Liver regeneration and function following portal vein occlusion and hepatectomy

Background: Portal vein occlusion (PVO) and associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) are two strategies employed to render patients with unresectable liver tumours resectable by increasing the size of the future liver remnant (FLR). There is still limited knowledge about several aspects of PVO and most aspects of ALPPS.

Aims: To evaluate tumour progression after portal vein embolization (PVE) in patients with colorectal liver metastases (CRLM) treated with pre-procedural chemotherapy. To investigate if ALPPS performed after failed PVO in patients with CRLM treated with neoadjuvant chemotherapy is safe and feasible. To assess and compare liver volume and function in patients subjected to ALPPS. To study the levels of liver regenerative growth factors in ALPPS.

Methods: In paper I, patients with CRLM and response to neoadjuvant chemotherapy, subjected to PVE at Skåne University Hospital (2005-2013) and Karolinska University Hospital (2004-2010) were included in the study and assessed for tumour progression. In paper II, patients subjected to ALPPS after failed PVO at Karolinska University Hospital were included and efficacy and safety of the procedure in these patients was evaluated. In paper III, the liver volume and function in patients subjected to ALPPS was studied with a multimodal approach (including repeated computed tomography and hepatobiliary scintigraphy). In paper IV, sequentially sampled tissue from patients operated with ALPPS was analysed to assess the levels of liver regenerative growth factors.

Results: In paper I, 34 patients were identified and included. The median time between ended chemotherapy and PVE was 16 days. Three patients had tumour progression in the embolized liver lobe and three in the non-embolized lobe. Only two patients experienced tumour progression in the FLR that inhibited curative resection. In paper II, eleven patients operated with ALPPS after failed PVO were included. Six days after stage 1 the median growth of the FLR was 61.8% and all patients could proceed to stage 2 and resection of the liver tumours on day 7, with low morbidity and no 90-day mortality. In paper III, nine patients were studied and the increase in FLR-volume exceeded the increase in FLR-function at day 6 after stage 1, where functional increase only reached 50% of the volume increase in the FLR. In paper IV, ten patients were studied. The levels of HGF in plasma correlated with the degree of growth of the FLR and the levels of IL-6 correlated with the HGF levels.

Conclusions: The rate of progression of CRLM after PVE with pre-procedural chemotherapy is lower than previously reported if the time between the end of chemotherapy and PVE is short. The powerful growth of the FLR associated with ALPPS seems to be maintained in patients with CRLM treated with neoadjuvant chemotherapy and previously failed PVO. In the interstage period of ALPPS the high volume increase is not paralleled by a corresponding functional increase. The levels of HGF in plasma correlates with the degree of growth of the FLR and the levels of IL-6 correlates with the HGF levels in patients operated with ALPPS.

List of scientific papers

I. Spelt L, Sparrelid E, Isaksson B, Andersson R, Sturesson C. Tumour growth after portal vein embolization with pre-procedural chemotherapy for colorectal liver metastases. HPB (Oxford). 2015, 17(6):529-35.
https://doi.org/10.1111/hpb.12397

II. Sparrelid E, Gilg S, Brismar TB, Lundell L, Isaksson B. Rescue ALPPS is efficient and safe after failed portal vein occlusion in patients with colorectal liver metastases. Langenbeck's Arch Surg. 2016, Oct 19.
https://doi.org/10.1007/s00423-016-1524-y

III. Sparrelid E, Jonas E, Tzortzakakis A, Dahlén U, Murquist G, Brismar TB, Axelsson R, Isaksson B. Dynamic evaluation of liver volume and function in associating liver partition and portal vein ligation for staged hepatectomy. [Submitted]

IV. Sparrelid E, Johansson H, Gilg S, Nowak G, Ellis E, Isaksson B. HGF levels correlates to the growth of the liver in patients operated with ALPPS. [Submitted]