Transcatheter arterial chemoembolization (TACE) has become the standard treatment for unresectable hepatocellular carcinoma (HCC). But this method has some shortages. p53 gene, which was found to be mutant in many hum...Transcatheter arterial chemoembolization (TACE) has become the standard treatment for unresectable hepatocellular carcinoma (HCC). But this method has some shortages. p53 gene, which was found to be mutant in many human tumors, has been proved with broadspectrum anti-tumor effects. We reported a 23-year-old patient with recurrent HCC after irregular hepatectomy. The p53 gene was applied to this patient. We injected percutaneously and infused transcatheterally p53 gene (Gendicine, Shenzhen Sibiono Bentech, China) into his recurrent nodules in liver respectively and 4 d later, the patient received TACE therapy. In the 2 mo follow-up, the patient was in good clinical condition with normal liver function and no recurrence was identified. The case report proposed that recurrent HCC could be successfully treated with p53 gene therapy combining TACE.展开更多
AIM: To investigate the relationship between the chemotherapeutic drug efficacy and the expression of P-glycoprotein (PGP) and p53 protein in advanced hepatocellular carcinoma (HCC). METHODS: The study was condu...AIM: To investigate the relationship between the chemotherapeutic drug efficacy and the expression of P-glycoprotein (PGP) and p53 protein in advanced hepatocellular carcinoma (HCC). METHODS: The study was conducted on 41 patients with advanced HCC who were treated by repeated arterial infusion chemotherapy. Biopsy specimens from the tumor were collected before the start of treatment in all the patients, and the specimens were stored frozen until immunohistochemical staining, which was performed after the start of treatment, to detect PGP and p53 protein expressions. Twenty of the fortyone patients were treated with an anthracycline drug (epirubicin hydrochloride; anthracycline group), and the remaining 21 were treated with a non-anthracycline drug (mitoxantrone hydrochloride in 11 patients and carboplatin in 10 patients; non-anthracycline group). The relationship between the chemotherapeutic efficacy and the results of immunostaining were compared between the two groups. RESULTS: Before the start of the treatment, PGPpositive rate was 90.2% (strongly-positive, 36.6%) and p53 protein-positive rate was 34.1% (strongly-positive, 19.5%). In the anthracycline group, the response rate was 40.0%. The number of patients showing poor response to the treatment was significantly larger in the patients with strongly positive PGP expression (P= 0.005), and their prognoses were poor (P= 0.001). in the nonanthracycline group, the response rate was 42.9%,and there was no significant relationship between the chemotherapeutic drug efficacy and the PGP or p53 protein expression. When only the data from the 11 patients treated with anthraquinone drug, mitoxantrone, were analyzed, however, the number of patients who showed poor response to treatment was significantly higher among the p53-positive patients (P= 0.012), irrespective of the survival outcome. CONCLUSION: The chemotherapeutic efficacy with an anthracycline drug for advanced HCC can be predicted by immunohistochemical analysis of PGP expression. Similarly, immunostaining to evaluate p53 protein may be useful to predict the response in patients treated with an anthraquinone drug.展开更多
AIM: To study the effect of adenovirus (Ad)-p53 gene therapy on hepatocellular carcinoma (HCC) in a rabbit model.METHODS: VX2 tumor was grown in the liver of 24rabbits. Animals were divided into four groups: gr...AIM: To study the effect of adenovirus (Ad)-p53 gene therapy on hepatocellular carcinoma (HCC) in a rabbit model.METHODS: VX2 tumor was grown in the liver of 24rabbits. Animals were divided into four groups: group A receiving trans-arterial gene therapy (Ad-p53) only,group B receiving combined Ad-p53 therapy and transarterial embolization (lipiodol), group C receiving transarterial chemoembolization (lipiodol + mitomycin C),control group (D) receiving sodium chloride. Tumor volume (V1) was measured by using MRI (d 13).Interventional procedure was applied (d 14).Tumor volume (V2) was assessed by MRT (d 21) and the mean ratio (V2/V1) was calculated. After the second MRI,specimens of the liver were abstained and examined immunohistochemically using mutant-type p53 antibody.The positive expression was scored.RESULTS: Compared with control group ((^-x) = 3.14± 0.64), therapeutic groups all showed a significant decrease in the tumor growth ratio (P 〈 0.05). A slight difference was found between group A ((^-x) =2.35 ±0.59) and group B ((^-x) = 1.75 ± 0.28) (P = 0.048). Nostatistically significant difference was observed between group B and group C ((^-x) = 2.00 ± 0.44). The positive expression rate of mutant-type p53 was the lowest in group B and significantly different between group A and group C (P 〈 0.05).Compared to the control subjects, groups A and C both showed a decrease in the expression of mutant-type p53, but there was no significant difference between them.CONCLUSION: Trans-arterial Ad-p53 gene therapy can reduce tumor growth of HCC in rabbit model.展开更多
Unresectable pancreatic cancers have an extremely dismal prognosis and chemoresistant nature. The treatment of pancreatic cancer is still problematic. Gemcitabine is a promising new agent that has been studied recentl...Unresectable pancreatic cancers have an extremely dismal prognosis and chemoresistant nature. The treatment of pancreatic cancer is still problematic. Gemcitabine is a promising new agent that has been studied recently for palliation of advanced pancreatic cancer. However,the response rates have been highly variable,and are often irreproducible. To improve this low response rate,various treatments are needed because no standard treatment exists. Intra-arterial chemotherapy is considered to take advantage of the first pass effect of the drug,generating higher local drug concentrations in tumor cells with lower toxicity. Regional intra-arterial chemotherapy may provide high levels of cytostatic concentrations within the tumor and,simultaneously,a low rate of systemic side effects compared with systemic administration of anti-neoplastic drugs. Intra-arterial chemotherapy has been introduced as an alternative treatment for advanced pancreatic cancer. Further clinical trials of this method should be subjected to a prospective randomized controlled study for advanced pancreatic cancer.展开更多
