Kangshun Zhu

Partial splenic embolization for hypersplenism in cirrhosis: A long-term outcome in 62 patients

BACKGROUND Although partial splenic embolization (PSE) has been widely used for treatment of leucocytopaenia and thrombocytopaenia in cirrhosis, only few studies on the correlation between splenic infarction rate and long-term outcome of partial splenic embolization have been reported so far. AIM To evaluate long-term results of partial splenic embolization with different infarction rates in cirrhotic patients with hypersplenism. METHODS Sixty-two consecutive patients with hypersplenism in cirrhosis received partial splenic embolization. According to the splenic infarction rate after partial splenic embolization, the patients were divided into three groups: more than 70% in group A (n=12), 50-70% in group B (n=34), and less than 50% in group C (n=16). The post-partial splenic embolization following-up time was 5 years. RESULTS Before partial splenic embolization, there were no significant differences among the three groups with respect to sex, age, splenic volume, Child-Pugh class, oesophageal varices, and peripheral blood cell counts. After partial splenic embolization, the short- and long-term outcomes of leucocyte and platelet counts showed significant difference among the three groups (P<0.001). In groups A and B, the leucocyte and platelet counts after partial splenic embolization remained significantly higher than those before partial splenic embolization for 2 weeks to 5 years (P<0.05), the post-partial splenic embolization leucocyte and platelet counts was even higher in group A than in group B; while in group C, leucocyte and platelet count improvement only lasted for 6 months after partial splenic embolization. No significant changes were observed concerning blood red cell counts and liver function parameters after partial splenic embolization among the three groups. Severe complications occurred in six patients (50%) in group A and three patients (8.8%) in group B (P<0.05), while in group C, no severe complications developed. CONCLUSIONS In partial splenic embolization, the splenic infarction rate should be limited to 50%-70% in order to ensure the long-term efficacy in alleviating hypersplenism and reduce complications.

Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: Treatment with Transarterial Chemoembolization Combined with Sorafenib—A Retrospective Controlled Study

PURPOSE To determine the safety and efficacy of transarterial chemoembolization (TACE) combined with sorafenib (hereafter, TACE-sorafenib) in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT). MATERIALS AND METHODS This study was approved by the institutional review board, and the requirement for informed consent was waived. The medical records of consecutive patients with HCC and PVTT who underwent TACE-sorafenib or TACE alone from January 2010 to December 2012 were retrospectively evaluated. Sorafenib (400 mg) was administered twice daily. Outcomes of patients who underwent TACE-sorafenib were compared with outcomes of patients who underwent TACE by using the Kaplan-Meier method according to types of PVTT: PVTT in the main portal vein (type A), PVTT in the first-order portal vein branch (type B), and PVTT in second- or lower-order portal vein branches (type C). RESULTS Ninety-one patients were included in the analysis; 46 patients underwent TACE-sorafenib and 45 underwent TACE. TACE-sorafenib showed significant survival benefits compared with TACE in patients with type B (median survival, 13 months vs 6 months; P = .002) or type C (median survival, 15 months vs 10 months; P = .003) PVTT. TACE-sorafenib and main PVTT were the independent prognostic factors for survival at uni- and multivariate analysis. Liver function after TACE-sorafenib worsened only in patients with main PVTT. Sorafenib-related adverse events of grade 3 or higher occurred in 16 patients (35%). CONCLUSION TACE-sorafenib side effects were acceptable, and this treatment may improve overall survival in patients with HCC with first-order or lower-branch PVTT when compared with patients who underwent TACE alone.

Uterine artery embolization combined with methotrexate in the treatment of cesarean scar pregnancy: results of a case series and review of the literature.

PURPOSE To explore the clinical value of uterine artery embolization (UAE) combined with methotrexate in the treatment of cesarean scar pregnancy (CSP) before and after uterine curettage. MATERIALS AND METHODS From August 2009 to April 2012, 15 patients with CSP treated with UAE (before or after uterine curettage) were analyzed retrospectively. Eleven subjects with a definite diagnosis of CSP were offered preventive UAE combined with methotrexate before uterine curettage. The other four patients, who were misdiagnosed as having an intrauterine pregnancy, were treated with emergency UAE for uncontrollable massive hemorrhage after uterine curettage. Clinical data, treatment sequence, and outcome were analyzed, and a brief review of the published literature summarizing UAE in the treatment of CSP was performed. RESULTS Eleven patients with definite CSP received preventive UAE combined with methotrexate followed by uterine curettage, and CSP was resolved successfully without hysterectomy. In the four misdiagnosed patients, three were treated successfully with emergency UAE. The other patient underwent uterine curettage and emergency UAE followed by repeat curettage, but hysterectomy was performed because of continued severe hemorrhage. CONCLUSIONS Based on a small number of patients, it appears that UAE may be an effective means of treating CSP, including treatment in an emergency setting. Further study is required before the safety and effectiveness of UAE can be confirmed.

