Regional Transarterial Chemoembolization TACE

Neither systemic or local chemotherapy nor chemoembolization are primary techniques normally used with the aim of curing liver metastases. They are mainly considered a second-line treatment in patients with metastases of colorectal carcinoma.

On the other hand TACE is frequently used for curative treatment of HCC, especially in Asia.

TACE therapy is based on the differential blood supply of normal liver tissue and hepatic tumors. Whereas arterial perfusion accounts for about 25% of the blood supply in normal liver parenchyma, it may account for as much as 95% in hepatic neoplasms, depending on the histology of the tumor. Thus, solid liver tumors are frequently accessible to arterial embolization and/or intra-arterially applied chemotherapy, while surrounding liver tissue is not affected to the same extent due to its mainly portal venous blood supply. The direct superselective arterial application of chemotherapeutics leads to an increased concentration of the chemotherapeutic drug within the lesion with a concomitant reduction of systemic side effects [3].

Typically, chemoembolization involves the injection of an emulsion of iodized oil (e.g. lipiodol) followed by a chemotherapeutic drug (e.g. doxoru-bicin) and embolization particles applied via an arterial catheter that is advanced into the segmental or subsegmental arteries that feed the tumor tissue.

Chemoembolization may lead to a partial reduction of tumor volume which may secondarily allow surgical resection or interventional ablation in the case of inaccessible tumors. Frequently it is performed in cases in which systemic chemotherapy is ineffective and in cases of therapy-resistant pain arising from dilatation of the liver capsule [21,30].

TACE is generally contraindicated in a number of situations: when significant reduction of synthetic liver function is apparent, when 75% or more of the liver tissue is affected by the neoplasm, in cases of ascites where the Karnowski Index is less than 50%, and in cirrhotic livers when the liver parenchyma unaffected by the tumor has an increased arterial supply. Additionally, TACE may only be performed in cases of portal-venous obstruction if sufficient collaterals are present [14].

MRI is increasingly being used for follow-up studies in patients after injection of iodized oil. MRI is generally preferred to computed tomography (CT) for post-TACE imaging since the high concentration of lipiodol within the tumor can make it very difficult to recognize possible disease recurrence on CT imaging. This is due to the hy-perdensity of lipiodol which tends to mask the hy-pervascular areas of residual or recurrent tumor which are also hyperattenuating after injection of iodinated contrast material [13,31].

Follow-up imaging after TACE is possible between the first week and approximately two to three months after the procedure. If T1-weighted dynamic imaging is performed within the first week after TACE, the increased signal intensity seen in tumor nodules that accumulate lipiodol can sometimes make it difficult to detect residual hy-pervascular tumor tissue (Fig. 11). On the other hand, persistent lipiodol retention for more than four weeks indicates therapeutic effectiveness. Decreased signal intensity on T2-weighted images may also be observed within one week of treatment. However, remaining areas of higher signal intensity on T2-weighted images may not necessarily indicate residual tumor tissue, since the T2 relaxation time is also influenced by early concomitant modifications, such as ischemia, hemorrhage, edema and initial colliquative necrosis [4,31].

Whereas early follow-up after TACE is often inconclusive for the detection of recurrent tumor, follow-up T2-weighted and arterial phase con-

Fig. 7a-k. Liver lesions post-cryotherapy / no residual tumor. Pre-cryotherapy, the T2-weighted (a) and contrast-enhanced Tl-weighted equilibrium phase (b) images show a partially necrotic metastasis of colorectal cancer (arrows). One week after cryotherapy, the T2-weighted image (c) shows a partially hyperintense, partially hypointense region surrounded by a high SI rim. On the corresponding Tl-weighted (d) and Tl-weighted fat-suppressed (e) images, high SI areas within the cryolesion can be detected, indicating hemorrhage. Dynamic imaging in the arterial phase (f) reveals segmental hypervascular-ization of the affected liver segment, which is even more obvious in the portal-venous phase (g). However, no peripheral enhancement of the cryolesion is detected, indicating no residual tumor. In the equilibrium phase (h) a closed hyperintense rim (arrows) surrounding the lesion is observed without any enhancement of central areas. This indicates complete destruction of the tumor tissue.

A T2-weighted image acquired six months after cryotherapy (i) shows that the cryolesion still has heterogeneous, partially high SI. On the corresponding Tl-weighted image (j), heterogeneously high SI can be observed. On contrast-enhanced images in the equilibrium phase (k), enhancement of the central areas of the lesion is still not visible and a closed hyperintense rim surrounding the lesion can still be seen

Fig. 8a-g. Liver lesion post-cryotherapy showing no residual tumor in a patient with previous liver resection. On the unenhanced T2-weighted (a) and Tl-weighted (b) images pre-cryotherapy, a metastasis (arrows) can be seen in the left liver lobe. Note that the patient underwent previous right hemi-hepatectomy. The T2-weighted image (c) acquired one month following cryotherapy, shows a heterogeneous, predominantly high SI lesion. On the Tl-weighted image (d), this lesion is hypointense with some high SI areas indicative of hemorrhage. On dynamic imaging, segmental hypervascularization can again be noted in the arterial phase (e) with homogeneous signal in the portal-venous phase (f). The equilibrium phase image (g) again shows a closed hypervascular rim surrounding the lesion, indicating complete destruction of the metastasis