AIM To determine the effect of tempol in normal rats fed high salt on arterial pressure and the balance between antagonist components of the renal renin-angiotensin system.METHODS Sprague-Dawley rats were fed with 8% ...AIM To determine the effect of tempol in normal rats fed high salt on arterial pressure and the balance between antagonist components of the renal renin-angiotensin system.METHODS Sprague-Dawley rats were fed with 8% NaCl high-salt (HS) or 0.4% NaCl (normal-salt, NS) diet for 3 wk, with or without tempol (T) (1 mmol/L, administered in drinking water). Mean arterial pressure (MAP), glomerular fltration rate (GFR), and urinary sodium excretion (UVNa) were measured. We evaluated angiotensin Ⅱ (Ang Ⅱ), angiotensin 1-7 (Ang 1-7), angiotensin converting enzyme 2 (ACE2), mas receptor (MasR), angiotensin type 1 receptor (AT1R) and angiotensin type 2 receptor (AT2R) in renal tissues by immunohistochemistry.RESULTSThe intake of high sodium produced a slight but signifcant increase in MAP and differentially regulated components of the renal renin-angiotensin system (RAS). This included an increase in Ang Ⅱ and AT1R, and decrease in ACE-2 staining intensity using immunohistochemistry. Antioxidant supplementation with tempol increased natriuresis and GFR, prevented changes in blood pressure and reversed the imbalance of renal RAS components. This includes a decrease in Ang Ⅱ and AT1R, as increase in AT2, ACE2, Ang (1-7) and MasR staining intensity using immunohistochemistry. In addition, the natriuretic effects of tempol were observed in NS-T group, which showed an increased staining intensity of AT2, ACE2, Ang (1-7) and MasR.CONCLUSION These findings suggest that a high salt diet leads to changes in the homeostasis and balance between opposing components of the renal RAS in hypertension to favour an increase in Ang Ⅱ. Chronic antioxidant supplementation can modulate the balance between the natriuretic and antinatriuretic components of the renal RAS.展开更多
AIM: To evaluate the efficacy of sequential use of transarterial chemoembolization (TACE) and percutaneous cryosurgery for unresectable hepatocellular carcinoma (HCC). METHODS: Four hundred and twenty patients were en...AIM: To evaluate the efficacy of sequential use of transarterial chemoembolization (TACE) and percutaneous cryosurgery for unresectable hepatocellular carcinoma (HCC). METHODS: Four hundred and twenty patients were enrolled in this study. The patients, who were considered to have unresectable tumors due to their location or size or comorbidity, were divided into sequential TACE-cryosurgery (sequential) group (n = 290) and cryosurgery alone (cryoalone) group (n = 130). Patients in the sequential group tended to have larger tumors and a greater number of tumors than those in the cryo-alone group. Tumors larger than 10 cm in diameter were only seen in the sequential group. TACE was performed with the routine technique and percutaneous cryosurgery was conducted under the guidance of ultrasound 2-4 wk after TACE. RESULTS: During a mean follow-up period of 42 ± 17 mo (range, 24-70 mo), the local recurrence rateat the ablated area was 17% for all patients, 11% and 23% for patients in sequential group and cryoalone groups, respectively (P = 0.001). The overall 1-, 2-, 3-, 4and 5-year survival rate was 72%, 57%, 47%, 39% and 31%, respectively. The 1and 2-year survival rates (71% and 61%) in sequential group were similar to those (73% and 54%) in cryo-alone group (P = 0.69 and 0.147), while the 4and 5-year survival rates were 49% and 39% in sequential group, higher than those (29% and 23%) in cryo-alone group (P = 0.001). Eighteen patients with large HCC (> 5 cm in diameter) survived for more than 5 years after sequential TACE while no patient with large HCC (> 5 cm in diameter) survived more than 5 years after cryosurgery. The overall complication rate was 24%, and the complication rates were 21% and 26% for the sequential and cryo-alone groups, respectively (P = 0.06). The incidence of hepatic bleeding was higher in cryo-alone group than in sequential group (P = 0.02). Liver crack only occurred in two patients of the cryoalone group. CONCLUSION: Pre-cryosurgical TACE can increase the cryoablation efficacy and decrease its adverse effects, especially bleeding. Sequential TACE and cryosurgery may be the better procedure for unresectable HCC, especially for large HCC.展开更多
AIM:To investigate the efficacy of transcatheter embolization/chemoembolization (TAE/TACE) in cirrhotic patients with single hepatocellular carcinoma (HCC) not suitable for surgical resection and percutaneous ablation...AIM:To investigate the efficacy of transcatheter embolization/chemoembolization (TAE/TACE) in cirrhotic patients with single hepatocellular carcinoma (HCC) not suitable for surgical resection and percutaneous ablation therapy. METHODS:A cohort of 176 consecutive cirrhotic patients with single HCC undergoing TAE/TACE was reviewed; 162 patients had at least one image examination (helical CT scan or triphasic contrastenhanced MRI) after treatment and were included into the study. TAE was performed with Lipiodol followed by Gelfoam embolization; TACE was performed with Farmorubicin prepared in sterile drip at a dose of 50 mg/m2,infused over 30 min using a peristaltic pump,and followed by Lipiodol and Gelfoam embolization. RESULTS:Patients characteristics were:mean age,62 years; male/female 117/45; Child-Pugh score 6.2 ± 1.1; MELD 8.7 ± 2.3; mean HCC size,3.6 (range 1.0-12.0) cm. HCC size class was ≤ 2.0 cm,n = 51; 2.1-3.0 cm,n = 35; 3.1-4.0 cm,n = 29; 4.1-5.0 cm,n = 22; 5.1-6.0 cm,n = 11; and > 6.0 cm,n = 14. Patients received a total of 368 TAE/TACE (mean 2.4 ± 1.7). Complete tumor necrosis was obtained in 94 patients (58%),massive (90%-99%) necrosis in 16 patients (10%),partial (50%-89%) necrosis in 18 patients (11%) and poor (< 50%) necrosis in the remaining 34 patients (21%). The rate of complete necrosis according to the HCC size class was:69%,69%,52%,68%,50% and,13% for lesions of ≤ 2.0,2.1-3.0,3.1-4.0,4.1-5.0,5.1-6.0,and > 6.0 cm,respectively. Kaplan-Mayer survival at 24-mo was 88%,68%,59%,59%,45%,and 53% for lesions of ≤ 2.0,2.1-3.0,3.1-4.0,4.1-5.0,5.1-6.0,and > 6.0 cm,respectively. CONCLUSION:Our study showed that in cirrhotic patients with single HCC smaller than 6.0 cm,TAE/TACE produces complete local control of tumor in a significant proportion of patients. TAE/TACE is an effective therapeutic option in patients with single HCC not suitable for surgical resection or percutaneous ablation therapies. Further studies should investigate if the new available embolization agents or drug eluting beads may improve the effect on tumor necrosis.展开更多
Coronary artery calcification (CAC) is highly prevalent in patients with coronary heart disease (CHD) and is associated with major adverse cardiovascular events. There are two recognized type of CAC--intimal and m...Coronary artery calcification (CAC) is highly prevalent in patients with coronary heart disease (CHD) and is associated with major adverse cardiovascular events. There are two recognized type of CAC--intimal and medial calcification, and each of them have specific risk factors. Several theories about the mechanism of vascular calcification have been put forward, and we currently believe that vascular calcification is an active, regulated process. CAC can usually be found in patients with severe CHD, and this asymptomatic phenomenon make early diagnosis of CAC important. Coronary computed tomographic angiography is the main noninvasive tool to detect calcified lesions. Measurement of coronary artery calcification by scoring is a reasonable metric for cardiovascular risk assessment in asymptomatic adults at intermediate risk. To date, effective medical treatment of CAC has not been identified. Several strategies of percutaneous coronary interven- tion have been applied to CHD patients with CAC, but with unsatisfactory results. Prognosis of CAC is still a major problem of CHD pa- tients. Thus, more details about the mechanisms of CAC need to be elucidated in order to improve the understanding and treatment of CAC.展开更多
