Embolization and Chemoembolization & Liver Metastases


Despite frequent tumor recurrence, the long-term outcome after liver resection for hepatic metastases from leiomyosarcoma is superior to that after chemotherapy and chemoembolization. 
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However, embolization or chemoembolization and intra-arterial infusion chemotherapy could be use for downsizing inoperable or unablatable  liver metastases.  The treated mets might then be operable.  [Neoadjuvant therapy]

 Also, this regional therapy may offer new hope for those sarcoma patients who have liver mets resistant to combination systemic chemotherapy.  Embolization or Chemoembolization can be used for downgrading of tumors prior to surgical resection, or for extension of survival time, or for treatment of symptomatic metastases.   

Embolization or chemoembolization is not curative by itself, and additional therapy is required to eradicate residual disease.  But these methods can be excellent de-bulkers.

Side effects and complications might include: liver pain, liver enzyme blood level increase, liver abscess, gastrointestinal reaction [paralytic ileus] requiring a nasogastric tube, urinary electrolyte losses requiring supplements, and occasionally mild but transient low white cell or platelet count. 

The normal liver presents a double circulation: 75% from portal circulation and 25% from hepatic artery. In malignant primary and secondary lesions the blood support to the tumors is given by the hepatic artery. Anticancer drugs mixed with some 'embolic' particles such as polyvinyl alcohol and gelatin powder can be injected selectively in the arteries that feed tumors. This causes clotting in those arteries, and infarcts [kills cells by obstructing their blood supply] tumors. Additionally, with Chemoembolization,  the anticancer drugs work on the tumor. Their work is enhanced by their not being quickly washed away by the blood circulation [which has been clotted or slowed]. Radio-opaque contrast media can also be present in the mixture, and the progress of the mixture monitored radiologically. 

Chemoembolization causes massive shrinkage due to ischemia, and increases the local drug intensity and drug exposure. 

The hepatic artery is reached by advancing a catheter from the femoral or other artery to the hepatic artery. The catheter can be advanced into the artery that feeds the tumor's  blood supply, and the embolization material is injected, followed by the chemotherapy regimen previously decided upon, until the feeder artery no longer transports liquid. 

<b>Side Effects and Complications</b> are obvious ones: 
liver trauma, liver failure, artery rupture, infection, abscess, reaction to the injected materials, the side effects due to the injected materials, fever, pain, misdirected drainage of the injected material resulting in damage to other structures.   Some of these "side effects" can be fatal.

Risk factors for liver failure after embolization include poor hepatic functional reserve, high-dose infusion of chemotherapeutic agents, and a history of multiple embolization procedures.

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References for this section are below.


<b>Arterial Embolization and Chemoembolization & Liver Metastases 
Selected Medical Journal Article Annotated Citations</b>
[For the full abstract, use the links provided, or search on Pubmed.  Ed.]


Ann Surg 2000 Apr;231(4):500-5 
<b>Hepatic metastases from leiomyosarcoma: A single-center experience with 34 liver resections during a 15-year period. </b>
Lang H, Nussbaum KT, Kaudel P, Fruhauf N, Flemming P, Raab R. 
Klinik fur Abdominal- und Transplantationschirurgie, Medizinische Hochschule Hannover, Hannover, Germany. hauke.lang@uni-essen.de 

... To describe a large single-center experience with hepatic resection for metastatic leiomyosarcoma. ... the role of liver resection for hepatic metastases from leiomyosarcoma has not been defined. 
...The records of 26 patients who between 1982 and 1996 underwent a total of 34 liver resections for hepatic metastases from leiomyosarcoma were reviewed. There were 23 first, 9 second, and 2 third liver resections. The records were analyzed with regard to survival and predictive factors. 
...In the 23 first liver resections, there were 15 R0, 3 R1, and 5 R2 resections. Median survival was 32 months after R0 resection and 20.5 months after R1/2 resection. The 5-year survival rate was 13% for all patients and 20% after R0 resection. 
...In 10 patients with extrahepatic tumor at the time of the first liver resection, 6 R0 and 4 R2 resections were achieved. After R0 resection, the median survival was 40 months (range 5-84 months), with a 5-year survival rate of 33%. 
...After repeat liver resection, the median survival was 31 months (range 5-51 months); after R0 resection, median survival was 31 months and after R1/2 resection it was 28 months. There was no 5-year survivor in the overall group after repeat liver resection. 
... Despite frequent tumor recurrence, the long-term outcome after liver resection for hepatic metastases from leiomyosarcoma is superior to that after chemotherapy and chemoembolization. Although survival after tumor debulking also seems to be more favorable than after nonoperative therapy, these data indicate that only an R0 resection offers the chance of long-term survival. The presence of extrahepatic tumor should not be considered a contraindication to liver resection if complete removal of all tumorous masses appears possible. In selected cases of intrahepatic tumor recurrence, even repeated liver resection might be worthwhile. In view of the poor results of chemoembolization and chemotherapy in hepatic metastases from leiomyosarcoma, liver resection should be attempted whenever possible. 
&&url PMID: 10749609 



