Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study.

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

Arterial chemotherapy for hepatocellular carcinoma in China: consensus recommendations.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy (HAIC) treatment is widely accepted as one of the alternative therapeutic modalities for HCC owing to its local control effect and low systemic toxicity. Nevertheless, although accumulating high-quality evidence has displayed the superior survival advantages of HAIC of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) compared with standard first-line treatment in different scenarios, the lack of standardization for HAIC procedure and remained controversy limited the proper and safe performance of HAIC treatment in HCC. Therefore, an expert consensus conference was held on March 2023 in Guangzhou, China to review current practices regarding HAIC treatment in patients with HCC and develop widely accepted statements and recommendations. In this article, the latest evidence of HAIC was systematically summarized and the final 22 expert recommendations were proposed, which incorporate the assessment of candidates for HAIC treatment, procedural technique details, therapeutic outcomes, the HAIC-related complications and corresponding treatments, and therapeutic scheme management.

Predicting disease progression in cirrhotic patients after transjugular intrahepatic portosystemic shunt implantation: A sex-stratified analysis.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) has been extensively used to treat portal hypertension-associated complications, including cirrhosis. The prediction of post-TIPS prognosis is important for cirrhotic patients, as more aggressive liver transplantation is needed when the post-TIPS prognosis is poor. AIM: To construct a nutrition-based model that could predict the disease progression of cirrhotic patients after TIPS implantation in a sex-dependent manner. METHODS: This study retrospectively recruited cirrhotic patients undergoing TIPS implantation for analysis. Muscle quality was assessed by measuring the skeletal muscle index (SMI) by computed tomography. Multivariate Cox proportional hazard models were utilized to determine the association between SMI and disease progression in cirrhotic patients after TIPS implantation. RESULTS: This study eventually included 186 cirrhotic patients receiving TIPS who were followed up for 30.5 ± 18.8 mo. For male patients, the 30-mo survival rate was significantly lower and the probability of progressive events was higher (3.257-fold) in the low-level SMI group than in the high-level SMI group. According to the multivariate Cox analysis of male patients, SMI < 32.8 was an independent risk factor for long-term adverse outcomes after TIPS implantation. A model was constructed, which involved creatinine, plasma ammonia, SMI, and acute-on-chronic liver failure and hepatic encephalopathy occurring within half a year after surgery. This model had an area under the receiver operating characteristic curve of 0.852, sensitivity of 0.926, and specificity of 0.652. According to the results of the DeLong test, this model outperformed other models (Child-Turcotte-Pugh, Model for End-Stage Liver Disease, and Freiburg index of post-TIPS survival) (P < 0.05). CONCLUSION: SMI is strongly associated with poor long-term outcomes in male patients with cirrhosis who underwent TIPS implantation.

Effectiveness of lenvatinib plus immune checkpoint inhibitors in primary advanced hepatocellular carcinoma beyond oligometastasis.

BACKGROUND: Targeted therapy combined with immune checkpoint inhibitors is considered a promising treatment for primary advanced hepatocellular carcinoma (HCC). Nevertheless, the difference between synchronous and asynchronous treatment of lenvatinib with programmed death receptor-1 (PD-1) inhibitor in advanced HCC is still unclear. The aim of this investigation is to evaluate the effectiveness of synchronous and asynchronous of lenvatinib and PD-1 inhibitor on the advanced HCC beyond oligometastasis. METHODS: In this study, 213 patients from four institutions in China were involved. Patients were split into two collections: (1) lenvatinib plus PD-1 inhibitor were used synchronously (synchronous treatment group); (2) patients in asynchronous treatment group received PD-1 inhibitor after 3 months of lenvatinib treatment prior to tumour progression. To analyse progression-free survival (PFS), overall survival (OS), efficacy and safety of patients in both groups, we employed propensity score matching (PSM). RESULTS: The 6-, 12- and 24-month OS rates were 100%, 93.4% and 58.1% in the synchronous treatment group and 100%, 71.5% and 25.3% in the asynchronous treatment group, respectively. In contrast to the asynchronous treatment group, the group treated synchronously exhibited a substantially enhanced OS (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.30-0.66; p < .001). The 6-, 12- and 18-month PFS rates were 82.6%, 42.6% and 10.8% in the synchronous treatment group and 63.3%, 14.2% and 0% in the asynchronous treatment group, respectively. A significant difference was observed in the PFS rate (HR, 0.46; 95% CI, 0.33-0.63; p < .001) between the two collections. CONCLUSIONS: Patients with advanced HCC beyond oligometastasis, simultaneous administration of lenvatinib and PD-1 inhibitor led to significant improvements in survival.