AIM:To evaluate the effectiveness of hepatic arterial infusion chemotherapy(HAIC) for advanced hepatocellular carcinoma(HCC) resistant to transarterial chemoembolization(TACE).METHODS:This study was conducted on 42 pa...AIM:To evaluate the effectiveness of hepatic arterial infusion chemotherapy(HAIC) for advanced hepatocellular carcinoma(HCC) resistant to transarterial chemoembolization(TACE).METHODS:This study was conducted on 42 patients who received HAIC for advanced HCC between 2001and 2010 at our hospital.5-fluorouracil(5-FU) was administered continuously for 24 h from day 1 to day 5 every 2-4 wk via an injection reservoir.Intra-arterial cisplatin or subcutaneous interferon was administered in combination with the 5-FU.The patients enrolled in this retrospective study were divided into two groups according to whether or not they fulfilled the criteria for resistance to TACE proposed by the Japan Society of Hepatology in 2010(written in Japanese);one group of patients who did not fulfill the criteria for TACE resistance(group A,n = 23),and another group who fulfilled the criteria for TACE resistance(group B,n = 19).We compared the outcomes in terms of the response and survival rates between the two groups.RESULTS:Both the response rate and tumor suppression rate following HAIC were significantly superior in group A than in group B(response rate:48% vs 16%,P = 0.028,tumor suppression rate:87% vs 53%,P = 0.014).Furthermore,both the progression-free survival rate and survival time were significantly superior in group A than in group B(3-,6-,12-,and 24-mo = 83%,70%,29% and 20% vs 63%,42%,16% and 0%,respectively,P = 0.040,and 9.8 mo vs 6.2 mo,P = 0.040).A multivariate analysis(Cox proportional hazards regression model) showed that resistance to TACE was an independent predictor of poor survival(P = 0.007).CONCLUSION:HAIC administrating 5-FU was not effective against advanced HCC resistant to TACE.Other tools for treatment,i.e.,molecular-targeting agents may be considered for these cases.展开更多
AIM:To evaluate the efficacy and safety of transcatheter arterial chemoembolization(TACE) for gastrointestinal stromal tumor(GIST) with liver metastases after the failure of tyrosine kinase inhibitors(TKIs).METHODS:Pa...AIM:To evaluate the efficacy and safety of transcatheter arterial chemoembolization(TACE) for gastrointestinal stromal tumor(GIST) with liver metastases after the failure of tyrosine kinase inhibitors(TKIs).METHODS:Patients with histologically confirmed CD117-positive GIST with liver metastases who were resistant and/or intolerant to prior imatinib and/or sunitinib and who received TACE for at least one treatment cycle or only best supportive care and TKI reintroduction were eligible for the study.The patients were divided into two groups:those in TACE group received TACE treatment containing 5-20 mL iodized oil and 40-80 mg doxorubicin hydrochloride and TKI reintroduction or best supportive care,those in control group only received TKI reintroduction or best supportive care.The primary end-point was overall survival and the secondary end-points were,progression-free survival(PFS),response rates,and safety.RESULTS:Sixty patients admitted between June 2008 and October 2011 were eligible for this study,including 22 in TACE group and 38 in control group.In the TACE group,12(54.5%) achieved liver partial response,5(22.7%) had stable disease,and 5(22.7%) had liver progressive disease.Disease control rate of liver metastases was 77.3% in the TACE group and 39.5% in the control group.The median liver PFS in TACE group was 47.1 wk(95% CI:23.9-70.3).The median PFS in TACE group was longer than in control group(30.0 wk,95% CI:20.1-39.9 vs 12.9 wk,95% CI:11.9-13.9)(P = 0.0001).The median overall survival in TACE group was also longer than in control group(68.5 wk,95% CI:57.4-79.6 vs 25.7 wk,95% CI:23.2-28.2)(P = 0.0001).TACE treatment significantly reduced the risk of death(hazard ratio:0.109).Patients without extrahepatic metastases treated with TACE had significantly better prognosis.Most of the adverse events were of grade 1 or 2 and tolerable.CONCLUSION:TACE is effective and well tolerated in GIST patients with liver metastases after TKI failure,and it may be an optional treatment for this disease.展开更多
AIM:To evaluate the efficacy and safety of combination therapy with recombinant adenovirus p53 injection (rAdp53) and transcatheter hepatic arterial chemoembolization (TACE) for advanced hepatocellular carcinoma (HCC)...AIM:To evaluate the efficacy and safety of combination therapy with recombinant adenovirus p53 injection (rAdp53) and transcatheter hepatic arterial chemoembolization (TACE) for advanced hepatocellular carcinoma (HCC).METHODS:A total of 82 patients with advanced HCC treated only with TACE served as control group.Another 68 patients with HCC treated with TACE in combination with recombinant adenovirus-p53 injection served as p53 treatment group.Patients were followed up for 12 mo.Safety and therapeutic effects were evaluated according to the improvement in clinical symptoms,leukocyte count,Karnofsky and RECIST criteria.Survival rate was calculated with Kaplan-Meier method.RESULTS:The total effective rate was 58.3% for p53 treatment group,and 26.5% for control group (P < 0.05).The incidence of gastrointestinal symptoms was lower in p53 treatment group than in control group (P < 0.05).The 3-,6-and 12-mo survival rates were significantly higher for p53 treatment group than for control group (P < 0.01).The combination treatment was well tolerated with such adverse events as fever (51.5%,P=0.006) and pain of muscles and joints (13.2%,P=0.003),which were significantly higher than the chemotherapy.Except for these minor adverse effects,no severe vector-related complications were identified.With respect to the efficacy,patients in p53 treatment group had less gastrointerestinal symptoms (P=0.062),better improvement in tumor-related pain (P=0.003),less downgrade of leukocyte counts (P=0.003) and more upgrade of Karnofsky performance score (P=0.029) than those in control group.The total effective rate (CR + PR) for p53 treatment group and control group was 58.3% and 26.5%,respectively,with distributions of different effect in two groups (P=0.042).The survival rates were 89.71%,76.13%,and 43.30% for p53 treatment group,and 68.15%,36.98%,and 24.02% for control group,respectively,3,6 and 12 mo after treatment,suggesting that the survival rates are significantly higher for p53 treatment group than for control group (P=0.0002).CONCLUSION:The rAd-p53 gene therapy in combination with TACE is a safe and effective treatment modality for advanced HCC.展开更多
