Perioperative management - Right hemihepatectomy

Resecting procedures in liver surgery are performed for very different diseases. The focus is on liver malignancies, followed by benign tumors, some non-tumorous diseases, and living liver donation.

Hemihepatectomy is a so-called major resection, defined as resection of at least four liver segments.

Common indications for liver resection

1. Malignancies

1.1 Primary

• Hepatocellular carcinoma (HCC)
• Cholangiocellular carcinoma (CCC)
• Cystadenocarcinoma

1.2 Metastases

1.3 Direct tumor invasion

2. Benign diseases

2.1 Liver tumors

• Adenoma (ß-catenin-mutated subtype; male patient)
• Focal nodular hyperplasia (in case of diagnostic uncertainty or complications due to displacing growth)
• Hemangioma (in case of compression of vessels (Budd-Chiari-like syndrome) and bile ducts; Kasabach-Merritt syndrome)
• Cystadenoma

The surgical treatment of benign liver tumors requires a high degree of critical indication and results from:

• Diagnostic uncertainty despite extensive diagnostics
• Clinical symptoms, e.g., upper abdominal pain, nausea or cholestasis due to tumor size, compression phenomena or significant size growth
• Risk of rupture and bleeding in adenoma with size > 5 cm
• Risk of degeneration in hepatocellular adenoma (ß-catenin-mutated subtype, male patient)

2.2 Non-tumorous diseases

• Liver cysts/polycystic liver degeneration (in case of rapid progression and clinical symptoms such as pressure sensation, pain, dyspnea or infection)
• Parasitic liver cysts (Echinococcus)
• Intrahepatic stones/Caroli syndrome
• Recurrent liver abscesses
• Liver trauma

3.0 Living liver donation

When indicating liver resection, oncological and surgical-technical aspects must be considered. Prerequisites are precise knowledge of the functional and segmental anatomy of the liver as well as its vascular and branching variants.

Oncological aspects

The goal of surgical therapy for liver malignancies is R0 resection, i.e., macro- and microscopically complete tumor resection. Only in symptomatic neuroendocrine liver metastases can an R2 resection also be indicated, as debulking of over 90% of the tumor mass leads to symptom freedom ("cytoreductive surgery").

Functional aspects

The most important cause of perioperative mortality after liver resection is liver failure. Risk evaluation is therefore of crucial importance, as therapeutic options in postoperative liver insufficiency are very limited. The occurrence of postoperative liver failure correlates with:

• Size and quality of the remaining liver tissue (cirrhosis, steatosis, fibrosis)
• Presence of cholestasis or cholangitis
• Extent of operative trauma (size of resection surface, blood loss, duration of any hilar occlusion)
• Pre-existing conditions (medication intake)
• Postoperative complications (bile leaks, infections, etc.)

If the liver is not pre-damaged and exhibits normal synthesis and excretion function, approximately 25-30% of the functional liver volume is to be regarded as a guideline for the liver parenchyma to be left at least in a resection. However, a prerequisite for this is impeccable arterial and portal venous blood supply as well as unimpeded hepatic venous and biliary drainage of the remaining liver tissue.

In pre-damaged liver, correspondingly higher values must be set. The assessment of the functional reserve of a cirrhotic liver is particularly difficult (see below).

If the planned resection is likely to fall below these values, the possibility of preconditioning (preoperative hypertrophy induction) should be evaluated.

Augmentation techniques:

• PVE/PVL (portal vein embolization/ligation): Unilateral selective embolization of a portal vein branch (of the liver half to be resected later) to achieve ipsilateral atrophy and contralateral hypertrophy of the liver tissue.
• "In-situ-split" concept/ALPPS (Associating Liver Partition and Portal vein ligation for Staged hepatectomy): Induction treatment in two surgical steps. In the first step, the right portal vein branch is ligated with simultaneous portal devascularization of segment 4, and the liver is transected along the falciform ligament. The completely portal devascularized segments 4 to 8 remain arterially perfused in situ. As a result, the left lateral liver lobe grows very quickly and achieves the ability to take over organ function alone. In the second surgical step, usually within 2 weeks, the extended right hemihepatectomy is performed.
• Two-/multi-stage resection. First, atypical resection of all tumors from the remaining liver to be left later. After hypertrophy of this lobe has occurred, the remaining tumors are removed in a second operation.