Early prediction of survival in hepatocellular carcinoma patients treated with transarterial chemoembolization plus sorafenib.

AIM: To identify clinical biomarkers that could early predict improved survival in patients with advanced-stage hepatocellular carcinoma (HCC) treated with transarterial chemoembolization combined with sorafenib (TACE-S). METHODS: We retrospectively evaluated the medical records of consecutive patients with advanced-stage HCC who underwent TACE-S from January 2012 to December 2015. At the first follow-up 4-6 wk after TACE-S (median, 38 d; range, 33-45 d), patients exhibiting the modified Response Evaluation Criteria in Solid Tumors (mRECIST)-evaluated complete response, partial response, and stable disease were categorized as early disease control. At this time point, multiple variables were analyzed to identify the related factors affecting survival. RESULTS: Ninety-five patients were included in this study, and 60 of these patients achieved early disease control, with an overall disease control rate (DCR) of 63.2%. Patients who got sorafenib at the first TACE (no previous TACE) and patients without portal vein tumor thrombus (PVTT) had a higher DCR than those who underwent previous TACE before TACE-S (72.4% vs 48.6%, P = 0.019) and those with PVTT (75.5% vs 50.0%, P = 0.010). Early disease control after TACE-S, no previous TACE, and no PVTT were the independent prognostic factors for survival in the uni- and multivariate analyses. CONCLUSION: The first follow-up 4-6 wk after TACE-S can be used as the earliest time point to assess the response to TACE-S, and patients with mRECIST-evaluated early disease control, no previous TACE, and no PVTT had better survival.

A multicentre retrospective study of transcatheter angiographic embolization in the treatment of delayed haemorrhage after percutaneous nephrolithotomy.

OBJECTIVE: The objective is to determine the timing and indications of transcatheter angiographic embolization (TAE) for delayed haemorrhage after percutaneous nephrolithotomy (PCNL). METHODS: The medical records of 144 patients who underwent arteriography and TAE for delayed post-PCNL haemorrhage at five university hospitals between January 2005 and December 2012 were reviewed retrospectively. RESULTS: The mean time to the onset of post-PCNL haemorrhage was 10.5 days (2 - 30 days). Clinical presentation included sudden onset bleeding in 51 patients (35.4 %), intermittent bleeding in 67 patients (46. 5 %), and continuous slow bleeding in 26 patients (18.1 %). Hemodynamic instability occurred in 32 patients (22.2 %). The mean haemoglobin decrease from the first post-PCNL day to the day of TAE was 49.5 g/L (31.0 - 79.0 g/L). Renal arteriography showed pseudoaneurysms in 69 (47.9 %) patients, arteriovenous fistulas in 28 (19.4 %) patients, mixed arterial and arteriovenous lesions in 17 (11.8 %) patients, arterial lacerations in 23 (16.0 %) patients, and negative angiographic finding in seven (4.9 %) patients. TAE was successful in stopping bleeding in all 137 patients with vascular lesions. There were no major complications associated with TAE. CONCLUSIONS: TAE should be the recommended treatment for delayed post-PCNL haemorrhage in patients with hemodynamic instability and/or corrected haemoglobin decrease >30 g/L following conservative management. KEY POINTS: • Delayed haemorrhage after percutaneous nephrolithotomy occurs more than 24 hours postoperatively. • Angio-embolization is a safe and effective treatment for delayed post-PCNL haemorrhage. • Angio-embolization can treat hemodynamic instability and/or corrected haemoglobin decrease >30 g/L.

Role of multi-detector computed tomography for biliary complications after liver transplantation.

