Материал: Advanced Imaging of the Abdomen - Jovitas Skucas

Computed tomography and MRI detect liver metastases from cystic ovarian carcinomas either as cystic or solid tumors; as expected, the cystic components are hypodense on CT and hypointense on T1-weighted imaging and thus mimic other cystic tumors, but solid components show early peripheral globular enhancement and delayed central enhancement both on CT and MR imaging (142).

Hypervascular Metastases

Hypervascular metastases tend to be hyperintense on T2-weighted images. They are best identified on early arterial-phase postcontrast MRI when they are hyperintense to normal liver parenchyma. They reveal an immediate postcontrast peripheral enhancement, which gradually extends centripetally, followed by peripheral washout. Some are heterogeneous and some show an inconstant tumor blush. Small hypervascular metastases tend toward initial homogeneous enhancement, similar to hemangiomas, and then gradually become isointense. In general, on delayed images these metastases tend to wash out earlier than hemangiomas, although especially with smaller hypervascular metastases some imaging overlap exists with hemangiomas.

Melanoma

Melanomas range from hyperto hypointense on both T1and T2-weighted MRI,probably due to paramagnetic property of melanin pigmentation. Some melanomas are heterogeneous in appearance. They are hypervascular (Fig. 7.44). A combination of precontrast and portal venous-phase CT images appears as effective as arterial and portal venous-phase images in detecting metastatic melanomas (143).

Therapy

Only sparse literature discusses multimodality therapy in patients with colorectal carcinoma and unresectable liver metastases. Occasional patients undergo primary colorectal carcinoma resection and hepatic arterial infusion chemotherapy; shrinkage of liver metastases then allows hepatic lobectomy.

Figure 7.44. Metastatic melanoma. Angiography reveals a large confluent hypervascular tumor (arrows). (Courtesy of Oscar Gutierrez, M.D., University of Chile, Santiago, Chile.)

Antiangiogenic therapy, inhibiting endothelial growth factor activity, is still in its infancy and few conclusions can be drawn.

Resection

Liver metastases of primary tumors that normally do not drain into the portal vein are generally not considered for resection. Systemic spread of these tumors is also generally evident. Resection of liver metastases of the upper gastrointestinal tract and small bowel and of pancreatic cancers is uncommon, although an aggressive surgical approach of gastric metastases suggests improved prognosis in patients with a solitary metastasis if adequate tumorfree margins can be obtained. Few metastases are resected from a gynecologic primary. Resection of metastatic renal cell carcinoma (discussed later), Wilms’ tumor, and adrenocortical carcinoma are probably still indicated. Longterm survival after hepatectomy for gallbladder carcinoma is anecdotal.

Practically, most hepatic resections are performed for metastatic colorectal and neuroendocrine tumors. With appropriate patient selection, hepatic resection of colorectal metastases to the liver can achieve 5-year survival in about one third; eventual liver failure is a common cause of death, but survival is often prolonged with resection, assuming that all metastatic foci are identified.

LIVER

Intraoperative liver palpation during initial colon cancer resection continues to be a common technique of detecting liver metastases. The liver cannot be palpated during laparoscopic cancer resection, and this useful technique, generally performed during an open resection, is thus lost. Intraoperative US, either open or laparoscopic, is superior not only to preoperative US but also to surgical exploration. In some institutions results of initial intraoperative US are used to decide whether to proceed with resection, perform cryosurgery, or whether the patient is considered unsuitable for these therapies and the incision is closed.While intraoperative US provides guidance to resection and possibly reduces the number of unnecessary resections, this optimistic outlook should be balanced against available long-term evidence. The results are mixed from a number of studies about whether intraoperative liver US is useful in patients undergoing curative colorectal cancer surgery.

Intraoperative laparoscopic US is feasible as part of laparoscopic colorectal cancer resection; all liver segments can be scanned by US through a single port site. Laparoscopic US is probably more sensitive in identifying metastases than CT or preoperative US.

Surgical resection is feasible in some patients with metachronous liver metastases from renal cell carcinoma. Mean survival can be increased with such an approach, realizing that such surgery is associated with significant morbidity and mortality. Also, often multiple organ metastases are present by the time liver metastases are discovered.

