Q1: What are the advantages and disadvantages of ultrasound for metastatic colorectal cancer?
A1: Ultrasound (US) was once widely used in the evaluation of liver metastases for its convenience and affordability, but now it has been mostly replaced by Multidetector Computed Tomography (MDCT) and MRI. A typical metastatic colorectal cancer presents as a solid hypoechoic lesion with well-defined margins, sometimes with a halo or characteristic “target sign” or “bull’s eye sign”, and generally shows a lack of blood supply on color Doppler US. Although US imaging is not currently approved by the FDA, studies have shown that it has similar characteristics and accuracy to MDCT in assessing dynamic enhancement in metastatic colorectal cancer.
Intraoperative US is a valuable method of applying US to the surgical procedure. It has higher sensitivity and specificity than preoperative abdominal US, especially when it is combined with intraoperative US angiography. Intraoperative US helps to detect new metastases in 33-42% of patients, while intraoperative US imaging helps to detect those “lost” liver metastases after chemotherapy.
The limitations of US are its dependence on operator experience, its less clear localization of liver segments important for surgical planning, and its poor results in fatty liver and diffuse or chronic liver disease.
Q2: What are the strengths and weaknesses of MDCT in the evaluation of metastatic colorectal cancer?
A2: MDCT is the most widely used imaging device for examining patients with metastatic colorectal cancer. MDCT can perform isovoxel volume scans of the same type, thus allowing the reconstitution of high-quality multiplanar images to improve the examination of small lesions and the accurate segmental localization of lesions.
Plain CT examination of liver metastases is very difficult to detect in the presence of fatty liver, which is often a drug-induced fatty liver from oncologic chemotherapy. Small hemangiomas and cysts smaller than 1 cm can sometimes be difficult to distinguish from metastases because of the volume effect of CT. The specificity of MDCT (67%) is lower than that of MRI (81%) in the demonstration of benign and malignant lesions.
Q3: What are the CT manifestations of metastatic colorectal cancer?
A3：On enhanced CT (iodine-containing contrast agent injected through the median vein of the elbow), the arterial phase of liver metastases shows hypointense expression of lack of blood supply, and in some cases, the edges of the lesions show circular enhancement with rich blood supply and blurred edges, and the portal vein phase shows inhomogeneous hypointensity. The portal vein phase (about 60-70 s after the start of contrast injection) is the most reliable phase for detecting liver metastases on MDCT, with a detection rate of 85% and a positive predictive value of 96%. Approximately 11% of colorectal cancer liver metastases show calcification. Pulmonary metastases may present as pulmonary nodules, carcinomatous lymphangitis, and pleural fluid. Peritoneal metastases present as foci of soft tissue implants on the greater omentum or mesentery with peritoneal thickening and ascites (sometimes as localized encapsulation). Peritoneal pseudomucinous tumors are seen in some cases of appendiceal cancer and appear on CT as low-density mucinous lesions overlying a fan-shaped visceral surface. Bone metastases, on the other hand, show a typical osteolytic or mixed osteolytic-sclerotic lesion, but it is nonspecific.
Q4: What are the advantages and disadvantages of MRI in the evaluation of metastatic colorectal cancer?
A4: MRI has a very high soft tissue resolution, and it is an indispensable key tool in the evaluation of liver lesions. MRI has a high sensitivity (nearly 95%) in the evaluation of metastatic colorectal cancer and a high accuracy (83%) in detecting metastases smaller than 1 cm.
Liver metastases are equivalent to normal liver parenchyma with low signal on T1WI and high signal on T2WI. The application of heavy T2WI technique imaging can distinguish hemangiomas and cysts from solid, malignant lesions. Diffuse-weighted imaging (DWI) is a functional MRI technique that examines the movement of water molecules in tissue and reflects the density of cells within the tissue. Apparent Diffusion Coefficient (ADC) values are used to quantitatively assess diffusion limitation. Metastatic colorectal cancer lesions are diffusion-limited and show high signal on DWI, with low ADC values.
MRI with a conventional contrast agent (gadolinium) can better show known lesions and also detect more lesions not shown on plain MRI. On enhanced MRI, liver metastases show a similar pattern of enhancement to enhanced CT, with low signal relative to normal liver parenchyma in both the arterial and portal phases. Liver-specific contrast agents detect more metastases than conventional Ga-agent-enhanced MRI, with sensitivities of 95% and 87% for both, respectively, and are particularly useful when following up metastases after direct systemic or hepatic treatment.
Q5: What exactly are the characteristics of MRI liver-specific contrast agents?