AIM:To investigate the efficacy of hepatic arterial infusion chemotherapy(HAIC) using floxuridine(FUDR) in patients with advanced hepatocellular carcinoma(HCC) confined to the liver.METHODS:Thirty-four patients who ha...AIM:To investigate the efficacy of hepatic arterial infusion chemotherapy(HAIC) using floxuridine(FUDR) in patients with advanced hepatocellular carcinoma(HCC) confined to the liver.METHODS:Thirty-four patients who had advanced HCC with unresectability or unsuccessful previous therapy in the absence of extrahepatic metastasis were treated with intra-arterial FUDR chemotherapy at ourhospital between March 2005 and May 2008.Among the 34 patients,9 patients were classified as Child class C,and 18 patients had portal vein tumor thrombus(PVTT).One course of chemotherapy consisted of continuous infusion of FUDR(0.3 mg/kg during day 1-14) and dexamethasone(10 mg on day 1,4,7 and 11),and this treatment was repeated every 28 d.RESULTS:Two patients(5.9%) displayed a complete response,and 12 patients(35.3%) had a partial response.The tumor control rate was 61.8%.The median overall survival times were 15.3 mo,12.4 mo and 4.3 mo for the patients who were classified as Child class A,Child class B and Child class C,respectively(P = 0.0392).The progression-free survival was 12.9 mo,7.7 mo and 2.6 mo for the patients who were classified as Child class A,Child class B and Child class C,respectively(P = 0.0443).The cumulative survival differed significantly according to the Child-Pugh classification and the presence of PVTT.In addition to hepatic reserve capacity and PVTT,the extent of HCC was an independent factor in determining a poor prognosis.The most common adverse reactions to HAIC were mucositis,diarrhea and peptic ulcer disease,but most of these complications were improved by medical treatment and/or a delay of HAIC.CONCLUSION:The present study demonstrates that intra-arterial FUDR chemotherapy is a safe and effective treatment for advanced HCC that is recalcitrant to other therapeutic modalities,even in patients with advanced cirrhosis.展开更多
Intractable bleeding from gastric and duodenal ulcers is associated with significant morbidity and mortality. Aggressive treatment with early endoscopic hemostasis is essential for a favourable outcome. In as many as ...Intractable bleeding from gastric and duodenal ulcers is associated with significant morbidity and mortality. Aggressive treatment with early endoscopic hemostasis is essential for a favourable outcome. In as many as 12%-17% of patients,endoscopy is either not available or unsuccessful. Endovascular therapy with selective catheterization of the culprit vessel and injection of embolic material has emerged as an alternative to emergent operative intervention in high-risk patients. There has not been a systematic literature review to assess the role for embolotherapy in the treatment of acute upper gastrointestinal bleeding from gastroduo-denal ulcers after failed endoscopic hemostasis. Here,we present an overview of indications,techniques,and clinical outcomes after endovascular embolization of acute peptic-ulcer bleeding. Topics of particular relevance to technical and clinical success are also discussed. Our review shows that transcatheter arterial embolization is a safe alternative to surgery for massive gastroduodenal bleeding that is refractory to endoscopic treatment,can be performed with high technical and clinical success rates,and should be considered the salvage treatment of choice in patients at high surgical risk.展开更多
To study the clinical characteristics and treatment of pulmonary embolism (PE) after transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). Methods: The clinical records of 13 512 p...To study the clinical characteristics and treatment of pulmonary embolism (PE) after transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). Methods: The clinical records of 13 512 patients diagnosed with HCC and received TACE from January 2000 to December 2009 were reviewed. Among these patients, 5 031 were allocated into group A who had one or more disorders like diabetes, hypertension, coronary heart disease, obesity or varicose vein of lower limb, while the other 8 481 patients who did not have such disorders were in group B. Results: A total of 39 185 TACE procedures were performed for the 13 512 patients. Five (0.01%) patients in group A developed PE after TACE, of whom two recovered 4 and 5 d later with early anticoagulant therapy while the hypertension, coronary heart disease, obesity or varicose vein of lower limb are possibly more likely to develop PE other 3 died of respiratory failure within 5 h. The mortality of PE was 60% (3/5). Conelusion: HCC patients with diabetes, after TACE than those without such disorders. Patients who have such disorders should be more carefully observed after TACE and early treatment with heparin should be applied once PE develops.展开更多
A recent explosion in the amount of cardiovascular risk has swept across the globe. Primary prevention is the preferred method to lower cardiovascular risk. Lowering the prevalence of obesity is the most urgent matter...A recent explosion in the amount of cardiovascular risk has swept across the globe. Primary prevention is the preferred method to lower cardiovascular risk. Lowering the prevalence of obesity is the most urgent matter, and is pleiotropic since it affects blood pressure, lipid profiles, glucose metabolism, inflammation, and atherothrombotic disease progression. Given the current obstacles, success of primary prevention remains uncertain. At the same time, the consequences of delay and inaction will inevitably be disastrous, and the sense of urgency mounts. Pathological and epidemiological data confirm that atherosclerosis begins in early childhood, and advances seamlessly and inexorably throughout life. Risk factors in childhood are similar to those in adults, and track between stages of life. When indicated, aggressive treatment should begin at the earliest indication, and be continued for many years. For those patients at intermediate risk according to global risk scores, C-reactive protein, coronary artery calcium, and carotid intima-media thickness are available for further stratification. Using statins for primary prevention is recommended by guidelines, is prevalent, but remains under prescribed. Statin drugs are unrivaled, evidence-based, major weapons to lower cardiovascular risk. Even when low density lipoprotein cholesterol targets are attained, over half of patients continue to have disease progression and clinical events. Though clinical evidence is incomplete, altering or raising the blood high density lipoprotein cholesterol level continues to be pursued. The aim of this review is to point out the attention of key aspects of vulnerable plaques regarding their pathogenesis and treatment.展开更多
文摘Transcatheter arterial chemoembolization (TACE) has become the standard treatment for unresectable hepatocellular carcinoma (HCC). But this method has some shortages. p53 gene, which was found to be mutant in many human tumors, has been proved with broadspectrum anti-tumor effects. We reported a 23-year-old patient with recurrent HCC after irregular hepatectomy. The p53 gene was applied to this patient. We injected percutaneously and infused transcatheterally p53 gene (Gendicine, Shenzhen Sibiono Bentech, China) into his recurrent nodules in liver respectively and 4 d later, the patient received TACE therapy. In the 2 mo follow-up, the patient was in good clinical condition with normal liver function and no recurrence was identified. The case report proposed that recurrent HCC could be successfully treated with p53 gene therapy combining TACE.