An imaging study is useful shortly after resection to establish the baseline appearance. Resection margins are hyperintense on T2-weighted MRI and vary in their postcontrast enhancement. These findings gradually subside over a several-month period.

Repeat resection of recurrent hepatic metastases is mostly anecdotal but seems to occasionally improve prognosis as long as the tumor is confined to the liver.

Radiotherapy

Stereotactic irradiation of liver metastases consists of a focused radiotherapy beam delivered to a tumor with relative sparing of surrounding liver tissue. “Significantly improved survival”

was achieved in 43 patients during a phase 2 trial compared to patients treated for palliation (144).

Systemic Chemotherapy

The MRI changes after systemic chemotherapy are complex and poorly understood. Some patients develop an increase in tumor signal intensity while others have a decrease.

Some evidence suggests that 18F- fluorouracil-PET of colorectal metastases is useful prior to fluorouracil chemotherapy; PET uptake by metastases predicts subsequent tumor growth rates after therapy.

Intraarterial Chemotherapy

Most clinical trials of intraarterial chemotherapy for liver metastases were performed in the late 1980s and early 1990s; most studies reported about half of patients responding, compared to 10% to 20% with systemic chemotherapy, but with little or no survival differences between the two regimens. The use of additional intraarterial agents appears to improve response, but few studies are available, so firm conclusions cannot be drawn. Currently intraarterial chemotherapy is used mostly for patients with unresectable colorectal liver metastases but without evidence of extrahepatic metastases.

An ideal intraarterial chemotherapeutic agent is extracted during its first pass through the liver. Most commonly used agents consist of 5-fluorouracil (FU) and its derivatives. A several times greater intrahepatic agent concentration is achieved with intraarterial injection compared to systemic delivery. A limiting factor for a therapeutic response is the rapid elimination of cytostatic agent from tumor cells. Another limitation is development of progressive extrahepatic tumors.

The primary toxicities of intraarterial chemotherapy are biliary and small artery intimal damage. Once damage is established, imaging findings mimic primary sclerosing cholangitis; the current data suggest that damage is primarily small vessel ischemic in nature. In one center, intrahepatic bilomas developed in almost 10% of treated patients with metastatic liver tumors (145).

Either DSA and CTA prior to each session of transcatheter arterial chemotherapy detects any underlying complications. Perfusion scintigraphy also evaluates pump function after implantation of an infusion pump. Injection of a radiotracer at a flow rate similar to that used with an infusion pump provides a distribution pattern for subsequently injected chemotherapeutic agents.

At times extrahepatic collateral vessels feed a metastasis. These collaterals can be occluded with a cyanoacrylate-Lipiodol mixture infusion into the feeding artery, performed under temporary proper hepatic artery balloon occlusion, thus improving subsequent chemotherapy.

Intraportal Chemotherapy

The rationale of portal vein infusion chemotherapy is that, compared to IV therapy, relatively high doses can be delivered to the liver.

Metastatic colorectal cancer presumably spreads to the liver via the portal venous system. With growth, these metastatic nodules are perfused primarily by arterial blood and thus most chemotherapy is via the hepatic artery route. Such delivery, however, may not reach very small metastatic nodules, and an intraportal venous infusion route appears necessary to cover these. In spite of such reasoning, cytotoxic portal vein infusion therapy has not lived up to expectations and is little practiced.

Hypoxic Perfusion

Some patients with liver metastases have been treated with hypoxic liver perfusion. The hepatic artery is occluded with a balloon catheter and perfused with saline–mitomycin C, followed by gelatin sponge embolization; any role for such a procedure in local disease control remains to be established.

Percutaneous Ethanol Injection

In distinction to hepatocellular carcinomas, liver metastases respond poorly to percutaneous ethanol injection, and such therapy currently is rarely performed, having been replaced by other percutaneous techniques.

