Exerts a Synergistic Cytotoxic Effect Against Breast Cancer Cells.

Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer death in women. Hormone receptor-positive breast cancer is usually subjected to hormone therapy, while triple-negative breast cancer is more formidable and poses a therapeutic challenge. Glucose transporters are potential targets for the development of anticancer drugs. In search of anticancer agents whose effect could be enhanced by a GLUT1 inhibitor WZB117, we found that MK-2206, a potent allosteric Akt inhibitor, when combined with WZB117, showed a synergistic effect on growth inhibition and apoptosis induction in breast cancer cells, including ER(+) MCF-7 cells and triple-negative MDA-MB-231 cells. The combination index values at 50% growth inhibition were 0.45 and 0.21, respectively. Mechanism studies revealed that MK-2206 and WZB117 exert a synergistic cytotoxic effect in both MCF-7 and MDA-MB-231 breast cancer cells by inhibiting Akt phosphorylation and inducing DNA damage. The combination may also compromise DNA damage repair and ultimately lead to apoptosis. Our findings suggest that the combination of Akt inhibitors and GLUT1 inhibitors could be a novel strategy to combat breast cancer.

Lobaplatin promotes 125I-induced apoptosis and inhibition of proliferation in hepatocellular carcinoma by upregulating PERK-eIF2α-ATF4-CHOP pathway.

We investigated the mechanism underlying the effect of a combination treatment of 125I radioactive seed implantation and lobaplatin (LBP) in hepatocellular carcinoma. The effects of administration of HCC cells and subcutaneous tumor model of mice with different doses of 125I or a sensitizing concentration of LBP alone, or in combination, on cellular apoptosis and proliferation were analyzed and it was confirmed that LBP promotes 125I-induced apoptosis and inhibition of proliferation of HCC. Furthermore, isobaric tag for relative and absolute quantification labeling analyses suggested that 125I promoted the apoptosis and inhibition of proliferation of HCC cells by upregulating the expression of PERK-eIF2α-ATF4-CHOP pathway, a well-known apoptosis-related pathway. Moreover, LBP was found to boost the 125I-induced upregulation of this pathway and increase the apoptosis. Our data indicate that LBP promotes the apoptotic and anti-proliferative effects of 125I and provide a firm foundation for better clinical application of this combination therapy.

Double-platelet Pd@ZnO microcrystals for NO2 chemical sensors: their facile synthesis and DFT investigation.

Double-platelet, single-platelet and spherical ZnO microcrystals were fabricated via a facile and controllable hydrothermal method. The morphology of the ZnO microcrystals and the exposure ratio of the (001) crystal surface were regulated by adjusting the pH of the solution. The ZnO microcrystals were modified with Pd nanoparticle loading by simple calcining, and the interaction of Pd nanoparticles (NPs) on the ZnO crystal surface increased its oxygen vacancy content. A micro-amount (0.05 wt%) of Pd NP-doped ZnO double-platelets (D-ZnO-0.05) enhanced the gas sensing of the sensor to 3.5 times that of pure double-platelet ZnO. The gas sensing results indicate that D-ZnO-0.05 exhibits a high response (71.2 for NO2 with 25 ppm), fast response/recovery (25 s/21 s), and superior long-term stability (remained at around 95.5% after 35 days). The enhancement in the gas sensing could be attributed to the catalysis of Pd NPs and the increase in the number of oxygen vacancies as a result of Pd loading. The band structure of D-ZnO-0.05 could be effectively tuned by introducing Pd nanoparticles, as shown in density functional theory (DFT) calculations. The Pd dopant and oxygen vacancies reduce the band gap of the ZnO(001) crystal materials, resulting in excellent sensor performance. It is believed that the D-ZnO-0.05 microcrystals could provide inspiration for crystal growth studies and high NO2 gas sensing.

Early Warning Models to Estimate the 30-Day Mortality Risk After Stent Placement for Patients with Malignant Biliary Obstruction.

