Guang-Yu Zhu

Self-expandable Esophageal Stent Loaded with 125I Seeds : Initial Experience in Patients with Advanced Esophageal Cancer

PURPOSE To prospectively compare the response to treatment with a self-expandable esophageal stent loaded with iodine 125 ((125)I) seeds for intraluminal brachytherapy versus the response to treatment with a conventional self-expandable covered stent in patients with advanced esophageal cancer. MATERIALS AND METHODS The study protocol was approved by the institutional ethics committee, and informed consent was obtained from each patient. Patients from one institution who had dysphagia caused by inoperable esophageal cancer were randomly assigned to receive treatment with a stent loaded with (125)I seeds (irradiation stent group) or a conventional covered stent (control group). After stent implantation, the outcomes were measured in terms of relief of dysphagia, survival time, and complications related to the procedure. Dysphagia was assigned a grade. A P value of less than .05 was considered to indicate a significant difference. RESULTS The stent was successfully placed in the diseased esophagus in all 53 patients (27 patients in the irradiation stent group and 26 patients in the control group). The dysphagia grades significantly improved in both groups within the 1st month after stent placement but were better in the irradiation stent group than in the control group after 2 months (P < .05). The median and mean survival times were better in the irradiation stent group than in the control group, and the differences were significant (P < .001). Hemorrhage occurred in 16 (30%) patients in both groups combined during follow-up. CONCLUSION In patients with advanced esophageal cancer, treatment with an esophageal stent loaded with (125)I seeds, compared with that with a conventional covered stent, has potential benefit in that it allows a slightly longer relief of dysphagia and extended survival.

Conventional stents versus stents loaded with 125iodine seeds for the treatment of unresectable oesophageal cancer: a multicentre, randomised phase 3 trial

BACKGROUND The combination of stent insertion and single high-dose brachytherapy is a feasible and safe palliative treatment regimen in patients with unresectable oesophageal cancer. We aimed to further assess the efficacy of this treatment strategy compared to a conventional covered stent in patients with dysphagia caused by unresectable oesophageal cancer. METHODS In this multicentre, single-blind, randomised, phase 3 trial, we enrolled patients with unresectable oesophageal cancer from 16 hospitals in China. We included adult patients (aged ≥ 20 years) with progressive dysphagia, unresectable tumours due to extensive lesions, metastases, or poor medical condition, and with clear consciousness, cooperation, and an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-3. Eligible patients were randomly assigned (in 1:1 ratio, no stratification) to receive either a stent loaded with (125)iodine radioactive seeds (irradiation group) or a conventional oesophageal stent (control group). The primary endpoint was overall survival. Survival analyses were done in a modified intention-to-treat group. This study is registered with ClinicalTrials.gov, number NCT01054274. FINDINGS Between Nov 1, 2009, and Oct 31, 2012, 160 patients were randomly assigned to receive treatment with either an irradiation stent (n=80) or a conventional stent (n=80). During a median follow-up of 138 days (IQR 72-207), 148 stents (73 in the irradiation group and 75 in the control group) were successfully placed into the diseased oesophagus in 148 participants. Median overall survival was 177 days (95% CI 153-201) in the irradiation group versus 147 days (124-170) in the control group (p=0.0046). Major complications and side-effects of the treatment were severe chest pain (17 [23%] of 73 patients in the irradiation group vs 15 [20%] of 75 patents in the control group), fistula formation (six [8%] vs five [7%]), aspiration pneumonia (11 [15%] vs 14 [19%]), haemorrhage (five [7%] vs five [7%]), and recurrent dysphagia (21 [28%] vs 20 [27%]). INTERPRETATION In patients with unresectable oesophageal cancer, the insertion of an oesophageal stent loaded with (125)iodine seeds prolonged survival when compared with the insertion of a conventional covered self-expandable metallic stent.

A novel biliary stent loaded with 125I seeds in patients with malignant biliary obstruction: Preliminary results versus a conventional biliary stent

BACKGROUND & AIMS Stenting is a palliative therapy method for relieving malignant biliary obstruction. The aim of this study was to evaluate the safety and effectiveness of an irradiation stent compared to a conventional biliary stent in patients with biliary obstruction caused by both primary and metastatic adenocarcinomas. METHODS Participants were randomly assigned to receive treatment with a biliary irradiation stent (irradiation stent group) or a conventional biliary stent (control group). After stent implantation, the outcomes were measured in terms of relief of obstructive jaundice, survival time, complications related to the procedure. A p value of less than 0.05 indicated a significant difference. RESULTS The stents were successfully placed in all the 23 patients. The obstructive jaundice was relieved in all patients except three in the control group. The median and mean overall survivals in the irradiation stent group were higher than those in the control group (7.40 months versus 2.50 months, 8.03 months versus 3.36 months, p=0.006). The patients with stent patent at 3, 6, and 12 months in the irradiation stent group were 11 (91.7%), 7 (58.3%), and 1 (8.3%), respectively. While in the control group, 4 (36.4%), 1 (9.1%), and 0 (0%), respectively. There were no significant differences in the complications related to stent insertion between the two groups. CONCLUSIONS This interim analysis shows that treatment with the biliary intraluminal irradiation stent in patients with biliary obstruction caused by adenocarcinomas appears safe and technically feasible, has benefits in relieving jaundice, and seems to extend survival when compared to a conventional biliary stent.

