MultifunctionalNanocarrierTargetingSurvivinsiRNAInhibitsProliferation ofHepatocellularCarcinoma / 中山大学学报(医学科学版)

@#【Objective】 To investigate the inhibitory effect of RGD- modified，MRI visualized nanocarrier（RGD- PEG-g-PEI-SPION）targeting for Survivin siRNA（siRNA）delivery to hepatocellular carcinoma（HCC）in nude mice； and to investigate the MRI imaging function of RGD-PEG-g-PEI-SPION in nude mouse liver cancer. 【Methods】Nude mice were subcutaneously injected with Bel- 7402 cells to establish a subcutaneous tumor- bearing model. Tumor growth inhibition test，HE staining，immunohistochemical staining and tumor cell apoptosis test were used to evaluate the therapeutic effect of RGD-PEG-g-PEI-SPION targeted Survivin siRNA on liver cancer in nude mouse ；MRI imaging was used to analyze the targeting imaging function of RGD-PEG-g-PEI-SPION on hepatocellular carcinoma【Results】The subcutaneous tumor- bearing model of nude mice was successfully established，and the tumor volume of subcutaneous graft of RGD-PEG-g-PEI-SPION /siRNA，PEG-g-PEI-SPION/siRNA，RGD-PEG-g-PEI-SPION /siNC，PEG-g-PEI-SPION/ siNC and PBS solution in nude mice after first injection in the tail vein for 25 days was 59±8，156±7，202±7，212±9 and 220±8（mm3），respectively. Tumor histological examination showed that the RGD-PEG-g-PEI-SPION/siRNA group had the widest range of tumor necrosis，the lowest Survivin protein expression，and the number of apoptotic tumor cells significantly increased. Three hours after injection of RGD-PEG-g-PEI-SPION vector and PEG-g-PEI-SPION vector into the tail vein，the standardized MRI signal intensity of subcutaneous transplanted tumor decreased to（51.6±4.3）% and（88.5±3.2）% ，respectively ，compared with that before injection. 【Conclusion】 RGD- PEG- g- PEI- SPION delivers Survivin siRNA to hepatocellular carcinoma，promotes tumor cell apoptosis，inhibits tumor growth，and achieves good anti-tumor effect；RGD-PEG-g-PEI-SPION has a well targeted MRI imaging function in nude mouse liver cancer tissues.

The clinical application of 320-slice Computed Tomography (CT) hepatic artery images in patients with liver transplantation / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the clinical significance of 320-slice CT hepatic artery images in patients with liver transplantation.</p><p><b>METHODS</b>A total of 58 patients underwent CT scanning by 320-slice scanner after liver transplantation. They were divided into 2 groups according to the concentration of contrast media as follows: Group A (27 cases, 350 mgI/ml iopromide), Group B (31 cases, 370 mgI/ml iopromide). Contrast medium was infused at 6 ml/s, with a total dose of 50 ml. Images were generated by dynamic volume scanning and were processed by 4D digital subtraction angiography (DSA) imaging software. The time-density curve (TDC) of the hepatic artery was delineated. The time to peak, peak contrast enhancement were recorded. The physiological parameters such as body weight and height were analyzed.</p><p><b>RESULTS</b>(1) There were no differences in clinical parameters such as age, sex, height, weight, or BMI between groups. The time to peak of hepatic artery of group A and B was (19.71+/-3.11) s and (20.06+/-3.67) s, and had no significant difference. The maximum peak enhancement of hepatic artery in groups B was higher than that group A (P < 0.05). (2) 4D DSA revealed hepatic artery pseudo-aneurysm (n = 2), and hepatic artery mild stenosis (n = 13), moderate stenosis (n = 5), severe stenosis (n = 9) and occlusion (n = 1), segmental moderate and severe stenosis (n = 4), and compensatory circulation with hepatic artery severe stenosis and occlusion (n = 6). hepatoportal arteriovenous fistulas (HPAVF, n = 12), donor-recipient hepatic artery mismatch (n = 3). Hepatic arterial branch are decreased and opened in 15 cases and 8 cases.</p><p><b>CONCLUSION</b>320-slice CT hepatic artery images is safe, noninvasive, and accurate technique to evaluate hepatic arterial complications after liver transplantation.</p>

