Perioperative management - Liver resection for recurrent liver metastasis

The indication for metastasis resection is an individual decision that must be made interdisciplinarily together with the patient. The curative R0 resection represents the gold standard of therapeutic options. The sequence of surgical measures in synchronous metastasis must also be decided individually.

In the demonstrated case, there was a suspicion of a liver metastasis recurrence in segment VI after liver metastasis resection 5 months ago.

Parenchyma-sparing techniques are favored in metastasis surgery. Limited or atypical resections are preferable to anatomical ones, as more liver parenchyma remains, which is particularly relevant in the recurrence situation. Resections with large parenchyma loss cannot enhance oncological safety/long-term prognosis.

Not the width but the tumor-free status of the resection margin is decisive for avoiding a recurrence. Even a presumed R1 resection is acceptable in exceptional cases because, through the resection technique (aspiration/electrocoagulation of liver tissue), despite microscopically detectable tumor tissue at the specimen margin, the resection margin in the patient can be tumor-free.

In the recurrence situation, the extent and form of resection (atypical, anatomical) depend on the location and extent of the initial operation. The intrahepatic vascular anatomy altered by the initial procedure must be particularly considered.

Despite good sectional imaging, differentiation between benign and malignant liver lesions can be difficult.

Bilobar involvement, extrahepatic tumor manifestation, or infiltration of larger vessels are no longer considered contraindications. The optimal treatment strategy results from the extent or number of tumors/metastases to be operated on.

In larger resections (multiple metastases), the remaining liver parenchyma must be calculated. The decisive factor is the liver volume remaining after resection ("future remnant liver volume" = FRLV) and the necessary vascular structures for this. This should be at least 30% of the remaining liver but must be calculated significantly higher in a pre-damaged liver (chemotherapy, liver cirrhosis).

If it is likely that these values will be undershot by the planned resection, the possibility of preoperative conditioning should be evaluated.

• Preoperative hypertrophy induction (e.g., PVE = portal vein embolization)
• In situ split/ALPPS (Associating Liver Partition and Portal vein ligation for Staged hepatectomy)
• Two-/multistage resections
• Combination with ablative procedures (e.g., RFA = radiofrequency ablation)
• Secondary surgical resection after neoadjuvant chemotherapy

Through the combination of surgical and interventional methods, possibly with systemic therapy, even very advanced findings can be subjected to a potentially curative resection.

Primarily non-resectable metastases can be converted from a palliative stage to a curative one through chemotherapy. Surgery should be performed as soon as resectability is achieved to keep drug toxicity as low as possible and to reduce the problem of difficult localization due to tumor regression.

Simultaneous resection with the primary tumor in synchronous metastases should be aimed for in easily accessible lesions. The postulate to generally perform the resection of liver metastases after 2-3 months cannot be maintained.

• Liver function impairment with insufficient residual function, Child-B/C cirrhosis

Assessing the functional reserve of a cirrhotic liver is challenging. Besides the general physical condition and the Child-Pugh score, the severity of portal hypertension is crucial. The most important parameters for adequate postoperative liver function are normal bilirubin levels and a hepatic venous pressure gradient of < 10 mmHg. Indicators of the extent of portal hypertension include spleen size, the presence of esophageal varices, and platelet count (Caution: < 100,000/μl).

• Insufficient residual liver volume (< 30%)

The most important cause of perioperative mortality after liver resection is liver failure. Therefore, risk evaluation is of crucial importance, as therapeutic options for postoperative liver insufficiency are very limited.

• General inoperability of the patient due to underlying diseases; cardiac risks, in particular, must be considered.

The correct preoperative imaging of the exact extent of metastatic burden is crucial for a curative treatment concept. Intraoperative discovery of additional lesions is extremely problematic, as this might have required a completely different multimodal concept.

The following requirements must be met by the imaging procedures:

• Clear visualization of all tumors to be resected
• Relationship of the same to vascular and biliary structures
• Depiction of anatomical variants
• Differentiation of any benign liver lesions (in this case subcapsular hematoma after previous surgery)
• Determination of tumor, total liver, and remnant liver volume
• Assessment of total and remnant liver function

Ultrasound with and without contrast agent (CA)

• Transabdominal ultrasound forms the backbone of primary imaging diagnostics (=screening).
• The assessment of focal liver lesions with native B-mode ultrasound and color-coded duplex ultrasound allows for a reliable classification in up to 60% of cases (e.g., cysts, typical hemangiomas, focal fat distribution disorders).
• CA ultrasound is suitable for diagnosing still unclear liver lesions. By assessing the vascular architecture and especially the contrast agent dynamics in the tissue, differential diagnostic classification of the lesions is often possible.
• Intraoperative ultrasound examination is standard for every liver resection. Often, additional lesions or findings not consistent with preoperative diagnostics are identified. It is indispensable for defining resection boundaries intraoperatively and for locating hard-to-palpate lesions (e.g., in tumor regression after pre-treatment).

