Percutaneous Ethanol Injection [PEI] & Liver Metastases 

Percutaneous interstitial [through the skin and into the tissue] systems to induce liver tumor necrosis [tissue death] can be classified  into two major groups: those using chemical agents (ethanol and acetic acid) and those adopting thermal effects (hot saline, radiofrequency, laser and microwave).

Percutaneous Ethanol Injection [PEI] is the injection of ethyl alcohol in high concentration, through the skin, directly into liver tumors. This is done under ultrasound or Xray visualization.   Injecting into the tissue or into the blood vessel feeding the tissue leads to cell death by destroying the cell membrane, cooking the cell enzymes, and blocking the blood vessels.   [Percutaneous infiltration or intravascular injection of ethanol leads to cell death by causing cell membrane lysis, protein denaturation, and vascular occlusion.]  Percutaneously injected ethanol is now used in the ablation of hepatic cysts and solid tumors.  As a treatment agent, ethanol combines the benefits of being widely available, inexpensive, efficacious, and relatively easy to administer. Optimal results require that the radiologist have considerable experience in scanning techniques and facility with percutaneous needle insertion under real-time visualization. Percutaneous ethanol injection therapy has a low complication rate.

Percutaneous ethanol injection therapy does not always completely ablate tumors, but can be used to debulk or downsize tumors, or to devascularize them prior to surgery.

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For discussion of results of treatment and of complications, see the abstracts below.


<b>Percutaneous Ethanol Injection [PEI] in the Treatment of Liver Metastases
Selected Annotated Medical Journal References</b>
[For the full abstract, use the links provided, or search on Pubmed.  Ed.]



Radiol Med (Torino) 1998 Sep;96(3):238-42 
<b>[Ultrasonography-guided percutaneous ethanol injection in large an/or multiple liver metastasis]. [Article in Italian]</b> 
Giorgio A, Tarantino L, Mariniello N, De Stefano G, Perrotta A, Aloisio V, Del Viscovo L, Alaia A. 
Servizio di Ecografia ed Ecointerventistica, Ospedale D. Cotugno, Napoli. assanui@tin.it 

INTRODUCTION: Percutaneous ethanol injection (PEI) under sonographic guidance is an effective therapy for hepatocellular carcinoma on cirrhosis, while less favorable results have been reported for liver metastases. Surgery and/or other new treatments (i.e., interstitial thermotherapy) are indicated only for small metastases (< 3 cm) and surgeons no longer perform the palliative debulking of neoplastic masses. 
...thirty-three patients with 62 large (> 3.5 cm) and/or multiple liver metastases, who were not eligible for surgery nor thermotherapy, were treated with one-shot PEI under general anesthesia. The diameter of the nodules ranged 35-92 mm (mean: 39); the lesions were single in 15 patients and localized in both the right and the left lobe in 19 patients. 25-110 ml ethanol were injected per session. Post-treatment results were assessed with dynamic or dual-phase spiral CT; therapeutic success was defined as the absence of hyperdense lesion areas. 
... Complete necrosis of the metastases was shown in 10 patients (30.3%). Necrosis rate ranged 70-90% in 21 patients (64%) and was 50% in 2 patients (5.7%). Survival rates were 94%, 80%, 80% and 44% at 12, 24, 36 and 44 months, respectively. No major complications were observed. Seeding of neoplastic cells along the needle tract has been never observed to date. ...
 Metastasis diameter and number impact on long-term survival. <b>PEI under general anesthesia allows to treat also the patients who are not eligible for other treatments and to inject large amounts of ethanol per session in different tumor areas because metastases usually set on in an otherwise healthy liver. ... One-shot PEI can cause major, even complete, tumor necrosis in large and multiple liver metastases. The absence of any important complications and the survival rates in our series seem to indicate that one-shot PEI is effective for tumor debulking in patients not eligible for surgery and other alternative treatments</b>. Publication Types: Clinical trial 
&&url PMID: 9850718 


Br J Radiol 2000 Aug;73(872):833-9 
<b>Percutaneous ethanol injection of the supplying artery to hepatocellular carcinoma that is not amenable to conventional treatment. </b>
Lin ZY, Wang JH, Hsieh MY, Yu ML, Chen SC, Chuang WL, Wang LY, Tsai JF, Chang WY. 
Department of Internal Medicine, Kaohsiung Medical University Hospital, Taiwan, Republic of China. 