Gan To Kagaku Ryoho 1997 Sep;24(12):1878-81 
<b>[A case of liver metastasis of gastric leiomyosarcoma successfully treated by transarterial hepatic chemo-embolization and intra hepato-arterial chemotherapy repeated with infusion-a-port]. [Article in Japanese]</b>
Miya A, Yasuda S, Morimoto O, Tsuji Y, Shiozaki K, Baba M, Ishida H, Masutani S, Tatsuta M, Kawasaki T, Satomi T. 
Dept. of Surgery, Sakai Municipal Hospital. 

The patient was a 68-year-old male, who underwent total gastrectomy for giant leiomyosarcoma of the stomach and then had multiple hepatic metastases one year and six months later. Thus, transarterial hepatic chemo-embolization therapy with Lipiodol, adriamycin and gelfoam was given. Moreover, using a reservoir catheter and infusion arterial port, intermittent arterial infusion therapy with adriamycin, cyclophosphamide, and vincristine was attempted. In the metastasis lesion where there were rich blood vessels, Lipiodol was accumulated and the tumor was reduced on abdominal CT. The result indicated the efficacy of this treatment. 
&&url PMID: 9382556 


Gan To Kagaku Ryoho 1997 Sep;24(12):1741-4 
<b>[A case of liver metastases from leiomyosarcoma in the chest wall which was made resectable by chemoembolization]. [Article in Japanese]</b>
Mori K, Yamada S, Kosaka A, Watabiki Y, Ohara M, Yamazaki M, Shikata A, Hoshiya Y. 
Dept. of Surgery, Shimizu Municipal Hospital. 

We here report a recently experienced case in which TAE and intra-arterial infusion chemotherapy for treatment of liver metastases of leiomyosarcoma in the chest wall caused a shrinking of the metastasized focus, thus facilitating liver resection. ... A 38-year-old man ... Resection of leiomyosarcoma in his chest wall was done in May 1994. However, a local recurrence was noted in September 1995, and the tumor was removed. Then, he received systemic chemotherapy with CDDP (100 mg) and ADM (45 mg). Abdominal CT and ultrasonic examinations made in February 1996 revealed liver metastases at S2, 5,8. Angiography detected densely stained images of tumors at a number of sites along with S2, 5,8. Since these were thought unresectable, TAE therapy with EPIR (30 mg) and lipiodol (4 ml) was attempted 3 times. Then, a reservoir for intra-hepatic arterial infusion was implanted in April, 1996 and EPIR at a dose of 30 mg (150 mg in total) was given through arterial infusion, resulting in tumor disappearance at S5, 8 but further growth of the tumor metastasizes at S2. Therefore, a resection of the left lateral segment of liver was done August 23. Though he was discharged in October, metastasis was found in the thoracic spine in December. Thus, he underwent resection of the vertebral arch including the tumor. 
&&url PMID: 9382521 


Cancer 1995 Apr 15;75(8):2083-8 
<b>Gastrointestinal leiomyosarcoma metastatic to the liver. Durable tumor regression by hepatic chemoembolization infusion with cisplatin and vinblastine. </b>
Mavligit GM, Zukwiski AA, Ellis LM, Chuang VP, Wallace S. Department of Clinical Immunology and Biological Therapy, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA. 
... Gastrointestinal leiomyosarcoma metastatic to the liver is considered most resistant to any combination of systemic chemotherapy containing doxorubicin and/or ifosphamide. ... Fourteen patients with gastrointestinal leiomyosarcoma metastatic to the liver were treated with hepatic chemoembolization infusion consisting of polyvinyl alcohol sponge particles mixed with cisplatin powder (150 mg) followed by an intrahepatic arterial infusion of vinblastine (10 mg/m2). ... Ten major (> 50% regression) tumor responses were observed (70%) in patients lasting from 8 to 31+ months (median, 12 months) after an average of two hepatic chemoembolization procedures, usually 4 weeks apart. Transient side effects included right upper quadrant pain requiring narcotics, significant hepatic enzyme elevation, particularly of lactic dehydrogenase with a minimal increase in bilirubin, paralytic ileus requiring nasogastric suction up to 72 hours, urinary electrolyte losses (potassium+, magnesium++, sodium+) requiring supplements, and occasionally mild but transient leukopenia and thrombocytopenia. ... Hepatic chemoembolization infusion appears to induce a high rate of durable tumor response in patients with notoriously chemoresistant gastrointestinal leiomyosarcoma metastatic to the liver.  [This is probably a GIST. Ed.]  
&&url PMID: 7697597 