A5: MRI liver-specific contrast agents are characterized by uptake by hepatocytes and excretion from the bile duct system. These contrast agents show a biphasic pattern after intravenous injection, with the first phase occurring immediately after contrast injection and the delayed phase occurring 10 to 120 minutes after contrast injection. The two liver-specific contrast agents currently in use are gadobente dimeglumine (Gd-BOPTA, MultiHance = Modis, Bracco, Milan, Italy) and gadoxetate disodium (Gd-EOB-DTPA, Primovist = Promethazine/ Gd-BOPTA at a dose of 1.0 mmol/kg is 95% excreted by the kidneys and 3% to 5% by the biliary system with a delay period of 1 to 2 hours, with the advantage of better T1 relaxation and better enhancement during dynamic imaging; Gd-EOB-DTPA at a dose of 0.025 mmol/kg is 50% excreted by the kidneys and 50% by the biliary system, with the advantage of better T1 relaxation and better enhancement during dynamic imaging; Gd-EOB-DTPA at a dose of 0.025 mmol/kg is 50% excreted by the kidneys and 50% by the biliary system. excreted by the kidney and 50% by the biliary system, with a delay period of 10-60 minutes, with the advantage of better visualization of the biliary system. With liver-specific contrast, metastases may show typical low signal in the delayed phase, while lesions containing hepatocytes such as focal nodular hyperplasia (FNH) show equal or high signal.
Q6: What are the advantages and disadvantages of PET/CT in the evaluation of metastatic colorectal cancer?
A6: PET/CT consists of PET (Positron Emission Tomography) imaging fused with CT (X-ray Computed Tomography, CT) imaging. FDG-PET is 2-[Fluorin-18]Fluoro-2-Deoxy-D-Glucose (2-[Fluorin-18]Fluoro-2-Deoxy-D-Glucose. The role of PET/CT in stage IV colorectal cancer is increasing, mainly because of its ability to detect extrahepatic lesions and its ability to modify surgical management.PET/CT has a high sensitivity (78%-95%) for detecting liver metastases >10 mm.) For potentially resectable liver metastases, the NCCN guidelines recommend PET/CT to exclude occult metastases. PET/CT can also be used to detect occult lesions with elevated carcinoembryonic antigen but no anatomical abnormalities. PET/CT has a low sensitivity (36%) for detecting liver metastases <1 cm, and false-negative results occur when the tumor is necrotic or contains mucus.
Q7: What can imaging do for surgical planning of metastatic colorectal cancer?
A7：The main determinants of whether metastatic colorectal cancer can be surgically resected are the number of liver metastases, the size of the tumor and its distribution, which in turn determine whether negative surgical margins and adequate liver function reserve can be obtained. Therefore, the primary goal of imaging for metastatic colorectal cancer is to detect as many liver metastases as possible with as much accuracy as possible, and imaging in turn provides important details of venous, arterial, and biliary tract anatomy. Reconstructed images can be an important reference for surgical and interventional procedure planning.
Q8: What role can imaging play in the follow-up of metastatic colorectal cancer?
A8: All lesions must be identified during preoperative imaging prior to treatment. Disappearing (disappearing) liver metastases are treated metastases that do not show up on follow-up imaging because the lesions are too small (i.e., undetectable), which is what we often refer to as a completely radiologically effective tumor after treatment. Pathologic analysis of surgical specimens of such lesions resected showed surviving tumor cells especially at the tumor-liver interface. Therefore, accurate preoperative localization of these lesions is essential, as the surgical margins are positive for the very sites that are prone to recurrence. Studies have shown that MRI-specific contrast agents are more sensitive than MDCT in detecting these liver metastases where treatment is fully effective; and a recent Meta-analysis found MRI to be the most appropriate test for preoperative neoadjuvant chemotherapy evaluation.
CT or MRI volumetric techniques can calculate the volume of the future postoperative residual liver.
[Note: The failure of imaging to show the primary tumor or metastases does not necessarily mean that there is no tumor, but rather that the tumor volume is too small to be shown by current imaging techniques, which we call undetectable. It can only be shown by other special examination methods (such as interventional imaging) or only when the tumor grows bigger. This is one of the important reasons why we always encounter some patients who have significantly elevated tumor indexes but no lesion can be found on imaging].
Q9: How can imaging help in the direct liver treatment of metastatic colorectal cancer?
