Arterial Chemoembolization Research Articles

Prognosis of hepatocellular carcinoma in relation to treatment: A multivariate analysis of 178 patients from a single European institution

<h2>Abstract</h2> <b>Background:</b> Because the prognosis of patients with hepatocellular carcinoma is not fully understood, particularly regarding therapy, we have evaluated it in a series of patients with a homogeneous diagnostic and therapeutic work-up. <b>Methods:</b> From 1985 to 1996, 42 variables were recorded prospectively in 178 consecutive patients who had a diagnosis of hepatocellular carcinoma. Treatment consisted of liver transplantation (n = 22), partial hepatectomy (n = 11), arterial chemoembolization (n = 52), systemic or regional chemotherapy (n = 51), and other therapies (n = 5); 37 patients received no specific therapy. Statistical analysis was performed according to a Cox model. <b>Results:</b> There were no differences between the survival of patients receiving chemotherapy, other therapies, or no treatment (control group, n=93). Survival rates at 1, 3, and 5 years were 81%, 74%, and 74% for liver transplantation, 72%, 58%, and 58% for hepatectomy, 55%, 26%, and 13% for chemoembolization, and 13%, 3%, and 0% for the control group. Cirrhosis, systemic syndrome, bilobar involvement, Child's stage C disease, and treatment were independent predictors of survival. <b>Conclusions:</b> This series shows that certain easily accessible parameters may help establish individual prognosis and stratify patients in clinical trials and indicates that chemoembolization, partial resection, and liver transplantation can prolong life expectancy of patients with hepatocellular carcinoma. (Surgery 1998;124:575-83.)

Role of adjuvant treatment in liver transplantation for advanced hepatocellular carcinoma.

The results of liver transplantation for advanced hepatocellular carcinoma have been disappointing because of high recurrence rates, leading to low long-term survival; this indication remains controversial in an era of organ shortage. To continue to offer this treatment possibility, efforts were made to reduce recurrence and improve survival. The first approach is to maintain a strict selection policy excluding patients with extraheptic disease. The second approach is to test the efficacy of perioperative adjuvant therapies in patients selected for transplantation. The reasons for recurrence include: (1) undetected preoperative micrometastases, (2) intraoperative dissemination by surgical manipulation, and (3) acceleration of tumor growth by immunosuppression. Preoperative treatment, which may include systemic chemotherapy or arterial chemoembolization, seems necessary to limit tumor progression during the waiting period. Systemic chemotherapy has been tested pre-, intra-, and postoperatively. It is considered essential postoperatively and should be used as soon as possible after surgery (i.e., in the 1st postoperative week). Several teams have performed pilot studies that included rather limited numbers of patients, and the results were compared with those for historic controls. Published results show that chemoembolization creates tumor necrosis in most instances. This is efficient in limiting tumor progression but the effect on recurrence and survival is unknown. All authors who used postoperative chemotherapy reported improved survival over controls, with 50%-60% 3-year survival and up to 50% 5-year survival. However, recent results suggest that late recurrence may occur. Chemotherapy was usually well tolerated, although leukopenia, sometimes severe, was observed in most patients. The use of granulocyte colony-stimulating factor seems useful to overcome this problem. Perioperative adjuvant treatments seem to prolong survival in patients undergoing liver transplantation for advanced hepatocellular carcinoma, but delayed recurrence remains possible. Further studies are necessary; these should ideally be multicentric, prospective, and randomized.

Percutaneous management of hepatocellular carcinoma: Patient selection for percutaneous alcohol injection alone or combined with arterial chemoembolization

SummaryThe purpose of our study was to assess the efficacy of percutaneous ethanol injection (PEI) alone or in combination with transarterial chemoembolization (TACE) for patients with hepatocellular carcinoma (HCC) not eligible for surgery. From January 1989 to December 1993, 46 patients (40 men, 6 women) with cirrhosis and histologically proven HCC were treated percutaneously. Twenty-six patients (56.5%) with single tumours smaller than 5 cm were treated with PEI alone. Twenty patients (43.5%) with multiple tumours or a single HCC 5cm or larger were treated with both PEI and TACE. Treatment results were evaluated by length of survival and findings on follow-up imaging studies. Survival rates in the group treated with PEI were 81% at 1 year, 70% at 2 years, and 56% at 3 years. In the group treated with PEI and TACE, survival was 79% at 1 year, 55% at 2 years, and 46% at 3 years. Treatment failed to control HCC in 16 patients (34.8%). There were no treatment-related major complications or deaths. As a means of palliative management, PEI is effective for solitary HCC smaller than 5cm, while PEI and TACE in combination are effective for larger or multiple turnours.