文摘AIM: To investigate the relationship between the chemotherapeutic drug efficacy and the expression of P-glycoprotein (PGP) and p53 protein in advanced hepatocellular carcinoma (HCC). METHODS: The study was conducted on 41 patients with advanced HCC who were treated by repeated arterial infusion chemotherapy. Biopsy specimens from the tumor were collected before the start of treatment in all the patients, and the specimens were stored frozen until immunohistochemical staining, which was performed after the start of treatment, to detect PGP and p53 protein expressions. Twenty of the fortyone patients were treated with an anthracycline drug (epirubicin hydrochloride; anthracycline group), and the remaining 21 were treated with a non-anthracycline drug (mitoxantrone hydrochloride in 11 patients and carboplatin in 10 patients; non-anthracycline group). The relationship between the chemotherapeutic efficacy and the results of immunostaining were compared between the two groups. RESULTS: Before the start of the treatment, PGPpositive rate was 90.2% (strongly-positive, 36.6%) and p53 protein-positive rate was 34.1% (strongly-positive, 19.5%). In the anthracycline group, the response rate was 40.0%. The number of patients showing poor response to the treatment was significantly larger in the patients with strongly positive PGP expression (P= 0.005), and their prognoses were poor (P= 0.001). in the nonanthracycline group, the response rate was 42.9%,and there was no significant relationship between the chemotherapeutic drug efficacy and the PGP or p53 protein expression. When only the data from the 11 patients treated with anthraquinone drug, mitoxantrone, were analyzed, however, the number of patients who showed poor response to treatment was significantly higher among the p53-positive patients (P= 0.012), irrespective of the survival outcome. CONCLUSION: The chemotherapeutic efficacy with an anthracycline drug for advanced HCC can be predicted by immunohistochemical analysis of PGP expression. Similarly, immunostaining to evaluate p53 protein may be useful to predict the response in patients treated with an anthraquinone drug.
文摘AIM: To study the effect of adenovirus (Ad)-p53 gene therapy on hepatocellular carcinoma (HCC) in a rabbit model.METHODS: VX2 tumor was grown in the liver of 24rabbits. Animals were divided into four groups: group A receiving trans-arterial gene therapy (Ad-p53) only,group B receiving combined Ad-p53 therapy and transarterial embolization (lipiodol), group C receiving transarterial chemoembolization (lipiodol + mitomycin C),control group (D) receiving sodium chloride. Tumor volume (V1) was measured by using MRI (d 13).Interventional procedure was applied (d 14).Tumor volume (V2) was assessed by MRT (d 21) and the mean ratio (V2/V1) was calculated. After the second MRI,specimens of the liver were abstained and examined immunohistochemically using mutant-type p53 antibody.The positive expression was scored.RESULTS: Compared with control group ((^-x) = 3.14± 0.64), therapeutic groups all showed a significant decrease in the tumor growth ratio (P 〈 0.05). A slight difference was found between group A ((^-x) =2.35 ±0.59) and group B ((^-x) = 1.75 ± 0.28) (P = 0.048). Nostatistically significant difference was observed between group B and group C ((^-x) = 2.00 ± 0.44). The positive expression rate of mutant-type p53 was the lowest in group B and significantly different between group A and group C (P 〈 0.05).Compared to the control subjects, groups A and C both showed a decrease in the expression of mutant-type p53, but there was no significant difference between them.CONCLUSION: Trans-arterial Ad-p53 gene therapy can reduce tumor growth of HCC in rabbit model.
文摘Unresectable pancreatic cancers have an extremely dismal prognosis and chemoresistant nature. The treatment of pancreatic cancer is still problematic. Gemcitabine is a promising new agent that has been studied recently for palliation of advanced pancreatic cancer. However,the response rates have been highly variable,and are often irreproducible. To improve this low response rate,various treatments are needed because no standard treatment exists. Intra-arterial chemotherapy is considered to take advantage of the first pass effect of the drug,generating higher local drug concentrations in tumor cells with lower toxicity. Regional intra-arterial chemotherapy may provide high levels of cytostatic concentrations within the tumor and,simultaneously,a low rate of systemic side effects compared with systemic administration of anti-neoplastic drugs. Intra-arterial chemotherapy has been introduced as an alternative treatment for advanced pancreatic cancer. Further clinical trials of this method should be subjected to a prospective randomized controlled study for advanced pancreatic cancer.