PURPOSE: To develop, validate, and compare early warning models of the 30-day mortality risk for patients with malignant biliary obstruction (MBO) undergoing percutaneous transhepatic biliary stent placement (PTBS). MATERIALS AND METHODS: Between January 2013 and October 2018, this multicenter retrospective study included 299 patients with MBOs who underwent PTBS. The training set consisted of 166 patients from four cohorts, and another two independent cohorts were allocated as external validation sets A and B with 75 patients and 58 patients, respectively. A logistic model and an artificial neural network (ANN) model were developed to predict the risk of 30-day mortality after PTBS. The predictive performance of these two models was validated internally and externally. RESULTS: The ANN model had higher values of area under the curve than the logistic model in the training set (0.819 vs 0.797), especially in the validation sets A (0.802 vs 0.714) and B (0.732 vs 0.568). Both models had high accuracy in the three sets (75.9-83.1%). Along with a high specificity, the ANN model improved the sensitivity. The net reclassification improvement and integrated discrimination improvement also demonstrated that the ANN model led to improvements in predictive ability compared with the logistic model. CONCLUSIONS: Early warning models were proposed to predict the risk of 30-day mortality after PTBS in patients with MBO. The ANN model has higher accuracy and better generalizability than the logistic model.

Highly enhanced photocatalytic H2 evolution of Cu2O microcube by coupling with TiO2 nanoparticles.

A Cu2O/TiO2 p-n heterojunction composite was created via a facile, controllable, one-pot hydrothermal method based on cubic Cu2O and TiO2 nanoparticles in the presence of dioctyl sulfosuccinate sodium salt (AOT) surfactant. The TiO2 nanoparticles with an average edge length of ∼10.1 nm were uniformly distributed on the crystal surface of a Cu2O cube {100}. The photocatalytic performance of the composite was effectively tuned by controlling the amount of TiO2. The Cu2O/TiO2 (60 wt%, labeled as CT-60) exhibits the highest enhanced photocatalytic activity in hydrogen production with H2 evolution of 3002.5 µmol g-1. The yield remained around 92.6% after three cycles. Hydrogen production of the CT-60 is 103 and 8.5 fold higher than the cubic Cu2O and TiO2 nanoparticles, respectively. The improvement in photocatalytic performance could be attributed to the formation of p-n heterojunction. Furthermore, the interface effect of Cu2O and TiO2 caused a broader absorbance in the visible-light region and the lower recombination of photogenerated electron-hole pairs. It is believed that the Cu2O/TiO2 p-n heterojunction composites could provide an alternative method to design highly efficient photocatalysts for solar energy.

Combined effect of 125I and gemcitabine on PANC-1 cells: Cellular apoptosis and cell cycle arrest.

BACKGROUND: 125I seed implantation has recently become an effective, safe, and feasible treatment for advanced pancreatic cancer in China. Gemcitabine (GEM), superior to fluorouracil, has been widely proved as effective chemotherapy for many solid tumors and become the standard treatment for locally advanced and metastatic pancreatic cancer. The study aimed to evaluate the combined effect of 125I and GEM on pancreatic carcinoma cells (PANC-1) cells and explore the underlying molecular basis. SUBJECTS AND METHODS: PANC-1 cells were treated with 125I continuously at a low dose of radiation, combined with or without sensitizing concentration of GEM. The clonogenic capacity, cellular proliferation, cell cycle distribution, apoptosis, and molecular pathways of the cells following these treatments were analyzed in vitro. RESULTS: The cell growth could be significantly inhibited after the treatment with GEM or 125I alone, while the inhibition effects would be greater with combination therapy than either monotherapy (72 h, C vs. GEM, t = 16.59, P < 0.01; C vs. 125I, t = 9.808, P < 0.05; C vs. 125I + GEM, t = 17.87, P < 0.01; 125I vs. 125I+GEM, t = 8.191, P < 0.05). GEM increased radiation-induced apoptosis (4 Gy, 125I vs. 125I+GEM, t = 10.43, P < 0.01) and induced the arrest of G1. Caspase-3 expression and the Bax/Bcl2 ratio were lower in cells receiving combination treatment than that of in cells treated with 125I or GEM alone. CONCLUSION: The combined treatment of 125I and GEM-induced stronger anti-proliferation effect than single-treatment, due to the cell cycle arrest and more cellular apoptosis in PANC-1 cells. The increased Bax/Bcl-2 ratio may lead to enhanced apoptosis.

Ursodeoxycholic acid combined with percutaneous transhepatic balloon dilation for management of gallstones after elimination of common bile duct stones.