Further alternatives are a

• Combination with ablative procedures (e.g., RFA = radiofrequency ablation)
• Secondary surgical resection after neoadjuvant chemotherapy (currently only for colorectal metastases).

In the example, we show the case of an intrahepatic cholangiocellular carcinoma (iCCC), the second most common primary liver tumor in the Western world.

The indication for liver resection in iCCC exists in technically resectable findings after exclusion of distant metastasis.

Liver cirrhosis:

• The assessment of the functional reserve of a cirrhotic liver is difficult. In addition to the physical general condition and the Child-Pugh Score, the severity of portal hypertension is of crucial importance. The most important parameters for sufficient postoperative liver function are normal bilirubin and a hepatic venous pressure gradient of < 10 mmHg. Indicators for the extent of portal hypertension are spleen size, the presence of esophageal varices, and platelet count (Cave: < 100.000/μl).
• In liver cirrhosis, the extent of resection is therefore limited (wedge excisions, mono- or bisegmentectomies). Only in Child-A stage without portal hypertension can a hemihepatectomy be possible in individual cases. Child-C cirrhosis represents a contraindication to liver resection. 
• There is a significantly increased risk in portal hypertension due to complication-prone, risky preparation in the liver hilum.
• Liver transplantation is considered the therapy of choice for HCC in the cirrhotic liver from an oncological perspective within defined limits (including Milan criteria), as not only the HCC but also the underlying liver disease is treated. There are 5-year survival rates of up to 70% and higher. In principle, macrovascular invasion, lymph node and distant metastases must be excluded before transplantation.
• However, in view of the organ shortage in Germany and improved surgical results of liver surgery even in cirrhotic liver with sufficient liver function, partial liver resection is also a legitimate alternative.

General inoperability of the patient due to underlying diseases. Pronounced heart failure, restricted kidney and/or lung function are considered contraindications for major liver resections.

Diffuse involvement also of the left liver lobe

Infiltration into the diaphragm or the hepatoduodenal ligament

Infiltration into the vena cava or the hepatic vein confluence

Further distant metastases (except resectable lung metastases)

Uncontrolled primary tumor

In HCCs with small tumor burden in liver cirrhosis, liver transplantation is considered the method of choice, but is relativized by the lack of organ availability.

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

No sufficient residual liver volume (< 30%)

• The most important cause of perioperative mortality after liver resection is liver failure. Risk evaluation is therefore of decisive importance, as the therapeutic options for postoperative liver insufficiency are very limited.
• For Klatskin tumors, a residual liver volume of 40% should be aimed for, as the liver is pre-damaged by cholestasis.
• Evaluation of hypertrophy conditioning on the side to be preserved. Corresponding hypertrophy can be expected after 12 days to 5 weeks depending on the method, but can take considerably longer in a cholestatic or cirrhotic liver.

For liver lesions, the early detection of malignancy using imaging diagnostics and histological confirmation through biopsy is the prerequisite for curative therapy.

An initial assessment is obtained through the medical history: pain, B-symptoms, previous malignant diseases, travel history, oral contraceptives, alcohol abuse, drug abuse, viral hepatitis, metabolic syndrome, liver cirrhosis. Risk factors for malignancy include liver cirrhosis, chronic hepatitis B or hepatitis C virus infection, tumor history.

Clinical examination and

laboratory tests:

Important parameters of liver function are coagulation, cholinesterase (CHE), and cholestasis parameters. The metabolic capacity can additionally be assessed through liver function measurements: indocyanine green (ICG) excretion test; 13C-methacetin breath test, known as LiMAx (Liver Maximum Capacity Test); a segmental liver function test is hepatobiliary scintigraphy (HBS).

Tumor markers: alpha-fetoprotein; CA 19-9 (carbohydrate antigen 19-9); CEA

Liver abscesses: fever, positive blood cultures, travel history

Parasitic diseases e.g. echinococcosis → serology

Ultrasound: 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 enables reliable classification in up to 60% of cases (e.g., cysts, typical hemangiomas, focal fat distribution disorders).