Gan To Kagaku Ryoho 1994 Sep;21(13):2233-6 
<b>[Analysis of cases with liver abscess following transcatheter arterial chemoembolization (TAE) for malignant hepatic tumors]. [Article in Japanese] </b>
Ishikawa H, Kanai T, Ono T, Shimoyama Y, Aizawa K, Ishida H, Saitoh Y, Hata H, Aoki A, Okuda S, et al. 
Dept. of Surgery and Radiology, Hiratsuka City Hospital. 

... These results suggest the major factor leading to abscess formation is biliary infection. Therefore, a previous bilio-enteric anastomosis should be regarded as a risk factor for liver abscess following TAE. 
&&url PMID: 7944448 


Gan To Kagaku Ryoho 1993 Jan;20(1):141-3 
<b>[Hepatic metastases from jejunal leiomyosarcoma treated effectively by repeated transarterial embolization with carboplatin]. [Article in Japanese] </b>
Kokufu I, Kurokawa E, Akashi H, Mizumoto S, Kishibuchi M, Aoki Y, Inoue Y. 
Dept. of Surgery, Minoh City Hospital. 

A 67-year-old man ... was diagnosed as having jejunal leiomyosarcoma and multiple liver metastases after examination. The jejunal leiomyosarcoma was resected by operation. Unresectable liver metastases were repeatedly treated by transarterial embolization with carboplatin and Lipiodol, and a significant reduction was achieved. ... He has remained well presently for 1 year 10 months after operation. 
&&url PMID: 8380684 


Cancer 1991 Jul 15;68(2):321-3 
<b>Regression of hepatic metastases from gastrointestinal leiomyosarcoma after hepatic arterial chemoembolization. </b>
Mavligit GM, Zukiwski AA, Salem PA, Lamki L, Wallace S. Department of Clinical Immunology, University of Texas M.D. Anderson Cancer Center, Houston 77030. 

Two patients with gastrointestinal leiomyosarcoma metastatic to the liver were treated by hepatic chemoembolization with cisplatin and polyvinyl sponge followed by hepatic arterial infusion of vinblastine. Effective palliation in terms of durable tumor regression was achieved in both patients after two chemoembolization-infusion procedures. These results suggest that regional therapy may offer new hope for the subset of sarcoma patients who have liver metastases resistant to combination systemic chemotherapy. 
&&url PMID: 2070331 


Zhonghua Yi Xue Za Zhi (Taipei) 2000 Nov;63(11):838-43 
<b>Abdominal wall necrosis following transcatheter arterial chemoembolization for hepatocellular carcinoma. </b>
Liu HJ, Chen TS, Lee RC, Ho DM, Lin JT, Chu LS, Chang FY. 
Division of Gastroenterology, Taipei Veterans General Hospital, 201, Section 2, Shih-Pai Road, Taipei, Taiwan 112, ROC. 

<b>We advise that embolization of the IMA [inferior mesenteric artery] in patients who have received radiotherapy should be avoided, if possible.</b> 
&&url PMID: 11155762 


Acta Radiol 2000 Mar;41(2):156-60 
<b>Ischemic complications of transcatheter arterial chemoembolization in liver malignancies. </b>
Tarazov PG, Polysalov VN, Prozorovskij KV, Grishchenkova IV, Rozengauz EV. 
Division of Angio/Interventional Radiology, St. Petersburg Research Institute of Roentgenology and Radiation Therapy, Russia. 

... To determine the frequency, character, methods of treatment, and outcome of ischemic complications after transcatheter hepatic artery chemoembolization (TACE). .. Ischemic complications appeared in 13 (4.6%) and included the following: hepatic (n=6) and splenic abscess (n= 1), cholecystitis (n=3), and bile duct necrosis (n=3). The treatment was US-guided drainage in 12 cases and systemic antibacterial therapy in 1. No negative influence of these complications on survival of patients was detected. ... Serious ischemic complications of TACE occur in about 5% of patients and can be successfully managed without open surgery. These complications do not worsen the survival of patients. 
&&url PMID: 10741789 


Bull Soc Sci Med Grand Duche Luxemb 1999;(2):29-36 
<b>Complications and hospitalisation--duration after chemoembolisation for liver metastases. </b>
Rauh S, Duhem C, Ries F, Dicato M. 
Dpt. of Hemato-Oncology, Centre Hospitalier, Luxembourg. 

