A preliminary study of associating liver partition and portal vein ligation for staged hepatectomy in a rat model of liver cirrhosis

Yang, Chuang; Qiu, Yiwen; Shen, Shu; Kong, Junjie; Wang, Wentao

doi:10.3892/etm.2019.7688

Cited by 4 publications

(7 citation statements)

References 46 publications

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“…In most of the studies, the study period ranges from 24 h to 7 or 8 days after the surgical procedures, which is the same period used in our model. Even though some studies refer to 3 days [ 31 , 36 , 37 ] as the point of peak hypertrophy, in our model we have observed that hypertrophy reached its maximum as early as 36 h after selective PVL. This is consistent with the studies of Higgins and Anderson, who had demonstrated that, after partial hepatectomy, the greatest increase in liver mass occurred in the first 24–48 h [ 38 ].…”

Section: Discussioncontrasting

confidence: 57%

“…For this purpose, some key points are the choice of the experimental model and the study time after the tested surgical procedure. Most of these studies have been carried out in a rat experimental model [ 29 , 30 , 31 , 32 , 33 ], although others have opted for rabbits [ 34 ], or even pigs [ 35 ]. In most of the studies, the study period ranges from 24 h to 7 or 8 days after the surgical procedures, which is the same period used in our model.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to registering liver weight, Ki-67 labeling is commonly used as an indicator of cell proliferation in liver parenchyma not subjected to PVL, as well as the counting of the number of nuclei in mitosis. In those studies that analyzed the differences in liver regeneration between selective PVL and ALPPS, a significantly higher number of hepatocytes positively labeled for Ki-67 was detected in the latter cases [ 15 , 29 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. In our study, because of the impossibility of conducting Ki-67 immunohistochemical studies, we used the measurement of the nuclear area of hepatocytes as an indirect measure of their proliferative/regenerating state.…”

Section: Discussionmentioning

confidence: 99%

“…Our therapeutic approach with FA allows us to associate the increase in FLR with slightly lower changes in the hepatic serum markers analyzed both at 36 h and at 7 days. It is true that most of the previous studies have shown that liver enzyme levels return into normal levels 7 to 14 days later without any specific treatment [ 30 , 31 , 32 , 33 , 36 ]. However, our experimental treatment with FA achieves significantly better values as early as 36 h in most of the analyzed parameters.…”

Section: Discussionmentioning

confidence: 99%

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Folinic Acid Potentiates the Liver Regeneration Process after Selective Portal Vein Ligation in Rats

María

Parte

Gutiérrez-Sánchez

et al. 2022

Cancers

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Liver resection remains the gold standard for hepatic metastases. The future liver remnant (FLR) and its functional status are two key points to consider before performing major liver resections, since patients with less than 25% FLR or a Child–Pugh B or C grade are not eligible for this procedure. Folinic acid (FA) is an essential agent in cell replication processes. Herein, we analyze the effect of FA as an enhancer of liver regeneration after selective portal vein ligation (PVL). Sixty-four male WAG/RijHsd rats were randomly distributed into eight groups: a control group and seven subjected to 50% PVL, by ligation of left portal branch. The treated animals received FA (2.5 m/kg), while the rest were given saline. After 36 h, 3 days or 7 days, liver tissue and blood samples were obtained. FA slightly but significantly increased FLR percentage (FLR%) on the 7th day (91.88 ± 0.61%) compared to control or saline-treated groups (86.72 ± 2.5 vs. 87 ± 3.33%; p < 0.01). The hepatocyte nuclear area was also increased both at 36 h and 7days with FA (61.55 ± 16.09 µm2, and 49.91 ± 15.38 µm2; p < 0.001). Finally, FA also improved liver function. In conclusion, FA has boosted liver regeneration assessed by FLR%, nuclear area size and restoration of liver function after PVL.