Diagnostic value of multislice spiral CT and MRI in detection of tumor recurrence after liver transplantation for hepatocellular carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the manifestation and diagnostic value of multislice spiral CT (MSCT) and MRI imaging in detection of tumor recurrence after liver transplantation for hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>The clinical data of 161 consecutive HCC patients who underwent orthotopic liver transplantation were retrospectively reviewed. Twenty-nine HCC patients were classified by pTNM according to the "Pittsburgh criteria". MSCT and MRI findings of tumor recurrence after liver transplantation were evaluated retrospectively in 29 stage II-IVb HCC patients. The recurrence site and relapse interval between liver transplantation and recurrence were analyzed.</p><p><b>RESULTS</b>Lung tumor recurrence were found in 21 cases, presented as cotton-like lesions in a diameter of 2 - 3 cm, with a clear margin and homogeneous density. Pleural tumor recurrence was detected in 4 cases. Liver tumor recurrence were found in 9 cases, which can be divided into four subtypes: multinodular in 4 cases, diffuse lesion in 2 cases, huge mass in 2 cases, and uninodular in 1 case. Two cases showed tumor thrombus in the inferior vena cava and portal vein. Lymph node tumor recurrence was found in 9 cases, presented as multiple nodules at hepatic hilum, lesser peritoneal sac, posterior mediastinum, retroperitoneum, or around pancreatic head, and accompanied with merging and necrosis in one case. Bone tumor recurrence were found as osteolytic destruction in 4 cases, and accompanied with adjacent soft-tissue mass in 2 cases. The recurrence sites of the 29 cases were as following: lung (21 cases, 72.4%), liver (9 cases, 31.0%), lymph nodes (9 cases, 31.0%), bone (4 cases, 13.8%) and other sites (3 cases, 10.3%). Lung tumor recurrence was found in all the 10 stage IVb patients with tumor recurrence after liver transplantation, significantly more frequent than that in stage IVa patients (P = 0.023). After liver transplantation, all 25 patients with stage III approximately IVb HCC developed recurrence within one year, but in the 4 cases with stage II HCC at one year later (P = 0.009).</p><p><b>CONCLUSION</b>The results of our study show that in hepatocellular carcinoma patients after liver transplantation, the lung and pleura are the most frequent site of recurrence, followed by liver, lymph node and bone as the second and third sites. The Stage IVb hepatocellular carcinoma should be regarded as a contradiction for liver transplantation due to rapid recurrence. Tumor recurrence occurs later in stage II HCC than in stage III approximately IVb patients. MSCT and MRI are of significant importance in diagnosis and formulating operation plan in HCC patients with recurrence after liver transplantation.</p>

Hepatic artery complications after orthotopic liver transplantation: interventional treatment or retransplantation? / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The main therapeutic treatments for hepatic artery complications after orthotopic liver transplantation (OLT) include thrombolysis, percutaneous transluminal angioplasty, stent placement, and liver retransplantation. The prognosis of hepatic artery complications after OLT is not only related to the type, extent, and timing but also closely associated with the selection and timing of the therapeutic methods. However, there is no consensus of opinion regarding the treatment of these complications. The aim of this study was to determine optimal treatment for hepatic artery complications after OLT.</p><p><b>METHODS</b>The clinical data of 25 patients diagnosed with hepatic artery thrombosis (HAT) and hepatic artery stenosis (HAS) between October 2003 and March 2007 were retrospectively reviewed. Treatments included liver retransplantation and interventions which contain thrombolysis, percutaneous transluminal angioplasty and stent placement.</p><p><b>RESULTS</b>Among five patients with HAT, 3 were treated with thrombolysis. One recovered, one died after thrombolysis and another one died of multi-organ failure after retransplantation because of recurrent HAT. The remaining 2 patients underwent successful retransplantation and have survived after that. Among 12 patients presented with HAS within 1 month postoperatively, 2 patients underwent retransplantation due to irreversible liver failure and another 10 patients were treated with interventions. The liver function failed to improve in 3 patients and retransplantations were performed in 4 patients after stent placement because of ischemic cholangitis. Among 6 patients undergoing liver retransplantations, two died of intracranial hemorrhage and infection respectively. Eight patients presented with HAS after 1 month postoperatively, 5 patients were treated with interventional management and recovered after stent placement. Among another 3 patients presented with HAS, 2 patients' liver function was stable and one patient received late liver retransplantation due to ischemic bile duct lesion.</p><p><b>CONCLUSIONS</b>Individualized therapeutic regimens should be adopted in treating hepatic artery complications after OLT, according to postoperative periods, types and whether ischemic bile duct lesion exists or not. Liver retransplantation is the best treatment for patients with hepatic artery thrombosis. Interventional treatments of late HAS without irreversible liver failure or bile duct ischemia are appropriate, whereas retransplantation is recommended for early HAS.</p>

