Magnetic Resonance Printed in the USA.
Imaging, Vol.9,pp.201-204, All rights reserved.
1991 Copyright
0730-725x/91 $3.00 + .OO 0 1991 Pergamon Press plc
0 Original Contribution
MR AND CT IMAGING OF ETHANOL-TREATED LIVER TUMORS IN AN ANIMAL MODEL JEFFREY J. PHILLIPS,* STANLEY L. CHANG,* PAUL S. DICKMAN,~
JOHN A.
Bumm,f’
HERNAN I. VARGAS,~
AND JAMES D. LIPCAMON*
Departments of *Radiology, tSurgery, and SPathology, Harbor-UCLA Medical Center, Torrance, California 90509, USA To characterize the radiographic appearance of liver lesions over time following ethanol injection, seven New Zealand white rabbits underwent surgical implantation of small fragments of VX-2 carcinoma within the liver. Upon reaching 1 cm in diameter, a tumor nodule was directly injected with absolute ethanol. Another nodule in the same animal was injected with saline as a control. Imaging was performed 6-24 days after the injections by high resolution CT and MRI, and correlation obtained with the pathologic specimens. Long TR spin-echo MR sequences were found to characterize the ethanol-treated regions of liver most accurately. Liver tissue infarcted by alcohol could be differentiated from tumor and necrosis by virtue of its short T2relaxation value. There were no distinguishing features by other imaging techniques between the ethanol-treated and control tumor nodules. Peripheral contrast enhancement was demonstrated in both, corresponding to fibrous tissue around the ethanolinjected regions, and to viable tumor in the case of controls. Keywords: Alcohol; Ethanol; Liver neoplasms, MR studies; Liver neoplasms, therapy; Magnetic resonance, comparative studies. INTRODUCTION
mind, we undertook to examine the MR appearance of liver lesions treated by injection of ethyl alcohol in an experimental model. CT scanning was performed simultaneously for the purpose of comparison.
An alternative to the surgical resection of small hepatic tumors is ultrasound-guided percutaneous injection of ethyl alcohol. As a therapeutic agent, its cytotoxicity proceeds through cellular dehydration followed by coagulation necrosis, fibrotic reaction and vascular thombosis. I-* A nonsurgical option is applicable to those patients who refuse surgery, or who are judged to be unresectable on the basis of bilobar disease, serious medical illness, or the presence of coexistent liver disease. Recently, this form of therapy has been performed successfully by several groups to treat unresectable hepatic neoplasms.‘-4 In those studies, evaluation of the treatments was done through ultrasonography, angiography and computed tomography. Although its applications to hepatic imaging are well recognized, we are not aware of any attempts to use MRI in the follow-up of direct ethanol injections. With that in RECEIVED 6/15/90;
ACCEPTED
MATERIALS Animal
AND METHODS
Model
The VX-2 rabbit carcinoma (Bogden Laboratory, Hopkinton, MA) is maintained through serial transplantations into the hind limb musculature of New Zealand White (NZW) rabbits. The tumor is a solid carcinoma whose histology and growth characteristics have been previously described.5-6 Following implantation into either soft tissue or liver, the tumor enlarges rapidly and develops increased vascularity along its advancing rim. Tumor fragments excised from the hind limb of VX-2 bearing rabbits were placed into RPMI-1640 medium, and these fragments were dissected into Address all correspondence to Jeffrey J. Phillips, M.D.,
10/17/90.
Harbor-UCLA Diagnostic mandie Avenue, Torrance,
This work was supported by a grant from the California Institute of Cancer Research and the American Cancer Society Institutional Grant #IN-131-I to the Jonsson Comprehensive Cancer Center of UCLA. 201
Imaging Center, 21828 S. NorCA 90502, USA.