AIM: To investigate the diagnostic performance of multi-detector computed tomography (MDCT) in detecting biliary complications after orthotopic liver transplantation (OLT). METHODS: Eighty-three consecutive OLT recipients, who presented with clinical or biochemical signs of biliary complications, underwent MDCT examination. Two experienced radiologists assessed MDCT images in consensus to determine biliary complications. Final confirmation was based on percutaneous transhepatic cholangiography or endoscopic retrograde cholangiography in 58 patients, surgery in four patients, liver biopsy in 10, and clinical and sonography follow-up in 11 patients. RESULTS: Biliary complications were eventually confirmed in 62 of 83 patients (74.7%), including anastomotic biliary strictures in 32, nonanastomotic biliary strictures in 21, biliary stones in nine (5 with biliary strictures), anastomotic bile leak in five, and biloma in six (all with nonanastomotic strictures, and 2 with biligenic hepatic abscess). Twenty-one patients had no detection of biliary complications. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of MDCT for detecting biliary strictures were 90.6%, 86.7%, 89.2%, 92.3% and 83.9%, respectively. For detecting biliary stones, anastomotic bile leak and biloma, the sensitivity, specificity, accuracy, positive predictive value and negative predictive value of MDCT were all 100%. CONCLUSION: MDCT is a useful screening tool for detecting biliary complications after OLT.

Renal aspergillosis after liver transplantation: clinical and imaging manifestations in two cases.

Renal aspergillosis (RAsp) is a rare complication in liver transplant (LT) recipients. Here we report RAsp in two LT recipients. In both patients, RAsp occurred more than 90 d after allogenetic orthotropic LT, and all the clinical findings were unspecific. RAsp involved unilateral kidney in Case one and bilateral kidneys in Case two. Both computed tomography (CT) and magnetic resonance imaging (MRI) revealed renal abscesses, with progressively enhanced walls and separations and unenhanced alveolate areas after contrast agent administration. On unenhanced CT images they showed inhomogeneous hypo-attenuation. On fat-suppressed T2-weighted images (T2WIs), the walls and separations of the abscesses showed slightly low signal intensity and the central parts of the lesions showed slightly high signal intensity. Both on CT and MRI, there were some hints of renal infarction or chronic ischemia. Both cases were treated by radical nephrectomy followed by adjuvant antifungal treatment. They all recovered well.

[Transarterial chemoembolization plus computed tomography-guided percutaneous radiofrequency ablation for small hepatocellular carcinoma in special locations].

OBJECTIVE: To evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) plus computed tomography (CT)-guided percutaneous radiofrequency ablation (RFA) for small hepatocellular carcinoma (HCC) in special locations. METHODS: From June 2008 to December 2011, a total of 36 patients with small HCC (39 lesions) received TACE plus CT-guided percutaneous RFA at our hospital. The follow-up period was over 6 months. They were divided into 2 groups according to the locations of HCC: special location (located at hepatic subcapsular, portal area, next to large blood vessels or other organs) and non-special location groups. All patients underwent TACE at one month pre-RFA.Follow-up imaging with enhanced computed tomography (CT) or magnetic resonance imaging (MRI) was performed one month after combined treatment to evaluate the complete ablation rate in two groups.If a complete ablation was achieved, enhanced CT or MRI was performed every 1-3 months to evaluate the local tumor progression. The occurrence rate of complications, complete ablation rate, local tumor progression and time to tumor progression (TTP) were compared between two groups. RESULTS: In the special location group, a total of 24 TACE and 26 ablations were performed in 20 patients with 22 lesions while there were 18 TACE and 17 ablations in 16 patients with 17 lesions in the non-special location group.In the special location group, 12 patients (46.2%) suffered procedure-related complications, including a major complication (n = 1, left ventricular failure) and a minor complication (n = 11) of vascular injury (n = 6), subcapsular hemorrhage (n = 3) and arterial-portal vein fistula (n = 2); whereas only 3 patients (17.6%) suffered a minor complication of subcapsular hemorrhage (n = 1) and arterial-portal vein fistula (n = 2) in the special location group. The occurrence rate of complications was similar between two groups (P = 0.101). The complete ablation rate after one month was 68.2% (15/22) in the special location group and it was significantly higher than that of the non-special location group (100%, P = 0.012).In the special location group, the 6-month, 1-, 2-, 3-year local tumor progression rates were 31.8%, 40.9%, 45.5%, 45.5% versus 0,0,0, 5.9% in the non-special location group respectively. The mean TTP of 14.4 months in the special location group was markedly shorter than that in the non-special location group (31.5 months, P = 0.001). CONCLUSION: The combined regimen of TACE and percutaneous RFA is both safe and feasible for small HCC in special location. And the rate of local tumor progression is significantly higher than that of non-special location tumor. Postoperative close imaging follow-up is needed for tumor residue or recurrence.