The purpose of this study was to evaluate the clinical usefulness of ultrasound-guided percutaneous ethanol injection of the supplying artery (PEISA) to the tumour in the palliative management of hepatocellular carcinoma (HCC) that is not amenable to conventional treatments. A total of 23 cases of HCC, measuring from 3.1 cm to larger than 15 cm (median 5.4 cm) in 17 cirrhotic patients, were treated by PEISA. PEISA was used to control rapid growth of the tumour in seven patients and to reduce abdominal discomfort caused by rapid expansion of the tumour in 10 patients. .... <b>Following treatment, one tumour disappeared, 13 tumours shrank and nine tumours were unchanged in size. All patients with abdominal discomfort had relief after treatment. The common complications of PEISA were local pain and fever. In conclusion, PEISA is effective at treating painful HCC unsuitable for conventional treatment.</b>  
&&url PMID: 11026857 


J Neurosurg. 1998 May;88(5):923-4. 
Comment in: J Neurosurg. 1999 Sep;91(3):521-3.
<b>Tumor devascularization by intratumoral ethanol injection during surgery. Technical note.</b>
Lonser RR, Heiss JD, Oldfield EH.
Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1414, USA.

<b>Preoperative reduction in tumor vascularity has been accomplished previously by selective catheterization of tumor vessels and delivery of occlusive materials. The results of percutaneous infusion of vertebral hemangiomas and other vascular lesions led the authors to speculate that rapid devascularization of tumors by direct injection of ethanol (ETOH) could be used to reduce bleeding and facilitate resection during surgery. Thus, the use of intratumoral injection of ETOH and its effects on tumor hemostasis and resectability were examined. Four patients received direct injection of ETOH into either a spinal epidural (two renal cell carcinomas and one rhabdomyosarcoma) or a large cerebellar neoplasm (hemangioblastoma). Intraoperative perfusion of the tumors with ETOH produced immediate blanching and devascularization and enhanced visualization and resection. Incremental tumor devascularization is achieved by careful injection of small amounts of ETOH directly into the lesion, producing immediate and complete regional tumor devascularization. Use of this technique reduces intratumoral bleeding and enhances the ease and effectiveness of resection.</b>  
&&url PMID: 9576266  


Eur J Surg Oncol 2000 Feb;26(1):67-72 
<b>Multimodality treatment for patients with hepatocellular carcinoma: a single institution retrospective series. </b>
Takano S, Watanabe Y, Ohishi H, Kono S, Nakamura M, Kubota N, Iwai S. 
Third Department of Surgery, Nihon University School of Medicine, Tokyo, Japan. 

... The main therapeutic options for hepatocellular carcinoma (HCC) are hepatic resection, transcatheter arterial embolization (TAE), percutaneous ethanol injection therapy (PEIT) and regional chemotherapy (RC). ... This study retrospectively examined the results of primary treatment of 600 patients with hepatocellular carcinoma .... RESULTS: The selected primary treatment was hepatic resection for 53.7% of the cases, TAE for 31.5%, PEIT for 8.2% and RC for 6.6%,. .... The cumulative 5 and 7-year survival rates after the primary treatments were 52.% and 40.1%, respectively, for hepatic resection; 46.5% and 38.7%, for TAE; 49.6% and 33.1% for PEIT; and 16.7% and 8.3% for RC. ... To improve the treatment results for HCC, early detection is essential and various modalities of treatments in combination should be used for recurrence after primary treatment. 
&&url PMID: 10718183 

 
Acta Radiol 1996 Sep;37(5):655-9 
<b>Complications following high-dose percutaneous ethanol injection into hepatic tumors. </b>
Tapani E, Soiva M, Lavonen J, Ristkari S, Vehmas T. 
Department of Radiology, Helsinki University Central Hospital, Finland. 

