Two-Stage Liver Surgery

Hepatic resection is the curative treatment for both primary hepatic tumors and metastases. The liver function after surgery must be preserved, and the future liver remnant (FLR) determines preoperatively the safety of the hepatic resection.

A FLR of 30%, calculated out of the total liver volume by CT scan, is usually considered sufficient in healthy conditions. It has also been determined at 0.5% according to the body weight ratio. Factors such as chemotherapy or cirrhosis, however, diminish the hepatic function, which means that volumetric evaluation must be combined by functional assessment in order to calculate the adequate FLR. Volumetry and scintigraphy have proved to be useful for this purpose, but the most appropriate test has yet to be established.

Advances in oncologic treatment and in hepatic surgery have increased the number of patients considered suitable for surgical treatment. Techniques inducing liver hypertrophy and therapeutic options reducing tumor size have increased the chances of resection in otherwise irresectable cases.

Liver regeneration has been summarized by two theories. Hemodynamic changes, particularly alterations in portal flow, can increase hepatocyte proliferation (blood flow theory). Hepatic regeneration is also mediated by cytokines, growth factors and hormones (humoral theory).

Portal vein embolization (PVE), introduced by Dr. Makuuchi and associates in the 1980s, and portal vein ligation (PVL), are intended to increase the blood flow and the hepatic growth factor production in the FLR. According to a meta-analysis published in 2008, an 8-27% increase in FLR is achieved with this technique. The rechannelling of branches of the embolized vein or neo-collateral formation can happen, impairing hypertrophy in some cases.

Two staged liver resections have been developed in recent years to increase the resectability of voluminous or bilobar malignant liver lesions. It was pioneered in the 2000s by the surgical team at Paul Brousse hospital for bilobar tumors that were not resectable in a single procedure.

A first hepatectomy is performed to achieve the resection of all malignancies in the FLR. In this surgery hepatic mobilization and vast dissection should be avoided to reduce adhesions for the next surgery. During the waiting time liver regeneration occurs, especially if a portal vein ligation is performed in the first procedure, which shortens the period between hepatectomies. A second and more extensive hepatectomy is then performed, to achieve complete eradication of tumor presence. Adhesions from the previous surgery can make dissection more difficult.

Adam and associates described a median interval of 4 months between both stages and a mortality of 15% in the second stage hepatectomy. Patients should be selected and only eligible if their tumors have been stabilized or downstaged by systemic chemotherapy. Only unresectable disease in the absence of an extrahepatic tumor is suitable for this treatment.

The major reason for failure of the two-stage hepatectomy (TSH) is tumor progression during the waiting period. Also, liver regeneration can be impaired by the action of chemotherapeutic agents.

Professor Hans Schlitt, in Germany, reported the accidental discovery of a new technique in 2007. After realizing intraoperatively that the FLR was too small to perform the surgery he had planned, he decided to perform a palliative hepaticojejunostomy. For optimal positioning he divided the liver parenchyma and ligated the right portal vein to induce hypertrophy. A rapid and large hypertrophy occurred as a result. This technique was named with the acronym “ALPPS” (associating liver partition and portal vein ligation for staged hepatectomy).

The excluded and deportalized liver after this in situ liver splitting serves as an auxiliary liver to assist the growing FLR. Recent studies have reported marked hypertrophy of FLR by 40-80% within 6-9 days. Also, simultaneous surgery of the primary tumor has been shown to be safe and effective in the first stage operation, and also in a laparoscopic setting. High operative morbidity rates (up to 64%) and mortality rates (up to 23%) have been reported in some series after ALPPS, and its oncologic outcomes are yet to be described to make sure it is comparable to conventional two-stage hepatectomy.

Summary

Resectability of hepatic tumor lesions can be improved by several techniques that induce liver hypertrophy to achieve an adequate FLR.

PVE and PVO provoke a hypertrophy of the healthy hepatic tissue by changing the portal blood flow and stimulating the hepatic growth factors.

Two-staged hepatectomy is conceived as a planned and potentially curative strategy for patients with unresectable bilobar metastatic disease. The waiting time between hepatectomies carries a risk of tumor progression.

The ALPPS procedure, by liver in situ partition and portal vein ligation, is associated with faster hepatic growth and less waiting time until definitive surgery but higher morbidity and mortality rates have been described.