Transportal variceal sclerotherapy with n-butyl-2-cyanoacrylate for gastric fundal varices / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the technique, safety and clinical efficacy of transportal variceal sclerotherapy with n-butyl-2-cyanoacrylate (NBCA) for gastric fundal varices.</p><p><b>METHODS</b>Twenty-one patients with gastric fundal varices confirmed by endoscopy were enrolled in this study. The causes of the gastric varices were cirrhosis caused by hepatitis virus B or C (n = 16) and hepatocellular carcinoma with portal venous obstruction (n = 5). Percutaneous transhepatic or transplenic portography were performed on all 21 patients. The gastric varices were treated with NBCA-lipiodol mixture injected via a microcatheter introduced into the varices. For 8 patients who had large gastrorenal shunts (GRS), a balloon-occluded catheter was introduced into the GRS via the right femoral and left renal veins before injecting the NBCA-lipiodol. During the NBCA-lipiodol injection, the balloon was inflated to block the flow of GRS. Follow-up evaluations included findings of the laboratory liver function tests, upper intestinal endoscopies, and the occurrences of rebleeding.</p><p><b>RESULTS</b>In 20 patients (95.2%), the gastric varices were successfully obliterated with 2-8 ml of NBCA-lipiodol. In one patient with a large GRS, sclerotherapy was not successfully performed because a balloon-occluded catheter was not available during the procedure. In five patients, small amounts of NBCA-lipiodol entered into the distal pulmonary artery branches. Two of them suffered from transient irritable coughs; no patient developed severe pulmonary embolism. Embolization of portal venous branches occurred in two patients, which were not treated specifically. In comparison with the findings before the treatments, the serum alanine aminotransferase levels decreased at both 3 and 6 months after treatments (P less than 0.05); serum albumin levels increased at 6 months (P less than 0.05); the prothrombin times decreased at 6 months (P less than 0.05); but no significant changes were seen in the serum bilirubin levels. Fifteen patients were followed-up endoscopically for 3 months after the treatment. Gastric varices were completely resolved in 10 patients (66.7%) and were markedly smaller in 4 patients (26.6%). Worsening of the esophageal varices occurred in 3 patients (20%). All the patients were followed-up from 1 to 30 months [(16.7+/-8.8) months]. Rebleeding was observed in 4 patients, and the cumulative rebleeding rate at 1 year was 9.52%.</p><p><b>CONCLUSION</b>Transportal variceal sclerotherapy with NBCA is a safe and effective method for treating gastric varices. Microcatheter technique and occlusion of the large gastrorenal shunt with a balloon-occluded catheter are necessary to ensure obliteration of gastric varices and prevent pulmonary embolism.</p>