Fig. 9a-g. Patient post-cryotherapy demonstrating late recurrent disease. T2-weighted (a) and contrast-enhanced Tl-weighted equilibrium phase (b) images acquired three weeks after cryotherapy show two large cryolesions (arrows). Hyperintense rims surrounding the lesions are apparent on the Tl-weighted equilibrium phase image (b). Significant reduction of the size of the cryolesion can be noted on both T2-weighted (c) and contrast-enhanced Tl-weighted equilibrium phase (d) images acquired six months post-cryotherapy. No signs of residual tumor or local recurrence are apparent. However, on a T2-weighted image acquired 12 months post-cryotherapy (e), again a homogeneous high SI lesion (arrow) in the area of one of the former cryolesions can be seen. On the corresponding Tl-weighted image in the arterial phase after contrast agent injection (f), an irregular peripheral enhancement of the affected region is evident. In the equilibrium phase (g), no hyperintense rim can be observed. Taken together, these observations indicate local recurrent disease

Fig. 9a-g. Patient post-cryotherapy demonstrating late recurrent disease. T2-weighted (a) and contrast-enhanced Tl-weighted equilibrium phase (b) images acquired three weeks after cryotherapy show two large cryolesions (arrows). Hyperintense rims surrounding the lesions are apparent on the Tl-weighted equilibrium phase image (b). Significant reduction of the size of the cryolesion can be noted on both T2-weighted (c) and contrast-enhanced Tl-weighted equilibrium phase (d) images acquired six months post-cryotherapy. No signs of residual tumor or local recurrence are apparent. However, on a T2-weighted image acquired 12 months post-cryotherapy (e), again a homogeneous high SI lesion (arrow) in the area of one of the former cryolesions can be seen. On the corresponding Tl-weighted image in the arterial phase after contrast agent injection (f), an irregular peripheral enhancement of the affected region is evident. In the equilibrium phase (g), no hyperintense rim can be observed. Taken together, these observations indicate local recurrent disease

Fig. 10a-f. HCC post-percutaneous ethanol injection (PEI) / residual tumor. The nodule (arrow) appears hypointense with slightly hy-perintense peripheral areas on the T2-weighted image (a) and hyperintense on the Tl-weighted image (b) after PEI treatment. A focal hy-pervascular area (arrowhead), representing focal residual tumor, is seen during the arterial phase after the bolus injection of Gd-BOPTA (c). The portal-venous and equilibrium phase images (d and e, respectively) reveal contrast agent wash-out from the residual tumor and an overall hypointense appearance. The delayed hepatobiliary phase image (f) indicates that the residual tumor does not significantly take up Gd-BOPTA. This case is typical of residual tumor in HCC treated by percutaneous ethanol injection. The arterial phase image after contrast agnet injection is most sensitive for the detection of residual or recurrent tumor in cases of HCC or other hypervascular lesions

Fig. 10a-f. HCC post-percutaneous ethanol injection (PEI) / residual tumor. The nodule (arrow) appears hypointense with slightly hy-perintense peripheral areas on the T2-weighted image (a) and hyperintense on the Tl-weighted image (b) after PEI treatment. A focal hy-pervascular area (arrowhead), representing focal residual tumor, is seen during the arterial phase after the bolus injection of Gd-BOPTA (c). The portal-venous and equilibrium phase images (d and e, respectively) reveal contrast agent wash-out from the residual tumor and an overall hypointense appearance. The delayed hepatobiliary phase image (f) indicates that the residual tumor does not significantly take up Gd-BOPTA. This case is typical of residual tumor in HCC treated by percutaneous ethanol injection. The arterial phase image after contrast agnet injection is most sensitive for the detection of residual or recurrent tumor in cases of HCC or other hypervascular lesions

Fig. 11a, b. Tl-weighted (a) and Tl-weighted fat-suppressed (b) imaging of an HCC within the first week after TACE.

Increased SI is seen within the treated tumor nodule due to accumulation of lipiodol (arrows). This can make it difficult to detect residual hypervascular tumor tissue on dynamic Gd-enhanced liver imaging

Fig. 11a, b. Tl-weighted (a) and Tl-weighted fat-suppressed (b) imaging of an HCC within the first week after TACE.

Increased SI is seen within the treated tumor nodule due to accumulation of lipiodol (arrows). This can make it difficult to detect residual hypervascular tumor tissue on dynamic Gd-enhanced liver imaging trast-enhanced T1-weighted MRI performed two to three months after therapy is very sensitive for detecting or excluding recurrent tumors. Typically, a reduction of the T2 relaxation time, resulting in a decrease of signal intensity, can be observed in completely destroyed tumors on T2-weighted images acquired two to three months post-TACE. At this time-point, the decreased T2-weighted signal intensity is more likely to be a result of coagulative necrosis induced by TACE than an effect of lipi-odol [15].

Completely destroyed tumors are similarly depicted as areas of low signal intensity on T1-weighted images. Thus, dynamic imaging after the injection of Gd-based contrast agents is very sensitive for the detection of tumor recurrence, especially in hypervascular lesions such as HCC, since good contrast between the necrosis and viable tumor can be achieved (Fig. 12). Two to three months after treatment, areas of high signal intensity on T2-weighted images and hypervascular areas on contrast-enhanced T1-weighted dynamic arterial phase images can be considered as indicative of tumor recurrence [4,31].

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