Austrian consensus guidelines on imaging requirements prior to hepatic surgery and during follow-up in patients with malignant hepatic lesions

Of the organizing members two (D. T. and K. K.) gathered and reviewed the current literature dealing with imaging in the setting of liver resections for malignant hepatic tumors. Due to advances in the field, only reports published in the last 15 years were considered relevant for this topic. The aim was to establish a consensus regarding imaging for CLM, HCC and CCC, since these represent the most common indications for a liver resection. A catalogue of 27 items was established that covered the most important topics in this field, grouped by various clinical areas of interest.

At an expert meeting conducted on 27 June 2017 in Vienna, Austria, 13 Austrian experts in the fields of gastrointestinal radiology and liver surgery were invited to participate in the first open discussion round table and 11 members were present during this first panel meeting. The meeting was moderated by two panel members (K. K. and D. T.) who kept track of the statements and additional comments made. All items were discussed and additional topics were included if requested by the majority of panelists. If required, an ad hoc review of the pertinent topic using a PubMed search was performed to clarify open questions. After this meeting, a list of 47 items was generated, which already included a selective approach for each entity, CLM, HCC and CCC.

For online voting, experts scored each item on a scale from 1 to 5, with 1 representing no agreement and 5 representing full agreement. The scores obtained for each item were added together, which resulted in minimum and maximum scores of 13 and 65, respectively. In addition, the degree of consensus obtained for each item was calculated in percent. Participants could elect to perform the voting anonymously. A total of 47 items were put to the vote, as mentioned above. Where applicable, the recommendations were rated separately for CLM, HCC and CCC. These attributions are discerned in the table by the use of the letters A, B and C, with A denoting CLM, B denoting HCC, and C denoting CCC.

All voting results were collected and it was decided whether consensus (≥80% agreement) had been obtained. Comments made by individual panelists were noted and were included in the discussion of this manuscript.

In the last step, after setting up the manuscript, each panel member was able to make additional comments on individual topics. Of note, if an item had already reached consensus in Step 3 and 4, no alterations to this item were possible at this stage.

The recommendations should be valid for any patient requiring imaging work-up before liver resection for malignancy and during follow-up. Certainly, specific circumstances, such as allergy to contrast agents or contraindications against MRI have to be considered individually by the treating physician.

The recommendations were created in accordance with the AGREE II tool [26], which can be used in the quality-assessment of guidelines and consensus statements. All items have been successfully verified to be fulfilled in the presented version of this manuscript.

With respect to imaging modalities to be used before surgery, the panel agreed that thoracic and abdominal CT constitutes the basic assessment method for all three entities. In cases of severe steatosis visible on CT, additional MRI might be considered even if no lesions are visible on CT. No consensus was obtained, whether sonography should be included in the initial assessment in lean patients; however, MRI should be definitely used in patients with resectable or potentially resectable CLM and in patients with HCC for whom locoregional techniques like resection or ablation appear feasible. In patients with CCC, contrast-enhanced MRI including MRCP sequences was recommended for further characterization of the lesions and should be performed prior to biliary stent placement. There was strong consensus among the panelists, that in all three tumor entities, the chest should be included in the preoperative staging CT. An exemption should be made in high-risk patients (e. g. patients with cirrhosis, chronic viral hepatitis or steatohepatitis) assessed for a liver lesion. In this case, a CT of the entire abdomen and chest should only be included if a lesion suspicious for HCC was detected in the liver (100% consensus).

The panelists strongly agreed (97% consensus) that an arterial and portal venous phase is recommended for the initial CT examination in patients with CLM. The HCC and CCC assessments require at least 3‑phasic scans with arterial/portal-venous/equilibrium phases, although there was no consensus on the ideal timing for the equilibrium phase, ranging from 3 to 5 min. Non-contrast scans are considered optional in all three entities. The slice thickness for reconstruction of the axial series should not exceed 3 mm in all entities. Thin-slice reconstructions with 1 mm especially for visualization of the arterial anatomy were considered optional in certain surgical situations and in patients with perihilar cholangiocarcinoma (Klatskin tumors). Coronal reconstructions were recommended for portal venous and arterial imaging, and sagittal reconstructions for spine assessment. With respect to the amount of contrast agent used for standard 64-slice CT, the panel recommended an iodine dose of 0.6 g/kg body weight. Dose reductions appear possible if modern generation scanners are used but have to be considered on an individual basis. Contrast material flow rates should be high, in the range of 3–5 ml/s for CLM and CCC, and 4 ml/s for HCC. In patients with HCC, a late arterial phase should be employed using bolus tracking. The panel agreed that PET/CT or PET/MRI has no role in the routine preoperative staging and should only be used as a problem solving tool in high-risk patients (e. g. with high tumor burden) as well as for the assessment of uncertain extrahepatic findings in CLM.