202
Magnetic Resonance Imaging 0 Volume 9, Number 2, 1991
1 mm3 fragments. Inbred female NZW rabbits, each weighing 3 to 4 kg, were used as recipients. Following anesthesia with ketamine and xylazine, the animals were explored through a midline incision and small nicks made in Glisson’s capsule of the left anterior and middle lobes of the liver. The tumor fragments were then placed into the hepatic parenchyma with sharp forceps. Approximately 14 days following implantation, the rabbits were evaluated by CT and MRI scans to determine the size of the tumors. When the tumors reached 1 cm in diameter, all rabbits except one underwent exploratory laparotomy under general anesthesia, and the tumor in the left anterior lobe was injected under direct vision with 2.3 f 0.7 ml of absolute ethyl alcohol through a 22-gauge needle. This was accomplished with multiple needle passes through the tumor and immediately adjacent hepatic parenchyma. The remaining rabbit was percutaneously injected with 5.5 cc of alcohol under CT guidance. In all but one rabbit, the tumor in the middle lobe was injected with an equal volume of saline and served as a control. The exception was a case where only one lesion grew in the liver, and was subsequently treated with alcohol. Seven rabbits were included in this project. Imaging Studies Between 6 and 24 days post injection, the rabbits were evaluated by CT and MRI scans under general anesthesia with ketamine and xylazine. CT scans were done on a Picker 1200 SX scanner (Highland Heights, OH) using contiguous S-mm-thick sections. The entire liver was imaged initially prior to contrast administration (8-10 slices). A second scan was performed immediately following a 10 cc bolus of 60% iothalamate meglumine, introduced by means of an ear vein. Comparable MR examinations were performed on the same day with a 0.5 T Picker Vista 2055 scanner in the transaxial plane using a dedicated head coil. The section thickness was 5 mm with an interslice gap of 1 or 2 mm. 7’,-weighted spin-echo images (T,-WI’s) were obtained using TR (repetition time) of 316 msec, TE (echo time) of 20 msec, 10 averages, and a 128 x 256 matrix both before and immediately after the administration of IV contrast (0.2 mmol/kg gadopentetate dimeglumine). Tz-weighted images (T’.-WI’s) obtained before contrast administration utilized a TR of 1800-2000 msec, TE of 100 msec, 2 averages, and a 192 x 256 matrix. Pathologic Studies The animals were sacrificed within 12-48 hr of the last imaging examination and the alcohol and salineinjected nodules fixed in neutral buffered formalin. Representative sections were obtained, oriented iden-
tically to the transaxial plane images obtained in vivo, and stained with hematoxylin and eosin. The sections were evaluated by light microscopy and correlated with the premortem MR and CT examinations. RESULTS Ethanol-treated Nodules Noncontrast h4RI The most distinguishing MR feature of ethanoltreated tumor was the low signal intensity manifested on long TR/TE SE sequences (Fig. l(A)). The appearance varied from uniform low signal to low signal intensity with central punctate high signal or strandy intermediate signal intensity. In the rabbit treated percutaneously with alcohol, a small zone of hypointensity was imaged adjacent to a larger area of high signal. On 7’,-weighted sequences, treated liver tumor was hypointense in 517 cases and isointense to liver in 217 (Fig. l(B)). Contrast A4RI Rim enhancement with gadopentetate dimeglumine (Fig. l(C)) was demonstrated in all but one case. Contrast improved lesion conspicuity as well as delineation from normal liver on Tr-weighted images. CT Tumor injected with ethyl alcohol appeared hypodense in 6/7 cases and isodense with the surrounding liver in the other case (Fig. l(D)). After contrast, an enhancing rim was seen in 6/7 cases, resulting in improved lesion conspicuity. This rim varied from being thin and smooth to markedly irregular. Saline-injected Nodules Noncontrast MRI Saline-injected nodules appeared hypointense relative to liver with Tr-weighting in 6/6 cases. All were hyperintense on long TR/TE sequences, in contrast to the low signal intensity seen following ethanol injection (Fig. l(A)). Contrast A4RI After administration of gadopentetate dimeglumine, peripheral enhancement was seen in 5/6 lesions. This resulted in improved delineation of the tumor margin. CT Saline-injected nodules were visuahzed on CT as areas of low attenuation in 516 and near isodense in one case. Peripheral contrast enhancement was observed in the same 5/6 cases where Gadolinium enhancement
MR and CT imaging of ethanol-treated
liver tumors 0 J.J.
PHILLIPS ET AL.
203
Fig. 1. (A) T,-weighted sequence (TR = 2.0 set, TE = 100 msec). The ethanol-treated region appears hypointense (solid arrow) while the saline-injected, partially necrotic tumor is hyperintense (open arrow). The hyperintense region to the right corresponds to the stomach (St). (B) The ethanoltreated lesion (arrow) appears isointense on precontrast 7’,weighted image (TR = 316 msec, TE = 20 msec). (C) Postcontrast, the treated area is better delineated due to peripheral rim enhancement (arrow). The precontrast (D) and the postcontrast (E) CT images are shown for comparison. The treated area is nearly isodense precontrast (arrow, D) but becomes better defined by a rim of enhancement postcontrast (arrow, E). Contrast enhancement is also seen around the periphery of the control nodule (arrowhead).
was demonstrated by MRI. In three advanced cases (27-39 days after implantation) additional tumor nodules were seen near the anterior surface of the liver. These were also seen by MRI.
