Assessment of perfusion patterns during hepatic artery infusion chemotherapy: EOE-13 CT and 99mTc-MAA scintigraphy

Hepatic perfusion patterns were evaluated in five patients receiving hepatic artery infusion chemotherapy. All patients underwent 99mTc macroaggregated albumin (99mTc-MAA) scintigraphy and CT with EOE-13. In each case, the diagnostic agent was administered through the infusion catheter at 0.66 ml/min. Hepatic perfusion patterns were identified with both imaging methods, but CT with EOE-13 yielded more precise anatomic detail and was unique in demonstrating the perfusion status of each hepatic metastasis. Further evaluation of EOE-13 for this purpose is warranted.     

Direct infusion of EOE-13 into the hepatic artery. Experimental evaluation of safety in monkeys

Ethiodized Oil Emulsion 13 (EOE-13) is an intravenous liver-spleen specific CT contrast agent. We infused EOE-13 directly into the hepatic arteries of five rhesus monkeys. Normal saline was administered in the same fashion in two control animals. Serial laboratory studies showed no major toxicity over a seven-day period. Intra-arterial EOE-13 has potential usefulness in the evaluation of hepatic artery infusion chemotherapy.     

Hepatic perfusion during hepatic artery infusion chemotherapy: evaluation with perfusion CT and perfusion scintigraphy

The standard method for the evaluation of hepatic perfusion during hepatic artery infusion (HAI) chemotherapy is planar hepatic artery perfusion scintigraphy (HAPS). Planar HAPS was performed with 2 mCi of [99mTc] macroaggregated albumin infused at 1 ml/min and compared with single photon emission CT (SPECT) HAPS and with a new study, CT performed during the slow injection of contrast material through the HAI catheter (HAI-CT). Thirteen patients underwent 16 HAI-CT studies, 14 planar HAPS studies, and 9 SPECT HAPS studies. In 13 of 14 studies (93%) HAI-CT and planar HAPS were in complete agreement as to the perfusion pattern of intrahepatic metastases and normal liver. In nine studies where all modalities were performed, the findings identified by HAI-CT and planar HAPS agreed in all cases, whereas the results of two SPECT scans disagreed with the other studies. With respect to perfusion of individual metastases, 14 of 14 HAI-CT studies, 12 of 13 planar HAPS studies, and 9 of 9 SPECT HAPS studies correctly demonstrated the perfusion status of individual lesions as indicated by the pattern of changes in tumor size determined on CT obtained before and after the perfusion studies. Hepatic artery infusion CT was superior for delineation of individual metastases, particularly small lesions, and for the evaluation of nonperfused portions of the liver. Planar HAPS detected extrahepatic perfusion in four patients, and this was not detected by HAI-CT. We conclude that HAI-CT and scintigraphy are complementary techniques. Hepatic artery infusion CT has advantages for the evaluation of intrahepatic perfusion, and planar HAPS is superior to HAI-CT for the detection of extrahepatic perfusion.     

Stabilization of a percutaneously implanted port catheter system for hepatic artery chemotherapy infusion

A port catheter system for hepatic artery infusion chemotherapy was implanted percutaneously via the left subclavian artery in 41 patients for treatment of unresectable liver metastases. The catheter tip was inserted into the gastroduodenal artery (GDA), the end hole was occluded with a guidewire fragment, and a side-hole for infusion was positioned at the bifurcation of the proper hepatic artery and the GDA. The GDA was embolized with steel coils around the infusion catheter tip via a transfemoral catheter. This procedure is designed to reduce the incidence of hepatic artery occlusion and infusion catheter dislocation.     

EOE-13 in the detection of hepatosplenic lymphoma

Thirty-nine patients with lymphoma were evaluated prospectively to determine the usefulness of Ethiodol-Oil-Emulsion-13 (EOE-13) in the detection of hepatosplenic lymphoma by computed tomography. The detection rate in the spleen increased from 8% (before EOE-13 infusion) to 92% (after EOE-13 infusion). In ten of 39 patients (25%) in this series, lymphomatous disease was recognized only on the postinfusion computed tomographic scan. The postinfusion EOE-13 study demonstrated additional visceral abnormalities in 38% of the patients. The potential usefulness, limitations, and toxicity of this hepatosplenic-specific imaging agent are discussed.     

