Ex-Vivo Liver Surgery

Fig. 18.1

Computerized tomography of a large cholangiocarcinoma of the right lobe invading the takeoff of the left portal vein (a) and inferior vena cava (b)

The confirmation of these relationships often requires three-dimensional image analysis. CT or MRI IVC invasion of <50% diameter or <3 cm in length is amenable to direct repair, or patch repair using either saphenous vein (autogenous or cryopreserved), bovine pericardium, or prosthetic material [14, 22, 23]. For IVC–hepatic vein junction tumors, we agree with Hemming in advocating EVAT versus modified TVE in order to provide a surgical field most conducive to complete tumor extirpation with acceptable parenchymal margins [24]. Complex vascular reconstructions, whether hepatic venous outflow or hilar, are facilitated by EVAT, as the reconstructions and parenchymal transection can be performed under cold preservation with minimal time constraints. Furthermore, the recipient remains hemodynamically stable through veno-venous bypass or decompressive shunting without the physiologic challenge of sustained volume loading or hypothermia that occurs with a prolonged performance of TVE.

Autograft volume assessment is performed utilizing three-dimensional image reconstructions. A future liver remnant (FLR) above 40% of predicted is ideal for hepatic parenchyma exposed to chemotherapy. A lower threshold of 25–30% is possible when the operative recipient is young and has not been exposed to chemotherapy [24, 29]. Estimation of FLR in EVAT does not typically require the degree of consideration given to larger in-situ hepatectomies. EVAT usually involves vast, bulky tumors that stimulate significant hypertrophy in the future liver remnant. When analyzing outcomes data, mortality secondary to early liver failure has steadily declined since the introduction of EVAT.

We routinely apply portal vein embolization (PVE) approximately 3–4 weeks before EVAT as a mechanism of graft conditioning. PVE not only optimizes the FLR, but hepatic regeneration secondary to PVE may stimulate growth of occult neoplasms within the planned remnant (Fig. 18.2).

Fig. 18.2

Portal vein embolization of a large cholangiocarcinoma of the right hepatic lobe with invasion of the inferior vena cava

Thus, we employ PVE as an attempt to avert early disease recurrence secondary to occult micrometastatic disease in the remnant, and also as a final screen for resectability. Two to 3 weeks after PVE and within 2 weeks of planned EVAT, the patient receives their final cross-sectional imaging prior to surgery to confirm volumetry and exclude radiographic disease in the remnant. Our experience with increasing FLR from PVE when planning EVAT has been variable, but the improvement of FLR by as much as 30% has been reported [24].

Operative Technique

Successful performance of EVAT integrates hepatobiliary surgery, partial-allografting in transplantation, pre-operative three-dimensional reconstruction imaging, volumetry, and advanced intraoperative imaging techniques. Pre-operative planning includes anesthesia, nursing, bloodbank/laboratories, and intensive care unit personnel [21]. Two complete surgical teams will be required during the period of ex-vivo hepatectomy to minimize the period of cold storage: one team to work in infusion of the allograft with preservation solution, resection of the tumor, and remnant preparation for implantation, and another team to recreate the IVC, perform a portacaval shunt, and prepare the arterial inflow.

The procedure begins with a diagnostic laparoscopy with intraoperative ultrasound to verify the anatomic relationships and exclude metastatic disease or radiologically occult disease in the anticipated hepatic remnant. Laparoscopic examination of hilar nodes is included with biopsy of any suspicious adenopathy. Upon completion of the diagnostic laparoscopy, a supraumbilical midline incision with bilateral subcostal extension is performed to include the previous laparoscopy port sites. The retractors are positioned and the liver mobilized as performed for OLT.

The type and extend of veno-venous bypass (VVB) is optional; however, VVB of the systemic and portal circulations must be immediately available should volume loading be insufficient to maintain cardiac output, occurrence of a cardiac arrythmia, rapidly increasing splenomegaly, or mesenteric congestion.