基金Supported by A grant from the Universidad de Buenos Aires(UBACYT 20020130200105BA)
文摘AIM To determine the effect of tempol in normal rats fed high salt on arterial pressure and the balance between antagonist components of the renal renin-angiotensin system.METHODS Sprague-Dawley rats were fed with 8% NaCl high-salt (HS) or 0.4% NaCl (normal-salt, NS) diet for 3 wk, with or without tempol (T) (1 mmol/L, administered in drinking water). Mean arterial pressure (MAP), glomerular fltration rate (GFR), and urinary sodium excretion (UVNa) were measured. We evaluated angiotensin Ⅱ (Ang Ⅱ), angiotensin 1-7 (Ang 1-7), angiotensin converting enzyme 2 (ACE2), mas receptor (MasR), angiotensin type 1 receptor (AT1R) and angiotensin type 2 receptor (AT2R) in renal tissues by immunohistochemistry.RESULTSThe intake of high sodium produced a slight but signifcant increase in MAP and differentially regulated components of the renal renin-angiotensin system (RAS). This included an increase in Ang Ⅱ and AT1R, and decrease in ACE-2 staining intensity using immunohistochemistry. Antioxidant supplementation with tempol increased natriuresis and GFR, prevented changes in blood pressure and reversed the imbalance of renal RAS components. This includes a decrease in Ang Ⅱ and AT1R, as increase in AT2, ACE2, Ang (1-7) and MasR staining intensity using immunohistochemistry. In addition, the natriuretic effects of tempol were observed in NS-T group, which showed an increased staining intensity of AT2, ACE2, Ang (1-7) and MasR.CONCLUSION These findings suggest that a high salt diet leads to changes in the homeostasis and balance between opposing components of the renal RAS in hypertension to favour an increase in Ang Ⅱ. Chronic antioxidant supplementation can modulate the balance between the natriuretic and antinatriuretic components of the renal RAS.
基金Supported by Scientific Foundation of Science Technology Department and Health Department of Guangdong Province
文摘AIM: To evaluate the efficacy of sequential use of transarterial chemoembolization (TACE) and percutaneous cryosurgery for unresectable hepatocellular carcinoma (HCC). METHODS: Four hundred and twenty patients were enrolled in this study. The patients, who were considered to have unresectable tumors due to their location or size or comorbidity, were divided into sequential TACE-cryosurgery (sequential) group (n = 290) and cryosurgery alone (cryoalone) group (n = 130). Patients in the sequential group tended to have larger tumors and a greater number of tumors than those in the cryo-alone group. Tumors larger than 10 cm in diameter were only seen in the sequential group. TACE was performed with the routine technique and percutaneous cryosurgery was conducted under the guidance of ultrasound 2-4 wk after TACE. RESULTS: During a mean follow-up period of 42 ± 17 mo (range, 24-70 mo), the local recurrence rateat the ablated area was 17% for all patients, 11% and 23% for patients in sequential group and cryoalone groups, respectively (P = 0.001). The overall 1-, 2-, 3-, 4and 5-year survival rate was 72%, 57%, 47%, 39% and 31%, respectively. The 1and 2-year survival rates (71% and 61%) in sequential group were similar to those (73% and 54%) in cryo-alone group (P = 0.69 and 0.147), while the 4and 5-year survival rates were 49% and 39% in sequential group, higher than those (29% and 23%) in cryo-alone group (P = 0.001). Eighteen patients with large HCC (> 5 cm in diameter) survived for more than 5 years after sequential TACE while no patient with large HCC (> 5 cm in diameter) survived more than 5 years after cryosurgery. The overall complication rate was 24%, and the complication rates were 21% and 26% for the sequential and cryo-alone groups, respectively (P = 0.06). The incidence of hepatic bleeding was higher in cryo-alone group than in sequential group (P = 0.02). Liver crack only occurred in two patients of the cryoalone group. CONCLUSION: Pre-cryosurgical TACE can increase the cryoablation efficacy and decrease its adverse effects, especially bleeding. Sequential TACE and cryosurgery may be the better procedure for unresectable HCC, especially for large HCC.
文摘AIM:To investigate the efficacy of transcatheter embolization/chemoembolization (TAE/TACE) in cirrhotic patients with single hepatocellular carcinoma (HCC) not suitable for surgical resection and percutaneous ablation therapy. METHODS:A cohort of 176 consecutive cirrhotic patients with single HCC undergoing TAE/TACE was reviewed; 162 patients had at least one image examination (helical CT scan or triphasic contrastenhanced MRI) after treatment and were included into the study. TAE was performed with Lipiodol followed by Gelfoam embolization; TACE was performed with Farmorubicin prepared in sterile drip at a dose of 50 mg/m2,infused over 30 min using a peristaltic pump,and followed by Lipiodol and Gelfoam embolization. RESULTS:Patients characteristics were:mean age,62 years; male/female 117/45; Child-Pugh score 6.2 ± 1.1; MELD 8.7 ± 2.3; mean HCC size,3.6 (range 1.0-12.0) cm. HCC size class was ≤ 2.0 cm,n = 51; 2.1-3.0 cm,n = 35; 3.1-4.0 cm,n = 29; 4.1-5.0 cm,n = 22; 5.1-6.0 cm,n = 11; and > 6.0 cm,n = 14. Patients received a total of 368 TAE/TACE (mean 2.4 ± 1.7). Complete tumor necrosis was obtained in 94 patients (58%),massive (90%-99%) necrosis in 16 patients (10%),partial (50%-89%) necrosis in 18 patients (11%) and poor (< 50%) necrosis in the remaining 34 patients (21%). The rate of complete necrosis according to the HCC size class was:69%,69%,52%,68%,50% and,13% for lesions of ≤ 2.0,2.1-3.0,3.1-4.0,4.1-5.0,5.1-6.0,and > 6.0 cm,respectively. Kaplan-Mayer survival at 24-mo was 88%,68%,59%,59%,45%,and 53% for lesions of ≤ 2.0,2.1-3.0,3.1-4.0,4.1-5.0,5.1-6.0,and > 6.0 cm,respectively. CONCLUSION:Our study showed that in cirrhotic patients with single HCC smaller than 6.0 cm,TAE/TACE produces complete local control of tumor in a significant proportion of patients. TAE/TACE is an effective therapeutic option in patients with single HCC not suitable for surgical resection or percutaneous ablation therapies. Further studies should investigate if the new available embolization agents or drug eluting beads may improve the effect on tumor necrosis.