A large lumen microcatheter for oncologic intervention.

A newly available Tracker-325 catheter (Target Therapeutics, Fremont, CA, USA), modified from the Tracker-18 catheter, has the same outer diameter but a larger lumen. This catheter was used in 15 patients during a 7-month period for superselective arterial catheterization when conventional catheters could not be placed successfully. Arterial embolization (n = 7), chemoembolization (n = 5), and chemoinfusion (n = 3), were performed. The increased luminal diameter of the Tracker-325 allowed an increased flow rate for diagnostic arteriography, accommodated larger embolic particles, and improved the ability to achieve a super-selective position.

Transcatheter arterial chemoembolization therapy with epirubicin hydrochloride, mitomycin C-iohexol-Lipiodol emulsion (EMILE) for hepatocellular carcinoma

The efficacy of transcatheter arterial Lipiodol chemoembolization (TALCE) using epirubicin hydrochloride, mitomycin C-iohexol-Lipiodol emulsion (EMILE) for hepatocellular carcinoma (HCC) was assessed retrospectively. EMILE was confirmed to have characteristics of fair dispersibility, stability, and slow drug release in vitro prior to clinical administration. TALCE without EMILE (simple infusion of anticancer drugs and Lipiodol) and with EMILE were preoperatively performed in two groups of candidates for hepatectomy, consisting of 17 patients each (non-EMILE and EMILE groups). Mean percentages of Lipiodol retention area to tumor area on computed tomographic (CT) scan following TALCE were 46.8 +/- 38.4% and 91.5 +/- 13.2% (mean +/- SD), respectively (P = 0.0005). Mean percentages of necrotic area to tumor area determined on histologic study of specimens were 42.9 +/- 43.8% and 63.2 +/- 44.0%, respectively (NS). In conclusion, TALCE with EMILE brought about longer retention of Lipiodol in HCC; however, gelatin sponge cubes and a higher dose of epirubicin hydrochloride were more significantly related to tumor necrosis than treatment with EMILE.

Hepatocellular carcinoma: update on diagnosis and treatment.

In this review, the current approach to the screening, diagnostic evaluation, staging, and treatment for hepatocellular carcinoma (HCC) is outlined. The serum alpha-fetoprotein (AFP) level and abdominal ultrasonography (US) remain the cornerstones of screening protocols for HCC. Other serum marker proteins, such as abnormal serum prothrombin (PIVKA-II), when used in conjunction with AFP, can increase the yield for HCC. For diagnosis and staging of HCC, other imaging modalities employed include CT scan, infusion hepatic angiography, CT with arterial portography or iodized oil enhancement, MRI with contrast enhancement, intraoperative US, and US-guided fine-needle aspiration cytology and biopsy. Treatment options which have afforded some improvement in survival and tumor regression include surgical resection, orthotopic liver transplantation, percutaneous injection of ethanol, arterial chemoembolization, cryotherapy, and systemic or regional chemotherapy. Despite these advances, the diagnosis of HCC still portends a dismal prognosis.

Controlled delivery of taxol from microspheres composed of a blend of ethylene-vinyl acetate copolymer and poly (d,l-lactic acid).

'Large' (30-100 microns) and 'small' (10-30 microns) size range taxol-loaded microspheres composed of a blend of biodegradable poly (d,l-lactic acid) (PLA) polymer and nondegradable ethylene-vinyl acetate (EVA) copolymer were prepared using the solvent evaporation method. Encapsulation efficiencies were between 95-100% for taxol in 50:50 EVA:PLA blend microspheres. Between 10-13% of the total taxol content of the microspheres (0.6% w/v taxol loading) was released in 50 days. Using the chick chorioallantoic membrane (CAM) model, the taxol microspheres released sufficient taxol to produce vascular regression and inhibition of angiogenesis. This taxol-loaded microsphere formulation may have potential for the targeted delivery of taxol to a tumor via arterial chemoembolization.

Complications of Hepatic Arterial Embolization and Chemoembolization: Treatment and Prevention

Complications of Hepatic Arterial Embolization and Chemoembolization: Treatment and Prevention

Percutaneous hepatic arterial chemotherapy and chemoembolization

Percutaneous hepatic arterial chemotherapy and chemoembolization are treatment options for patients who have been diagnosed with hepatocellular carcinomas or with metastatic carcinomas of the liver. Nursing care of these patients is challenging and complex. Patients present with varying symptoms of the disease, and progression requires varying degrees of intervention. Some patients may have already had systemic chemotherapy, and others may be facing their first experience with chemotherapy. Patient and family education requires presentation of correct, thorough information on an ongoing basis. To care for these patients, the nurse must understand the techniques of chemoembolization and hepatic arterial chemotherapy administration. This article addresses the introduction of hepatic arterial chemotherapy through the process of chemoembolization, as well as the nursing management to be considered throughout the treatment.