In a retrospective study, all patients of the hemato-oncology department of the Centre Hospitalier who were treated from 1988 to 1997 by chemoembolisation for liver metastases were analysed for treatment-related hospitalisation duration, side effects and complications, in order to assess the treatment burden. Major side-effects were: pain in 17 of 29 patients, nausea in 8, vomiting in 7, persistent hiccup in 3, fever in 12, a temporary confusional state in 4 patients. 1 patient experienced syncope, 2 patients developed homolateral pleural effusions, 1 patient suffered transient supraventricular arrhythmias. Major complications included 1 hemoperitoneum (under anticoagulant therapy), 1 hemorrhagic gastritis, 1 acute cholecystitis due to inflammatory tumoral choledochal obstruction and one iatrogenous acute pancreatic ischemic necrosis. Two patients died of post-embolic acute hepatic insufficiency, one 10 days, one 41 days after the last treatment session). In summary, chemo-embolisation of liver metastases is a complication-burdened treatment in a strictly palliative setting with inestimable efficacy. The treatment modalities have to be discussed with the patient beforehand and preferably in controlled study setting. Large randomised trials may indicate patients' subgroups for benefit. 
&&url PMID: 11100173 


Cardiovasc Intervent Radiol 1999 Jul-Aug;22(4):293-7 
<b>Hepatic chemoembolization: effect of intraarterial lidocaine on pain and postprocedure recovery. </b>
Hartnell GG, Gates J, Stuart K, Underhill J, Brophy DP. 
Department of Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School, 1 Deaconess Road, Boston, MA 02215, USA. 
.
.. Intraarterial lidocaine during chemoembolization reduces the severity and duration of pain after chemoembolization resulting in faster recovery thus reducing the length of hospitalization. 
&&url PMID: 10415218 


Zhonghua Zhong Liu Za Zhi 1996 Sep;18(5):365-7 
[The clinical efficacy of hepatic artery infusion chemotherapy and chemoembolization in the treatment of liver metastases]. [Article in Chinese] 
Zeng X, Wang S, Wei C. Department of Radiology, Wuhan General Hospital of Guangzhou Miliary Region. 
The efficacy and clinical experience of transcatheter hepatic artery infusion chemotherapy alone or chemoembolization in 118 patients with hepatic metastases were reviewed. Hepatic arterial infusion chemotherapy followed by embolization with lipiodol suspension and gelatin sponge pieces was carried out in 72 cases, infusion chemotherapy followed by embolization with lipiodol suspension in 32, and arterial infusion chemotherapy alone in 14. The results showed that the clinical efficacy of the first method was the best while that of the third method was the worst. The best effect was seen in patients with the single and hypervascular metastatic focus. The overall survival rate was 86.0%, 25.0%, 3.0% in 1 year, 3 years and 5 years, respectively. 
&&url PMID: 9387277 


Eur Radiol 1997;7(3):323-6 
<b>Arteritis following intra-arterial chemotherapy for liver tumors.</b> 
Belli L, Magistretti G, Puricelli GP, Damiani G, Colombo E, Cornalba GP. 
Department of Radiology, Ospedale Multizonale, Viale Borri 57, I-21100 Varese, Italy. 

... with transcatheter chemoembolization (TACE) during selective arterial catheterization... Arteritis is a possible referred side effect which can lead to tortuosity of the arteries, stenosis and occlusion of vessels. In our hospitals 117 consecutive patients were treated with TACE from January 1990 to December 1992.... Selective angiography performed 30-62 days after the first chemoembolization showed artery stenosis in 7 patients and thrombosis in 2 cases related to toxic arteritis due to chemoembolization. Reports about arteritis during TACE treatments are discussed. 
&&url PMID: 9087350 