The intraoperative ultrasound examination is standard for every liver resection. Often, additional lesions or through the assessment of vascular architecture and especially the contrast medium dynamics in the tissue, a differential diagnostic classification of the lesions is often possible.

For further assessment of a liver lesion, a dynamic examination with evaluation of the contrast medium behavior in the different perfusion phases of the liver is necessary.

CEUS (contrast-enhanced ultrasound): Through the assessment of vascular architecture and especially the contrast medium dynamics in the tissue, a differential diagnostic classification of the lesions is often possible. Contrast-enhanced ultrasound represents the gold standard in the diagnosis of benign liver changes. With contrast-enhanced ultrasound, the depiction of liver perfusion in "real time" is achieved. The contrast medium behavior of a liver lesion can be observed in the arterial, portal venous, and late venous phase. The different entities show characteristic patterns here. The advantage is independence from kidney and liver function, the disadvantage is examiner dependence and lack of objective comparability.

3(4)-phase i.v. contrast CT (native, arterial, portal venous, venous)

• The standard procedure for surgical planning and assessment of resectability is multiphasic contrast-enhanced rapid spiral computed tomography with thin slices.
• This achieves high-resolution depiction of arterial, portal venous, and venous structures. Most liver lesions can thus be classified with high sensitivity and specificity.
• Advantages of CT are wide availability and short examination duration. Disadvantages are radiation exposure, situations with thyroid diseases or renal function impairments.
• 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 existing steatosis, the informative value regarding liver lesions is limited.
• A disadvantage is the inadequate depiction of the biliary system.

MRI (Magnetic Resonance Imaging)

• Use of liver-specific, primarily biliary excreted contrast agents (Gd-EOB = biliary contrast agent)
• Advantage of MRI is the good differentiation between benign and malignant liver tumors
• The detection accuracy and characterization of lesions in cirrhosis also appear increased compared to conventional contrast agents.
• Limitations arise with implants, claustrophobia, or renal function impairments.
• With the possibility of 3-D sequences, exact volumetry of the liver and virtual resection planning through anatomical depiction of liver vessels, similar to contrast-enhanced CT, can be performed.
• MRCP (magnetic resonance cholangiopancreatography) is the ideal instrument for non-invasive depiction of the biliary system.
• For iCCC, MRI with cholangiography (MRI/MRCP) based on a liver-specific contrast agent with depiction of intra- and extrahepatic bile ducts represents the gold standard.

PET-CT (Positron Emission Tomography in combination with CT) 

• Positron emission tomography (PET) in combination with CT and F18-fluoro-deoxy-D-glucose (FDG) as radiopharmaceutical is suitable for detecting most hepatic metastases, especially in colorectal carcinoma.
• Due to poorer single-lesion detection compared to MRI, it has value in whole-body staging when comprehensive environmental diagnostics for both intrahepatic and extrahepatic primary tumors is required, i.e., before concrete surgical planning.
• Detection of occult distant metastasis.

Summary:

The correct preoperative imaging depiction of the exact extent of the tumor burden is crucial for a curative treatment concept.

The following requirements are placed on the imaging procedures:

• Clear visualization of all tumors to be resected
• Relationship of the same to vascular and biliary structures
• Detection of anatomical variants of vascular supply. The most common are a (proper or accessory) right hepatic artery from the superior mesenteric artery and a (proper or accessory) left hepatic artery from the left gastric artery.
• Differentiation from any benign liver lesions
• Determination of tumor, total liver, and remnant liver volume
• Assessment of total and remnant liver function: The postoperative liver function after liver resection can be anticipated preoperatively based on volumetry via CT or MRI (surgical planning software) and liver function measurement e.g. via LiMAx.

Endoscopic Drainage before Resection:

• A preoperative biliary drainage is always required in cases of acute cholangitis, cholestasis, malnutrition induced by hyperbilirubinemia, as well as before portal vein embolization or neoadjuvant chemotherapy.
• Stents should generally be avoided, as every intervention with contrast medium administration in the biliary system leads to bacterial contamination with the risk of cholangitis and perioperative infection. However, under cholestasis, liver dysfunction increases, which is responsible for increased morbidity and mortality. Therefore, stents are often unavoidable.
• If drainage is required, the bile ducts of the remaining liver should primarily be decompressed.
• Endoscopic drainage is preferable to percutaneous transhepatic drainage, as puncture increases the risk of bacteremia, tumor cell dissemination, and trauma to the remaining liver portion after resection.
• Before stent insertion, the necessary imaging to clarify resectability should be completed. An indwelling stent also complicates the intraoperative assessment of resectability.

