Perioperative management - Left lateral liver resection, open

In liver surgery, resections are indicated for a broad range of diseases. The list is headed by malignant liver lesions, followed by benign tumors, some non-tumorous benign diseases, and living-donor liver transplantation.

Common indications for liver resection

1. Malignancies

1.1 Primary

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

1.2 Metastases

• Colorectal cancer
• Non-colorectal non-endocrine malignancies
• Endocrine malignancies

1.3 Direct tumor invasion

• Gallbladder cancer
• Colon cancer
• Hilar cholangiocarcinoma
• Gastric cancer
• Kidney cancer
• Adrenal cancer
• Retroperitoneal / Vena cava sarcoma

2. Benign disorders

2.1 Liver tumors

• Adenoma
• Focal nodular hyperplasia
• Hemangioma
• Cystadenoma

2.2 Non-tumorous conditions

• Liver cysts/polycystic liver degeneration (with rapid progression and clinical symptoms such as sensation of pressure, pain, dyspnea, and infection)
• Parasitic liver cysts (echinococcosis)
• Intrahepatic calculi
• Caroli disease
• Recurrent liver abscess
• Liver trauma
• Living-donor liver transplantation

The indication for liver resection must consider functional aspects as well as surgical technique, and in case of malignancy also oncological considerations.

Oncological aspects

The goal in surgical treatment of hepatic malignancies is R0 resection, i.e., complete gross and microscopic tumor resection. The only case for R2 resection is in symptomatic neuroendocrine liver metastasis because debulking of more than 90% of tumor mass will provide the patient with symptomatic relief (cytoreductive surgery).

Functional aspects

Liver failure following hepatic resection is the most important factor in perioperative mortality. Therefore, risk assessment is of vital importance because treatment options in postoperative liver failure are rather limited. The presence of postoperative liver failure correlates with:

• Volume and quality of the liver remnant (cirrhosis, fatty liver, fibrosis)
• Presence of cholestasis and cholangitis
• Extent of surgical trauma (size of resection area, blood loss, duration of any hilar occlusion)
• Postoperative complications (bile leakage, infections etc.)

In the absence of hepatic damage and if the liver exhibits normal synthesis and excretion, the rule of thumb in resection is to leave at least 25%-30% of the functional parenchymal volume of the liver. However, this assumes that the arterial and portovenous blood supply is sound and the hepatovenous and biliary drainage of the liver remnant will be unhampered. While routine lab parameters (bilirubin, albumin, cholinesterase, and coagulation) provide a guesstimate of liver synthesis and excretion, they are less important when assessing the functional hepatic reserve after extensive resection.

Thus, assessing the functional hepatic reserve of a cirrhotic liver becomes much harder. Apart from the general physical condition and the Child-Pugh score the severity of any portal hypertension present is of vital importance.The parameters most indicative of adequate postoperative liver function are normal bilirubin levels and a pressure gradient in the hepatic veins of <10mmHg. Indicators of the degree of portal hypertension include: Size of spleen, presence of esophageal varices and platelet level (beware: < 100,000/μL). Therefore, cirrhotic livers only tolerate limited resections (wedge resection, mono-/bisegmental resection). Only selected Child A patients without portal hypertension will become possible candidates for hemihepatectomy. Stage Child C cirrhosis of the liver is one of the contraindications for liver resection. Aspects of surgical technique

Because of functional and technical aspects in appropriate indications, liver resection should always be considered if the remnant comprises at least two sufficiently large liver segments with adequate vascular and biliary supply/drainage.

Surgical treatment of benign liver tumors requires a high degree of critical indication resulting from (in decreasing frequency):

• Diagnostic uncertainty despite extensive diagnostics
• Clinical symptoms, e.g., upper quadrant pain, nausea or cholestasis due to tumor size, compression symptoms, and significant increase in size
• Risk of rupture and bleeding in adenomas > 5cm
• Risk of malignant transformation

• Marked cirrhosis of the liver (Child C, possibly also stage B)
• Patient generally inoperable because of underlying disease; assessment must include cardiac risks in particular
• In advanced hepatic cirrhosis and in hepatocellular cancer with a tumor load of no more than three masses <5cm liver transplantation should also be considered

Patient history and clinical examination

Lab studies

• Standard preoperative lab study with coagulation panel, blood group and possibly, depending on the underlying disease, other studies as well
• Specific liver parameters: Transaminases, bilirubin, alkaline phosphatase, hepatitis serology (pathologic lab parameters do not contribute significantly to the differential diagnosis of liver lesions)
• Tumor markers: AFP (alpha-1 fetoprotein), TPA (tissue polypeptide antigen), CEA, CA19-9

AFP is the definitive tumor marker in hepatocellular carcinoma (HCC); the presence of HCC may be assumed in 95% of cases with AFP levels >400μL/L. Beware: Chronic hepatitis B and C may also elevate the AFP level without HCC being present.