基金This work were supported by the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (No. ZYLX201303), the National Natural Science Foundation of China (No. 81470429, No.81270285), and The capital health research and development of special (No 2011-2006-14).
文摘Coronary artery calcification (CAC) is highly prevalent in patients with coronary heart disease (CHD) and is associated with major adverse cardiovascular events. There are two recognized type of CAC--intimal and medial calcification, and each of them have specific risk factors. Several theories about the mechanism of vascular calcification have been put forward, and we currently believe that vascular calcification is an active, regulated process. CAC can usually be found in patients with severe CHD, and this asymptomatic phenomenon make early diagnosis of CAC important. Coronary computed tomographic angiography is the main noninvasive tool to detect calcified lesions. Measurement of coronary artery calcification by scoring is a reasonable metric for cardiovascular risk assessment in asymptomatic adults at intermediate risk. To date, effective medical treatment of CAC has not been identified. Several strategies of percutaneous coronary interven- tion have been applied to CHD patients with CAC, but with unsatisfactory results. Prognosis of CAC is still a major problem of CHD pa- tients. Thus, more details about the mechanisms of CAC need to be elucidated in order to improve the understanding and treatment of CAC.
基金Supported by A Grant-in-Aid for research on the Third Term Comprehensive Control Research for Cancer from the Ministry on Health,Labour and Welfare,Japan,to Atsushi Nakajimaa grant from the National Institute of Biomedical Innovation (NBIO) to Atsushi Nakajima+1 种基金a grant from the Ministry of Education,Culture,Sports,Science and Technology,Japan(KIBAN-B), to Atsushi Nakajima,(KIBAN-C),to Satoru Saitothe grant program,"Collaborative Development of Innovative Seeds," from the Japan Science and Technology Agency(JST)
文摘AIM:To evaluate the effectiveness of hepatic arterial infusion chemotherapy(HAIC) for advanced hepatocellular carcinoma(HCC) resistant to transarterial chemoembolization(TACE).METHODS:This study was conducted on 42 patients who received HAIC for advanced HCC between 2001and 2010 at our hospital.5-fluorouracil(5-FU) was administered continuously for 24 h from day 1 to day 5 every 2-4 wk via an injection reservoir.Intra-arterial cisplatin or subcutaneous interferon was administered in combination with the 5-FU.The patients enrolled in this retrospective study were divided into two groups according to whether or not they fulfilled the criteria for resistance to TACE proposed by the Japan Society of Hepatology in 2010(written in Japanese);one group of patients who did not fulfill the criteria for TACE resistance(group A,n = 23),and another group who fulfilled the criteria for TACE resistance(group B,n = 19).We compared the outcomes in terms of the response and survival rates between the two groups.RESULTS:Both the response rate and tumor suppression rate following HAIC were significantly superior in group A than in group B(response rate:48% vs 16%,P = 0.028,tumor suppression rate:87% vs 53%,P = 0.014).Furthermore,both the progression-free survival rate and survival time were significantly superior in group A than in group B(3-,6-,12-,and 24-mo = 83%,70%,29% and 20% vs 63%,42%,16% and 0%,respectively,P = 0.040,and 9.8 mo vs 6.2 mo,P = 0.040).A multivariate analysis(Cox proportional hazards regression model) showed that resistance to TACE was an independent predictor of poor survival(P = 0.007).CONCLUSION:HAIC administrating 5-FU was not effective against advanced HCC resistant to TACE.Other tools for treatment,i.e.,molecular-targeting agents may be considered for these cases.
文摘AIM:To evaluate the efficacy and safety of transcatheter arterial chemoembolization(TACE) for gastrointestinal stromal tumor(GIST) with liver metastases after the failure of tyrosine kinase inhibitors(TKIs).METHODS:Patients with histologically confirmed CD117-positive GIST with liver metastases who were resistant and/or intolerant to prior imatinib and/or sunitinib and who received TACE for at least one treatment cycle or only best supportive care and TKI reintroduction were eligible for the study.The patients were divided into two groups:those in TACE group received TACE treatment containing 5-20 mL iodized oil and 40-80 mg doxorubicin hydrochloride and TKI reintroduction or best supportive care,those in control group only received TKI reintroduction or best supportive care.The primary end-point was overall survival and the secondary end-points were,progression-free survival(PFS),response rates,and safety.RESULTS:Sixty patients admitted between June 2008 and October 2011 were eligible for this study,including 22 in TACE group and 38 in control group.In the TACE group,12(54.5%) achieved liver partial response,5(22.7%) had stable disease,and 5(22.7%) had liver progressive disease.Disease control rate of liver metastases was 77.3% in the TACE group and 39.5% in the control group.The median liver PFS in TACE group was 47.1 wk(95% CI:23.9-70.3).The median PFS in TACE group was longer than in control group(30.0 wk,95% CI:20.1-39.9 vs 12.9 wk,95% CI:11.9-13.9)(P = 0.0001).The median overall survival in TACE group was also longer than in control group(68.5 wk,95% CI:57.4-79.6 vs 25.7 wk,95% CI:23.2-28.2)(P = 0.0001).TACE treatment significantly reduced the risk of death(hazard ratio:0.109).Patients without extrahepatic metastases treated with TACE had significantly better prognosis.Most of the adverse events were of grade 1 or 2 and tolerable.CONCLUSION:TACE is effective and well tolerated in GIST patients with liver metastases after TKI failure,and it may be an optional treatment for this disease.