Contrast-enhanced CT

• The standard procedure for surgical planning and clarification of resectability is multiphase contrast-enhanced fast spiral computed tomography with thin slices.
• This achieves high-resolution depiction of arterial, portal venous, and venous structures.
• With appropriate evaluation software, tumor volume, total liver volume, and remaining liver volume after resection can be estimated.
• Regarding liver function, CT provides only indirect indications: enlarged spleen, recanalized umbilical vein, prominent caudate lobe, dilated bile ducts.
• In the presence of steatosis, the significance regarding liver lesions is limited.
• A disadvantage is the inadequate depiction of the bile duct system.
• Exclusion of a local recurrence of the primary tumor.
• Completion of tumor staging (detection/exclusion of lung metastases) through a CT of the thorax

Magnetic Resonance Imaging

• For colorectal metastases, contrast-enhanced MRI seems to be superior to contrast-enhanced CT in detection accuracy, especially for lesions < 1 cm.
• An additional improvement appears to be the use of liver-specific contrast agents (Gd-EOB = hepatobiliary contrast agent).
• Apart from enhanced detection performance, the improved characterization of the lesion, e.g., differentiation of nodular hyperplasia and hepatic adenoma from each other and from metastases, is an advantage.
• The detection accuracy and characterization of lesions in cirrhosis also seem to be increased compared to conventional contrast agents.
• With the possibility of 3-D sequences, exact volumetry of the liver and virtual resection planning through anatomical depiction of liver vessels as with contrast-enhanced CT can be performed.
• The possibility of diffusion-weighted imaging (DWI) increases the detection of regressive-changed liver metastases, which are often difficult to see in conventional CT and MRI imaging.
• MRCP (Magnetic Resonance Cholangiopancreatography) is the ideal tool for non-invasive depiction of the bile duct system, especially in metastasis surgery, when usually no dilation of the bile ducts is present.

PET-CT (Positron Emission Tomography combined with CT)

• Positron Emission Tomography (PET) combined with CT and F18-Fluorodeoxyglucose (FDG) as a radiopharmaceutical is suitable for detecting most hepatic metastases, especially in colorectal carcinoma.
• Due to the poorer single lesion detection compared to MRI, it has a role in whole-body staging when comprehensive environmental diagnostics are required for extrahepatic primary tumors, i.e., even before concrete surgical planning.

• Blood group determination with sufficient transfusion reserve (4-6 RBCs, if necessary FFP or platelets)!
• For increased cardiopulmonary risk, clarification of the surgical risk through further diagnostics (stress ECG, cardiac echo, coronary angiography, lung function test)
• Adequate intensive care capacity for high-risk patients
• A mild laxative or enema is recommended the day before.
• Preoperative administration of antibiotics as a single shot of a 2nd generation cephalosporin ½ hour before skin incision

Standardized consent forms should be used for patient education. These also include appropriate anatomical drawings where findings can be recorded. Alternatives and additional treatment options should be explained, and interventional measures or extensions of the primary procedure should always be discussed.

Prior to any planned liver resection, cholecystectomy should also be discussed.

General Risks

• Bleeding
• Rebleeding
• Hematoma
• Need for transfusions with associated transfusion risks
• Thromboembolism
• Wound infection
• Abscess
• Injury to adjacent organs/structures (stomach, esophagus, spleen, diaphragm)
• Wound dehiscence
• Incisional hernia
• Follow-up surgery
• Mortality

Specific Risks

• Liver parenchyma necrosis
• Bile fistula
• Bilioma
• Hemobilia
• Biliary peritonitis
• Bile duct stricture
• Pleural effusion
• Air embolism (due to unintended or unnoticed opening of liver veins)
• Portal vein thrombosis
• Hepatic artery thrombosis
• Chronic liver failure
• Liver failure with hepatic coma
• Tumor recurrence

Intubation anesthesia

Intra- and postoperative analgesia with epidural catheter

Follow the link here to PROSPECT (Procedure specific postoperative pain management) or to the current guideline Treatment of acute perioperative and post-traumatic pain

In liver resections, anesthesia plays an important role in intraoperative blood-saving measures.
The pressure in the hepatic sinusoids depends on the pressure in the hepatic veins, which in turn depends on the central venous pressure (CVP). Therefore, during the transection of the liver parenchyma, the CVP should be lowered to 2-5 mmHg, which can significantly reduce intraoperative blood loss and transfusion volume.
In the event of accidental opening of large hepatic veins or the vena cava, the PEEP can be temporarily increased to prevent impending air embolisms.