Contrast- and non-contrast-enhanced ultrasonography (CEUS/NCEUS)

Assessment of focal hepatic lesions with non-contrast-enhanced B-mode ultrasonographyand color-coded Doppler ultrasound allows reliable classification of liver lesions in up to 60% of patients (e.g., cysts, typical hemangiomas, focal fatty infiltration/sparing).

The echo texture in HCC may vary. About 75% of HCCs appear as hypoechoic round masses. Demonstration of arterial blood flow in color-coded Doppler ultrasonography is indicative of HCC. CEUS lends itself for further diagnostic work-up of liver lesions with ambiguous findings on non-contrast-enhanced ultrasonography.For CEUS to differentiate between benign and malignant neoplasias and allow differential diagnostic classification, it is necessary to assess vessel architecture and particularly the dynamics of the contrast agent.

• Benign liver lesions are characterized by sustained contrast during the portocaval and sinusoidal perfusion phase.
• CEUS in HCC typically demonstrates hyperperfusion during the early arterial phase, i.e., there is rapid contrast agent wash-in. In well differentiated HCC the contrast agent is only washed out slowly, while in moderately/poorly differentiated hepatic cancer the contrast agent is washed out rapidly.
• Since intrahepatic CCC does not demonstrate characteristic behavior on ultrasonography, this modality cannot differentiate CCC from other intrahepatic masses. Ultrasonography of extrahepatic lesions yields indirect information such as dilation of the biliary tree.

Contrast-enhanced CT

Today, contrast-enhanced CT studies with non-enhanced, arterial and portocaval phases are regarded standard in the diagnostic work-up of HCC. During the arterial phase HCC demonstrates as a hyperdense mass while it becomes isodense or hypodense during the portocaval phase.

Magnetic resonance imaging

MRI should be performed whenever CT findings are ambiguous, and particularly when HCC is suspected.

On MRI intrahepatic CCC appears as a nonspecific finding. One important diagnostic modality in the work-up of extrahepatic CCC is MR-cholangiopancreatography (MRCP) which allows better assessment of suprahilar tumor spread than ERCP.

Combined positron emission tomography and CT

Combined with CT imaging “18-F-fluorodesoxyglucose positron emissions tomography“, better known as FDG-PET, has seen increasing application in the diagnostic work-up and treatment monitoring of solid malignancies. The principle behind this modality is the increased enhancement of FDG in tumor tissue.

• Increased enhancement of HCC is indicative of a low degree of differentiation and thus poorer prognosis. Lack of FDG enhancement denotes a differentiated tumor.
• FDG-PET plays an important role in the diagnostic work-up of locoregional lymph nodes in CCC and in the detection of distant metastases; the modality is markedly better in this than computerized tomography alone.
• PET-CET may also be considered whenever extrahepatic primaries demand full-scale diagnostic work-up.

Endoscopic retrograde cholangiopancreatography (ERCP)

• ERCP plays a secondary role in the HCC diagnostics. Therapeutic indications include ERCP stenting in tumor obstruction of the common bile duct.
• ERCP in CCC is employed as both diagnostic and therapeutic modality. In extrahepatic CCC the tumor is easily localized and confirmed by histology. This includes brush cytology, forceps biopsy and bile aspiration; combining these modalities will improve sensitivity.

Liver biopsy

Under certain conditions liver biopsy may be indicated in HCC. According to the American Association for the Study of Liver Diseases (AASLD) this should be performed in:

• Intrahepatic masses between 1cm and 2cm in diameter.
• Mass without definitive characteristics on imaging.

Intrahepatic tumors with a diameter >2cm should be biopsied if the mass does not demonstrate characteristic behavior on imaging and the AFP level is <200ng/mL.

• In case of increased cardiovascular risk, better detail the risk of surgery by further diagnostic studies (exercise ECG, echocardiography, coronary angiography, pulmonary function testing)
• For patients at risk sufficient bed capacity on the ICU
• Allocate 4-6 PRBCs, possibly FFP and PRP
• Preoperative single-shot 2^ndgeneration cephalosporin + metronidazole half an hour before skin incision

In general, the patient does not require special preparation, although an enema is recommended.

When obtaining informed consent, the standard forms for patient information should be used because these include pertinent anatomical figures where the patient’s findings can be entered. Informed consent must include a discussion of the alternatives and possible additional treatment options; in particular, it should involve explanation of interventional measures including intraoperative radio frequency ablation and the possibility of broadening the original planned procedure.

Informed consent in planned liver resection should always include cholecystectomy.

General risks

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

Special risks

• Hepatic parenchymal necrosis
• Biliary fistula
• Bilioma
• Hemobilia
• Biliary peritonitis
• Bile duct stenosis
• Pleural effusion
• Air embolism (when hepatic veins are opened accidentally/unnoticed)
• Portal vein thrombosis
• Hepatic artery thrombosis
• Chronic liver failure
• Liver failure with hepatic coma
• Tumor recurrence