Single-episode percutaneous ethanol injection in patients with large or multiple liver metastases, not eligible for other treatments,

ADVANCED IMAGING OF THE ABDOMEN

results in tumor necrosis in a minority of patients. Accurate tumor localization, of necessity, is vital with any percutaneous ablation technique. Fusion of CT and FDG-PET images appears useful for lesions difficult to visualize with one imaging modality alone. Also, wholebody FDG-PET imaging identifies extrahepatic metastases.

Radiofrequency Ablation

Indications and contraindications for RF tumor ablation, photocoagulation (laser-induced thermotherapy), microwave therapy, and cryoablation of metastases are similar. Small solitary metastases are ideal candidates for ablation.

Radiofrequency tumor ablation efficacy varies considerably depending on the tumor size and type. Either percutaneous or intraoperative therapy is feasible, with the latter performed in conjunction with partial hepatectomy to destroy unresectable metastases. Most percutaneous ablation is performed using US guidance, although for tumors not visualized by US, MRI guidance in an open magnet is an option (146). Focal tumors smaller than about 3 to 4cm in diameter yield the best results. Using US guidance, 91% of 100 treated metastases (mostly colorectal) were eradicated (147); follow-up revealed tumor control to be similar for percutaneous (90%) and intraoperative ablations (94%). Among 117 treated patients estimated 1- and 3-year survival rates were 93% and 46%, respectively (148); of note is that a majority of local recurrence occurred within 1 year of therapy. After US-guided percutaneous RF ablation of breast cancer metastases, serial CT follow-up showed complete necrosis in over 90% of tumors (149); on the other hand, in a majority of these patients new metastases developed during follow-up.

Reported complications consist of subcapsular hematomas, bilioperitoneal fistulas, and abscesses. Portal vein thrombosis is more common in cirrhotic than in noncirrhotic livers. Hypertensive crises have developed. Liver insufficiency can lead to death. Similar to other procedures, new metastases rather than local recurrence often develop.

Either CT, contrast-enhanced US, or MR are used to detect residual tumors shortly after ablation (Fig. 7.45). Dynamic contrast enhanced MR appears to be more promising than the other modalities.

Results of radiofrequency ablation of colon cancer metastases approach those of resection, keeping in mind that patient selection is often not comparable for these two groups. As expected, better success is achieved with small tumors.

Photocoagulation (Thermotherapy)

Laser-induced thermotherapy using a percutaneous approach results in coagulation necrosis of metastatic nodules and adjacent liver parenchyma. Using an interventional 0.5-T MRI unit for guidance, laser irradiation with a nearinfrared laser source and cooled laser light guide of 58 colorectal liver metastatic foci resulted in no residual tumor in nodules <2cm in diameter, necrosis occurred in 71% of metastases between 2 and 3cm, and lesser amounts in larger tumors (150). In a prospective study of patients with colorectal metastases, MR-guided laser-induced thermotherapy achieved a mean 1-year survival of 94%, 3-year survival of 56% and 5-year survival of 37% (151); to achieve these results, patient inclusion criteria consisted of the absence of extrahepatic tumor, fewer than five intrahepatic metastases, and metastases

smaller than 50mm in diameter, but included were patients with recurrent liver metastases after partial liver resection, metastases in both lobes, unresectable tumors and those patients with contraindications for surgery. Longer follow-up suggests that thermotherapy results are similar to surgical resection.

To limit arterial blood flow, degradable starch microspheres have been injected into the proper hepatic artery; whether such a technique increases percutaneous laser-induced thermotherapy effectiveness remains to be seen.

One should keep in mind that tumor volume measurements with a low field strength MR unit differ somewhat from those obtained with a 1.5-T unit. Likewise, CT volume measurements differ from MR values.

Microwave Coagulation Therapy

Currently microwave coagulation therapy of metastatic liver tumors is rarely performed. A Beijing study achieved cumulative survival rates of 91% at 1 year and 29% at 5 years, with tumor grade, number of metastases and local recurrence or new metastases each having a significant effect on survival (152).

Cryoablation

Cryoablation therapy for metastases is similar in its approach to that used for hepatocellular carcinomas (discussed above; see Hepatocellular Carcinoma). In spite of numerous cryotherapy studies published, its role in treating metastatic disease is not yet established. Should it be an alternative to surgery or is its primary role that of adjuvant therapy? In fact, whether cryotherapy has a major impact on metastatic liver disease is still debatable.