[Clinical observation of transcatheter arterial chemoembolization plus sorafenib in the treatment of advanced hepatocellular carcinoma with different types of portal vein tumor thrombosis].

OBJECTIVE: To explore the efficacy and safety of transcatheter arterial chemoembolization (TACE) plus sorafenib in the treatment of advanced hepatocellular carcinoma with different types of portal vein tumor thrombosis. METHODS: A total of 32 patients of advanced hepatocellular carcinoma with tumor thrombosis in portal vein were retrospectively analyzed. All of them took oral sorafenib after TACE. They were divided into 3 groups according to imaging examinations of tumor thrombosis in portal vein. Tumor thrombosis in main portal vein was group A, tumor thrombosis in right/left portal branch group B and tumor thrombosis in the second branch of portal vein group C. Tumor response rate, disease control rate (DCR), overall survival (OS) and time to tumor progression (TTP) was followed up. Liver functions were compared with the pre-treatment level. The occurrences of adverse events were recorded. RESULTS: DCR was 20.0% (Group A), 70.0% (Group B) and 91.7 % (Group C) at 2 months post-treatment. DCR in groups B and C had significant differences with group A (P < 0.05). The median OS was 3 (Group A), 9 (Group B) and 14 months (Group C) and the median TTP 0 (Group A), 3 (Group B) and 6 months (Group C) respectively. The median OS and median TTP were significantly longer in Groups B and C than those in Group A (P < 0.05). Liver function at 2 months post-treatment had no statistical difference with the baseline. The most common adverse effects included hand foot skin reaction (n = 23, 3 cases of grade 3), hypertension (n = 3), diarrhea (n = 25, 3 cases of grade 3), hair loss (n = 12), oral ulcers (n = 1) and gastrointestinal bleeding (n = 2). CONCLUSION: The combined use of TACE and sorafenib is both safe and efficacious in the treatment of advanced hepatocellular carcinoma with tumor thrombosis in portal vein. And it may prolong OS and TTP in hepatocellular carcinoma with tumor thrombosis in right/left portal vein and second branch of portal vein.

The role of transarterial embolization in the management of hematuria secondary to congenital renal arteriovenous malformations.

OBJECTIVE: To evaluate the efficacy and safety of transarterial embolization (TAE) in the management of hematuria secondary to congenital renal arteriovenous malformations (AVM). PATIENTS AND METHODS: Between May 2007 and February 2012, 6 patients with congenital AVM treated with TAE were analyzed retrospectively, followed by a brief review of TAE in the treatment of congenital AVM. Clinical records with respect to general conditions, location, embolic materials, complications and overall outcome were collected from the original hospital charts and outpatient medical records. RESULTS: Three patients with AVM were confirmed by contrast-enhanced CT scans, and the other 3 patients were detected by renal angiography. TAE was performed with steel coils in 2 patients and n-butyl-2-cyanoacrylate (NBCA) in 4 patients. After a mean follow-up of 22 months, no serious adverse effects were observed in all patients. There were no complaints of hematuria at the end of the follow-up period. CONCLUSION: For unexplained massive hematuria, congenital renal AVM needs to be considered as a differential diagnosis. Selective renal angiography and embolization should be recommended as the first choice to treat massive hematuria secondary to congenital renal AVM.

Effects of percutaneous transhepatic interventional treatment for symptomatic Budd-Chiari syndrome secondary to hepatic venous obstruction.