Radiofrequency ablation with or without transcather arterial chemoembolization for management of hepatocellular carcinoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the efficacy and complications of radiofrequency ablation (RFA) with or without transcatheter arterial chemoembolization (TACE) for management of hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>A retrospective analysis was conducted for 62 small HCC cases undergoing RFA with or without TACE, and in each case, the tumors were not more than 3 with a diameter below 5 cm. Nineteen cases were managed with RFA alone (RFA group) while the other 27 underwent RFA combined with TACE (TACE+RFA group). Percutaneous RFA (RITA 1500) procedure was performed under CT guidance 1-3 weeks after TACE in TACE+RFA group.</p><p><b>RESULTS</b>The complete tumor necrosis rate was 77.8% (21/27) in TACE+RFA group, significantly higher than that in RFA group [57.9% (11/19), P<0.01], and the former group had a significantly lower local recurrence rate than the latter [22.2% (6/27) vs 42.1% (8/19), P<0.01]. Postoperative fever, local pain and temporary hepatic function abnormality were the common complications that were relieved after proper interventions, and mortality did not occur in these cases.</p><p><b>CONCLUSION</b>The combination of TACE and RFA significantly increases the complete tumor necrosis rate and decreases the recurrence rate of small HCC. CT-guided percutaneous RFA can be a safe and effective therapy for small HCC.</p>

Stent placement in treating hepatic artery stenosis after liver transplantation / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To evaluate the feasibility and effectiveness of stent placement in treating hepatic artery stenosis after orthotopic liver transplantation (OLT).</p><p><b>METHODS</b>From November 2003 to September 2005, 14 patients who had hepatic artery stenosis after OLT underwent stent placement in their narrowed hepatic arteries. This included early interventional treatment in 10 patients and delayed interventional treatment in 4 patients. The technical results, clinical outcomes, and the hepatic artery patencies were reviewed.</p><p><b>RESULTS</b>Technical and immediate success was 100%. After a mean follow-up of 146 days (range, 9-345 days), all patients' hepatic arteries were patent, except that hepatic arterious restenosis occurred in 2 patients at 26 and 45 days after the stent placement. Of the 10 patients who received early treatment, 8 survived with normal results of liver function test and 2 patients died of septic multiple-organ failure at 9 and 30 days after the stent procedure. One patient received a retransplantation because of refractory biliary infection. Of the 4 patients who received a delayed interventional treatment, 1 patient survived for 345 days but with abnormal liver functional test results, the other 3 patients died of septic multiple-organ failure resulting from liver abscesses biliary infection.</p><p><b>CONCLUSION</b>Hepatic artery stenosis after OLT can successfully be treated with stent placement and an early interventional treatment is the key for a good clinical outcome.</p>

Diagnostic capability of multidetector CT for arterioportal shunt in hepatocellular carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the capability of multidetector CT (MDCT) for the diagnosis of arterioportal shunt (APS) associated with hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>Two hundred and eighty-two patients with HCC were examined by both enhanced thin slice MDCT scanning in early hepatic arterial phase, late hepatic arterial phase, portal venous phase and digital subtraction angiography (DSA). The criteria for diagnosis of APS: (1) Earlier enhancement or stronger opacification of main portal trunk and/or the first order branches compared with that of superior mesenteric vein or splenic vein; (2) Earlier enhancement or stronger opacification of the second order and smaller portal venous branches compared with that of main portal trunk. The presence and degree of APS demonstrated with MDCT and DSA were analysed by double blind method.</p><p><b>RESULTS</b>In 282 HCC patients, 56 were complicated with APS. MDCT demonstrated central APS in 48 patients with 41 severe and 7 moderate shunt, one revealing no APS by DSA due to the giant HCC focus. Among 7 patients with light peripheral APS, two lesions were not revealed by DSA due to faint shunt and the last lesion in the patient with mixed APS was revealed both by APS and DSA.</p><p><b>CONCLUSION</b>Multidetector CT was a simple, effective and noninvasive new technique for the diagnosis of arterioportal shunt associated with hepatocellular carcinoma.</p>

