Sustained function in atrophying liver tissue after portal branch ligation in the rat

Müeller, Lars; Grotelueschen, Rainer; Meyer, J.; Vashist, Yogesh K.; Abdulgawad, A.; Wilms, Christian; Hillert, C.; Rogiers, Xavier; Bröering, Dieter C.

doi:10.1016/s0022-4804(03)00252-x

Cited by 21 publications

(18 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…rPVL did neither affect body weight recovery nor the release of serum transaminases compared to the sham operation. This indicates that liver function was not impaired after rPVL in our study, as was also reported by Mueller et al [13]. They stated that the regressive lobe did not lose its functional integrity after portal occlusion.…”

Section: Discussionsupporting

confidence: 90%

Intrahepatic Size Regulation in a Surgical Model: Liver Resection-Induced Liver Regeneration Counteracts the Local Atrophy following Simultaneous Portal Vein Ligation

Wei

Zhang²,

Fang³

et al. 2016

Eur Surg Res

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 90%

Intrahepatic Size Regulation in a Surgical Model: Liver Resection-Induced Liver Regeneration Counteracts the Local Atrophy following Simultaneous Portal Vein Ligation

Wei

Zhang²,

Fang³

et al. 2016

Eur Surg Res

View full text Add to dashboard Cite

show abstract

“…Previous reports (15,16,20,25,29) have demonstrated a pronounced reduction of weight, size, and number of hepatocytes at 5-8 days after PBL. The later course of the weight of the ligated lobe, however, was not monitored in these studies.…”

Section: Discussionmentioning

confidence: 79%

“…In contrast to the compensatory hypertrophy, which is initiated directly by an early proliferative response (9), the rapid shrinkage of the ligated lobe is thought to be associated with a reduction in size and number of hepatocytes, most probably due to sustained hypoxia and metabolic deprivation of portal hepatotrophic factors (15,20,34). The PBL-induced atrophy involves both centrolobular necrosis and apoptotic cell death in a timedependent manner, however, without affecting the hepatic microarchitecture (15,16,20,25,29).…”

mentioning

confidence: 99%

Portal branch ligation induces a hepatic arterial buffer response, microvascular remodeling, normoxygenation, and cell proliferation in portal blood-deprived liver tissue

Kollmar

Corsten²,

Scheuer³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Portal branch ligation (PBL) may prevent liver failure after extended hepatic resection. However, clinical studies indicate that tumors within the ligated lobe develop accelerated growth. Although it is well known that tumor growth depends on the host's microvascularization, there is no information about how PBL affects the hepatic microcirculation. Our aims were to determine hepatic artery response, liver microcirculation, tissue oxygenation, and cell proliferation after PBL. Therefore, we used intravital multifluorescence microscopy, laser-Doppler flowmetry, immunohistochemistry, and biochemical techniques to examine microcirculatory responses, microvascular remodeling, and cellular consequences after left lateral PBL in BALB/c mice. During the first 7 days, PBL induced a reduction of left hilar blood flow by ∼50%. This resulted in 80% sinusoidal perfusion failure, significant parenchymal hypoxia, and liver atrophy. After 14 days, however, left hilar blood flow was found to be restored. However, remodeling of the microvasculature included a rarefaction of the sinusoidal network, however, without substantial perfusion failure, compensated by a hepatic arterial buffer response and significant sinusoidal dilatation. This resulted in normalization of tissue oxygenation, indicating arterialization of the ligated lobe. Interestingly, late microvascular remodeling was associated with increased endothelial nitric oxide synthase expression, significant hepatocellular proliferation, and weight gain of the ligated lobe. Thus PBL induces only an initial microcirculatory failure with liver atrophy, followed by a hepatic arterial buffer response, microvascular remodeling, normoxygenation, and hepatocellular proliferation. This may explain the accelerated tumor progression occasionally observed in patients after PBL.

show abstract

“…Several cytokines and growth factors are known to play important roles in liver regeneration (Kusaka et al, 2006;Yokoyama et al, 2007), and could Effect of portal vein embolisation V Pamecha et al increase tumour growth after PVE. Mueller et al, reported, in a rat model of portal branch ligation, an association between hepatic atrophy and increased expression of genes known to promote tumour growth and angiogenesis (Mueller et al, 2003). Expression of hepatocyte growth factor (HGF)-mRNA is markedly increased after portal vein ligation (Uemura et al, 2000), which is known to stimulate growth of colorectal carcinoma cells in vitro (Ueno et al, 1996;Nabeshima et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Effect of portal vein embolisation on the growth rate of colorectal liver metastases

et al. 2009

View full text Add to dashboard Cite

Portal vein embolisation (PVE) is used to increase the remnant liver volume before major liver resection for colorectal metastases. The resection rate after PVE is 60 -70%, mainly limited by disease progression. The effect of PVE on tumour growth rate has not been investigated. The objective of this study was to compare the growth characteristics of resected colorectal liver metastases in patients undergoing pre-operative PVE with those of matched controls who had not undergone PVE. There were 22 patients who had undergone preoperative PVE and 20 matched controls. Tumour growth rate was calculated by the change in tumour volume (CT/MRI volumetric assessment) from diagnosis to resection. Resected histological specimens were examined by two histopathologists independently for cell differentiation, percentage tumour cell necrosis and mitotic rate. Immunochemical staining with Ki67 was carried out using the MIB-1 monoclonal antibody and quantified using a Glasgow cell-counting graticule. The groups were comparable in demographics, stage of primary disease, volume of liver metastases at presentation and chemotherapy received. The tumour growth rate calculated from imaging was more rapid in the PVE group compared with that in controls (control: 0.05 ± 0.25 ml day À1 , PVE: 0.36 ± 0.68 ml day À1 , P ¼ 0.06). Histology showed no difference in the degree of differentiation, extent of necrosis or apoptosis between the two groups. However, mitotic rate was higher post PVE, as was the proliferation index Ki67 (P ¼ 0.04). This study has confirmed that tumour growth rate increased following PVE and that this is related to increased tumour cell division.

show abstract

Sustained function in atrophying liver tissue after portal branch ligation in the rat

Cited by 21 publications

References 25 publications

Intrahepatic Size Regulation in a Surgical Model: Liver Resection-Induced Liver Regeneration Counteracts the Local Atrophy following Simultaneous Portal Vein Ligation

Intrahepatic Size Regulation in a Surgical Model: Liver Resection-Induced Liver Regeneration Counteracts the Local Atrophy following Simultaneous Portal Vein Ligation

Portal branch ligation induces a hepatic arterial buffer response, microvascular remodeling, normoxygenation, and cell proliferation in portal blood-deprived liver tissue

Effect of portal vein embolisation on the growth rate of colorectal liver metastases

Contact Info

Product

Resources

About