Primary treatment of hepatocellular carcinoma by arterial chemoembolization

Two hundred and ninety-one patients with hepatocellular carcinoma were treated by chemoembolization (CE), using ethiodized oil, doxorubicin, and a gelatin sponge. Patients with thrombosis of either the portal vein or a main branch were excluded. The mortality rate in the first 2 months after treatment was 7% in noncirrhotic patients, 2.8% in patients with class A cirrhosis, 8% in patients with class B cirrhosis, and 37% in patients with class C cirrhosis. The tumor diameter remained the same in 55.3% of patients, was reduced by up to 50% in 20% of the patients, was reduced by more than 50% in 7.3% of the patients, and almost completely disappeared in 1.8% of the patients. The diameter of the tumor increased in 15.6% of patients. Forty-three patients underwent a resection or transplantation after chemoembolization. Histologic examination of the specimens revealed significant necrosis of the tumor. The long-term survival rate at 2 years was 49% for class A cirrhotics, 29% for class B cirrhotics, and 9% for class C cirrhotics. Complications included cholecystitis (10%), vasculitis (14%), renal decompensation (13%), an increase in ascites (14%), and jaundice (12%). Chemoembolization is an effective and safe initial treatment for hepatocellular carcinoma. It is effective in producing tumor necrosis and reducing the size of the tumor. Improvement in survival was noted when patients who underwent chemoembolization were compared with an historical series of untreated patients, and resection and transplantation are kept as options.

Energy metabolism changes and oxidative attack after hepatic arterial embolization and chemoembolization in thioacetamide-induced cirrhotic livers

Hepatic energy metabolism and oxidative attack were studied after transcatheter arterial embolization (TAE) and chemoembolization (TAC) of the left and median lobes of the liver using thioacetamide (TAA)-induced cirrhotic rats. TAE was carried out using gelatin sponge (1.5 mg/cm3) dissolved in saline solution (SS). TAC was performed by adding mitomycin C (MMC) (1.6 mg/kg body weight) to the previous embolic solution. The energy charge (EC) of embolized lobes decreased from 0.86 to 0.78 and 0.74 1 h after TAE and TAC, respectively, but was restored 3 h later. Adenosine 5'-triphosphate (ATP) and total adenine nucleotide content (TAN) of embolized and non-embolized lobes was also temporarily decreased. Total hepatic blood flow (THBF) of embolized and chemoembolized lobes was reduced in almost 50%, and it took 1 week to become normalized. After TAC (3 and 6 h, respectively), total glutathione (TGSH) content was reduced from 7.02 mumol/g of liver to around 4.5 mumol/g, and malondialdehyde (MDA) content increased from 196.94 nmol/g of liver to values above 300 nmol/g. TAE in cirrhotic livers did not induce any changes in these parameters. In conclusion, after TAE and TAC the hepatic energy metabolism is temporarily altered by ischemia. TAC-induced oxidative attack, in addition to ischemia and MMC, could be one of the mechanisms explaining the effectiveness of this therapy.

A case of necrosis of hepatocellular carcinoma and tumor thrombus in the portal vein induced by transcatheter arterial lipiodol chemoembolization.

A case of hepatocellular carcinoma is reported in which the main tumor, intrahepatic metastases and a tumor thrombus in the portal vein were necrotized completely after Lipiodol chemoembolization. In this case, the tumor thrombus seemed to act as a portal embolus. This phenomenon is interesting because Lipiodol chemoembolization alone usually can not necrotize intra- or extra-capsular invasion, intrahepatic metastasis or tumor thrombus in the portal vein. This case is considered to be suggestive of a possible therapy for hepatocellular carcinoma.

Hepatic artery infusion and chemoembolization in the management of liver metastases

Hepatic metastases rather than the primary neoplasm usually dictate the course of the disease and patient's survival. For unresectable disease, intraarterial infusion of chemotherapy, embolization, and chemoembolization are viable alternatives. Intraarterial therapy for hepatic metastases is based on the dual blood supply of the normal liver (portal vein, 75%, and hepatic artery, 25%) and that of the tumors (hepatic artery, 90%). Intraarterial infusion delivers a higher concentration of chemotherapy, whereas chemoembolization adds ischemia and increased contact time with the tumor. Selective vascular occlusion for infusion, redistribution of the blood supply and pulsatile flow enhance the delivery of therapeutic agents to the liver.