Cancer 1996 Nov 15;78(10):2216-22 Comment in: Cancer. 1996 Nov 15;78(10):2039-42 
<b>Positron emission tomography with F-18-fluorodeoxyglucose to evaluate the results of hepatic chemoembolization. </b>
Vitola JV, Delbeke D, Meranze SG, Mazer MJ, Pinson CW. 
Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2675, USA. 
... Positron emission tomography (PET) using F-18-flurodeoxyglucose (18FDG) is an imaging modality allowing direct evaluation of cellular glucose metabolism. The purpose of this study was to examine the role of 18FDG-PET in monitoring chemoembolization therapy of patients with liver metastases from adenocarcinoma. ... patients were evaluated with 18FDG-PET before and 2-3 months after interventional therapy. All patients underwent transcatheter arterial chemoembolization. A total of nine PET studies were performed. ... Twenty-five of 34 lesions had decreased 18FDG uptake ...as expected in successful tumor chemoembolization. These findings were associated with a significant decrease in serum tumor marker levels ... after treatment. However, there were 3 new lesions, and 6 of the 34 lesions demonstrated persistent or increased 18FDG uptake after treatment ... consistent with the presence of residual viable tumor. These findings led to further interventional therapy in all patients. ... 18FDG-PET allows monitoring of response to treatment with hepatic chemoembolization in patients with liver metastases from adenocarcinoma. PET is a useful diagnostic tool and has the potential to be used to guide further interventional therapy. 
&&url PMID: 8918417 


Acta Chir Belg 1996 Feb;96(1):37-40 
<b>Initial experience with the use of preoperative transarterial chemoembolization in the treatment of liver metastasis. </b>
Ceelen W, Praet M, Villeirs G, Defreyne L, Pattijn P, Hesse U, de Hemptinne B. 
Department of Surgery, Gent University Hospital, Belgium. 

We retrospectively evaluated the influence of preoperative Transarterial Chemoembolization (TAE) on technique and complications, tumour histology, and disease-free survival after surgery for hepatic metastasis. In a 2-year period, a total of 23 patients were treated. In a first group of 14 patients, preoperative TAE was performed; in a second group of 9 patients only surgical resection was done. Extensive tumour necrosis was seen in the majority of patients treated with TAE; in tumours with an important fibrotic component, embolization was less effective. No significant effect was seen on operating time, transfusion requirement or perioperative complication rate. In the group of patients who underwent TAE, survival rate was 93% after a mean follow-up period of 15.5 months (SD: 12.5); recurrence was seen in only 8% of the survivors. In the second group, however, mortality was 33% after a median follow-up of 17.5 months (SD: 10), and recurrence was present in 66.7% of the survivors. These results indicate that preoperative TAE reduces the recurrence rate in the first postoperative year. Thereby survival may be improved in patients with resectable metastatic liver cancer. Publication Types: Clinical trial Randomized controlled trial 
&&url PMID: 8629387 


J Surg Oncol 1995 Oct;60(2):116-21 
<b>Hepatic artery chemoembolization or embolization for primary and metastatic liver tumors: post-treatment management and complications.</b> 
Berger DH, Carrasco CH, Hohn DC, Curley SA. 
Department of Surgical Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA. 
...The morbidity rate following HACE and HAE in this study was 5.1%. The major complications included portal vein thrombosis, hepatic abscess, and liver failure. The treatment-related mortality rate was 4.1%. Fever and ileus were the most common management problems ... Median survival for patients with liver metastases varied according to histologic type, .... Morbidity and mortality ... can be minimized by proper selection and careful management of patients. HACE or HAE alone was not curative in any of these 121 patients. An understanding of treatment-related side effects is necessary to aid in the management of patients .... 
&&url PMID: 7564377 


Radiology 1994 Dec;193(3):743-6 
Multiple intrahepatic aneurysms following transcatheter arterial embolization. Work in progress. 
Aso N, Matsunaga N, Fukuda T, Sakamoto I, Ashizawa K, Aikawa H, Isomoto I, Hayashi K, Fukushima T, Morikawa M. 
Department of Radiology, Nagasaki University School of Medicine, Nagasaki, Japan. 
... To discuss the mechanism of multiple intrahepatic aneurysm formation after transcatheter arterial embolization (TAE) performed in five patients with hepatocellular carcinoma. ... TAE was performed with gelatin sponge particles and iodized oil as embolic materials. Mitomycin C was also used in four cases. ... Three to 14 aneurysms 1-6 mm in diameter were found in third-to sixth-order branches of the hepatic arteries at repeat angiography performed 25-45 days after TAE. Follow-up angiograms in three cases revealed that most aneurysms were no longer apparent except in one patient in whom two aneurysms remained and were larger than before. In none of the five cases were any signs of aneurysm rupture noted. ... Radiologists should be aware of this complication of TAE. It is speculated that the main cause of aneurysm formation in these patients was the embolic agents used.  
&&url PMID: 7972817 