Upon complete mobilization of the liver and establishment of VVB, as desired, total vascular exclusion is performed and the liver is explanted. The principal surgical team remains with the liver to immediately initiate cold preservation through infusion of 2 l of HTK via the portal vein, 1 l via the artery, and 300 cm³ via the bile duct. We prefer to flush only the potential remnant.

Upon completion of organ flush, the dissection is performed in cold preservation. Parenchymal transection is at the discretion of the surgeon but has been described utilizing clamp–crush, sharp dissection, and the Cavitron ultrasonic dissector. Vascular structures are sharply dissected in preparation for reconstruction. Vascular reconstructions may involve vessels salvaged from the explant specimen when necessary. Upon completion of parenchymal transection, oversew of biliary and vascular structures, and any vascular reconstructions, the remnant is again flushed with 1 liter of HTK in the portal vein, 500 cm³ in the hepatic artery and 50 cm³ gently flushed in the bile duct immediately prior to implantation.

With an EVAT, surgery on the liver can be extended between 3 and 5 h, while vascular exclusions alone mostly remain between 30 and 35 min. In the majority of reported cases for extreme surgery, the exclusion period of up to 55 min sufficed to perform vascular reconstructions required to obtain an R0 resection.

Major reports of the success of extended partial hepatectomies for metastatic diseases fostered a surge of procedures using isolated liver perfusion for prevention of hepatic ischemia to extend the time for operating on the liver.

The vast majority of procedures, however, avoided the ex-vivo approach and instead reported vascular exclusion with hypothermic perfusion, in-situ or ante-situm operations with a hypothermic protection of the liver while an extracorporeal bypass was introduced [23, 33, 34].

The last report of a series of ex-vivo liver resections and autotransplantation was published by Wen et al. [29] including 15 patients with end-stage alveolar echinococcosis (benign disease). The indication was highly selective, arguing that their procedure requires no organ donor nor immunosuppression. They performed temporary IVC interposition and portosystemic shunting for hemodynamic stability. The postoperative complications were minimal, with only one death due to liver failure and 20% requiring postoperative reintervention. Hence, the peculiarity of a unilocular located tumor, obstructing the portal vein entrance, works like an artificial portal vein occlusion, thus leading to a regenerative growth of the remnant liver. The volume of the reimplanted livers, not affected by chemotherapy or other toxic agents, all remained satisfactory.

Another successful ex-situ operation was reported by Hanoun et al. [15], but the one patient with metastatic disease developed recurrence after 11 months.

Chui et al. [33] reports a single case of hilar cholangiocarcinoma, and there are other reports of technically successful operations, but the results reported for the treatment of malignancies do not yet warrant a broader application.

The only report with long-term experience after ex-situ liver surgery derives again from the Hannover group, published in 2000 after the untimely demise of Rudolf Pichlmayr in 1997 [22]. In 22 patients, ex-vivo partial hepatectomies were performed with ten patients presenting with metastatic disease from primary colorectal cancer.

Six patients could be followed up for up to 2 years and 7 months, ultimately dying from the recurrent disease with the majority having a lesser survival time (Table 18.1).

Table 18.1

Results of the two major reports of EVAT for malignancies

Author	N	Hospitalization (days)	Survival time (months)	Cause of death
Oldhafer [22]	10
	1	14	13	Tumor recurrence
	2	44	0	Liver failure
	3	56	21	Tumor recurrence
	4	60	2	Intracerebral bleeding
	5	60	2	Sepsis
	6	24	15	Tumor recurrence
	7	27	31	Tumor recurrence
	8	61	36	Tumor recurrence
	9	14	0	Pneumonia
	10	42	0	Sepsis
Lodge [23]	4
	1	42	30	Tumor recurrence
	2	15	0.5	Liver failure
	3	9	NA	Tumor recurrence
	4	10	NA	Tumor recurrence

Including other metastatic and primary malignant diseases, only seven patients survived more than 18 months. The intraoperative mortality for primary Klatskin tumors was three out of four patients, demonstrating, that the courageous attempt for a curative resection failed. By looking closely into the results of two other relevant publications, it becomes evident that the price for a possible extended life span included a long hospital stay up to 61 days, eventually dying from recurrence after 36 months [23, 35, 36].

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