Transarterial interventional therapy is one of the most widely used treatment methods in patients with primary hepatocellular carcinoma. With the progress in interventional technology and the use of new drugs, transarterial interventional therapy has achieved favorable results in the treatment of primary hepatocellular carcinoma and has become the first choice non-surgical treatment for advanced liver cancer. However, at present, there are great differences in the drugs used in transarterial interventional treatment and the combined application of other drugs among centers, and there is no uniform consensus or guideline. Based on the latest research data and clinical practice experience, as well as the characteristics of Chinese patients, the Specialist Group of Interventional Drugs, Interventionalists Branch of the Chinese Medical Doctor Association was organized to formulate the Chinese expert consensus on intra-arterial drug and combined drug administration for primary hepatocellular carcinoma. The purpose of this consensus is to explore the efficacy and safety of drugs and drug combinations related to intra-arterial interventional therapy, the use of drugs in special populations, the management of adverse reactions, and adjuvant drugs to provide a reference for clinical practice.
Humans ; Carcinoma, Hepatocellular/pathology* ; Consensus ; East Asian People ; Liver Neoplasms/pathology* ; Pharmaceutical Preparations ; Infusions, Intra-Arterial/methods* ; Antineoplastic Agents/therapeutic use* ; Drug Therapy, Combination/methods*

OBJECTIVETo explore the advantages, feasibility and limitations of hepatic arterial infusion under temporary hepatic circulation occlusion.

METHODSTwelve rabbits were randomly divided into two groups: hepatic artery infusion group (HAI group) and hepatic artery infusion under temporary hepatic circulation occlusion group (HAI-THCO). Microcatheters were separately inserted into the proper hepatic artery and right hepatic vein. For the HAI group, 5-Fu (10 mg/ml and 100 mg/kg) was infused into the common hepatic artery with a high pressure injector for 10 minutes. For the HAI-THCO group, the common hepatic artery and hepatic portal vein were temporarily occluded for 15 minutes using artery clamp when 5-Fu was being infused. For the two groups, at 2, 5, 10, 15, 20 and 30 min after the start of infusion, blood samples of the hepatic flow were collected from the right hepatic vein and of the systemic blood flow from the inferior vena cava, 1 ml at each time point. The blood drug concentration of these blood samples was determined by high performance liquid chromatography (HPLC).

RESULTSExcept that at 20 and 30 min after infusion, in the HAI group, the blood drug concentration of hepatic circulation was significantly higher than that of systemic circulation (P < 0.05). But in the HAI-THCO group, the blood drug concentration of hepatic circulation was significantly higher than that of systemic circulation at all the time points (P < 0.05). The hepatic circulation blood drug level of the HAI-THCO group was always significantly higher than that of the HAI group (P < 0.05), but the systemic circulation blood drug concentration of the HAI-THCO group was always lower (P < 0.05). The hepatic circulation maximum concentration (Cmax) of blood drug concentration of the HAI-THCO and HAI groups was (23.057±3.270) µg/ml and (4.408±1.092) µg/ml, respectively, and the Cmax of HAI-THCO group was significantly higher (P < 0.001), being 5.23 times of that of HAI group. The systemic circulation Cmax of the two groups was (1.456±0.217) µg/ml and (2.335±0.669) µg/ml, respectively, and the Cmax of HAI group was 1.60 times higher than that of the HAI-THCO group (P = 0.022). The hepatic circulation AUC of HAI-THCO and HAI groups was (368.927±52.416) µg·min·ml(-1) and (65.630±14.928) µg·min·ml(-1), respectively. The AUC of HAI-THCO group was 5.62 times higher than that of the HAI group (P < 0.001). The systemic circulation AUC of the two groups was (27.193±3.948) µg·min·ml(-1) and (45.301±12.275) µg·min·ml(-1), respectively. The AUC of HAI group was 1.67 times higher than that of the HAI-THCO group (P = 0.014).