CT of the liver and spleen with EOE-13: review of 225 examinations

EOE-13 is an experimental liver-spleen-specific computed tomographic (CT) contrast agent developed at the National Institutes of Health. Experience with this agent in 225 clinical examinations is described. On average, use of EOE-13 increases the attenuation of normal liver by 32.5 H and that of normal spleen by 52.3 H. Tumors in these organs increase only 2.6 H, making them more easily detectable. Most of the iodine in EOE-13 appears to clear from the liver and spleen by 24 hr after injection. No deaths or permanent morbidity have been observed. The complication rate is 3.6%. EOE-13 is valuable for the detection of hepatic and splenic tumors.     

Experimental comparison of EOE-13 and perfluoroctylbromide for the CT detection of hepatic metastases

The relative advantages of EOE-13 and perfluoroctylbromide (PFOB) as contrast agents were evaluated using CT scanning in animals with implanted liver tumors. Three criteria were used to compare these compounds: (1)the density difference between liver and tumor, (2)the presence of opacification of intrahepatic vascular structures, and (3)the presence of ring enhancement around the tumors. All three radiographic features were superior in the scans after injection of 5 g/kg of PFOB. When a reduced dose (1.7 g/kg) of PFOB was used, however, the scans obtained with EOE-13 were of approximately equal quality. It is concluded that if toxicity problems prevent administration of PFOB in humans, then EOE-13 will probably remain the contrast agent of choice for tumor imaging in the liver.     

Minimally invasive catheter implantation for regional chemotherapy of the liver: A new percutaneous transsubclavian approach

Purpose Development of a percutaneously implantable catheter system for regional chemotherapy of liver metastases and its application in patients with surgically implanted but dislocated catheters. Methods Thirty-three patients with liver metastases of colorectal tumors were submitted to percutaneous puncture of the subclavian artery and insertion of a catheter whose tip was placed in the proper hepatic artery and whose end was subcutaneously connected with an infusion pump. Results The mean duration of therapy via the percutaneously inserted catheter was 27 weeks (±14 weeks). The most frequent complication was disconnection of the therapy catheter from the tube of the infusion pump. Eighty percent of all complications were corrected by reintervention. The therapy drop-out rate due to catheter-associated complications was 9%. Conclusion Percutaneous insertion of a catheter for regional chemotherapy of the liver is a relatively uncomplicated method with high patient acceptance and simple access for reintervention.     

Gastric toxicity related to perfusion of the stomach via the left inferior phrenic artery during hepatic arterial infusion chemotherapy: report of two cases

We present two cases of gastric toxicity related to hepatic arterial infusion chemotherapy (HAIC) for liver metastases. The gastric toxicity was caused by the inflow of infused drugs into the stomach via the left inferior phrenic artery arising from the celiac arterial trunk. The catheter hole was placed in the celiac arterial trunk with occlusion of the splenic and many gastric arteries. It must be kept in mind that perfusion of the stomach may occur through the left inferior phrenic artery in HAIC.     

Heparinized catheters for long-term intraarterial infusion of 5-fluorouracil in liver metastases

A heparinized catheter was used for the regional infusion of 5-fluorouracil in seven patients with liver metastases. The hepatic artery was catheterized from the left brachial artery. The period of treatment varied from one to 13 weeks. Pull-out angiograms, obtained after eight catheterizations, revealed complete occlusion of the brachial artery in five and partial occlusion in three, although no patient had ischemic symptoms in the hand. Thus, heparinization of the catheter did not prevent thrombosis during long-term infusion therapy.     