In case of increased cardiopulmonary risk, clarification of operability through further diagnostics (stress ECG, heart echo, coronary angiography, lung function test)

If necessary, targeted nutritional intervention in case of malnutrition

Sufficient intensive care capacity for high-risk patients

Blood type determination with sufficient transfusion reserve ( 4-6 units, if necessary FFP or platelets) !

Mild laxative or enema on the day before is recommended.

Preoperative antibiotic administration as single-shot (2nd generation cephalosporin ½ h before skin incision)

For informing the patient, standardized informed consent forms should be used. These also include corresponding anatomical drawings where the findings can be entered. Alternatives and additional treatment options should be explained, in particular, interventional measures or extensions of the primary procedure should always be discussed.

Before every planned liver resection, information should also be provided about a cholecystectomy.

General Risks

• Bleeding
• Postoperative bleeding
• Hematoma
• Necessity of transfusions with corresponding transfusion risks
• Thromboembolism
• Wound infection
• Abscess
• Injury to adjacent organs/structures (stomach, esophagus, spleen, diaphragm)
• Burst abdomen
• Incisional hernia
• Secondary intervention
• Mortality

Specific Risks

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

Intubation anesthesia

Intra- and postoperative analgesia with CVP

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

Normothermia (warm patients)

Keep CVP low

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 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 case of accidental opening of large hepatic veins or the vena cava, the PEEP can be temporarily increased to avoid impending air embolisms.

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

Depending on liver function and blood loss, disturbances in the coagulation and fibrinolysis systems can occur. This requires close intraoperative monitoring and, if necessary, early substitution of coagulation factors.

Supine position, right arm adducted, left arm abducted, slight hyperextension in the thoracolumbar junction

• Surgeon to the right of the patient
• 1st Assistant to the left of the patient
• 2nd Assistant to the right of the patient, headward of the surgeon
• Scrub nurse to the left of the patient, footward of the 1st Assistant

Bile sieve + vessel sieve or LTX sieve

Cable pull hook system, Mercedes retractor (Aesculap)

Vessel loops

Multi-clipper

Aids for parenchyma resection, here ultrasound aspirator (CUSA®), more information on aids for parenchyma resection can be found under Dissection techniques in liver surgery.

Ultrasound device

Aids for punctual hemostasis of the liver: e.g. clips, bipolar and monopolar coagulation, Argon beamer, infrared coagulation etc.

Aids for vessel sealing on the resection surface e.g. hemostatic collagen fleece 

Postoperative Analgesia
Adequate pain therapy; for stronger pain, systemic analgesics in addition to the PDK, taking into account potential liver toxicity. Follow the link here to PROSPECT (Procedures Specific Postoperative Pain Management) or the link to the current guideline Treatment of acute perioperative and posttraumatic pain.

Medical Follow-up Care
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 suture material 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 prophylactic, possibly weight- or risk-adapted dosage, in addition to physical measures. Note: Renal function, HIT II (history, platelet monitoring). Follow the link here to the current guideline Prophylaxis of venous thromboembolism (VTE).

Mobilization
As early as possible, especially for pneumonia prophylaxis, which is essential for every liver resection. Gradual resumption of physical activity up to full load.

Physical and Respiratory Therapy
Pneumonia prophylaxis is vital and has absolute priority in liver resections! , e.g. breathing assistant (Bird) and/or  Triflow exercise device and appropriate physical therapy.

Diet Build-up
Rapid diet build-up; on the 1st postoperative day tea, soup, rusk. Full diet build-up should be completed by the 3rd postoperative day.

Bowel Regulation
From the 3rd day, the patient should have a bowel movement, this can be stimulated e.g. with an enema.

Inability to 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 observe postoperative rest for at least four to six weeks. Light work, especially office activities, can be resumed earlier.