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Portal vein ligation (PVL) has been adopted to induce hypertrophy of the future liver remnant (FLR) in patients with primarily irresectable liver tumor. However, regeneration of the FLR is not always sufficient to allow curative resection of the portally-deprived tumor-bearing liver lobe. We hypothesize that simultaneous hepatectomy (PHx) and PVL augments regeneration of the FLR and that the effect is related to the extent of the additional resection. Seventy-two Lewis rats were enrolled into 3 groups: 20%PVL + 70%PHx; 70%PVL + 20%PHx; 90%PVL. Animals were observed for 1, 2, 3 and 7 days postoperatively (n = 6/time point). Liver enzymes, caudate liver/body-weight-ratio, BrdU-proliferation-index (PI), proliferating-cell-nuclear-antigen (PCNA)-mRNA-expression level and autophagy-related-proteins were evaluated. Compared with 90% PVL, additional PHx induced significantly more hypertrophy during the observation time, which was confirmed by significantly higher PI and higher level of PCNA-mRNA expression. Similarly, the additional PHx induced more autophagy in the FLR compared with PVL alone. However, both effects were not clearly related to the extent of additional resection. Additional resection augmented liver regeneration and autophagy substantially compared with PVL alone. Therefore, we concluded that autophagy might play a critical role in regulating hepatocyte proliferation and the size of the FLR after simultaneous PVL + PHx.

The liver has the ability to maintain its total size by adjusting the size of the individual liver lobes differently in response to regeneration- and atrophy-stimuli. Portal vein ligation (PVL) drives the ligated lobe to undergo atrophy whereas partial hepatectomy (PHx) drives the total remnant liver to regenerate. We hypothesize that the size of the PVL-lobe is dependent on the balance between the extent of PVL and the extent of PHx inducing a complex interplay between hepatocyte proliferation, apoptosis and autophagy. Lewis-rats were subjected to either 20%PVL + 70%PHx or 70%PVL + 20%PHx. Control groups consisted of 20%PVL and 70%PVL. Liver lobe weight, BrdU-proliferation-index, proliferating-cell-nuclear-antigen-mRNA-expression level, apoptotic density and autophagy-related-proteins were investigated. The PVL-liver lobe adjusted its weight differently, increasing by 40% after 20%PVL + 70%PHx, but decreasing by 25% after 70%PVL + 20%PHx. Additional resection induced a low, but substantial size-dependent hepatocyte proliferation rate (maximal 6.3% and 3.6% vs. 0.3% and significantly suppressed apoptotic density in the deportalized-liver-lobe (3 and 14 cells/mm 2 comparing with above 26 cells/mm 2 , p < 0.01). Autophagy was more activated in PVL-liver lobe after simultaneous PHx than after PVL only. In summary, atrophy of the PVL-liver lobe after simultaneous PHx was counteracted by promoting hepatocyte proliferation, inducing autophagy and suppressing apoptosis in a PHx-extent-dependent manner.

Background: We adapted the anatomically oriented parenchyma-preserving resection technique for associating liver partition with portal vein ligation (PVL) for staged hepatectomy (ALPPS) in rats and examined the role of revascularization in intrahepatic size regulation., Methods: We performed the procedures based on anatomic study. The ALPPS procedure consisted of a 70% PVL (occluding the left median, left lateral, and right lobes), parenchymal transection (median lobe) and partial (10%) hepatectomy (PHx; caudate lobe). The transection effect was evaluated by measuring the extent of hepatic atrophy or regeneration of individual liver lobes in the ALPPS and control groups (70% PVL and 10% PHx without transection). The survival rates after stage II resection and collateral formation within the portal vein system was examined., Results: Anatomic study revealed a close spatial relationship between the demarcation line and the middle median hepatic vein. This enabled placing the transection plane without injuring the hepatic vein. Transection was achieved via stepwise clamping, followed by 2-3 parenchyma-preserving piercing sutures on both sides of the clamp. Ligated liver lobes atrophy was significantly enhanced after ALPPS compared with the control group. In contrast, both a significantly greater relative weight of the regenerated lobe and proliferation index on the first postoperative day were observed. All animals tolerated stage II-resection without complications. Portoportal collaterals were only observed in the control group., Conclusion: We developed an anatomically precise technique for parenchymal transection. The lack of a dense vascular network between the portalized and deportalized lobes may play an important role in accelerating regeneration and atrophy augmentation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background/aim: Liver size regulation is based on the balance between hepatic regeneration and atrophy. To achieve a better understanding of intrahepatic size regulation, we explored the size regulation of a portally deprived liver lobe on a liver subjected to concurrent portal vein ligation (PVL) and partial hepatectomy (PHx)., Materials and Methods: Using a surgical rat model consisting of right PVL (rPVL) plus 70% PHx, we evaluated the size regulation of liver lobes 1, 2, 3, and 7 days after the operation in terms of liver weight and hepatocyte proliferation. Portal hyperperfusion was confirmed by measuring portal flow. The portal vascular tree was visualized by injection of a contrast agent followed by CT imaging of explanted livers. Control groups consisted of 70% PHx, rPVL, and sham operation., Results: The size of the ligated right lobe increased to 1.4-fold on postoperative day 7 when subjected to rPVL + 70% PHx. The right lobe increased to 3-fold when subjected to 70% PHx alone and decreased to 0.3-fold when subjected to rPVL only. The small but significant increase in liver weight after the combined procedure was accompanied by a low proliferative response. In contrast, hepatocyte proliferation was undetectable in the right lobe undergoing atrophy after PVL only. The caudate lobe in the rPVL + 70% PHx group increased to 4.6-fold, which is significantly more than in the other groups. This increase in liver weight was paralleled by persisting portal hyperperfusion and a prolonged proliferative phase of 3 days., Conclusions: A discontinued portal blood supply does not always result in atrophy of the ligated lobe. The concurrent regenerative stimulus induced by 70% PHx seemed to counteract the local atrophy after a simultaneously performed rPVL, leading to a low but prolonged regenerative response of the portally deprived liver lobe. This observation supports the conclusion that portal flow is not necessary for liver regeneration. The persisting portal hyperperfusion may be crucial for the specific kinetics of prolonged liver regeneration after rPVL + 70% PHx in the portally supplied caudate lobe. Both observations deserve more attention regarding the underlying mechanism in further studies., (© 2016 S. Karger AG, Basel.)