Total vascular exclusion leads to a decrease of 10 % of blood pressure, 25 % of the pulmonary arterial pressure, 40 % of cardiac index, and 80 % of systemic vascular resistance [4, 5]. These hemodynamic changes are variable and depend on the volume of blood circulating and cardiac function of the patient. The inferior vena cava flow (3.5 l/min) contributes to 70 % of the total cardiac output (5 l/min). The remaining 30 % of the cardiac output comes from the superior vena cava. The inferior vena cava carries deoxygenated blood from the lower half of the body (abdomen, pelvis, and legs) into the right atrium of the heart. Inferior vena cava clamping has two consequences: (i) a significant decrease in venous return and an impaired cardiac output and (ii) clamping of the venous renal outflow and the venous drainage of the gastrointestinal tract that causes congestion of the kidney and the gastrointestinal tract. If the consequences of the infrahepatic inferior vena cava clamping are usually well tolerated, infrahepatic inferior vena cava clamping combined with suprahepatic inferior vena cava clamping induced much more marked hemodynamic consequences with a risk of cardiovascular collapse.

The liver can safely tolerate total vascular occlusion for only about 60–90 min [3, 6]. The vast majority of hepatectomies performed under standard vascular exclusion can be made in less than 60–90 min. Periods of ischemia of this order are usually well tolerated by a healthy liver, unlike the pathological liver (steatosis, cirrhosis, chemotherapy) which cannot tolerate prolonged warm ischemia [7–9].

This ischemic period may be too short for complex tumors which are in the vicinity of major hepatic veins and/or the retrohepatic vena cava. Recently, we showed that preoperative factors such as portal vein embolization and/or large tumors and/or a planned vascular reconstruction were predictive for total vascular exclusion > 60 min in patients needing this vascular control [10]. A prolonged total vascular exclusion may lead to severe hepatic ischemia, hemodynamic disturbances, and potential acute kidney injury [10]. To reduce liver damage, the technique of hypothermic liver surgery has been developed [11]. The hypothermia technique has been used as an adjunct to increase the tolerance of the liver to prolonged ischemia [12]. It has been demonstrated that every 10 °C fall in temperature of liver parenchyma decreases the liver enzyme activity by 1.5–2-fold [13–17]. The principle of hypothermia approach is to perfuse the liver with conservation liquid used in organ transplantation. The temperature of the liver decreased then to about 20 °C. The most popular methods of cooling for liver surgery include hypothermia portal perfusion and topical cooling. Total body cooling technique is abandoned [18], and extracorporeal cooling (used in cardiopulmonary bypass with profound and circulatory arrest) should be considered in highly selected patients with a huge tumor associated with cardiac tumor thrombus [19].

Longmire et al. was the person to report in 1961 the use of hypothermia induced by external body cooling during a hepatectomy for liver cancer [18]. The in situ hypothermic liver resection was employed by Heaney et al. in 1956 [1] and Fortner et al. in 1974 [20]. In their technique, the liver is perfused with preservation solution at 4 °C and packed with ice during the period of total vascular exclusion. This technique has been shown to prolong safely the vascular exclusion up to several hours [10]. Pichlmayr et al. reported the technique of ex situ liver resection (Fig. 6.2) [21]. The main steps of this technique include the installation of total vascular exclusion, venovenous bypass, and the removal of the whole liver. The latter is then perfused ex situ via portal and arterial route with preservation solution. The liver is maintained in cold solution packed with ice for optimal preservation during bench hepatectomy. The remaining liver is reimplanted as an auto-transplantation. To improve the access to the dorsal part of the liver without resorting to the division of the portal triad, Hannoun et al. developed the ante situm technique in which the hepatic veins are divided, allowing mobilization of the liver anteriorly (Fig. 6.3) [22]. The future remnant liver is perfused with the Belzer’s University of Wisconsin solution chilled at 4 °C (UW solution) via the portal vein or the hepatic artery [13]. The remaining hepatic veins are reimplanted into the vena cava. Then, Belghiti et al. [23] described a variation of the latter technique in which the vena cava is cut above and below the liver, enabling the resection to be done while the liver is being perfused to induce the hypothermia via the portal vein [24]. The vena cava is reconstructed after liver resection using synthetic [23, 25–30], autogenous [31–33], or pericardial grafts [34].

Besides the need to protect the liver parenchyma, prolonged total vascular exclusion requires protection of the renal function altered by the caval clamping, decongestion of the splanchnic venous system subsequent to portal triad clamping, and maintenance of systemic hemodynamics since the caval clamping decreases the cardiac preload. The cavo-porto-jugular venovenous bypass achieves these triple goals (Fig. 6.4) [10, 25, 35–37]. The venovenous bypass circuit is used to divert blood during the vena caval interruption to the right heart from the portal venous system (i.e., inferior mesenteric vein or portal vein) and inferior caval venous system (femoral vein) through the superior caval venous system (the internal jugular or axillary veins). Venovenous bypass is indicated when resection followed by complex reconstruction of the inferior vena cava is performed or if caval cross clamping is not hemodynamically tolerated despite adequate feeling measures.