Pathologic Findings The saline-injected, control tumor nodules were composed of poorly differentiated adenocarcinoma, with epithelial cells arranged in cords and poorly
Magnetic Resonance Imaging 0 Volume 9, Number 2, 1991
204
formed glands. Viable tumor was present predominantly at the periphery of the nodules, with extensive central necrosis. The centrally necrotic tumor correlated with the regions seen on Ti-WI’s as low signal intensity and on Tz-WI’s as high signal intensity. Viable tumor in the periphery demonstrated the observed contrast enhancement on T, -weighted images. In several cases, satellite tumor nodules were present at the periphery of the dominant mass. The alcohol-treated areas were predominantly composed of infarcted liver with tiny foci of necrotic tissue, often with cystic change, at the center. The acellular regions of infarcted liver correlated well with the MR appearance of low signal intensity on T1WI’s and very low signal intensity on T,-WI%. The central small necrotic foci appeared on MR as strandy or punctate regions of higher signal intensity. The periphery of the ethanol-treated liver was necrotic with polymorphonuclear cells invading the infarcted tissue. Beyond that, vascular fibrotic tissue circumscribed the infarcted region, and was distinguishable on contrast MR (and CT) by peripheral enhancement. Any remaining viable tumor was limited to nodules at the edge of infarcted liver, suggesting incomplete ablation of the tumor by the ethanol injection, or to foci similar to the satellite nodules seen in saline-injected nodules. DISCUSSION
Short TR/TE spin-echo sequences were comparable to CT in terms of lesion definition and characterization. Both were judged superior to T,-weighted SE sequences for visualizing the extent of abnormality, due to better spatial resolution. Rapidly acquired SE images following gadolinium administration demonstrated peripheral enhancement around both ethanoltreated and control (saline-injected) regions. In the former instance this correlated well with vascular fibrotic tissue surrounding areas of infarcted hepatic parenchyma, and provided better delineation from normal liver. Enhancement in the periphery of control nodules corresponded to viable tumor around central necrosis. Hence, while contrast improved MR characterization in this experimental setting, it appeared to lack specificity. The pattern of enhancement with io-
dinated contrast (CT) was virtually identical to that of gadopentetate dimeglumine. Long TR/TE spin-echo sequences provided the greatest contrast differentiation between treated and control tumors in the liver. The histology of ethanolinjected liver was that of infarcted hepatic parenchyma. Because the short T2-relaxation value of such tissue, the predominant MR appearance of treated tumor nodule was low signal intensity on both T,- and T2-weighted images. The presence of internal or peripheral high signal correlated histologically with areas of necrosis and in some cases viable tumor foci which escaped the ethanol effects. These viable cells often occurred in satellite nodules adjacent to the ethanol treated area. As this mode of therapy becomes more commonplace in clinical practice, MR may come to be used in patient management. The high image contrast between tumor and infarcted tissue on T2-WI’s could be utilized in the setting of patient follow-up. The appearance of increasing or de novo high signal regions on T,-weighted images, or contrast enhancement on T,weighted images, would indicate the need for further intervention. REFERENCES 1. Livraghi, T.; Salmi, A.; Bolondi, L.; et al. Small hepatocellular carcinoma: Percutaneous alcohol injectionresults in 23 patients. Radiology 168:313-317; 1988. 2. Livraghi, T.; Festi, D.; Monti, F.; Salmi, A.; Vettori, C. US-guided percutaneous alcohol injection of small hepatic and abdominal tumors. Radiology 161:309-312; 1986. 3. Shiina, S.; Yasuda, H.; Muto, H.; et al. Percutaneous ethanol injection in the treatment of liver neoplasms. AJR 149:949-952;
1987.
4. Sheu, J.C.; Huang, G.T.; Chen, D.S.; et al. Small hepatocellular carcinoma: Intratumor ethanol treatment using new needle and guidance systems. RadioZogy I63:43-48; 1987.
5. Stewart, H.L.; Snell, K.C.; Dunham, L.F.; et al. Transplantable and transmissible tumors of animals. Atlas of Tumor Pathology, National Research Council, Washington, D.C., 1959. 6. Galasko, C.S.; Muckle, D.S. Intrasarcolemmal proliferation of the VX-2 carcinoma. Br. J. Cancer 29:59-65; 1974.