CONCLUSIONSHAI-THCO is a simple and effective regional hepatic infusion chemotherapy technique. It can be performed through occluding the common hepatic artery and the hepatic portal vein by balloon catheter. HAI-THCO can not only increase the blood drug concentration in the hepatic circulation, but also decrease the blood drug concentration in the systemic circulation, therefore, distinctly lowering the systemic toxicity.

Animals ; Coronary Occlusion ; Fluorouracil ; Hemodynamics ; Hepatic Artery ; Hepatic Veins ; Infusions, Intra-Arterial ; methods ; Liver ; Liver Circulation ; Portal Vein ; Rabbits

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. The only curative treatment modalities for HCC are surgery, percutaneous ablation, and liver transplantation. Unfortunately, the majority of patients have unresectable disease at diagnosis. Therefore, effective treatment options are needed for patients with advanced HCC. The current standard treatment for patients with advanced HCC, according to the Barcelona Clinic Liver Cancer staging system, is the multikinase inhibitor sorafenib. Other alternative therapies are required, due to the limited treatment response to, and tolerance of, this molecular target agent. Clinical trials of hepatic artery infusion chemotherapy, radioembolization, and multimodal treatments have shown favorable results in advanced HCC patients. This article introduces new treatment modalities for advanced HCC and discusses future therapeutic possibilities.
Antineoplastic Agents/administration & dosage/*therapeutic use ; Carcinoma, Hepatocellular/enzymology/pathology/*therapy ; Combined Modality Therapy ; Embolization, Therapeutic/*methods ; Hepatic Artery ; Humans ; Infusions, Intra-Arterial ; Liver Neoplasms/enzymology/pathology/*therapy ; Molecular Targeted Therapy ; Niacinamide/analogs & derivatives/therapeutic use ; Phenylurea Compounds/therapeutic use ; Protein Kinase Inhibitors/therapeutic use ; Radiopharmaceuticals/therapeutic use ; Signal Transduction/drug effects ; Treatment Outcome

OBJECTIVETo investigate the efficacy of hematopoietic stem cell (HSC) transplantation via the hepatic artery vs. the portal vein for end-stage liver disease (ESLD).

METHODSPatients with hepatic decompensation were prospectively recruited from September 2010 to September 2012 to receive HSC transplantation via the hepatic artery or the portal vein. Liver function was examined at 3, 6, and 12 months after transplantation. Liver biopsy Results were analyzed using the Knodell score.

RESULTSEighty patients (58 males and 22 females) were enrolled in the study. The Child-Pugh score was grade B in 69 cases, and grade C in the remaining 11 cases. HSC transplantation was performed via the portal vein in 36 patients and via the hepatic artery in 44 patients. ALT levels decreased while serum albumin levels increased significantly in both groups at 6 and 12 months after HSC transplantation (P<0.05 compared with pre-transplantation levels). Total bilirubin levels decreased significantly in both groups at 3, 6, and 12 months after HSC transplantation (P<0.05 compared with pre-transplantation levels). Additionally, prothrombin time decreased in both groups at 12 months after HSC transplantation (P<0.05 compared with pre-transplantation level). There were no significant differences in ALT, total bilirubin and prothrombin time between the two groups either before or after transplantation. Moreover, Knodell score decreased significantly at 6 and 12 months. Histological examination showed that liver cell edema, degeneration, necrosis, and inflammation were significantly relieved at 3, 6, and 12 months after transplantation. The incidence of portal vein thrombosis, upper gastrointestinal bleeding, and hepatic encephalopathy were 1.25%, 3.75%, and 2.5% respectively. The one-year survival rate was 100%.

CONCLUSIONSAutologous HSC transplantation improves liver function and histology in ESLD patients. The administration route of HSC has no significant impact on the efficacy of transplantation.