The conventional technique for establishing vascular access for bypass involves cannulation of the portal (or inferior mesenteric vein) and right femoral veins to provide pump inflow and cannulation of the left axillary vein to accept pump outflow. This procedure implies a surgical dissection of the inferior mesenteric or portal veins that can be technically demanding in case of portal cavernoma, can prolong operating time, and can be associated with significant complications such as hematoma or bleeding. The puncture and cannulation of femoral and left axillary vein is then done under ultrasonography control as described by Oken et al. in 1994 [38].

In our center, the vascular control is planned preoperatively based on the morphologic evaluation of the liver anatomy and relations of the tumor with the hepatic veins, the vena cava, and the portal triad. The common basis for in situ and ante situm liver resection is total vascular exclusion of the liver and perfusion of the liver by preservation solution under hypothermic conditions. With this technique, the use of venovenous bypass is relatively high due to hemodynamic intolerance and/or the need for complex reconstruction of the inferior vena cava. Vascular resections are performed only when the vessels cannot be separated safely from the tumor, irrespective of the preoperative procedure planned. In this paragraph, we will not describe the ex situ technique (for review, see Chap. 7).

The major indication for this complex surgery are liver tumors, including primary (Figs. 6.6, 6.7, 6.8, 6.9, 6.10, 6.11 and 6.12) [31, 52] or secondary [53, 54] tumors and some huge benign tumors, that involve the retrohepatic vena cava and/or the confluence of the main hepatic veins or are in close proximity to them. In addition, extrahepatic tumors such as renal cancer [55–61], adrenal tumors [62–65], and leiomyosarcomas of the vena cava [66–73] involving the main hepatic veins or the retrohepatic vena cava may also be indications for this surgery. Severe liver trauma with injury of the inferior vena cava and/or hepatic veins may be another indication. Several reports have reported in situ, ante situm [19–21, 24, 41–51, 74–88], or ex situ [21, 44, 47, 48, 78–84, 89–104] resection techniques for these indications.

The debate over whether hypothermic perfusion of the liver should be performed in or ex situ remains unresolved. The decision which type of resection techniques is suitable depends on the location of the tumor, the vascular reconstruction required, and the experience of the centers. Compared to the in situ technique, the ex situ technique includes the division of the hepatic pedicle and then requires reconstruction of the portal triad following bench hepatectomy. In theory, ex situ hepatic resection is the optimal treatment option for lesions affecting the main vessels of the hepatic hilum. But ex situ liver resection is an invasive procedure and is associated with significant morbidity and mortality rates as high as 27.4 % [41], the main cause of perioperative mortality being liver failure. These high rates of mortality limit the use of this technique (for review, see Chap. 7).

It is not mandatory to remove the liver from the body completely (ex situ) but to mobilize it ventrally as much as necessary (ante situm), since this avoids the additional morbidity of arterial and biliary reconstruction. With this approach, the ante situm technique would be the most appropriate technique in the majority of patients in whom the portal pedicle can be usually maintained. The ante situm technique for liver resection is usually employed in tumors of the liver located centrodorsally extending to the hepatic venous confluence. In this technique, the hepatic veins are excised allowing the mobilization of the liver ventrally (ante situm). After the resection phase, the hepatic veins are reconstructed and reimplanted to the inferior vena cava or, in case of inferior vena cava infiltration, to the interposition graft. The final decision between in situ or ante situm resection can only be made intraoperatively.

To review the current clinical application of these techniques, the English language literature was analyzed (Table 6.1). From 1974 to 2015, 205 cases of in situ (n = 158) or ante situm (n = 47) hepatectomy have been reported. Malignant liver tumors included primary (hepatocellular carcinoma and cholangiocarcinoma) and secondary liver cancers. Benign liver tumors were mostly hemangioma. Other tumors such as leiomyosarcoma or schwannoma were most common among the extrahepatic tumors. Postoperative mortality occurred in 23 cases (11.2 %). The most frequent causes of death were liver failure, respiratory complications, bleeding, and sepsis. Recently, we have reported a case series of 77 cases of in situ hypothermic liver resection [41]. This series is the largest reported to date. Seventy-two cases were malignancies, including hepatocellular carcinoma (10 cases), cholangiocarcinoma (24 cases), and other malignant tumors (7 cases). Interestingly, complex liver resection using hypothermic perfusion was performed in five cases of benign lesions. This complex procedure achieved a 5-year survival rate of 30.4 % and a high 90-day mortality of 19.5 %. Yet, all 4 cirrhotic patients died after surgery. By multivariate analysis, an age-adjusted Charlson comorbidity index ≥3 (indicating at least 2 comorbid conditions), the maximum tumor diameter ≥10 cm, and the presence of 50/50 criteria on postoperative day 5 were independent predictors of surgical mortality measured in 90 days.