Imaging, Vol.9,pp.201-204, All rights reserved.
1991 Copyright
0730-725x/91 $3.00 + .OO 0 1991 Pergamon Press plc
0 Original Contribution
MR AND CT IMAGING OF ETHANOL-TREATED LIVER TUMORS IN AN ANIMAL MODEL JEFFREY J. PHILLIPS,* STANLEY L. CHANG,* PAUL S. DICKMAN,~
JOHN A.
Bumm,f’
HERNAN I. VARGAS,~
AND JAMES D. LIPCAMON*
Departments of *Radiology, tSurgery, and SPathology, Harbor-UCLA Medical Center, Torrance, California 90509, USA To characterize the radiographic appearance of liver lesions over time following ethanol injection, seven New Zealand white rabbits underwent surgical implantation of small fragments of VX-2 carcinoma within the liver. Upon reaching 1 cm in diameter, a tumor nodule was directly injected with absolute ethanol. Another nodule in the same animal was injected with saline as a control. Imaging was performed 6-24 days after the injections by high resolution CT and MRI, and correlation obtained with the pathologic specimens. Long TR spin-echo MR sequences were found to characterize the ethanol-treated regions of liver most accurately. Liver tissue infarcted by alcohol could be differentiated from tumor and necrosis by virtue of its short T2relaxation value. There were no distinguishing features by other imaging techniques between the ethanol-treated and control tumor nodules. Peripheral contrast enhancement was demonstrated in both, corresponding to fibrous tissue around the ethanolinjected regions, and to viable tumor in the case of controls. Keywords: Alcohol; Ethanol; Liver neoplasms, MR studies; Liver neoplasms, therapy; Magnetic resonance, comparative studies. INTRODUCTION
mind, we undertook to examine the MR appearance of liver lesions treated by injection of ethyl alcohol in an experimental model. CT scanning was performed simultaneously for the purpose of comparison.
An alternative to the surgical resection of small hepatic tumors is ultrasound-guided percutaneous injection of ethyl alcohol. As a therapeutic agent, its cytotoxicity proceeds through cellular dehydration followed by coagulation necrosis, fibrotic reaction and vascular thombosis. I-* A nonsurgical option is applicable to those patients who refuse surgery, or who are judged to be unresectable on the basis of bilobar disease, serious medical illness, or the presence of coexistent liver disease. Recently, this form of therapy has been performed successfully by several groups to treat unresectable hepatic neoplasms.‘-4 In those studies, evaluation of the treatments was done through ultrasonography, angiography and computed tomography. Although its applications to hepatic imaging are well recognized, we are not aware of any attempts to use MRI in the follow-up of direct ethanol injections. With that in RECEIVED 6/15/90;
ACCEPTED
MATERIALS Animal
AND METHODS
Model
The VX-2 rabbit carcinoma (Bogden Laboratory, Hopkinton, MA) is maintained through serial transplantations into the hind limb musculature of New Zealand White (NZW) rabbits. The tumor is a solid carcinoma whose histology and growth characteristics have been previously described.5-6 Following implantation into either soft tissue or liver, the tumor enlarges rapidly and develops increased vascularity along its advancing rim. Tumor fragments excised from the hind limb of VX-2 bearing rabbits were placed into RPMI-1640 medium, and these fragments were dissected into Address all correspondence to Jeffrey J. Phillips, M.D.,
10/17/90.
Harbor-UCLA Diagnostic mandie Avenue, Torrance,
This work was supported by a grant from the California Institute of Cancer Research and the American Cancer Society Institutional Grant #IN-131-I to the Jonsson Comprehensive Cancer Center of UCLA. 201
Imaging Center, 21828 S. NorCA 90502, USA.