Effects of superselective arterial embolization and chemoembolization on energy charge and total blood flow of the rat liver.

The superselective transcatheter arterial embolization (TAE) and chemoembolization (TAC) of the periphery of the left and median lobes of the rat liver were performed using 1.5 mg of gelatin sponge dissolved in saline solution and mitomycin (MMC) at a dose of 1.6 mg/kg b.wt. The energy charge (EC) of the embolized and chemoembolized lobes decreased after the embolization but was restored 3 h later. The total hepatic blood flow (THBF) was reduced to about one half and required 1 week to be restored to the preembolization levels in both groups. Microscopic centrilobular necrosis and vacuolization were found. The addition of MMC did not produce marked untoward effects. Thus, the normal liver is able to restore its energy pool despite a reduction in the THBF after superselective arterial embolization, and this recovery is not altered even by the use of a high dose of MMC.

5] Biophysical drug targeting: Magnetically responsive albumin microspheres

Publisher Summary Biophysical approaches to specific drug targeting encompass a wide range of modalities, including local implantation of drug reservoirs, hyperthermia, arterial perfusion, arterial chemoembolization, intracavity injection, and the use of extracorporeal magnetic fields. Magnetic targeting has several unique advantages that allow for effecting very high local concentration of therapeutic agents. Magnetically responsive microspheres may find utility as carriers for a wide variety of therapeutic agents that are used in the treatment of localized disease processes. The ability to restrict drug activity to a specific body region allows for administration of small doses and therefore decreased side effects. Particular applications including treatment of localized cancers (whether curative or palliative) or ablation of aberrant physiological functions (hyperthyroidism, for example) are a few of the many areas in which the concentrating ability of this targeting system could be of value. Clinical application, however, is the ultimate test for any drug targeting system. Magnetic microspheres offer unique advantages as solid supports for a variety of applications, including cell sorting, solid phase immunoassays, supports for immobilized enzymes, and bioaffinity adsorbents.

Arterial chemoembolization with mitomycin C microcapsules in the treatment of primary or secondary carcinoma of the kidney, liver, bone and intrapelvic organs.

Selective intraarterial infusion of the ethylcellulose microcapsules of mitomycin C (MMC-mc) exerts its potential therapeutic effects through both infarction and prolonged local, drug activity, i.e., chemoembolization. Twenty patients with intractable primary, recurrent or metastatic carcinoma were treated with single or fractionated infusion of MMC-mc via percutaneous arterial catheterization. The target sites were the kidney, liver, prostate, urinary bladder, uterus, sigmoid colon, Douglas' pouch and bone. Fourteen patients had over 30% reduction in measurable maximum tumor diameter, 5 had 10 to 30% reduction and 1 showed less than 10% reduction, but concurrent 2 bone lesions had no reduction. Improvement of symptoms and signs such as pain, massive hemorrhage, dysuria, anorexia and hydronephrosis was observed at an early stage of the treatment in all patients. Eight patients with highly invasive carcinoma of the kidney, urinary bladder and cervix were initially treated with MMC-mc followed by successful radical operation. Systemic toxicity was mild and all patients tolerated the treatment. Although the follow-up periods are less than 21 months, 12 patients are alive with or without tumor and 11 of them are doing well. The present results indicate that chemoembolization with MMC-mc is effective as a preoperative or palliative measure in the treatment of invasive carcinoma of various organs.

Arterial chemoembolization with microencapsulated anticancer drug. An approach to selective cancer chemotherapy with sustained effects

Selective intra-arterial infusion of ethylcellulose microcapsules containing mitomycin exerts its therapeutic effects through infarction and sustained drug action—ie, chemoembolization. Sixty primary or secondary carcinomas in the kidney, liver, urinary bladder, prostate, cervix, vagina, sigmoid colon, Douglas' pouch, and bone were treated with single or repeated chemoembolizations using microcapsules delivered through percutaneous catheterization as a preoperative or palliative measure. Substantial tumor reduction of greater than 30% in measurable maximum diameter was found in 65% of the tumors; pain relief occurred in 80% and hemostasis in 100%. Preoperative chemoembolization remarkably facilitated radical surgery in 18 (82%) of 22 patients. The summed response rate was 77%. Systemic toxic effects were mild, and all patients tolerated the treatment. Though the follow-up periods are less than two years, 37 patients are alive with or without tumor. (<i>JAMA</i>1981;245:1123-1127)