A positive end-expiratory pressure (PEEP, English positive end-expiratory pressure) is a parameter in artificial ventilation. It refers to a positive pressure in the lungs at the end of expiration. It is generated by a PEEP valve.

Depending on liver function and blood loss, there may be disturbances in the coagulation and fibrinolysis system. This requires close intraoperative monitoring and, if necessary, early substitution of coagulation factors.

Supine position, both arms adducted, slight hyperextension at the thoracolumbar junction

• Surgeon on the right side of the patient
• 1st assistant on the left side of the patient
• 2nd assistant on the right side of the patient, towards the head of the surgeon
• Scrub nurse on the left side of the patient, towards the feet of the 1st assistant

• Gallbladder, vascular tray, or LTX tray
• Cable retraction system,
• Vessel loops
• Aids for parenchymal resection, here ultrasonic aspirator (CUSA®), further information on aids for parenchymal resection can be found under dissection techniques in liver surgery

• Ultrasound device

• Aids for focal hemostasis of the liver: e.g., clips, bipolar and monopolar coagulation, argon beam, infrared coagulation, etc.

• Aids for vascular sealing at the resection surface. In the demonstrated case, a hemostatic powder HaemoCer PLUS is used:
  • This is a ready-to-use powder made from polymerized plant extracts.
  • The product is biocompatible and contains no animal or human components.
  • HaemoCer is applicable for both diffuse and active bleeding.
  • The completely resorbable material accelerates natural blood coagulation (hemostasis) due to its extremely high water absorption capacity.
  • There is an accumulation of fibrin, thrombin, and red blood cells at the bleeding source. A natural clot forms, and the bleeding is stopped. After hemostasis is achieved, the wound is surrounded by a stable and firmly adhering gel layer. This serves as an additional barrier to protect against renewed blood leakage.
  • Independent studies also show that the use of plant-based hemostatic powders (polysaccharides) contributes to the reduction of postoperative adhesions.
  • The product is manufactured and certified in Germany.
  • Within 48 hours, it is completely broken down by amylase in the body.

Postoperative Analgesia
Adequate pain management; for more severe pain, systemic analgesics in addition to the epidural catheter should be considered, taking into account potential hepatotoxicity. Follow the link to PROSPECT (Procedures Specific Postoperative Pain Management) or the link to the current guideline Treatment of acute perioperative and post-traumatic pain.

Medical Follow-up
If the drainage does not produce bile on the 2nd postoperative day, a later bile fistula is extremely rare, so the drainage can be removed on the 2nd/3rd day.
Removal of skin sutures around the 12th postoperative day

Thrombosis Prophylaxis
In the absence of contraindications, due to the high risk of thromboembolism, low molecular weight heparin should be administered in a prophylactic, possibly weight- or risk-adapted dosage in addition to physical measures. Note: Kidney function, HIT II (history, platelet control). Follow the link to the current guideline Prophylaxis of venous thromboembolism (VTE).

Mobilization
As early as possible, especially for pneumonia prophylaxis, which is essential in any liver resection. Gradual resumption of physical activity until full load.

Physical and Respiratory Therapy
Pneumonia prophylaxis is vital and takes absolute priority in liver resections! For example, ventilatory assistance (Bird) and/or Triflow exercise device and appropriate physical therapy.

Diet Progression
Rapid diet progression; on the 1st postoperative day, tea, soup, rusks. Full diet progression should be completed by the 3rd postoperative day.

Bowel Regulation
From the 3rd day, the patient should be evacuated, which can be stimulated, for example, with an enema.

Incapacity for Work
In open procedures with median laparotomy extension into the right flank, the risk of postoperative incisional hernia is not insignificant, so the patient should adhere to postoperative rest for at least four to six weeks. Light work, especially office work, can be resumed earlier.