OBJECTIVE: Budd-Chiari syndrome (BCS) is a rare and life-threatening disorder characterized by hepatic venous outflow obstruction. The management of BCS includes anticoagulation and thrombolysis, percutaneous transhepatic stent angioplasty (PTSA), and transjugular intrahepatic portosystemic shunt (TIPS), but the effect of these approaches varies greatly. The aim of our study was to retrospectively evaluate the medium-term effects of PTSA and TIPS of BCS secondary to hepatic venous outflow obstruction and to determine the critical factors affecting the efficacy. METHODS: From June 2007 to June 2012, 18 patients (15 males and 3 females; mean age, 36 ± 9 years) with BCS (obstruction of the hepatic veins) treated by PTSA (n = 15) and TIPS (n = 3) were studied retrospectively. Clinical records were analyzed with respect to underlying disease, therapeutic interventions, complications, quality of life, and overall outcome. RESULTS: Percutaneous transhepatic interventional treatment was technically successful in all patients. In PTSA group, the primary and secondary stent patency rates were 80% and 86.7%, respectively. In the TIPS group, ascites resolved completely, and liver congestion and function were relieved greatly in all three patients. Hemodynamic features and clinical symptoms in patients with successful treatment improved significantly. Physical aspects evaluated by SF-36 were improved greatly at the end of follow-up. CONCLUSIONS: For segmental stenosis or occlusion of hepatic vein caused by thrombosis or membranous webs, PTSA should be recommended as the first choice. TIPS should be applied for diffuse stenosis or occlusion in all the hepatic veins and branches. Standard anticoagulation may promote stent patency. Quality of life after interventional treatment was improved partially, and the mental aspects need to be further investigated.

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.

[Evaluation of graft perfusion in patients with ischemic-type of biliary lesions after liver transplantation].

OBJECTIVE: To investigate the value of 320-rows CT perfusion (CTP) imaging in the study of hepatic hemodynamic characters in ischemic-type biliary lesions (ITBL) after liver transplantation. METHODS: A total of 11 ITBL patients received 320-slice CT angiography (CTA) and CTP after liver transplantation scheduled at 5-10 min away. Four patients underwent liver biopsy While 7 patients with normal liver after transplantation were selected as the control group. The parameters of hepatic artery perfusion (HAP), portal vein perfusion (PVP), total hepatic perfusion (TLP) and hepatic arterial perfusion index (HPI) were measured and compared for all patients. And the blood perfusion characters of liver with ITBL after transplantation were analyzed. RESULTS: (1) In 11 ITBL patients, 3 patients had no vascular complications on CTA, 1 with simple hepatic artery stenosis (HAS), 1 with HAS and arterioportal shunt (APS), 2 with HAS and portal vein stenosis/right hepatic vein stenosis (PVS/RHVS), 1 with simple APS, 2 with simple PVS and 1 with portal vein thrombosis and cavernous transformation of portal vein (PVT and CTPV). And 4/11 patients underwent liver biopsy, 2 in which confirmed mild acute rejection and 2 confirmed biliary obstruction associated with ascending biliary infection.(2) HAP of the ITBL and control groups were (66 ± 38) and (40 ± 8) ml×min(-1)·(100 ml)(-1), PVP (128 ± 35) and (163 ± 21) ml×min(-1)·(100 ml)(-1), TLP (194 ± 58) and (203 ± 19) ml×min(-1)·(100 ml)(-1), HPI 34% ± 14% and 21% ± 4% respectively. The differences in the value of HAP, PVP and HPI between the groups were statistically significant (P < 0.05) excluding TLP. CONCLUSION: Various liver perfusion abnormalities of ITBL may be evaluated objectively by CTP. ITBL might occurred when HAP and HPI increased with a decreased of PVP.

[Diagnosis and treatment of carotid-cavernous fistula: analysis of 28 patients].