Repeat vertebroplasty for unrelieved pain at previously treated vertebral levels with osteoporotic vertebral compression fractures.

Study Design. A retrospective study was performed in patients with a repeat percutaneous vertebroplasty (PV) at the vertebral levels previously undergoing vertebroplasty. Objective. Our purpose of this study is to examine if a repeat PV is effective on pain-relief at the vertebral levels previously undergoing vertebroplasty. Summary of Background Data. Although pain-relief is usually high with the treatment of PV in the painful osteoporotic vertebral compression fractures, there are still about 5% to 22% of such patients experiencing no improvement on pain after PV. A repeat PV at the same vertebrae previously treated with PV may be an option for these patients without a pain-relief. Methods. Out of 334 procedures of PV in 242 patients with osteoporotic vertebral compression fractures from October 2000 to June 2006 in our institute, 15 vertebrae in 15 patients with unrelieved pain in 4 to 32 days after an initial PV were treated with a repeat vertebroplasty. The clinical outcomes were assessed by measurements of visual analog scale, and the imaging features were analyzed pre- and postprocedure. Results. The mean volume of Polymethylmethacrylate injected in each vertebra was 4.0 mL (range, 1.5–9 mL) in the repeat PV. During the first month of follow-up after repeat PV in this series, a mean visual analog scale scores of the pain level was reduced from 8.6 (range, 7–10) preprocedure to 1.67 points (range, 0–4) postprocedure, with a mean reduction of 6.93 points (range, 4–8). Complete and partial pain relief were reached in 11 (73%) and 4 patients (27%), respectively in a mean follow-up of 15 months. No serious complications related to the procedures occurred, but asymptomatic Polymethylmethacrylate leakage around vertebrae was demonstrated on radiograph or computed tomography in 2 patients. Conclusion. The outcomes of this series suggest that repeat PV is effective at the same vertebral levels in patients without pain-relief who underwent previous PV. Absent or inadequate filling of cement in the unstable fractured areas of the vertebral body may be responsible for the unrelieved pain after the initial PV.

Risk Factors for New Vertebral Fractures after Percutaneous Vertebroplasty in Patients with Osteoporosis: A Prospective Study

PURPOSE To determine the risk factors for new vertebral compression fractures (VCFs) following percutaneous vertebroplasty (PV) in patients with osteoporosis. MATERIALS AND METHODS This prospective study included 132 consecutive patients with osteoporosis treated with PV in a single institution over 46 months from March 2005 to December 2008. Multivariable logistic regression and univariate analysis were employed to identify risk factors for new VCFs after PV, including patient demographic data, parameters of the initial and new fractured vertebrae, procedure-related information, and follow-up data. RESULTS During the follow-up period (22.4 months ± 12.1), 80 new vertebral fractures occurred in 36 (27.3%) patients. Multivariate analysis showed that number of VCFs per time frame, computed tomography (CT) value of nonfractured vertebrae (T11-L2), activity level after discharge, duration of follow-up, and cement distribution in the inferior part of the vertebral body or close to the endplate were statistically correlated with new fractures (odds ratios, 2.63, 0.96, 3.59, 1.00, 0.30, and 0.05; P = .006, P = .001, P = .007, P = .004, P = .021 and P = .029). Univariate analysis showed preexisting old VCFs were correlated with new VCFs (P = .045). Subsequent compression fractures in adjacent vertebrae (45 of 80) occurred more frequently and sooner than nonadjacent vertebral fractures (both P < .05). CONCLUSIONS The incidence of new VCFs after PV is relatively high and affected by several risk factors that are related to both the PV procedure and the natural course of osteoporosis.

Enhancement of p53 gene transfer efficiency in hepatic tumor mediated by transferrin receptor through trans-arterial delivery

Transferrin-DNA complex mediated by transferrin receptor in combination with interventional trans-arterial injection into a target organ may be a duel-target-oriented delivery means to achieve an efficient gene therapy. In this study, transferrin receptor expression in normal human hepatocyte and two hepatocellular-carcinoma cells (Huh7/SK-Hep1) was determined. p53-LipofectAMINE with different amounts of transferrin was transfected into the cells and the gene transfection efficiency was evaluated. After VX2 rabbit hepatocarcinoma model was established, the transferrin-p53-LipofectAMINE complex was delivered into the hepatic artery via interventional techniques to analyze the therapeutic p53 gene transfer efficiency in vivo by Western blot, immunohistochemical/immunofluorescence staining analysis and survival time. The results were transferrin receptor expression in Huh7 and SK-Hep1 cells was higher than in normal hepatocyte. Transfection efficiency of p53 was increased in vitro in both Huh7 and SK-Hep1 cells with increasing transferrin in a dose-dependent manner. As compared to intravenous administration, interventional injection of p53-gene complex into hepatic tumor mediated by transferrin-receptor, could enhance the gene transfer efficiency in vivo as evaluated by Western blot, immunohistochemical/immunofluorenscence staining analyses and improved animal survival (H = 12.567, p = 0.0019). These findings show the transferrin-transferrin receptor system combined with interventional techniques enhanced p53-gene transfer to hepatic tumor and the duel-target-oriented gene delivery may be an effective approach for gene therapy.

