Abstract

Associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a two-stage hepatectomy technique which can be associated with a hypertrophic stimulus on the future liver remnant (FLR) stronger than other techniques–such as portal vein ligation (PVL). However, the reason of such hypertrophy is still unclear, but it is suggested that liver transection combined with portal vein ligation (ALPPS) during the first stage of this technique may play a key role. The aim of this study is to compare the hypertrophic stimulus on the FLR and the clinical changes associated with both ALPPS and PVL in a rat surgical model. For this purpose, three groups of SD rats were used, namely ALPPS (n = 30), PVL (n = 30) and sham-treated (n = 30). The second stage of ALPPS (hepatectomy of the atrophic lobes), was performed at day 8. Blood and FLR samples were collected at 1, 24, 48 hours, 8 days and 12 weeks after the surgeries. ALPPS provoked a greater degree of hypertrophy of the FLR than the PVL at 48 hours and 8 days (p<0.05). The molecular pattern was also different, with the highest expression of IL-1β at 24h, IL-6 at 8 days, and HGF and TNF-α at 48 hours and 8 days (p<0.05). ALPPS also brought about a mild proliferative stimulus at 12 weeks, with a higher expression of HGF and TGF-β (p<0.05) than PVL. Clinically, ALPPS caused a significant liver damage during the first 48 hours, with a recovery of liver function at day 8. In conclusion, ALPPS seems to induce higher functional hypertrophy on the FLR than PVL at day 8. Such regenerative response seems to be leaded by a complex interaction between pro-mitogenic (IL-6, HGF, TNF-α) and antiproliferative (IL1-β and TGF-β) cytokines.

Highlights

  • The two-stage hepatectomy is a surgical strategy for patients with unresectable liver metastases or primary malignancies

  • No deaths were registered during the portal vein ligation (PVL) procedure, a result which contrasts with the ALPPS procedure, in which a 17% of mortality (5/30 animals) was registered within the first 48 hours after the procedure

  • Combining PVL and hepatic transection of the medium lobe led to a higher hypertrophy of the future liver remnant (FLR), with higher mitotic index (MI) and proliferative rate than the PVL in a similar way to the previously described partial hepatectomy model for rats [10] or mice [15], and continues in a lower degree up to 12 weeks after surgery, where the weight and volume reached by PVL FLR is similar to those observed in the ALPPS FLR at day 8

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Summary

Objectives

The aim of this study is to compare the hypertrophic stimulus on the FLR and the clinical changes associated with both ALPPS and PVL in a rat surgical model. The aim of this study is to explore the morphometric, immunohistopathologic and molecular changes of the FLR and the clinical effects that the ligation of the tributaries of the portal vein simultaneously with a hepatic transection bring about in a rat surgical experimental model

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