... Percutaneous ethanol injection therapy (PEIT) with a 2-10 ml ethanol dose per session is widely used in the treatment of small hepatocellular carcinoma. Larger doses have been restricted for fear of complications. The aim of the present study was to make a retrospective evaluation of the complications following treatment of hepatic tumors with high doses of ethanol (up to 200 ml). ... ....: Serious complications did not occur. Pain was a common side effect, occurring in 48% of the procedures. Immediate pain during the treatment was related to the ethanol dose and increased significantly with increasing doses (p < 0.01). Other side effects were rare. ... PEIT with doses higher than previously reported seems to be safe. This should encourage further clinical studies that aim at fully working out the clinical value of such treatment. 
&&url PMID: 8915270 


J Ultrasound Med 1998 Aug;17(8):531-3 Comment in: J Ultrasound Med. 1999 Apr;18(4):314 
<b>Complications of percutaneous ethanol ablation.</b> 
Gelczer RK, Charboneau JW, Hussain S, Brown DL Department of Diagnostic Radiology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA. 
Percutaneous ethanol injection therapy performed with sonographic visualization is a steadily growing therapeutic method that can be used in the ablation of solid and cystic masses in a variety of anatomic locations.... Local infiltration or intravascular injection of ethanol leads to cell death by causing cell membrane lysis, protein denaturation, and vascular occlusion. ... percutaneously injected ethanol is now used in the ablation of hepatic cysts and solid tumors, ...As a treatment agent, ethanol combines the benefits of being widely available, inexpensive, efficacious, and relatively easy to administer. Optimal results require that the radiologist have considerable experience in ultrasonographic scanning techniques and facility with percutaneous needle insertion under real-time visualization. Alternatively, the radiologist may choose CT as a method to visualize needle placement. Percutaneous ethanol injection therapy ... has a low complication rate. We present two patients in whom hypotensive complications occurred during percutaneous ethanol injection therapy and discuss the likely causative mechanisms. 
&&url PMID: 9697961 


Liver Transpl Surg 1998 Jul;4(4):271-5 
<b>An appraisal of percutaneous treatment of liver metastases. </b>
Mazziotti A, Grazi GL, Gardini A, Cescon M, Pierangeli F, Ercolani G, Jovine E, Cavallari A. 
Policlinico S. Orsola, University of Bologna, Italy. 

"Percutaneous treatments, such as ethanol injection and radiofrequency, have been recently proposed for the treatment of liver metastases. The aim of this study was to evaluate the effects of these treatments in ... 8 patients who subsequently underwent liver resection." "These patients had been treated with percutaneous methods between December 1995 and May 1997.... the primary tumor was... in 1 patient, ileal leiomyosarcoma. The lesions were all initially small...The number of...[treatments]... ranged from 2 to 21. In all patients, a progression of the disease occurred... <b>Histologic examination of all surgical specimens revealed the presence of vital neoplastic tissue; only two specimens of carcinoid tumors showed more than 50% necrosis of the nodules treated percutaneously. These results led us to express doubts as to the efficacy of percutaneous ablative treatment for liver metastases."</b> Copyright 1998 W.B. Saunders Company. 
&&url PMID: 9649639 



Acad Radiol 1997 Sep;4(9):634-8 
<b>Liver tumor ablation: real-time monitoring with dynamic CT. [In rabbits. ed.] </b>
Hahn PF, Gazelle GS, Jiang DY, Compton CC, Goldberg SN, Mueller PR. Department of Radiology, Massachusetts General Hospital, Boston 02114, USA. 
... To determine whether incomplete contact of ethanol with tumor limits the success of percutaneous ethanol injection therapy. ... Percutaneous ethanol injection was performed in seven normal New Zealand white rabbits and 18 rabbits with 1-3-cm liver tumors .... ... In normal animals, virtually all injected ethanol tracked to the hepatic capsule. As ethanol was injected into tumors, peripheral tracking, similar to that seen in normal livers, or extratumoral puddling was observed. Ethanol-tumor contact was incomplete in 16 of 18 animals (89%). Histopathologic analysis showed incomplete tumor necrosis. CONCLUSION:<b> In this model of hepatic carcinoma metastasis, the tumor failed to hold sufficient ethanol for successful ablation by means of percutaneous ethanol injection therapy</b>. 
&&url PMID: 9288191 


Gan To Kagaku Ryoho. 2001 Aug;28(8):1083-9. 
<b>[Less invasive medical therapy for hepatocellular carcinoma]</b>[Article in Japanese]
Ikeda K.
Dept. of Gastroenterology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo 105-8470, Japan.