Enhanced apoptosis of ovarian cancer cells via nanocarrier-mediated codelivery of siRNA and doxorubicin

A folate conjugated ternary copolymer, FA–PEG–PEI–PCL, of poly(ethylene glycol) (PEG), poly(ethylene imine) (PEI), and poly(ɛ-caprolactone) (PCL) was synthesized. The copolymer self-assembled into cationic micelles capable of co-delivering siRNA and the anticancer drug doxorubicin (DOX). This dual functional nanocarrier demonstrated low cytotoxicity and high performance in drug/siRNA delivery. Upon the codelivery of siRNA, targeting the Bcl-2 gene, and DOX, using the folate-targeted nanocarrier, DOX-induced apoptosis in the skov-3 cells overexpressing folate receptor was significantly enhanced through a mechanism of downregulating the antiapoptotic protein Bcl-2, while simultaneously upregulating the proapoptotic protein Bax. This work suggested that the combination of Bcl-2 siRNA and DOX therapies is feasible, based on our dual functional nanocarrier, which set up a good basis for a future in vivo test.

An MRI-visible non-viral vector for targeted Bcl-2 siRNA delivery to neuroblastoma

Polyethylene glycol-grafted polyethylenimine (PEG-g-PEI) which was functionalized with a neuroblastoma cell-specific ligand, the GD2 single chain antibody (scAbGD2), was synthesized in order to effectively deliver Bcl-2 siRNA into neuroblastoma cells. This polymer was complexed first with superparamagnetic iron oxide nanoparticle (SPION) to get a MRI-visible targeted non-viral vector (scAbGD2-PEG-g-PEI-SPION) and then with Bcl-2 siRNA to form nanoparticles showing low cytotoxicity. The targeting capacity of scAbGD2-PEG-g-PEI-SPION was successfully verified in vivo and in vitro by magnetic resonance imaging. The single chain antibody encoded targeted polyplex was more effective in transferring Bcl-2 siRNA than the nontargeting one in SK-N-SH cells, a human neuroblastoma cell line, resulting in a 46.34% inhibition in the expression of Bcl-2 mRNA. Consequently, a high level of cell apoptosis up to 50.76% and a significant suppression of tumor growth were achieved, which indicates that scAbGD2-PEG-g-PEI-SPION is a promising magnetic resonance imaging-visible non-viral vector for targeted neuroblastoma siRNA therapy and diagnosis.

Percutaneous Transsplenic Portal Vein Catheterization: Technical Procedures, Safety, and Clinical Applications

PURPOSE To evaluate the safety and feasibility of percutaneous transsplenic portal vein catheterization (PTSPC) by retrospective review of its use in patients with portal vein (PV) occlusion. MATERIALS AND METHODS From July 2004 to December 2010, 46 patients with a history of uncontrolled gastroesophageal variceal bleeding secondary to portal hypertension underwent endovascular PV interventions via a percutaneous transsplenic approach. All patients had occlusion of the main PV or central intrahepatic PV branches, which prevented the performance of a transhepatic approach. A vein within the splenic parenchyma was punctured under fluoroscopic guidance by referencing preoperative computed tomography images. PTSPC-related complications and clinical applications were analyzed. RESULTS PTSPC was successfully performed in 44 of 46 patients (96%); two failures were caused by inaccessible small intrasplenic veins. PTSPC-related major bleeding complications occurred in three patients (6.5%), including large intraperitoneal hemorrhage in one patient and large splenic subcapsular hemorrhage in two patients. Two of the three patients developed hypotension, and one developed severe anemia. All three of the patients required blood transfusions. PTSPC-related minor bleeding complications occurred in six patients (13%) as a result of a small splenic subcapsular hemorrhage. In addition, three patients exhibited mild left pleural effusion, which subsided spontaneously 1 week later. All 44 patients successfully treated via PTSPC received gastroesophageal variceal embolization. Eight patients received PV stents, five for treatment of PV occlusion and three during transjugular intrahepatic portosystemic shunt placement. CONCLUSIONS PTSPC is a safe and effective access for endovascular PV interventions in patients without a transhepatic window.

Chemoembolization with Lobaplatin Mixed with Iodized Oil for Unresectable Recurrent Hepatocellular Carcinoma after Orthotopic Liver Transplantation

PURPOSE To determine whether chemoembolization can benefit patients with unresectable recurrent hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT). MATERIALS AND METHODS Twenty-eight of 71 patients (39%) with unresectable recurrent HCC following OLT and without contradictions to chemoembolization were included: 14 patients received chemoembolization after OLT (chemoembolization group) and 14 matched control subjects who did not receive chemoembolization (non-chemoembolization group). Tumor response was determined with follow-up computed tomography after each chemoembolization procedure and classified into four grades according to Response Evaluation Criteria in Solid Tumors. Overall survival was evaluated from OLT and from the diagnosis of recurrent HCC. RESULTS Within a median follow-up of 14.5-months, 12 of the 14 patients in the chemoembolization group (86%) and 13 of the 14 in the non-chemoembolization group (93%) developed new recurrences. Eight of the 14 patients in the chemoembolization group (57%) showed partial tumor response (>30% reduction in the size of target lesions). Moreover, patients who underwent chemoembolization had a significantly longer overall survival after OLT (P = .0133) and after the diagnosis of HCC recurrence (P = .0338) compared to those who did not. No severe complications developed in patients receiving chemoembolization during follow-up. CONCLUSIONS Lobaplatin-based chemoembolization may elicit effective tumor response for recurrent HCCs and improve the overall survival of patients with unresectable HCC recurrence following OLT.