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Section: Discussioncontrasting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Folinic Acid Potentiates the Liver Regeneration Process after Selective Portal Vein Ligation in Rats

María

Parte

Gutiérrez-Sánchez

et al. 2022

Cancers

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“…More specifically, ALPPS surgery in patients with cirrhosis resulted in sustained proliferation and accelerated second stage hepatectomy within a short time. Meanwhile, in the normal liver, days 1 and 3 after ALPPS tend to be the cardinal periods for liver regeneration, with the rate of liver regeneration decreasing after 7 days (17). Indeed, ALPPS augmented liver regeneration to the point where increases in standardized future liver remnant and liver-to-body-weight-ratio were sufficient for a resection after a median of 9 days (18).…”

Section: Discussionmentioning

confidence: 99%

MMP2/9 downregulation is responsible for hepatic function recovery in cirrhotic rats following associating liver partition and portal vein ligation for staged hepatectomy

Qin¹,

Li²,

Ge³

et al. 2022

Ann Transl Med

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Background: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) was introduced in 2007. The current study explored the mechanisms of rapid liver hypertrophy after ALPPS in cirrhotic rats.Methods: A cirrhotic rat model was constructed and portal vein ligation (PVL) or ALPPS treatments were administered. The liver hyperplasia rate of the rats was calculated, and hepatic function was evaluated using biochemical factors and the indocyanine green excretion test. Subsequently, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and hematoxylin and eosin (HE) staining were performed to determine the degree of liver regeneration. Differentially expressed genes during the rapid liver hypertrophy were detected by bioinformatics analysis, followed verification using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry. Results:The body weight of rats that underwent PVL and ALPPS changed during the first 1-4 days postoperatively, and the alterations were more pronounced in rats receiving ALPPS. The recovery of body weight in cirrhotic rats was slower than that in normal rats. The levels of biochemical factors and the indocyanine green retention rate increased 1 day after PVL and ALPPS, and then decreased gradually. PVL and ALPPS elevated the levels of cytokines, inflammatory factors, and proliferating cell nuclear antigen (PCNA) in rats at 1 day postoperatively. HE observation of rat liver condition showed that rats recovered faster within the first 4 days postoperatively. ALPPS surgery resulted in a significant downregulation of matrix metalloproteinase (MMP)2/9 expression in cirrhotic rats at postoperative day 4.Conclusions: Liver function was partially recovered in cirrhotic rats after ALPPS, and the underlying mechanisms may involve PCNA and MMP2/9.

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Liver Histology Predicts Liver Regeneration and Outcome in ALPPS

Lopez-Lopez,

Linecker,

Caballero-Llanes

et al. 2023

Annals of Surgery

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Background and Aims: Alterations in liver histology influence the liver´s capacity to regenerate, but the relevance of each of the different changes rapid liver growth induction is unknown. This study aimed to analyze the influence of the degree of histological alterations during the first and second stages on the ability of the liver to regenerate. Methods: This cohort study included data obtained from the International ALPPS Registry between November 2011 and October 2020. Only patients with colorectal liver metastases were included in the study. We developed a histological risk score based on histological changes (stages 1 and 2) and a tumor pathology score based on the histological factors associated with poor tumor prognosis. Results: In total, 395 patients were included. The time to reach stage 2 was shorter in patients with a low histological risk stage 1 (13 vs. 17 d, P˂0.01), low histological risk stage 2 (13 vs. 15 d, P˂0.01) and low pathological tumor risk (13 vs. 15 d, P˂0.01). Regarding interval stage, there was a higher inverse correlation in high histological risk stage 1 group compared to low histological risk 1 group in relation with future liver remnant body weight (r=−0.1 and r=−0.08, respectively), and future liver remnant (r=−0.15 and r=−0.06, respectively). Conclusion: ALPPS is associated with increased histological alterations in the liver parenchyma. It seems that the more histological alterations present and the higher the number of poor prognostic factors in the tumor histology, the longer the time to reach the second stage.

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A preliminary study of associating liver partition and portal vein ligation for staged hepatectomy in a rat model of liver cirrhosis

Cited by 4 publications

References 46 publications

Folinic Acid Potentiates the Liver Regeneration Process after Selective Portal Vein Ligation in Rats

Folinic Acid Potentiates the Liver Regeneration Process after Selective Portal Vein Ligation in Rats

MMP2/9 downregulation is responsible for hepatic function recovery in cirrhotic rats following associating liver partition and portal vein ligation for staged hepatectomy

Liver Histology Predicts Liver Regeneration and Outcome in ALPPS

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