Unsatisfactory hepatic perfusion after placement of an implanted pump and catheter system: angiographic correlation

Thirty-five patients with scintigrams showing unsatisfactory hepatic artery perfusion after surgical placement of an implanted pump and catheter system were examined with selective angiography (33 cases) or digital subtraction angiography (DSA) during which the contrast material was injected through the side port of the pump (six cases). In 34 of 35 cases, the cause of the unsatisfactory (either extrahepatic or incomplete) hepatic perfusion was defined. DSA was definitive in only two cases, in which extrahepatic flow through collateral vessels was demonstrated. The cause of the perfusion defect was hepatic artery thrombosis in 14 cases, extrahepatic flow through collateral vessels in 14 cases, a misplaced catheter in four cases, and a short proper hepatic artery without adequate length for mixing in two cases. Although hepatic artery perfusion scintigraphy is the primary tool for evaluation of hepatic perfusion after catheter placement, angiography plays an important role in treating the subset of patients with unsatisfactory hepatic perfusion.     

Arterial perfusion abnormalities of the liver after hepatic arterial infusion chemotherapy and their correlation with changes in the metastases: evaluation with CT and angiography

We studied the progress of hepatic arterial perfusion abnormalities in 50 patients receiving long-term arterial infusion chemotherapy for palliative treatment of liver metastases from colorectal cancers and correlated the findings with changes in the metastases. Intraarterially and IV enhanced CT scans and digital subtraction angiograms of the liver were made in all patients before chemotherapy and at 3-month intervals during chemotherapy for 1 year. Before the chemotherapy, all patients had normal hepatic arterial perfusion. Arterial perfusion abnormalities were detected in 30 patients (60%) after 6 months of chemotherapy and in 41 patients (82%) after chemotherapy for 1 year. After 6 months of chemotherapy, 36% of the regressive and 39% of the progressive metastases were located in areas with arterial perfusion abnormalities. After 1 year of chemotherapy, 54% of the regressive and 60% of the progressive metastases were situated in portions of the liver with perfusion abnormalities. Hepatic arterial perfusion abnormalities were found to be progressive during intraarterial infusion chemotherapy. No relationship between arterial perfusion abnormalities and tumor response to chemotherapy could be detected.     

Movement of the side hole occurring in a port-catheter system percutaneously implanted for hepatic arterial infusion chemotherapy

The authors report a case in which catheter-related difficulties occurred with a port-catheter system implanted to perform repeated hepatic arterial infusion chemotherapy for advanced hepatocellular carcinomas. The port-catheter system had been percutaneously implanted with the catheter tip fixation method, and a side hole had been created in the indwelling catheter for placement in the common hepatic artery. Four months after port-catheter placement, however, the indwelling catheter became bent at the location of the side hole in the proper hepatic artery. Subsequently, the side hole moved into the left hepatic artery, resulting in a lack of distribution of chemotherapeutic agents to the tumours in the segments of the liver supplied by the right hepatic artery. This situation was easily corrected with a simple interventional radiological method so that hepatic arterial infusion chemotherapy could be resumed with sufficient distribution over the entire liver. To our knowledge, such a problem involving a port-catheter system implanted with the catheter tip fixation method and its management thereafter has not been reported in the published literature.     

经肝动脉化疗栓塞术联合重组人血管内皮抑制素对兔VX_2肝移植瘤生长及转移的影响

目的 观察重组人血管内皮抑制素(rh-Endostatin)联合经肝动脉化疗栓塞术(TACE)对兔VX_2肝移植瘤生长及转移的影响. 方法 30只家兔肝内肿瘤种植后2周,随机分为3组,每组10只:生理盐水灌注组(对照组)、TACE组及rh-Endostatin联合TACE组.治疗后5周,所有动物均处死,取出肝脏及双肺标本观察.测量动物体重、肝脏的重量、计算肝脏指数(HI),计算肝移植瘤的体积、坏死面积,观察肝内、双肺肿瘤转移的发生率.结果 肿瘤植入后5周,各处理组动物体重均有明显的下降,肝脏重量增加,计算的肝指数各组分别为10.2±2.8、8.5±6.1、6.2±4.4;肿瘤体积各组分别为(36.2±3.4) cm~3、(23.6±4.5) cm~3、(10.9±5.1) cm~3,各组间差异有统计学意义.平均坏死率分别为(52.0±2.3)%、(63.6±3.5)%、(78.6±4.8)%,各组间差异有统计学意义.双肺转移结节的数目各组分别为50.3±31.3、53.6±35.1、16.8±18.4;转移结节的直径各组分别为(3.6±1.4) mm、(3.8±0.6) mm、(1.2±0.6) mm.rh-Endostatin联合TACE组与其它各组相比差异有统计学意义(P <0.01).肝内转移率、转移结节数目、rh-Endostatin联合TACE组与其它各组相比差异有明显的统计学意义( P<0.01). 结论 rh-Endostatin联合TACE治疗抑制肝移植瘤的生长,并对其肺转移也有抑制作用.     