Since hepatocellular carcinoma (HCC) usually occurs in chronic liver disease, especially viral cirrhosis, it often recurs even after surgical resection. Because of the high recurrence rate of HCC, less invasive therapies have become more common recently, including percutaneous ethanol injection (PEI), percutaneous microwave coagulation therapy(PMCT), and radiofrequency ablation(RFA). A PEI needle or a coagulation electrode is usually inserted into an HCC nodule under ultrasonographic-guidance, and chemical or heat ablation is carried out with local or general anesthesia. A patient with a few numbers of small HCCs of 3 cm or less in diameter is a good candidate for these therapy modalities. Although RFA is the easiest and most effective of these therapies the best therapy for each patient is selected according to the number, size, and location of target lesions.  
&&url PMID: 11525022  


Langenbecks Arch Surg 1999 Aug;384(4):339-43 
<b>Percutaneous ethanol injection and radio-frequency ablation for the treatment of nonresectable colorectal liver metastases - techniques and results</b>. 
Becker D, Hansler JM, Strobel D, Hahn EG. 
Department of Medicine I, Friedrich-Alexander-University Erlangen-Nuremberg, Krankenhausstr. 12, D-91054 Erlangen, Germany, dirk.becker@med1.med.uni-erlangen.de 

BACKGROUND: Percutaneous ethanol injection (PEI) and radio-frequency (RF) ablation are possible palliative treatment modalities for patients with non-resectable liver metastases of colorectal carcinomas. The different techniques are explained and reviewed. ... PEI did not show promising results for the treatment of liver metastases. RF results were more encouraging; some studies showed improved mean survival times for patients when a complete necrosis of the metastases could be achieved. The maximum diameter of the necrotic area possible in a single session is about 5 cm. ... <b>PEI and RF are palliative last-line treatment strategies for patients with non-resectable liver metastases and should only be applied if chemotherapy is not sufficient or not possible.  The long-term efficacy of RF ablation in this group of patients has to be evaluated.</b>  
&&url PMID: 10473853 


Acta Radiol 2000 Sep;41(5):458-63 
<b>High-dose percutaneous ethanol injection therapy of liver tumors. Patient acceptance and complications.</b> 
Elgindy N, Lindholm H, Gunven P. 
Department of Diagnostic Radiology, Karolinska Hospital, Stockholm, Sweden. 

... To study the safety of high-dose ethanol injections in liver tumors and their acceptability as out-patient procedures under local anesthesia. ... High-dose injections with an average volume of 39 ml gave a mean pain score of 5.1, with a weak relationship between pain and volume. Other side effects and complications were unrelated to the ethanol dose. They comprised 1 syncopation, 1 occasion of hypoventilation requiring antidote to opiates, 12 short episodes of nausea or vomiting without need for i.v. fluids, 2 instances of sepsis, and 1 abscess that was drained percutaneously. Thirty-nine of the 62 sessions were performed in day care. .... Low-dose injections resulted in a mean pain score of 4.7 with the same requirement of i.v. analgesics as high doses, fewer instances of nausea and no infectious complications. ... High-dose ethanol injections in patients with liver malignancy had no mortality and a reasonable complication rate. They could be given without general anesthesia, often in day care. 
&&url PMID: 11016766 


Eur J Gastroenterol Hepatol 2000 Mar;12(3):285-90 
<b>Early detection of haemobilia associated with percutaneous ethanol injection for hepatocellular carcinoma. </b>
Obi S, Shiratori Y, Shiina S, Hamamura K, Kato N, Imamura M, Teratani T, Sato S, Komatsu Y, Kawabe T, Omata M. Department of Gastroenterology, University of Tokyo, Japan. 

... Haemobilia [bile in the blood] often results from iatrogenic [doctor-caused] injury [to the gall bladder] caused by therapeutic procedures. ... Early diagnosis of haemobilia based on ultrasonographic findings of the gallbladder lumen effectively reduces the severity of haemobilia-related complications due to immediate interruption of the interventional procedure. 
&&url PMID: 10750648 


Int J Clin Pract 1999 Jun;53(4):257-62 
<b>Percutaneous ethanol injection therapy in 47 cirrhotic patients with hepatocellular carcinoma 5 cm or less: a long-term result. </b>
Lin SM, Lin DY, Lin CJ.      Liver Research Unit, Chang Gung University, Taipei, Taiwan. 