Adult ; Aged ; Disease-Free Survival ; End Stage Liver Disease ; pathology ; therapy ; Female ; Hematopoietic Stem Cell Transplantation ; methods ; Hepatic Artery ; Humans ; Infusions, Intra-Arterial ; Infusions, Intravenous ; Liver Function Tests ; Male ; Middle Aged ; Portal Vein ; Prospective Studies ; Treatment Outcome

This paper focuses on the animal experiment of automatic drug delivery based on predictive control for vascular interventional therapy. Improvement of drug delivery system based on predictive control used in simulated experiments was put forward after the presence of time varying parameters and the characteristics of individual differences of animal had been studied. The adaptability of time varying parameters and fault tolerance of the system were also enhanced. Different injection methods were tested on animals. It is proved that higher target blood concentration can be reached while injecting during diastolic than that while injecting during systolic or injecting at a constant speed within the whole cardiac cycle. The results also showed that the improved drug injection system based on predictive control which synchronizes with the cardiac cycle could be applied to clinical trials.
Algorithms ; Animals ; Automation ; Dipyrone ; administration & dosage ; analogs & derivatives ; Forecasting ; Infusion Pumps ; Infusions, Intra-Arterial ; methods ; Pharmaceutical Preparations ; administration & dosage ; Swine

OBJECTIVETo compare the neuroprotective effects of intracarotid cold saline infusion (ICSI), ice cap and systemic cooling in rats with early cerebral ischemia.

METHODSSD rats were randomly divided into model group, ice cap group, systemic cooling group and ICSI group (n=13). Cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 2 h. In the 3 hypothermic groups, the target temperature of 33-34 degrees celsius; was achieved and maintained for 20 min. In each group, the neurological scores were recorded at 48 h after the reperfusion, and the brains were removed for measuring the infarct size using 2,3,5-triphenyltetrazolium chloride staining. The brain water contents and serum levels of neuron-specific enolase (NSE), S100β and matrix metalloproteinase 9 (MMP9) were also measured.

RESULTSCompared with the model group, the ice cap, systemic cooling and ICSI groups all showed significantly reduced infarct size by 27.4% (P<0.05), 47.6% (P<0.01) and 61.6% (P<0.01), respectively. The systemic cooling and ICSI groups, but not the ice cap group, had significantly lower brain water contents than the model group (P<0.05). Among the 3 hypothermic methods, only ICSI significantly improved the neurological scores (P<0.05) and reduced serum NSE and S100β levels (P<0.05).

CONCLUSIONOf the 3 hypothermic groups, ICSI has the best neuroprotective effects, and systemic cooling produces better effect than ice cap in rats with ischemic stroke.

Animals ; Brain Ischemia ; therapy ; Cryotherapy ; methods ; Hypothermia, Induced ; methods ; Infusions, Intra-Arterial ; Male ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; prevention & control ; Sodium Chloride ; administration & dosage

BACKGROUNDPre-operative chemotherapy has gained widespread interest while treating advanced gastric cancer in eastern countries. However, there is currently no established standard regimen for gastric cancer. The aim of this research was to explore the value of preoperative chemotherapy with a combination of intravenous and intra-arterial intensified chemotherapy in advanced gastric cancer.

METHODSA total of 56 histologically proven gastric cancer patients, who were considered to be stage II or higher with metastatic lymph nodes and with or without distant metastasis (T2-4, N1-3, and M0-1), were treated with a neoadjuvant chemotherapy. Patients received a combination of intravenous 5-Fu (370 mg/m2) and leucovorin (200 mg/m2) on days 1-5, and intra-arterial etoposide (80 mg/m2) and cisplatin (80 mg/m2) on days 6 and 20. After two cycles of preoperative chemotherapy, patients with resectable tumors underwent laparotomy.