Single photon emission computed tomographic studies (SPECT) of hepatic arterial perfusion scintigraphy (HAPS) in patients with colorectal liver metastases: improved tumour targetting by microspheres with angiotensin II

As intra-arterial chemotherapy for liver metastases of colorectal origin becomes accepted, methods of further improving drug delivery to the tumour have been devised. Degradable microspheres have been shown to reduce regional blood flow by transient arteriolar capillary block, thereby improving uptake of a co-administered drug, when injected into the hepatic artery. In our study of five patients, we combined hepatic arterial perfusion scintigraphy (HAPS) and SPECT to assess the localization of approximately 1 X 10(5) labelled microspheres of human serum albumin (99Tcm MSA) in tumour. In addition, in three patients, we assessed the effect of an intra-arterial infusion of the vasoactive agent angiotension II during HAPS. Results were interpreted by comparing transaxial slices with corresponding slices of a tin colloid liver-spleen scan. Two of five patients showed good localization of 99Tcm MSA in tumour without an angiotensin II infusion. Of the three patients receiving angiotensin II, all showed good tumour targetting with the vasoconstrictor compared with only one of these three before its use. Thus, hepatic arterial infusion of angiotensin II greatly improves microsphere localization in tumour in some patients with colorectal liver metastases. This technique may be useful in the assessment of tumour targetting before and during locoregional therapy.     

Evaluation of Intrahepatic Perfusion on Fusion Imaging Using a Combined CT/SPECT System: Influence of Anatomic Variations on Hemodynamic Modification Before Installation of Implantable Port Systems for Hepatic Arterial Infusion Chemotherapy

BACKGROUND: In some patients with hepatic tumors, anatomic variations in the hepatic arteries may require hemodynamic modification to render effective hepatic arterial infusion chemotherapy delivered via implantable port systems. We used a combined CT/SPECT system to obtain fused images of the intrahepatic perfusion patterns in patients with such anatomic variations and assessed their effects on the treatment response of hepatic tumors. METHODS: Using a combined SPECT/CT system, we obtained fused images in 110 patients with malignant liver tumors (n = 75) or liver metastasis from unresectable pancreatic cancer (n = 35). Patients with anatomic hepatic arteries variations underwent hemodynamic modification before the placement of implantable port systems for hepatic arterial infusion chemotherapy. We evaluated their intrahepatic perfusion patterns and the initial treatment response of their liver tumors. The perfusion patterns on the fused images were classified as homogeneous, local hypoperfusion, and/or perfusion defect. Using the WHO criteria of complete response (CR), partial response (PR), no change (NC), and progressive disease (PD), we evaluated the patients' tumor responses after 3 months on multislice helical CT scans. The treatment was regarded as effective in patients who achieved a complete response or partial response. RESULTS: Anatomic hepatic artery variations were present in 15 of the 110 patients (13.6%); 5 manifested replacement of the left hepatic artery (LHA), 8 of the right hepatic artery (RHA), and 1 each had replacement of the RHA and LHA, and replacement of the LHA plus an accessory RHA. In 13 of these 15 patients (87%), occlusion with metallic coils was successful. On fusion imaging, the perfusion patterns were recorded as homogeneous in 6 patients (43%), as hypoperfusion in 7 (50%), and 1 patient had a perfusion defect (7.1%) in the embolized arterial region. Of the 8 patients with RHA replacement, 4 manifested a homogeneous distribution and 3 hypoperfusion. In 2 of 5 patients with LHA replacement, the distribution was homogeneous. In 1 patient with RHA and LHA replacement, and in 1 patient with LHA replacement and an accessory RHA, we noted hypoperfusion in the RHA territory. All 6 patients with homogeneous distribution were classified as PR or NC on follow-up multidetector CT. Of the 7 patients manifesting hypoperfusion, 3 were classified as PD (43%), 3 as NC (43%), and 1 as PR (14%) on follow-up CT. CONCLUSION: Hemodynamic modification of anatomic hepatic artery variations resulted in hypoperfusion on fusion images. Differences in the intrahepatic perfusion patterns may affect the response to hepatic arterial infusion chemotherapy.     