AIM: To evaluate the effectiveness and safety of combined ursodeoxycholic acid and percutaneous transhepatic balloon dilation for management of gallstones after expulsion of common bile duct (CBD) stones. METHODS: From April 2014 to May 2016, 15 consecutive patients (6 men and 9 women) aged 45-86 (mean, 69.07 ± 9.91) years suffering from CBD stones associated with gallstones were evaluated. Good gallbladder contraction function was confirmed by type B ultrasonography. Dilation of the CBD and cystic duct was detected. Percutaneous transhepatic balloon dilation of the papilla was performed, ursodeoxycholic acid was administered, and all patients had a high-fat diet. All subjects underwent repeated cholangiography, and percutaneous transhepatic removal was carried out in patients with secondary CBD stones originating from the gallbladder. RESULTS: All patients underwent percutaneous transhepatic balloon dilation with a primary success rate of 100%. The combined therapy was successful in 86.7% of patients with concomitant CBD stones and gallstones. No remaining stones were detected in the gallbladder. Transient adverse events include abdominal pain (n = 1), abdominal distension (n = 1), and fever (n = 1). Complications were treated successfully via nonsurgical management without long-term complications. No procedure-related mortality occurred. CONCLUSION: For patients with concomitant CBD stones and gallstones, after percutaneous transhepatic removal of primary CBD stones, oral ursodeoxycholic acid and a high-fat diet followed by percutaneous transhepatic removal of secondary CBD stones appear to be a feasible and effective option for management of gallstones.

Percutaneous transhepatic extraction and balloon dilation for simultaneous gallbladder stones and common bile duct stones: A novel technique.

AIM: To evaluate the clinical efficacy and safety of an innovative percutaneous transhepatic extraction and balloon dilation (PTEBD) technique for clearance of gallbladder stones in patients with concomitant stones in the common bile duct (CBD). METHODS: The data from 17 consecutive patients who underwent PTEBD for clearance of gallbladder stones were retrospectively analyzed. After removal of the CBD stones by percutaneous transhepatic balloon dilation (PTBD), the gallbladder stones were extracted to the CBD and pushed into the duodenum with a balloon after dilation of the sphincter of Oddi. Large stones were fragmented using a metallic basket. The patients were monitored for immediate adverse events including hemorrhage, perforation, pancreatitis, and cholangitis. During the two-year follow-up, they were monitored for stone recurrence, reflux cholangitis, and other long-term adverse events. RESULTS: Gallbladder stones were successfully removed in 16 (94.1%) patients. PTEBD was repeated in one patient. The mean hospitalization duration was 15.9 ± 2.2 d. Biliary duct infection and hemorrhage occurred in one (5.9%) patient. No severe adverse events, including pancreatitis or perforation of the gastrointestinal or biliary tract occurred. Neither gallbladder stone recurrence nor refluxing cholangitis had occurred two years after the procedure. CONCLUSION: Sequential PTBD and PTEBD are safe and effective for patients with simultaneous gallbladder and CBD stones. These techniques provide a new therapeutic approach for certain subgroups of patients in whom endoscopic retrograde cholangiopancreatography/endoscopic sphincterotomy or surgery is not appropriate.

Irradiation stents vs. conventional metal stents for unresectable malignant biliary obstruction: A multicenter trial.

BACKGROUND & AIMS: Placement of an irradiation stent has been demonstrated to offer longer patency and survival than an uncovered self-expandable metallic stent (SEMS) in patients with unresectable malignant biliary obstruction (MBO). We aim to further assess the efficacy of an irradiation stent compared to an uncovered SEMS in those patients. METHODS: We performed a randomized, open-label trial of participants with unresectable MBO at 20 centers in China. A total of 328 participants were allocated in parallel to the irradiation stent group (ISG) or the uncovered SEMS group (USG). Endpoints included stent patency (primary), technical success, relief of jaundice, overall survival, and complications. RESULTS: The first quartile stent patency time (when 25% of the patients experienced stent restenosis) was 212 days for the ISG and 104 days for the USG. Irradiation stents were significantly associated with a decrease in the rate of stent restenosis (9% vs. 15% at 90 days; 16% vs. 27% at 180 days; 21% vs. 33% at 360 days; p = 0.010). Patients in the ISG obtained longer survival time (median 202 days vs. 140 days; p = 0.020). No significant results were observed in technical success rate (93% vs. 95%; p = 0.499), relief of jaundice (85% vs. 80%; p = 0.308), and the incidence of grade 3 and 4 complications (8.5% vs. 7.9%; p = 0.841). CONCLUSIONS: Insertion of irradiation stents instead of uncovered SEMS could improve patency and overall survival in patients with unresectable MBO. LAY SUMMARY: For patients with unresectable malignant biliary obstruction (MBO), placement of a self-expandable metallic stent (SEMS) is a recommended palliative modality to relieve pruritus, cholangitis, pain, and jaundice. However, restenosis is a main pitfall after stent placement. Data from this first multicenter randomized controlled trial showed that insertion of an irradiation stent provided longer patency and better survival than a conventional metal stent. ClinicalTrials.gov ID: NCT02001779.