To elucidate the long-term results of percutaneous ethanol injection (PEI) for hepatocellular carcinoma (HCC), 47 cirrhotic patients with HCC < or = 5 cm after PEI were analysed. ... 5-10 ml 95% ethanol was injected into the tumour every three to seven days until the echogenicity of the tumour changed to a hyperechoic or heterogeneous one. A booster PEI was given in 34 (56%) lesions with viable tumour, which was detected by dynamic computed tomography. The one, two, three and four-year survival rates were 85%, 75%, 61% and 39% respectively for all patients. Good liver reserve significantly improved the survival rate ... The one, two, three and four-year recurrence rates were 24%, 55%, 69% and 79% for all patients. HCC recurred more frequently in patients with multiple tumours (p < 0.02). 
&&url PMID: 10563068 


Eur J Gastroenterol Hepatol 1998 Nov;10(11):915-8 
Comment in: Eur J Gastroenterol Hepatol. 1998 Nov;10(11):907-9 
<b>Hepatic infarction following percutaneous ethanol injection therapy for hepatocellular carcinoma.</b> 
Seki T, Wakabayashi M, Nakagawa T, Imamura M, Tamai T, Nishimura A, Yamashiki N, Okamura A, Inoue K. 
Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan. 

We report on two patients who developed hepatic infarction after undergoing percutaneous ethanol injection therapy (PEIT) for hepatocellular carcinoma (HCC). In both cases, liver function parameters deteriorated immediately after the ethanol injection, and enhanced computed tomography images showed a wedge-shaped avascular low-density area due to hepatic infarction. ... When PEIT is used for patients with HCC who have previously undergone TAI, especially with SMANCS, PEIT may induce hepatic infarction. 
&&url PMID: 9872612 


Abdom Imaging 1998 Nov-Dec;23(6):608-10 
<b>Fatal thrombosis of the portal vein following single-session percutaneous ethanol injection therapy of hepatocellular carcinoma. </b>
Lencioni R, Cioni D, Uliana M, Bartolozzi C. 
Department of Oncology, University of Pisa, Italy. 

Two weeks after percutaneous ethanol injection therapy for hepatocellular carcinoma, performed by injecting 110 mL ethanol in a single session with general anesthesia, a 69-year-old woman with well-compensated liver cirrhosis developed an extensive thrombosis of the whole portal tree that caused severe uncorrectable ascites and progressive deterioration of her general condition, resulting in death 6 weeks after the procedure. 
&&url PMID: 9922194 


Acta Gastroenterol Belg 1999 Jan-Mar;62(1):49-51 
<b>Acute renal failure requiring haemodialysis after high doses percutaneous acetic acid injection for hepatocellular carcinoma. </b>
Van Hoof M, Joris JP, Horsmans Y, Geubel A. 
Department of Gastroenterology, Saint Luc University Hospital, Bruxelles, Belgium. 

Recently, ultrasound-guided percutaneous acetic acid injection has been proposed in the treatment of hepatocellular carcinoma ...We report the case of severe renal failure requiring haemodialysis that occurred in a patient with 4 cm hepatocellular carcinoma treated adequately by high dose percutaneous acetic acid injection. The risk of such a serious side effect, likely related to a direct toxic effect of acetic acid, should be of concern when considering percutaneous treatment of hepatocellular carcinoma. Acute renal failure has been reported as a complication of acetic acid poisoning, but to our knowledge, we report here the first case of acute renal failure following high dose percutaneous acetic acid injection. 
&&url PMID: 10333599 


Gastroenterol Clin Biol 1998 Apr;22(4):459-61
<b>[Massive hepatic necrosis secondary to treatment of hepatocellular carcinoma by percutaneous alcoholization].[Article in French] </b>
Boucher E, Carsin A, Raoul JL, Marchetti C, Joram F, Kerbrat P. 
Centre Regional de Lutte contre le Cancer, Rennes. 

Fatal complication ... We report a case of massive hepatic necrosis after treatment by percutaneous ethanol injection of a 4 cm diameter hepatocellular carcinoma, which resulted in the death of the patient. The mechanism of this complication was probably an intratumoral aterioportal shunt, which allowed ethanol to spread through the blood vessels. 
&&url PMID: 9762276 