202
Magnetic Resonance Imaging 0 Volume 9, Number 2, 1991
1 mm3 fragments. Inbred female NZW rabbits, each weighing 3 to 4 kg, were used as recipients. Following anesthesia with ketamine and xylazine, the animals were explored through a midline incision and small nicks made in Glisson’s capsule of the left anterior and middle lobes of the liver. The tumor fragments were then placed into the hepatic parenchyma with sharp forceps. Approximately 14 days following implantation, the rabbits were evaluated by CT and MRI scans to determine the size of the tumors. When the tumors reached 1 cm in diameter, all rabbits except one underwent exploratory laparotomy under general anesthesia, and the tumor in the left anterior lobe was injected under direct vision with 2.3 f 0.7 ml of absolute ethyl alcohol through a 22-gauge needle. This was accomplished with multiple needle passes through the tumor and immediately adjacent hepatic parenchyma. The remaining rabbit was percutaneously injected with 5.5 cc of alcohol under CT guidance. In all but one rabbit, the tumor in the middle lobe was injected with an equal volume of saline and served as a control. The exception was a case where only one lesion grew in the liver, and was subsequently treated with alcohol. Seven rabbits were included in this project. Imaging Studies Between 6 and 24 days post injection, the rabbits were evaluated by CT and MRI scans under general anesthesia with ketamine and xylazine. CT scans were done on a Picker 1200 SX scanner (Highland Heights, OH) using contiguous S-mm-thick sections. The entire liver was imaged initially prior to contrast administration (8-10 slices). A second scan was performed immediately following a 10 cc bolus of 60% iothalamate meglumine, introduced by means of an ear vein. Comparable MR examinations were performed on the same day with a 0.5 T Picker Vista 2055 scanner in the transaxial plane using a dedicated head coil. The section thickness was 5 mm with an interslice gap of 1 or 2 mm. 7’,-weighted spin-echo images (T,-WI’s) were obtained using TR (repetition time) of 316 msec, TE (echo time) of 20 msec, 10 averages, and a 128 x 256 matrix both before and immediately after the administration of IV contrast (0.2 mmol/kg gadopentetate dimeglumine). Tz-weighted images (T’.-WI’s) obtained before contrast administration utilized a TR of 1800-2000 msec, TE of 100 msec, 2 averages, and a 192 x 256 matrix. Pathologic Studies The animals were sacrificed within 12-48 hr of the last imaging examination and the alcohol and salineinjected nodules fixed in neutral buffered formalin. Representative sections were obtained, oriented iden-
tically to the transaxial plane images obtained in vivo, and stained with hematoxylin and eosin. The sections were evaluated by light microscopy and correlated with the premortem MR and CT examinations. RESULTS Ethanol-treated Nodules Noncontrast h4RI The most distinguishing MR feature of ethanoltreated tumor was the low signal intensity manifested on long TR/TE SE sequences (Fig. l(A)). The appearance varied from uniform low signal to low signal intensity with central punctate high signal or strandy intermediate signal intensity. In the rabbit treated percutaneously with alcohol, a small zone of hypointensity was imaged adjacent to a larger area of high signal. On 7’,-weighted sequences, treated liver tumor was hypointense in 517 cases and isointense to liver in 217 (Fig. l(B)). Contrast A4RI Rim enhancement with gadopentetate dimeglumine (Fig. l(C)) was demonstrated in all but one case. Contrast improved lesion conspicuity as well as delineation from normal liver on Tr-weighted images. CT Tumor injected with ethyl alcohol appeared hypodense in 6/7 cases and isodense with the surrounding liver in the other case (Fig. l(D)). After contrast, an enhancing rim was seen in 6/7 cases, resulting in improved lesion conspicuity. This rim varied from being thin and smooth to markedly irregular. Saline-injected Nodules Noncontrast MRI Saline-injected nodules appeared hypointense relative to liver with Tr-weighting in 6/6 cases. All were hyperintense on long TR/TE sequences, in contrast to the low signal intensity seen following ethanol injection (Fig. l(A)). Contrast A4RI After administration of gadopentetate dimeglumine, peripheral enhancement was seen in 5/6 lesions. This resulted in improved delineation of the tumor margin. CT Saline-injected nodules were visuahzed on CT as areas of low attenuation in 516 and near isodense in one case. Peripheral contrast enhancement was observed in the same 5/6 cases where Gadolinium enhancement
MR and CT imaging of ethanol-treated
liver tumors 0 J.J.
PHILLIPS ET AL.
203
Fig. 1. (A) T,-weighted sequence (TR = 2.0 set, TE = 100 msec). The ethanol-treated region appears hypointense (solid arrow) while the saline-injected, partially necrotic tumor is hyperintense (open arrow). The hyperintense region to the right corresponds to the stomach (St). (B) The ethanoltreated lesion (arrow) appears isointense on precontrast 7’,weighted image (TR = 316 msec, TE = 20 msec). (C) Postcontrast, the treated area is better delineated due to peripheral rim enhancement (arrow). The precontrast (D) and the postcontrast (E) CT images are shown for comparison. The treated area is nearly isodense precontrast (arrow, D) but becomes better defined by a rim of enhancement postcontrast (arrow, E). Contrast enhancement is also seen around the periphery of the control nodule (arrowhead).
was demonstrated by MRI. In three advanced cases (27-39 days after implantation) additional tumor nodules were seen near the anterior surface of the liver. These were also seen by MRI.