OBJECTIVE: To evaluate the feasibility and efficacy of endovascular treatment for different types of carotid cavernous fistula (CCF) via the approach of internal carotid artery (ICA) or inferior petrosal sinus (IPS). METHODS: From April 2005 to June 2010, 28 CCF patients underwent endovascular treatment at our institution. There were 13 males and 15 females with a mean age of 39 years (range: 21 - 71). According to the Barrow's classification, they were classified into type A (n = 21), type B (n = 2) and type D (n = 5). Patients of type A underwent detachable balloon embolization of ipsilateral cavernous sinus or stent-graft placement via the ICA approach. Patients of types B and D received detachable coil plus n-BCA (n-butyl-2-cyanoacrylate) embolization of ipsilateral cavernous sinus via the IPS approach. The technical results, complications and therapeutic outcomes were reviewed. RESULTS: Detachable balloons (number: 1 - 4) were used in 16 patients of type A. Angiography at immediate postembolization showed a complete occlusion of fistula in 15 patients and a small residual fistula (< 20%) in 1 patient. Five patients of type A received stent-graft placement. One stent was placed in 4 patients and 2 stents in 1 patient. Complete fistula closures with preserved ICA were documented on immediate angiogram in 3 patients whereas a large residual flow (> 50%) persisted in 1. The fistula was completely occluded after 3 detachable balloons were deployed in affected cavernous sinus through a gap between stent and vascular wall. Both fistula and ICA were occluded in 1 patient after stenting. No cerebral infarction was observed due to the adequate collateral blood flow from contralateral ICA. Complete closures of affected cavernous sinus were achieved in 6 patients of types B and D while residual flow (< 50%) persisted in 1. The number of detachable coils for each embolization ranged from 3 to 8 (mean: 6.0). The volume of n-BCA mixture varied from 1.0 to 2.1 ml (mean: 1.3). The mean duration of n-BCA injection was 65 s (range: 45 - 90). Clinical symptoms were completely relieved in 26 patients. During the mean follow-up period of 30 months (range: 12 - 60), no recurrence of clinical symptoms was observed. No thrombosis or stenosis was found in the lumina of stents. CONCLUSION: Detachable balloon embolization is the preferential treatment for direct CCF. Detachable coil plus n-BCA embolization of cavernous sinus via the IPS approach is an efficient and safe treatment for indirect CCF.

The inhibitory effect of MSCs expressing TRAIL as a cellular delivery vehicle in combination with cisplatin on hepatocellular carcinoma.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been demonstrated to induce cell apoptosis in many types of tumors, while many hepatocellular carcinoma (HCC) cells display high resistance to TRAIL. Another outstanding limitation of TRAIL is the short half-life in vivo. Stem cell-based therapies provide a promising approach for the treatment of many types of tumors because of the ability of tropism. Therefore, as a new therapeutic strategy, the combination of chemotherapeutic agents and TRAIL gene modified MSCs (TRAIL-MSCs) would improve the therapeutic efficacy of HCC in vivo. This is the first time to show the potential of combination of chemotherapeutic agents and MSCs as a gene vector in the therapy of HCC.

Different methods of detaching adherent cells significantly affect the detection of TRAIL receptors.

AIMS AND BACKGROUND: As a powerful technique allowing analysis of large numbers of cells, fluorescence-activated cell sorting (FACS) is used more and more widely. For FACS analysis, adherent cells are usually detached by trypsinization, followed by centrifugation and resuspension. However, trypsinization can cut off some receptors from the cell surface like fine scissors, which will affect the accuracy of FACS results. Though non-enzymatic methods such as citric saline buffer have been used to determine cell surface receptors, how much of the receptors is cut off by trypsinization has been rarely studied. This work aimed to investigate whether different methods of detaching adherent cells could affect the detection of cell surface receptors. METHODS: Human hepatocellular carcinoma cell lines (HepG2, Huh7 and Hep3B) were detached enzymatically with trypsin-EDTA solution or non-enzymatically with citric saline buffer, and then the receptors of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were detected by FACS analysis. Cell viability, cell cycle and apoptosis (sub-G1 fraction detected by FACS) of the trypsin-EDTA group and citric saline buffer group were also studied. RESULTS: Different methods of detaching adherent cells could significantly affect the detection of TRAIL receptors. Compared to the conventional trypsin-EDTA group, the non-enzymatic group showed a 3.42-fold increase in the mean fluorescence intensity index of DcR HepG2 and a 1.25-fold increase in DR Huh 7 (P <0.05). However, the viability, cell cycle and apoptosis of these cells were not affected. CONCLUSIONS: Citric saline buffer might be recommended as the first choice to detach adherent cells for FACS analysis of cell surface receptors.

[The diagnosis and treatment of isolated celiac and superior mesenteric artery dissection: 2 cases report and literature review].