For all aspects of liver MRI, the panel endorsed the recent recommendations made by the European Society of Gastrointestinal and Abdominal Radiology [26], with only slight modifications with respect to the preoperative setting. The panel agreed that a minimum field strength of 1.5 T is required for liver MRI. Mandatory MRI sequences include axial single-shot T2w-turbo spin echo (TSE) and intermediate T2w-TSE, at least one T2w sequence with fat suppression. Furthermore, 2D/3D-T1w gradient echo (GRE) with chemical shift imaging (in-phase and opposed-phase), and dynamic 3D-T1w GRE with fat saturation after administration of the contrast material should be applied. If hepatocyte-specific contrast agents are used, a hepatobiliary phase after 20 min (gadoxetic acid or Gd-EOB-DTPA, Bayer Healthcare [Berlin, Germany]) or 60–120 min (gadobenate dimeglumine, Bracco [Milan, Italy]), is recommended. Diffusion-weighted sequences (DWI) should be conducted with low, intermediate and high b‑values, e. g. 50, 400 and 800s/mm², according to the manufacturer and field strength.

A MRI protocol streamlining is possible by performing T2w-sequences and DWI after contrast application and T2w MRCP beforehand. In patients with considerable ascites, paracentesis prior to imaging should be considered in order to improve image quality. The required slice thickness for MRI was unanimously agreed on with 5 mm for 2D sequences and a maximum of 3 mm for 3D sequences.

The experts generally agreed that non-specific gadolinium (Gd) chelates should be used at a dose of 0.1 mmol/kg body weight, while the recommended dose for the hepatocyte-specific agent gadoxetic acid is 0.025 mmol/kg body weight. Concerning flow rate, it is recommended to apply contrast agents manually or by means of an injector at a dose of 1 ml/s, followed by a sodium chloride flush. Bolus triggering is recommended for the arterial phase.

While the proposal to use gadoxetic acid in all patients with CLM was clearly supported by the majority of the panel (93% consensus), no consensus was obtained for the use of this contrast agent in HCC. Instead, it is recommended to apply any Gd-containing agent for the assessment of HCC (82% consensus). For CCC, the panel favored gadoxetic acid in patients with peripheral CCC, whereas any Gd-containing contrast agent should be used in the work-up of perihilar CCC (85% consensus). In general, the panelists noted that imaging studies should always be conducted using identical parameters for the purpose of comparison. In patients receiving neoadjuvant chemotherapy for CLM, it is strongly recommended to perform gadoxetic acid-enhanced MRI both before and after systemic treatment and prior to surgery.

A 100% degree of consensus was achieved concerning the necessary information to be included in the report. Almost all of the recommendations relate to CLM findings. The panel concluded that a detailed description of metastatic lesions, with minimum requirements including the number of lesions, the size of the largest lesions and the description of their segmental distribution should be mandatory. Importantly, unaffected segments should be mentioned, as this enables surgeons to consider or preclude resection up front. Other notable items refer to proximity of lesions to vital inflow/outflow structures, presumed preservability and the quality of the parenchyma, since the focus of technical resectability relies on the future liver remnant. Any observed anatomical variant needs to be noted in the report. In the context of neoadjuvant therapy, it is important to describe the response to treatment, which includes reporting lesions that have disappeared after chemotherapy and the description of signs of chemotherapy-induced liver injury. Size measurements should be included in the report to enable assessment of treatment response.

For HCC, the experts agreed that the number and distribution of unequivocal lesions, as well as parenchyma quality should be stated in the report. Portal or hepatic vein thrombosis as a marker of vascular invasion distinctly needs to be reported as well.

The recommendations on postoperative follow-up received the maximum degree of consensus. A CT assessment using the arterial and portal venous phases was strongly recommended. A non-contrast phase should be added in cases of suspected bleeding. Both MRI and MRCP were recommended for the work-up of suspected biliary complications.

For long-term follow-up most of the experts favored 3‑6 month intervals according to local preference. In general, the panelists noted that imaging studies should always be conducted using identical parameters for the purpose of comparison. An exception to this rule is the arterial phase during follow-up, which might be dispensable for CT examinations in patients with CLM, which is known to seed hypovascular liver metastases. A PET/CT should be performed in patients presenting with equivocal findings and was not recommended as a routine imaging examination after liver resection.