Either a percutaneous or an open surgical approach is used for cryoablation. Magnetic resonance guidance during percutaneous cryoablation identifies the tumor nodule in question and the size of the surrounding frozen liver tissue. An open MR unit reveals resultant ice balls as sharply defined expanding regions of signal loss encasing tumors; these ice balls correlate with resultant necrosis (Fig. 7.46). The mass seen immediately after therapy should be larger than the original tumor; otherwise, incompletely treatment should be suspected. Surrounding hemorrhage is common. Occasionally CT identifies gas within a tumor; it does not imply infection. In time these tumors shrink.

Thirty patients with colorectal cancer metastases confined to the liver, not deemed resectable and with <50% liver involved by

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tumor, underwent cryoablation followed by hepatic artery infusion chemotherapy with 5- FU, achieving a median survival of 18 months from the time of cryoablation (153); survival in this group of patients appears to be improved by such dual therapy.

Several patients undergoing synchronous hepatic cryoablation and colon cancer resection developed hepatic abscesses, although an abscess is rare after cryoablation alone.

Follow-Up

The use of bile CEA levels as early markers of occult liver metastases in patients with colorectal cancer has met with limited success; raised bile CEA occurs at initial colorectal cancer resection even without liver metastases but a raised biliary CEA level later, after the primary tumor has been resected, does predict tumor recurrence, either within the liver or at some other site. Bile sampling can be obtained by either cholangiography or, even simpler, by transhepatic gallbladder puncture.

Imaging is often used to follow the size of metastases and the response to therapy. The usefulness of a baseline posttherapy study cannot be overemphasized. In general, the same imaging modality should be used for follow-up; comparing tumor size with different imaging modalities is fraught with uncertainty. Even

LIVER

CT 3D measurement of metastasis size can be used.

Magnetic resonance imaging is useful in evaluating metastases after therapy. Any viable tumor should enhance with gadolinium. Necrosis does not enhance or reveals only minimal delayed peripheral enhancement.

Some metastases undergo considerable change in their imaging features after chemotherapy; some mimic a benign lesion such as a cyst or hemangioma, while others develop such extensive fibrosis and distortion that the overall appearance mimics cirrhosis. Postcontrast MR of treated lesions tends to reveal no immediate enhancement, but fibrosis gradually becomes hyperintense on delayed images.

the severity of symptoms and indolent course argue for aggressive therapy.

Surgical resection is curable in some and palliative in most. Chemotherapy, somatostatin analogues, percutaneous ablation techniques and hepatic artery embolization of metastatic foci are used individually or as part of a global therapeutic approach. Long term palliation is feasible with transarterial chemoembolization but insufficient data is available to place this procedure in a proper perspective (154). The role of liver transplantation in a setting of metastatic neuroendocrine tumors is not settled. Cryoablation therapy appears useful in some of these patients. Most palliation procedures for liver neuroendocrine tumors result both in symptomatic relief and prolonged survival.

Other neoplasms

This section includes miscellaneous tumors not discussed previously and that are not readily classifiable either under benign or malignant categories.

Neuroendocrine Tumors

Clinical

Primary liver neuroendocrine tumors range from undifferentiated carcinomas to one with varying differentiation. The vast majority are metastatic rather than primary. Overall, they are not common.

Untreated, neuroendocrine metastases approximately double in size in 1 year. Typically,

Imaging

These tumors are generally identified by con- trast-enhanced imaging, with imaging-guided biopsy used to establish a specific diagnosis (Fig. 7.47).

Octreotide is a synthetic somatostatin analogue. Somatostatin receptor scintigraphy using octreotide labeled with indium 111 aids in localizing carcinoids and some other neuroendocrine tumors. Metastatic islet cell carcinomas, regardless of type, also accumulate this radiotracer as long as a tumor contains sufficient somatostatin receptors, keeping in mind that not all neuroendocrine tumors fulfill this condition. Somatostatin receptor scintigraphy is useful for several reasons: It confirms