The incidence of intrahepatic cholangiocarcinoma (iCCA) has increased over recent decades [1
]. This might be due to improvements in diagnostic tools or increases in metabolic disorders and obesity [4
]. Advances in local therapies, targeted chemotherapies and adjuvant chemotherapy are promising [5
]; however, liver resection remains the only potential curative therapy [9
]. At presentation, about 50% of patients have unresectable disease and another 30% will be found unresectable during surgical exploration [11
]. Therefore, the resectability rate of iCCA is described as 15–35% [11
]. When the tumor is confined to the liver, complete tumor resection results in a 5-year survival rate of up to 40% [11
]. The survival and recurrence rates are affected by nodal metastasis, tumor size, multifocal tumor growth and macrovascular invasion [12
]. Central localization of iCCA is quite common and vascular invasion of the hepatic veins is often a limiting factor for R0-resection. Regarding these circumstances, non-conventional surgical techniques, such as ante situm procedures, offer a possibility for resection [17
]. In addition, portal vein resection is often needed and complex constructions are described as safe for selected patients in high-volume centers [9
A sufficient future liver remnant (FLR) is critical in decreasing postoperative morbidity and mortality [24
]. Tumor size and location represent important factors for the resection strategy. Not seldom, complex liver resections such as meso-hepatectomy or trisectionectomy with reconstruction of the extrahepatic biliary duct are necessary [12
In case of a non-sufficient FLR, portal vein embolization (PVE) or associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) are strategies to enhance FLR [12
]. Whereas PVE is considered as safe and standard technique for small FLR [9
], the role of ALPPS is currently controversially discussed [28
However, in liver resection for iCCA, the main focus is to accomplish R0-resection, even with the use of complex surgical techniques, such as ante situm or extended resections with or without vascular reconstructions, if necessary. The aim of this study is to analyze the role of complex liver resections for iCCA in terms of morbidity and long-term survival.
Liver resection is the only curative treatment option for iCCA, and therefore, major efforts should be made to achieve tumor resection [9
]. ICCAs are frequently centrally localized and often infiltrate portal and hepatic veins. Therefore, to achieve complete tumor removal, complex liver resections with vascular reconstructions including two-stage procedures are often necessary. In some circumstances, only ante situm resection represents the sole surgical option.
It is well-known that complex liver resections are generally associated with an increased morbidity and mortality [12
]. This was clearly observed in the present study. The CCI with a median of 29.6 was significantly higher in the group after complex liver resections compared to the group after conventional liver resections with a CCI of 8.7. The documented mortality rate of 10% after complex liver resections with vascular reconstructions including ALPPS is high but lies within the published range and reflects the complexity of the procedure [22
]. In a recent multicenter study of 270 patients with vascular resection in combination with liver resection for iCCA, Conci et al. reported a mortality rate of 6.7% for patients after portal vein resection and 12.5% after vena cava resection [23
]. Reames et al. reported a 90-day mortality rate of 7% after 128 liver resections with major vascular resection for iCCA in a large multi-institutional analysis [22
]. PHLF represents one main reason for postoperative morbidity and mortality. In the present study, the rate was 10% in the group after complex liver resections. Generally, a small FLR is mainly the cause for PHLF. Various hypertrophy concepts such as PVE or ALPPS are available to increase the FLR. However, the use of ALPPS for iCCA has been a matter of debate since its introduction [38
]. Recently, Li et al. could show in a group of 102 patients with advanced iCCA from the ALPPS registry that the initially high rates of morbidity and mortality decreased steadily to a 29% severe complication rate and 7% 90-day mortality in the last 2 years [28
]. Furthermore, Li et al. reported a high efficacy of 85% in achieving R0 resections. However, they only have seen an overall survival benefit for ALPPS in patients with a single lesion, not in patients with multiple lesions and, therefore, recommend ALPPS for this group [28
A novel procedure to increase FLR is hepatic vein embolization in combination with PVE [39
], which shows promising results for FLR hypertrophy compared to ALPPS [39
]. Even for extended resection, the embolization of the right and middle hepatic vein is described [42
]. The role of hepatic vein embolization for iCCA needs to be investigated, but seems to be a promising tool for future resection strategies [43
It is noteworthy that we had a 0% mortality rate after our ante situm resections. The experience with ante situm resections for iCCA is limited; mostly case reports or case series are available [17
]. Without doubt, the surgical procedure is challenging due to the use of an extracorporeal bypass, in situ cold perfusion and complex vascular reconstruction of the IVC and hepatic veins. However, ante situm resection offers a reasonable chance of good, long-term outcome. One may speculate that in some circumstances, ante situm or in situ resections after cold perfusion with the aim of parenchymal-sparing might be superior to complicated long-lasting two-stage procedures.
Patients with unresectable tumors have a poor prognosis [10
]. During exploration, 30% of the patients that were preoperatively considered as resectable were found to be unresectable [11
]. In our cohort, the survival of the exploration group was 50% at 12 months and 0% at 28 months. Surprisingly, a high 90-day mortality rate of 25% was observed in this group. This is most likely due to the fast tumor progression, which highlights the aggressiveness of iCCA. In addition, for large central iCCA, reconstruction of the bile duct is necessary, because of liver hilum involvement. In those patients, a differentiation between iCCA or perihilar cholangiocarcinoma is often challenging.
In the current study, we found no significant difference in overall survival between patients after complex and after conventional liver resections. Survival in our study depends more on resection margin status and UICC staging and not on the complexity of the resection. This is in accordance with the published data [9
]. High UICC staging, large or multifocal tumors and vascular invasion are reported to be negative prognostic parameters in iCCA patients [12
In conclusion, the effort of complex resections, such as ante situm, ALPPS, and extended resections with reconstructions of one or several hepatic vessels, is justified and results in favorable long-term outcome. Overall survival in iCCA seems to be affected by UICC stage and resections margins and not by the complexity of the surgical procedure.