An RGD-Modified MRI-Visible Polymeric Vector for Targeted siRNA Delivery to Hepatocellular Carcinoma in Nude Mice

RNA interference (RNAi) has significant therapeutic promise for the genetic treatment of hepatocellular carcinoma (HCC). Targeted vectors are able to deliver small interfering RNA (siRNA) into HCC cells with high transfection efficiency and stability. The tripeptide arginine glycine aspartic acid (RGD)-modified non-viral vector, polyethylene glycol-grafted polyethylenimine functionalized with superparamagnetic iron oxide nanoparticles (RGD-PEG-g-PEI-SPION), was constructed as a magnetic resonance imaging (MRI)-visible nanocarrier for the delivery of Survivin siRNA targeting the human HCC cell line Bel-7402. The biophysical characterization of the RGD-PEG-g-PEI-SPION was performed. The RGD-modified complexes exhibited a higher transfection efficiency in transferring Survivin siRNA into Bel-7402 cells compared with a non-targeted delivery system, which resulted in more significant gene suppression at both the Survivin mRNA and protein expression levels. Then, the level of caspase-3 activation was significantly elevated, and a remarkable level of tumor cell apoptosis was induced. As a result, the tumor growth in the nude mice Bel-7402 hepatoma model was significantly inhibited. The targeting ability of the RGD-PEG-g-PEI-SPION was successfully imaged by MRI scans performed in vitro and in vivo. Our results strongly indicated that the RGD-PEG-g-PEI-SPION can potentially be used as a targeted non-viral vector for altering gene expression in the treatment of hepatocellular carcinoma and for detecting the tumor in vivo as an effective MRI probe.

MR tracking of magnetically labeled mesenchymal stem cells in rats with liver fibrosis

PURPOSE In vivo magnetic resonance (MR) tracking of magnetically labeled bone marrow mesenchymal stem cells (BMSCs) administered via the mesenteric vein to rats with liver fibrosis. MATERIALS AND METHODS Rat BMSCs were labeled with superparamagnetic iron oxide (SPIO) and the characteristics of the BMSCs after labeling were investigated. Eighteen rats with CCL4-induced liver fibrosis were randomized to three groups to receive SPIO-labeled BMSCs (BMSC-labeled group), cell-free SPIO (SPIO group), or unlabeled BMSCs (control group). MR imaging of the liver was performed at different time points, and signal-to-noise ratio (SNR) of the liver was measured. In vivo distribution of delivered BMSCs was assessed by histological analysis. RESULTS Labeling of BMSCs with SPIO did not significantly alter cell viability and proliferation activity. In BMSC-labeled group, the liver SNR immediately decreased from 8.56+/-0.26 to 3.53+/-0.41 at 1 h post injection and remained at a significantly lower level till 12 days (P<.05 versus the level before). By contrast, the liver SNR of the SPIO group almost recovered to the preinjection level (P=.125) at 3 days after a transient decrease. In control group, the liver SNR demonstrated no significant difference at the tested time points. Additionally, Prussian blue-positive cells were mainly distributed in the liver parenchyma, especially in injured areas. CONCLUSION The magnetically labeled BMSCs infused through the mesenteric vein can be detected in the fibrotic liver of rats using in vivo MR imaging up to 12 days after injection.

Value of endovascular stent placement for symptomatic spontaneous isolated superior mesenteric artery dissection

OBJECTIVE To evaluate the feasibility and efficacy of endovascular stent placement for the treatment of symptomatic spontaneous isolated superior mesenteric artery dissection. MATERIALS AND METHODS This retrospective study was undertaken in 12 consecutive patients who suffered from symptomatic spontaneous isolated superior mesenteric artery dissection. Seven patients with severe clinical symptoms underwent endovascular stent placement as a primary treatment and the other 5 patients received conservative treatment. The technical results, complications and clinical outcomes were analyzed. Follow-up was performed with computed tomographic angiography. RESULTS Primary endovascular stent placement was successfully performed in 7 patients with severe clinical symptoms. Successful conservative treatment was achieved in 3 patients. Endovascular stent placement was additionally performed in 2 patients with unsuccessful conservative treatment. A stent was misplaced in the false lumen in one of those two patients due to a severely stenotic true lumen. The fasting time and length of stay were significantly shorter in patients with successful endovascular therapy (median: 3 days and 5.5 days) than in those conducted conservatively (median: 9 days and 14 days) (p<0.05). During the follow-up period (median, 21 months; range, 10-36 months), 1 patient with endovascular stent placement had recurrent abdominal pain because of the wall adherent thrombus in the proximal segment of the superior mesenteric artery during the first follow-up month. No thrombosis or stenosis was found in the lumina of the stents. CONCLUSION Endovascular stent placement is a safe and feasible therapeutic approach for symptomatic spontaneous isolated superior mesenteric artery dissection with immediate success and satisfactory outcomes.