RESULTSAll patients finished two cycles of chemotherapy. The overall response rate was 78.57% (44 cases), of which 7.14% (four cases) clinical complete response. Forty-six patients underwent resection, including 21 initially unresectable diseases. R0 resection rate for prechemotherapy resectable and unresectable diseases was 96.15% (25/26 cases) and 66.67% (20/30 cases), respectively. Pathological complete response was observed in 8.70% of patients. Toxicity was moderate and there were no chemotherapy-related deaths. With a median follow-up of 31 months (range 6-76 months), the 5-year survival rate for the whole group and patients with initially resectable tumors were 21.8% and 42.3%, respectively. The median survival for initially resectable and unresectable patients were 41 months (95%CI, 31.006-50.994) and 18 months (95%CI, 13.399-22.601; P<0.01), respectively.

CONCLUSIONPreliminary results proved that the combined intensive chemotherapy was a safe and promising regimen for pre-operative treatment of advanced gastric cancer.

Adult ; Aged ; Cisplatin ; administration & dosage ; therapeutic use ; Etoposide ; administration & dosage ; therapeutic use ; Female ; Fluorouracil ; administration & dosage ; therapeutic use ; Humans ; Infusions, Intra-Arterial ; Infusions, Intravenous ; Leucovorin ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; Neoadjuvant Therapy ; methods ; Retrospective Studies ; Stomach Neoplasms ; drug therapy ; surgery

OBJECTIVETo investigate the safety of treatment with ophthalmic artery cannulation for intra-arterial chemotherapy (IAC) for children with intraocular retinoblastoma (RB).

METHODIn the RB Treatment Center of General Hospital of Armed Police Forces between January 2009 and September 2011, 42 patients who were diagnosed intraocular RB and treated with ophthalmic artery cannulation for IAC, 8 patients were treated 1 circle, 31 patients were treated 2 circles and 3 patients were treated 3 circles (total, 96 times). Each month had IAC once. The ophthalmic and the whole body evaluations were performed during IAC and after IAC for each circle, the blood cell count, alanine aminotransferase (ALT), serum creatinine (Scr), CK-MB content before and after IAC for 1 circle, 2 circles and 3 circles were determined.

RESULT(1) In 52 eyes of 42 patients, 44 eyes (84.6%) were in remission. (2) Successful IAC was achieved in all cases, no severe side effects occurred during IAC. (3) The main ophthalmic complications were eyelid edema and blepharoptosis after IAC, the incidence for 1 circle was 18% (2/11) and 9% (1/11); for 2 circles was 29% (11/38) and 21% (8/38); for 3 circles was all 100% (3/3). The rare complications were vitreous hemorrhage and heterotropia, the incidence was all 2% (1/42). The incidence of eyelid edema and blepharoptosis had no significant differences for 1 circle IAC compared with 2 circles (P > 0.05); the incidence of eyelid edema and blepharoptosis had significant differences for 3 circles IAC compared with 2 circles and 1 circle (P < 0.01). (4) No fever, septicemia and other systemic toxic effects occurred. (5) ALT of 19% patients (8/42) elevated temporarily and CK-MB of 24% patients (10/42) increased. The blood cell counts, ALT, Scr, and CK-MB content before IAC had no significant differences compared with that at 24 h after IAC for 1 circle, 2 circles and 3 circles (P > 0.05).

CONCLUSIONOphthalmic artery cannulation for IAC is a safe and effective method in treating intraocular stage retinoblastoma.

Antineoplastic Agents, Alkylating ; administration & dosage ; therapeutic use ; Catheterization ; methods ; Child, Preschool ; Female ; Humans ; Infant ; Infusions, Intra-Arterial ; Liver Function Tests ; Male ; Melphalan ; administration & dosage ; therapeutic use ; Neoplasm Staging ; Ophthalmic Artery ; Postoperative Complications ; epidemiology ; Retinal Neoplasms ; drug therapy ; pathology ; Retinoblastoma ; drug therapy ; pathology ; Retrospective Studies ; Treatment Outcome

BACKGROUNDRegional intra-arterial infusion chemotherapy (RIAC) has been more valuable to improve prognosis and quality of life of patients with inoperable pancreatic adenocarcinomas, and adjuvant RIAC plays an important role in prolonging survival and reducing risk of liver metastasis after radical resection of pancreatic cancer, but the effect of preoperative or multiple-phase RIAC (preoperative combined with postoperative RIAC) for resectable pancreatic cancers has not been investigated. In this prospective study, the effect of multiple-phase RIAC for patients with resectable pancreatic head adenocarcinoma was evaluated, and its safety and validity comparing with postoperative RIAC were also assessed.