文摘AIM:To evaluate the efficacy and safety of combination therapy with recombinant adenovirus p53 injection (rAdp53) and transcatheter hepatic arterial chemoembolization (TACE) for advanced hepatocellular carcinoma (HCC).METHODS:A total of 82 patients with advanced HCC treated only with TACE served as control group.Another 68 patients with HCC treated with TACE in combination with recombinant adenovirus-p53 injection served as p53 treatment group.Patients were followed up for 12 mo.Safety and therapeutic effects were evaluated according to the improvement in clinical symptoms,leukocyte count,Karnofsky and RECIST criteria.Survival rate was calculated with Kaplan-Meier method.RESULTS:The total effective rate was 58.3% for p53 treatment group,and 26.5% for control group (P < 0.05).The incidence of gastrointestinal symptoms was lower in p53 treatment group than in control group (P < 0.05).The 3-,6-and 12-mo survival rates were significantly higher for p53 treatment group than for control group (P < 0.01).The combination treatment was well tolerated with such adverse events as fever (51.5%,P=0.006) and pain of muscles and joints (13.2%,P=0.003),which were significantly higher than the chemotherapy.Except for these minor adverse effects,no severe vector-related complications were identified.With respect to the efficacy,patients in p53 treatment group had less gastrointerestinal symptoms (P=0.062),better improvement in tumor-related pain (P=0.003),less downgrade of leukocyte counts (P=0.003) and more upgrade of Karnofsky performance score (P=0.029) than those in control group.The total effective rate (CR + PR) for p53 treatment group and control group was 58.3% and 26.5%,respectively,with distributions of different effect in two groups (P=0.042).The survival rates were 89.71%,76.13%,and 43.30% for p53 treatment group,and 68.15%,36.98%,and 24.02% for control group,respectively,3,6 and 12 mo after treatment,suggesting that the survival rates are significantly higher for p53 treatment group than for control group (P=0.0002).CONCLUSION:The rAd-p53 gene therapy in combination with TACE is a safe and effective treatment modality for advanced HCC.
文摘AIM:To investigate the efficacy of hepatic arterial infusion chemotherapy(HAIC) using floxuridine(FUDR) in patients with advanced hepatocellular carcinoma(HCC) confined to the liver.METHODS:Thirty-four patients who had advanced HCC with unresectability or unsuccessful previous therapy in the absence of extrahepatic metastasis were treated with intra-arterial FUDR chemotherapy at ourhospital between March 2005 and May 2008.Among the 34 patients,9 patients were classified as Child class C,and 18 patients had portal vein tumor thrombus(PVTT).One course of chemotherapy consisted of continuous infusion of FUDR(0.3 mg/kg during day 1-14) and dexamethasone(10 mg on day 1,4,7 and 11),and this treatment was repeated every 28 d.RESULTS:Two patients(5.9%) displayed a complete response,and 12 patients(35.3%) had a partial response.The tumor control rate was 61.8%.The median overall survival times were 15.3 mo,12.4 mo and 4.3 mo for the patients who were classified as Child class A,Child class B and Child class C,respectively(P = 0.0392).The progression-free survival was 12.9 mo,7.7 mo and 2.6 mo for the patients who were classified as Child class A,Child class B and Child class C,respectively(P = 0.0443).The cumulative survival differed significantly according to the Child-Pugh classification and the presence of PVTT.In addition to hepatic reserve capacity and PVTT,the extent of HCC was an independent factor in determining a poor prognosis.The most common adverse reactions to HAIC were mucositis,diarrhea and peptic ulcer disease,but most of these complications were improved by medical treatment and/or a delay of HAIC.CONCLUSION:The present study demonstrates that intra-arterial FUDR chemotherapy is a safe and effective treatment for advanced HCC that is recalcitrant to other therapeutic modalities,even in patients with advanced cirrhosis.
文摘Intractable bleeding from gastric and duodenal ulcers is associated with significant morbidity and mortality. Aggressive treatment with early endoscopic hemostasis is essential for a favourable outcome. In as many as 12%-17% of patients,endoscopy is either not available or unsuccessful. Endovascular therapy with selective catheterization of the culprit vessel and injection of embolic material has emerged as an alternative to emergent operative intervention in high-risk patients. There has not been a systematic literature review to assess the role for embolotherapy in the treatment of acute upper gastrointestinal bleeding from gastroduo-denal ulcers after failed endoscopic hemostasis. Here,we present an overview of indications,techniques,and clinical outcomes after endovascular embolization of acute peptic-ulcer bleeding. Topics of particular relevance to technical and clinical success are also discussed. Our review shows that transcatheter arterial embolization is a safe alternative to surgery for massive gastroduodenal bleeding that is refractory to endoscopic treatment,can be performed with high technical and clinical success rates,and should be considered the salvage treatment of choice in patients at high surgical risk.
基金Supported by the Scientific Research Found Projects of Shanghai Health Bureau(2009Y066)
文摘To study the clinical characteristics and treatment of pulmonary embolism (PE) after transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). Methods: The clinical records of 13 512 patients diagnosed with HCC and received TACE from January 2000 to December 2009 were reviewed. Among these patients, 5 031 were allocated into group A who had one or more disorders like diabetes, hypertension, coronary heart disease, obesity or varicose vein of lower limb, while the other 8 481 patients who did not have such disorders were in group B. Results: A total of 39 185 TACE procedures were performed for the 13 512 patients. Five (0.01%) patients in group A developed PE after TACE, of whom two recovered 4 and 5 d later with early anticoagulant therapy while the hypertension, coronary heart disease, obesity or varicose vein of lower limb are possibly more likely to develop PE other 3 died of respiratory failure within 5 h. The mortality of PE was 60% (3/5). Conelusion: HCC patients with diabetes, after TACE than those without such disorders. Patients who have such disorders should be more carefully observed after TACE and early treatment with heparin should be applied once PE develops.
文摘A recent explosion in the amount of cardiovascular risk has swept across the globe. Primary prevention is the preferred method to lower cardiovascular risk. Lowering the prevalence of obesity is the most urgent matter, and is pleiotropic since it affects blood pressure, lipid profiles, glucose metabolism, inflammation, and atherothrombotic disease progression. Given the current obstacles, success of primary prevention remains uncertain. At the same time, the consequences of delay and inaction will inevitably be disastrous, and the sense of urgency mounts. Pathological and epidemiological data confirm that atherosclerosis begins in early childhood, and advances seamlessly and inexorably throughout life. Risk factors in childhood are similar to those in adults, and track between stages of life. When indicated, aggressive treatment should begin at the earliest indication, and be continued for many years. For those patients at intermediate risk according to global risk scores, C-reactive protein, coronary artery calcium, and carotid intima-media thickness are available for further stratification. Using statins for primary prevention is recommended by guidelines, is prevalent, but remains under prescribed. Statin drugs are unrivaled, evidence-based, major weapons to lower cardiovascular risk. Even when low density lipoprotein cholesterol targets are attained, over half of patients continue to have disease progression and clinical events. Though clinical evidence is incomplete, altering or raising the blood high density lipoprotein cholesterol level continues to be pursued. The aim of this review is to point out the attention of key aspects of vulnerable plaques regarding their pathogenesis and treatment.