Superselective uterine arterial embolization with pingyangmycin-lipiodol emulsion for management of symptomatic uterine leiomyoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Uterine arterial embolization (UAE) is a safe and effective therapy for symptomatic uterine leiomyoma. This study was to assess the effectiveness and the feasibility of pingyangmycin-lipiodol emulsion (PLE) for the management of symptomatic uterine leiomyoma.</p><p><b>METHODS</b>One hundred consecutive patients (aged 21 - 53 years, with 38 in average) with symptomatic uterine leiomyoma underwent superselective UAE with PLE. Clinical symptoms of the patients (including menorrhagia, bulk-related symptoms, and postprocedure-related abdominal pain) and the changes in uterine volume and tumor size after the embolization were analyzed. The patients were followed up for 8 - 21 months (mean, 15 months).</p><p><b>RESULTS</b>Ninety-nine patients (99%, 99/100) were interviewed in their first menses circle after embolization, showing improvements in their abnormal bleeding and bulk-related symptoms to some extent. Imagiological results during follow-up showed a mean of 48% reduction in uterine volume at 6 months and a mean of 75% reduction in tumor size at 9 months. Eighty-three percent of the patients reported complete resolution of postprocedure pain within 7 days.</p><p><b>CONCLUSIONS</b>PLE is effective in the management of uterine leiomyoma, having superiority in alleviating postprocedure-related pain.</p>

Clinical application of endovascniar stent-graft in the treatment of portal stenosis of cancerous thrombus / 中华放射学杂志

Objective To explore the approach and early effects of endovascular stent-graft deployment in the treatment of portal stenosis of cancerous thrombus.Methods Six cases with portal vein stenosis of cancerous thrombus,which caused by primary hepatic carcinoma(5 cases)and eholangiocarcinoma(1 case)and the severity of stenosis showed on contrast enhanced CT were more than 75% or occluded,were performed percutaneous transhepatie or transsplenic portography.FLUENCY~(TM) endovascular stent-graft(10 mm diameter)was placed at the position of stenosis after gastroesophageal varices embolization.Portal pressure was measured pre-and post-deployment.Results Stents were successfully placed in all patients.The average portal pressure decreased from 50.7 cm H_2O(1 cm H_2O = 0.098 kPa)to 41.3 cm H_2O after endovascular stent-graft deployment.The restenosis were found in 2 cases after one month.Haematemesis and refractory aseites appeared in one case respectively,the other 4 cases showed no significant symptoms above caused by portal hypertension.Conclusion It is safe and feasible for endovaseular stent-graft deployment in the treatment of portal stenosis of cancerous thrombus.Selecting the suitable indications,the symptoms of portal hypertension can be controlled effectively.

Interventional therapy for biliary stricture after orthotopic liver transplantation / 中国普通外科杂志

Objective To evaluate interventional therapy for biliary stricture (BS) after orthotopic liver transplantation (OLT). Methods The efficacy of interventional therapy for BS after OLT from Oct 2003 to Jan 2006 was analyzed retrospectively. Fifty-three patients received 107 times of interventional therapy through endoscopic retrograde cholangiography ( ERC) which included 68 nasobiliary catheter placements,26 biliary balloon dilatations and stent placements and 13 ERC. Nine patients received 11 times of interventional therapy through percutaneous transhepatic cholangiography ( PTC) including 2 PTC, 7 percutaneous drainages,3 biliary balloon dilatations and 1 biliary stent replacement. One patient received bile drainage through T tube. Results The success rate of ERC was 88. 8% (95/107) , that of nasobiliary catheter placement 94% (64/68) , biliary stent placement 88. 5% (23/26). The success rate of PTC was 81. 8% (9/11) , that of percutaneous drainage was 100% (7/7) , biliary stent replacement 100% (1/1). The curative rate of interventional therapy for 53 patients with BS was 28. 3% (15/53) ,the improvement rate was 41. 5% (22/53). The curative rate of interventional therapy for anastomotic, extrahepatic, intrahepatic hilar and diffuse BS was respectively 66. 7% (4/6)、66. 7% (10/15)、50% (1/2)、0 (0/7) and 0 (0/22). Conclusions The efficacy of interventional therapy for BS after OLT was not satisfactory. The result relates to the type of BS, for anastomotic, extrahepatic and solitary intrahepatic BS this therapy was effective, while that for hilar and diffuse BS the prognosis was poor.