METHODSPatients with resectable pancreatic head cancer were randomly assigned to two groups. Patients in group A (n=50) were treated with new therapeutic mode of extended pancreaticoduodenectomy combined with multiple-phase RIAC, and those in group B (n=50) were treated with extended pancreaticoduodenectomy combined with postoperative RIAC in the same period. The feasibility, compliance and efficiency of the new therapeutic mode were evaluated by tumor size, serum tumor markers, clinical benefit response (CBR), surgical complications, mortality and toxicity of RIAC. The disease-free survival time, median survival time, incidence of liver metastasis, survival rate at 1, 2, 3 and 5 years were also observed. Life curves were generated by the Kaplan-Meier method.

RESULTSThe pain relief rate and CBR in group A was 80% and 84% respectively. Serum tumor markers decreased obviously and tumors size decreased in 26% of patients after preoperative RIAC in group A. No more surgical complications, mortality or severe systemic side effects were observed in group A compared with group B. The incidence of liver metastasis in group A was 34% which was lower than 50% in group B. The disease-free survival time and median survival time in group A were 15.5 months and 18 months respectively. The 1-, 2-, 3- and 5-year survival rates were 54.87%, 34.94%, 24.51% and 12.25% respectively. There was no significant difference of survival time or survival rates between two groups.

CONCLUSIONSMultiple-phase RIAC is effective in combined therapy of resectable pancreatic head carcinomas by enhancing inhibition of tumor growth and reduction of liver metastasis, without negative effect on patients' safety or surgical procedure.

Adenocarcinoma ; drug therapy ; mortality ; pathology ; surgery ; Adult ; Aged ; Deoxycytidine ; analogs & derivatives ; therapeutic use ; Disease-Free Survival ; Female ; Fluorouracil ; therapeutic use ; Humans ; Infusions, Intra-Arterial ; methods ; Liver Neoplasms ; secondary ; Male ; Middle Aged ; Mitomycin ; therapeutic use ; Neoplasm Metastasis ; Pancreas ; drug effects ; pathology ; surgery ; Pancreatic Neoplasms ; drug therapy ; mortality ; pathology ; surgery ; Pancreaticoduodenectomy

Despite remarkable advancement in the surveillance and treatment of hepatocellular carcinoma (HCC) and the availability of novel curative options, a great proportion of HCC patients are still not eligible for curative treatment due to an advanced tumor stage or poor hepatic functional reserve. Therefore, there is a continuing need for effective palliative treatments. Although practiced widely, it has only recently been demonstrated that the use of transarterial chemoembolization (TACE) provides a survival benefit based on randomized controlled studies. Hence, TACE has become standard treatment in selected patients. TACE combines the effect of targeted chemotherapy with the effect of ischemic necrosis induced by arterial embolization. Most of the TACE procedures have been based on iodized oil utilizing the microembolic and drug-carrying characteristic of iodized oil. Recently, there have been efforts to improve the delivery of chemotherapeutic agents to a tumor. In this review, the basic principles, technical issues and complications of TACE are reviewed and recent advancement in TACE technique and clinical applicability are briefed.
Antineoplastic Agents/therapeutic use ; Carcinoma, Hepatocellular/*therapy ; Chemoembolization, Therapeutic/*methods ; Gelatin Sponge, Absorbable/therapeutic use ; Humans ; Infusions, Intra-Arterial ; Iodized Oil/therapeutic use ; Liver Neoplasms/*therapy