OBJECTIVE: To investigate the diagnosis and treatment of isolated celiac artery (CA) dissection and superior mesenteric artery (SMA) dissection. METHODS: Integrating clinical data of 119 cases with isolated dissection of the visceral arteries (IDVA) reported in literature and 2 patients with spontaneous isolated dissections of both CA and SMA treated in the Third Affiliated Hospital of Sun Yat-sen University, the diagnosis and treatment of IDVA were analyzed retrospectively. RESULTS: Among 119 cases reported in the literature, 69 cases were symptomatic. All of the cases were diagnosed by contrast-enhanced abdominal CT or MRI. After IDVA was discovered, surgical treatment and endovascular stent placement was performed in 8 and 5 patients respectively, although the remaining 106 patients were managed conservatively with good results. In our 2 cases, the diagnosis of CA and SMA dissection was established by contrast-enhanced CT and confirmed by conventional angiography. One patient was treated with anticoagulation and antihypertension, and the other patient was treated with endovascular stenting. Both of the patients didn't have discomfort during the follow-up period of 12 and 3 months respectively. CONCLUSIONS: Contrast-enhanced abdominal CT is the main tool for detection of IDVA. Most of the patients with IDVA can be managed conservatively, but close surveillance with imaging studies is necessary for early recognition of dissection progression. Patients with persistent or relapsed symptoms, and dissection progression, should undergo surgical or endovascular treatment.

[Labeling of liver cancer cell for fluorescence imaging study by far-red fluorescence protein reporter gene mKate2].

OBJECTIVE: To create far-red fluorescence protein reporter gene mKate2 lentivirus, label human liver cancer cell line HepG2 with lentivirus and explore the feasibility of in vitro fluorescence imaging of labeled tumor cells so as to provide experimental rationales for in vivo fluorescence tumor imaging. METHODS: mKate2 gene was amplified from pmKate2-N plasmid. Then the fragment was inserted into the lentivirus expression vector pLenti6.3/V5-DEST. The expression plasmids pLenti6.3-mKate2 and the packaging plasmids were cotransfected into 293T cells. The biological titer of lentivirus was determined. HepG2 cells were infected with mKate2 lentivirus at a MOI (virus multiplicity of infection) of 6 for 96 hours. The infection efficiency was assayed through fluorescence microscope and fluorescent-activated cell scanning (FACS). And 2 × 10(6) mKate2-HepG2 cells were collected for fluorescence imaging through an optical imaging system. And the optimal imaging parameters were determined. RESULTS: DNA sequencing analysis confirmed that mKate2 gene sequence was correct and there was no mutation or deletion. The biological titer of produced mKate2 lentivirus was 1.6 × 10(6) TU/ml. At 96 hours after mKate2 lentivirus infection, fluorescence microscope showed that mKate2 was expressed in a large percentage of cells. FACS assay showed that the mKate2 positive rate was 93.8% ± 0.4%. Excitation light 530 ± 15 nm and emission light 710 ± 28 nm were the optimal imaging parameters for mKate2-HepG2 cells. CONCLUSION: Lentivirus can mediate efficiently the mKate2 reporter gene labeling of human liver cancer cell line HepG2. The mKate2-labeled HepG2 cells can be detected through in vitro fluorescence imaging. Further tracing studies of in vivo tumor fluorescence imaging are technically feasible.

[Construction and validation of dual fusion reporter gene expression vector for molecular imaging study].

OBJECTIVE: To construct dual fusion reporter gene expression vector containing enhanced green fluorescence protein (EGFP) and human transferrin receptor (TfR), and validate the reconstructed plasmid, which will provide experimental foundation for in vivo dual-modality optical/Magnetic Resonance (MR) imaging. METHODS: Clone TfR into the pEGFP-C1 vector to construct pEGFP-C1-TfR plasmid.pEGFP-C1-TfR plasmid was transfected into 293T cells for 48 h, then investigate EGFP expression under a fluorescence microscope; detect TfR expression through PT-PCR; inspect the subcellular location of EGFP-TfR fusion protein through Confocal Scanning Laser Microscopy; evaluate the function of EGFP-TfR fusion protein through Tf probe uptake and competition assays. RESULTS: DNA sequencing analysis confirmed that EGFP-TfR gene sequence was correct, and there was no mutation and deletion. After transfecting the reconstructed plasmid into 293T cells, fluorescence microscope observation and RT-PCR results demonstrated that EGFP and TfR were expressed efficiently. EGFP-TfR fusion protein was located predominantly in the cellular membrane, and could specifically mediate internalization of Tf. CONCLUSION: EGFP-TfR dual fusion reporter gene expression vector has been successfully constructed, and could be expressed efficiently with functional features. Thus, the expression vector could be applied for in vivo dual-modality optical/Magnetic Resonance (MR) imaging.