Pathologic Findings The saline-injected, control tumor nodules were composed of poorly differentiated adenocarcinoma, with epithelial cells arranged in cords and poorly
Magnetic Resonance Imaging 0 Volume 9, Number 2, 1991
204
formed glands. Viable tumor was present predominantly at the periphery of the nodules, with extensive central necrosis. The centrally necrotic tumor correlated with the regions seen on Ti-WI’s as low signal intensity and on Tz-WI’s as high signal intensity. Viable tumor in the periphery demonstrated the observed contrast enhancement on T, -weighted images. In several cases, satellite tumor nodules were present at the periphery of the dominant mass. The alcohol-treated areas were predominantly composed of infarcted liver with tiny foci of necrotic tissue, often with cystic change, at the center. The acellular regions of infarcted liver correlated well with the MR appearance of low signal intensity on T1WI’s and very low signal intensity on T,-WI%. The central small necrotic foci appeared on MR as strandy or punctate regions of higher signal intensity. The periphery of the ethanol-treated liver was necrotic with polymorphonuclear cells invading the infarcted tissue. Beyond that, vascular fibrotic tissue circumscribed the infarcted region, and was distinguishable on contrast MR (and CT) by peripheral enhancement. Any remaining viable tumor was limited to nodules at the edge of infarcted liver, suggesting incomplete ablation of the tumor by the ethanol injection, or to foci similar to the satellite nodules seen in saline-injected nodules. DISCUSSION
Short TR/TE spin-echo sequences were comparable to CT in terms of lesion definition and characterization. Both were judged superior to T,-weighted SE sequences for visualizing the extent of abnormality, due to better spatial resolution. Rapidly acquired SE images following gadolinium administration demonstrated peripheral enhancement around both ethanoltreated and control (saline-injected) regions. In the former instance this correlated well with vascular fibrotic tissue surrounding areas of infarcted hepatic parenchyma, and provided better delineation from normal liver. Enhancement in the periphery of control nodules corresponded to viable tumor around central necrosis. Hence, while contrast improved MR characterization in this experimental setting, it appeared to lack specificity. The pattern of enhancement with io-
dinated contrast (CT) was virtually identical to that of gadopentetate dimeglumine. Long TR/TE spin-echo sequences provided the greatest contrast differentiation between treated and control tumors in the liver. The histology of ethanolinjected liver was that of infarcted hepatic parenchyma. Because the short T2-relaxation value of such tissue, the predominant MR appearance of treated tumor nodule was low signal intensity on both T,- and T2-weighted images. The presence of internal or peripheral high signal correlated histologically with areas of necrosis and in some cases viable tumor foci which escaped the ethanol effects. These viable cells often occurred in satellite nodules adjacent to the ethanol treated area. As this mode of therapy becomes more commonplace in clinical practice, MR may come to be used in patient management. The high image contrast between tumor and infarcted tissue on T2-WI’s could be utilized in the setting of patient follow-up. The appearance of increasing or de novo high signal regions on T,-weighted images, or contrast enhancement on T,weighted images, would indicate the need for further intervention. REFERENCES 1. Livraghi, T.; Salmi, A.; Bolondi, L.; et al. Small hepatocellular carcinoma: Percutaneous alcohol injectionresults in 23 patients. Radiology 168:313-317; 1988. 2. Livraghi, T.; Festi, D.; Monti, F.; Salmi, A.; Vettori, C. US-guided percutaneous alcohol injection of small hepatic and abdominal tumors. Radiology 161:309-312; 1986. 3. Shiina, S.; Yasuda, H.; Muto, H.; et al. Percutaneous ethanol injection in the treatment of liver neoplasms. AJR 149:949-952;
1987.
4. Sheu, J.C.; Huang, G.T.; Chen, D.S.; et al. Small hepatocellular carcinoma: Intratumor ethanol treatment using new needle and guidance systems. RadioZogy I63:43-48; 1987.
5. Stewart, H.L.; Snell, K.C.; Dunham, L.F.; et al. Transplantable and transmissible tumors of animals. Atlas of Tumor Pathology, National Research Council, Washington, D.C., 1959. 6. Galasko, C.S.; Muckle, D.S. Intrasarcolemmal proliferation of the VX-2 carcinoma. Br. J. Cancer 29:59-65; 1974.