A Simplified Method of Opacifying and Mixing Acrylic Cement for Percutaneous Vertebroplasty: A Clinical and In Vitro Study

The objective of this study was to simplify the opacifying mixing process of the bone cement and contrast used for percutaneous vertebroplasty (PVP). We performed a biomechanical study of polymethyl methacrylate (PMMA) (CorinplastTM 3) using three different mixtures of PMMA, monomer, and contrast: group I, 2:1; group II, 3:2; group III, 3:2:1 ratio of powder/monomer/iodinated contrast (Omnipaque). In vitro biomechanical testing of ultimate compressive strength was carried out in all samples. Following the conclusion of a proper bone cement mixture regimen drawn from the in vitro study, PVP was performed in 125 patients: 58 with cancer, 12 with hemangioma, and 54 with osteoporotic fracture. The ultimate compressive strength in group III was decreased by 38% compared to groups II and I. Proper fluoroscopic visualization was achieved in all PVP procedures using this mixture. There were no major complications associated with injection of the cement mixture. Complete (CR) and partial response (PR) was obtained in 64% and 32.8%, respectively. No further vertebral collapse occurred during follow-up. The regimen using iodinated contrast for cement visualization during PVP provides a simple and convenient new method for mixing. Although the biomechanical strength is altered by the contrast medium added, it seems insignificant in clinical practice based on the authors’ limited experience.

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.

Preventive effects of 125I seeds on benign restenosis following esophageal stent implantation in a dog model

The present study aimed to evaluate the effects of iodine-125 (125I) seeds on the proliferation of primary esophageal fibroblasts in dogs, and to assess the safety and preventive efficacy of 125I seed-pre-loaded esophageal stents in benign restenosis following implantation. Primary fibroblasts were cultured with various 125I seed activities, which were then evaluated using cell proliferation and apoptosis assays as well as cell cycle analysis using Annexin V/propidium iodide (PI) double staining and PI staining. Prior to sacrification, animals were submitted to esophageal radiography under digital subtraction angiography. Esophageal tissues were collected and examined for macroscopic, microscopic and pathological alterations. The results demonstrated a significant and dose-dependent inhibition of fibroblast proliferation and increased apoptosis following exposure to 125I seeds. G0/G1 fibroblast populations increased in a dose-dependent manner following treatment with 125I seeds, in contrast to cells in S phase. Four weeks following implantation, α-smooth muscle actin and proliferating cell nuclear antigen expression levels in the experimental group were significantly lower compared with those in the control group; in addition, eight weeks following implantation, esophageal inner diameters were increased in the experimental group. 125I seeds inhibited proliferation of dog esophageal fibroblasts via cell cycle arrest and apoptosis. In conclusion, 125I seed-pre-loaded esophageal stents inhibited benign hyperplasia in the upper edge of the stent to a certain extent, which relieved benign restenosis following implantation with a good safety profile.

A Modified Model for Assessment for Retreatment with Transarterial Chemoembolization in Chinese Hepatocellular Carcinoma Patients

PURPOSE To develop a modified assessment for retreatment with transarterial chemoembolization (mART) score that may be more suitable for Chinese patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS Chinese patients with HCC who were treated with transarterial chemoembolization in four hospitals were included. A univariate analysis and a multivariate forward Cox regression analysis were used to identify significant prognostic factors of overall survival (OS). A point scoring model was subsequently developed from the training cohort, and the validation process was performed in the validation cohort. RESULTS The study included 259 patients (124 patients in the training cohort and 135 patients in the validation cohort). Increase in Child-Pugh scores relative to the baseline (P < .001), Barcelona Clinic Liver Cancer (BCLC) stage B before first transarterial chemoembolization (P = .001), and absence of radiologic tumor response (P < .001) were identified as negative prognostic factors for OS and were used to create the mART scores. BCLC staging was substituted for aspartate aminotransferase increase in the mART scores. The mART scores differentiated two groups with distinct prognosis by a cutoff score of 2.5 points (22.9 mo [95% confidence interval (CI), 17.4-28.4] vs 8.9 mo [95% CI, 7.5-10.3] in median survival; P < .001). In the validation cohort, the C index in assessment for retreatment with transarterial chemoembolization (ART) criteria was 0.64, whereas it was 0.82 in mART criteria. CONCLUSIONS In Chinese patients with HCC, mART score of > 2.5 before second transarterial chemoembolization was associated with poor prognosis. The mART score was probably better validated compared with the ART score.