A9：Most direct liver treatments are guided by US and CT. Imaging is mainly used to select the type and method of interventional procedures and the follow-up after treatment. Patients undergoing ablative therapy should avoid heat sink effects and biliary system injury, and preoperative knowledge of the relationship of the treated lesion to the great vessels and gallbladder has an important role. The results of direct treatment of the liver differ from those of systemic chemotherapy, and percutaneous ablative therapy generally results in enlargement of the treated lesion in the first month due to intra-tumor hemorrhage and coagulative necrosis. Enhancement immediately after ablation shows a transient enhancement around the ablation site as a thin ring of enhancement around the edge of the lesion, which disappears after 1 month of ablation. This change must be differentiated from residual or recurrent tumors, which show thick irregular nodular marginal enhancement. Intra-lesional air bubbles and arteriovenous shunts are also common after ablation. Although peritumoral edema and hemorrhage can lead to transient tumor enlargement, the effect of radiotherapy and chemoembolization is assessed by tumor reduction, tumor necrosis, and complete absence of blood supply to the tumor (angiography is fully effective). The circumferential enhancement of such lesions resembles the congestion around the lesion after ablation, which implies a fibrotic focus around the treated lesion rather than a recurrence. Perivascular edema is a transient manifestation in the embolic vascular distribution and should not be confused with infiltrative lesions. Radiotherapy leads to ischemia and hepatitis of normal liver parenchyma, followed by the formation of abnormal patchy substantial enhancement in the treated liver segment causing difficulty in assessing the treatment effect. Envelope retraction and resulting portal hypertensive liver fibers are seen with radiotherapy.
Q10: How does imaging assess systemic chemotherapy for metastatic colorectal cancer?
A10：Assessment of treatment outcome in metastatic colorectal cancer plays an important role in treatment selection. MDCT is most widely used in the assessment of treatment outcome. Traditionally, the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines have been used to evaluate the effectiveness of treatment in solid tumors. Both RECIST and RECIST 1.1 define treatment as effective when the tumor is 30% smaller by measuring the size of the tumor in one dimension. Some studies have shown that RECIST is inadequate for assessing treatment efficacy, especially for molecularly targeted therapies. To overcome this deficiency, several alternative criteria have been proposed that incorporate tumor morphology and size.Choi et al. suggested the use of a combined size and density alteration assessment criterion to evaluate the treatment efficacy of gastrointestinal mesenchymal tumors.Smith et al. proposed to combine size and CT density criteria as well as MASS (Morphology, Attenuation, Size and Structure, i.e. Size and Structure) criteria were applied to metastatic renal cell carcinoma after sunitinib (sunitinib, sulforaphane) treatment.
For anti-angiogenic targeted therapeutics, reduced density, uniform internal density, and sharpness of the tumor-liver interface in metastatic tumors were considered good or optimal for effective morphologic treatment. The disappearance of the reinforcing ring at the tumor margin prior to treatment was also considered to be a good therapeutic effect. In addition to morphologic criteria, physiologic alterations in tumor blood supply are used as a new method of assessing treatment efficacy with anti-angiogenic targeted therapeutics. Dynamic enhancement CT allows the assessment of qualitative and quantitative perfusion data on the efficacy of anti-angiogenic targeted therapeutics in liver metastases.
Notably, three uncommon patterns of treatment effectiveness in neoadjuvant chemotherapy-treated liver metastases resemble the “pseudoprogression” of tumor progression: first, lesions that are isointense before treatment and hypointense after treatment are easily misclassified as neoplastic lesions; second, some lesions increase in size after treatment. Secondly, some lesions increase in size after treatment, and at the same time, the lesions show hypodensity and hypoenhancement due to intratumoral edema or isodense components of previous lesions, and this increase in size can be mistaken for lesion progression using traditional efficacy criteria. Pseudoprogression can be avoided by comparing old and new images, understanding the patient’s clinical status, tumor parameters, and the effectiveness of treatment of other lesions. Intratumoral hemorrhage can also be better identified by careful analysis of the internal texture of the tumor (e.g., liquid-fluid flat or homogeneous to heterogeneous lesions) and by scanning CT or MRI.
An uncommon treatment-effective pattern can also be seen in bevacizumab-treated pulmonary metastases, which have an enlarged lesion but a typical central hypodensity and cavity formation due to central necrosis. Spontaneous pneumothorax can occur in subpleural metastases that present with cavities. Similar to liver metastases, peritoneal metastases have reduced lesion size and diminished enhancement when chemotherapy is effective. Reduction in ascites and bowel obstruction may also be indirect signs of effective treatment of peritoneal metastases. Follow-up examinations after treatment of bone metastases typically show a sclerotic presentation.
Although MRI is not useful in assessing the effectiveness of treatment, it can resolve many suspected pseudoprogressions: high signal on T1WI can identify intratumoral hemorrhage, liver-specific contrast can help detect disappearing (disappearing) liver metastases (still low signal in the hepatobiliary stage), and it can also help detect liver metastases in the setting of chemotherapy-induced fatty liver [MRI can detect more liver metastases under 1 cm than CT MRI can detect more liver metastases under 1 cm than CT (66% vs. 11%)]. Dynamic-enhanced MRI can also evaluate the efficacy of bevacizumab, and DWI can detect lesions that cannot be detected with other devices (<10 mm). lesions) and false positives (inflammation and surgery).