Multidetector CT arteriography with volumetric three-dimensional rendering to evaluate patients with metastatic colorectal disease for placement of a floxuridine infusion pump

OBJECTIVE: We sought to evaluate the usefulness of multidetector CT (MDCT) arteriography with volumetric three-dimensional (3D) rendering to depict the hepatic vascular anatomy. Our study population was patients who had undergone arterial mapping in preparation for placement of a hepatic arterial floxuridine infusion pump for treatment of metastatic hepatic colorectal carcinoma. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 26 patients with hepatic colorectal metastases who had been scheduled for implantation of a hepatic artery pump. Before surgery, all patients underwent MDCT arteriography with volumetric 3D rendering of the hepatic vessels. The axial and 3D arteriograms were evaluated for their usefulness in depicting hepatic arterial anatomy. Subsequently, three patients also underwent catheter angiography. Twenty-two of the 26 patients imaged had a hepatic artery floxuridine infusion pump implanted. Results of the CT arteriography were correlated with findings at surgery or on catheter angiography if surgery was not performed. RESULTS: MDCT arteriography correctly revealed hepatic arterial anatomy in all 25 patients with angiographic or surgical confirmation. One patient with aberrant hepatic arterial anatomy did not have angiographic or surgical confirmation. Classic hepatic arterial anatomy was identified in 16 (64%) of 25 patients. The following hepatic arterial variants were found in one patient each: the common hepatic artery arising directly from the aorta; a replaced left hepatic artery; an accessory right hepatic artery; a replaced left hepatic artery and accessory right hepatic artery; a replaced right hepatic artery; a right hepatic arterial branch arising early (before the origin of the gastroduodenal artery); and replaced right and left hepatic arteries. Three patients were not suitable candidates for placement of a hepatic artery floxuridine pump. The patient who had no angiographic or surgical confirmation was also not considered a good surgical candidate because of replaced right and left hepatic arteries. Two patients (8%) had an accessory left hepatic artery. CONCLUSION: MDCT arteriography with volumetric 3D rendering is an accurate, noninvasive method of depicting hepatic arterial anatomy and, therefore, of selecting patients with colorectal metastatic disease who could benefit from hepatic artery pump implantation. Catheter angiography provides no additional information, and we have eliminated it as a routine preoperative imaging examination.     

CT evaluation of hepatic and splenic trauma with EOE-13. An experimental study in monkeys

EOE-13 is a liver-spleen specific CT contrast agent currently undergoing clinical trials. It is an aqueous emulsion of iodinated fatty acids. We studied eight rhesus monkeys with surgically created blunt trauma to the liver and spleen. The animals were examined using CT scans without contrast material and CT scans with EOE-13. Scans were performed at times between 3 hours and 24 hours after trauma. The presence of parenchymal injury was shown better EOE-13 (P less than 0.01). The use of EOE-13 permitted earlier diagnosis in both the liver and spleen. This contrast agent has potential for the evaluation of trauma in clinical practice, and may be particularly useful in children.     

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 the 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.     

Hepatic falciform artery: anatomy, angiographic appearance, and clinical significance

Three patients developed supraumbilical skin rashes during hepatic artery infusion chemotherapy by a surgically placed perfusion catheter and drug-infusion pump. In one patient, hepatic arterial scintigraphy with technetium-99m macroaggregated serum albumin showed increased uptake corresponding to the rash, and a hepatic arteriogram showed a dilated falciform branch of the left hepatic artery. Surgical ligation of the falciform artery permitted further treatment without recurrent rash. Based on a review of 100 celiac arteriograms, the incidence of the falciform artery on angiographic studies is approximately 2%. The angiographic appearance of this artery is presented, and its potential clinical significance in hepatic artery perfusion chemotherapy is discussed.