The effect of partial hepatectomy on tumor growth in rats:In vivo andin vitro studies

Jong, Koert P. de; Lont, Harold E.; Bijma, Amelie M.; Brouwers, Mark A. M.; Vries, Elisabeth G.E. de; Veen, M.L. van; Marquet, R. L.; Slooff, Maarten J. H.; Terpstra, Onno T.

doi:10.1002/hep.1840220436

Cited by 59 publications

(20 citation statements)

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“…In experiments using rats, partial hepatectomy led to a more significant increase in the engraftment and growth of HCC in the residual liver than sham surgery. (31)(32)(33) However, in studies by Picardo et al and de Jong et al, no difference of engraftment and growth of HCC was found in extrahepatic sites based on whether partial hepatectomy was performed or not. (31,32) In contrast, Asaga et al reported growth enhancement in tumor cells following in vitro administration of serum obtained from rats that had been subjected to partial hepatectomy.…”

Section: Discussionmentioning

confidence: 93%

“…(31)(32)(33) However, in studies by Picardo et al and de Jong et al, no difference of engraftment and growth of HCC was found in extrahepatic sites based on whether partial hepatectomy was performed or not. (31,32) In contrast, Asaga et al reported growth enhancement in tumor cells following in vitro administration of serum obtained from rats that had been subjected to partial hepatectomy. (33) In this study, extrahepatic recurrence as well as intrahepatic recurrence was found to increase in patients with HCC beyond the Milan criteria who received SFSG.…”

Section: Discussionmentioning

confidence: 93%

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Small‐for‐size grafts increase recurrence of hepatocellular carcinoma in liver transplantation beyond milan criteria

et al. 2017

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Living donor liver transplantation (LDLT) has been reported to have high rates of hepatocellular carcinoma (HCC) recurrence compared with deceased donor liver transplantation (DDLT). This has been assumed to be due to the frequent use of small-for-size grafts (SFSGs) in LDLT rather than DDLT, but the relationship between graft size and prognosis remains controversial. This study aimed to clarify the effect of SFSGs on the oncologic outcomes of patients with HCC who underwent LDLT. Between January 2005 and December 2015, 597 consecutive patients underwent LDLT. Among these patients, those with HCC who underwent LDLT were randomly matched at a 1:3 ratio (graft-to-recipient body weight ratio [GRWR] < 0.8%:GRWR > 0.8%) according to propensity score. HCC recurrence and patient survival were analyzed using the Kaplan-Meier method and log-rank test. In addition, stratified subgroup analysis based on the Milan criteria was performed. SFSG was defined as a GRWR < 0.8%. Using propensity score matching, 82 patients with GRWR < 0.8% and 246 patients with GRWR 0.8% were selected. For patients with HCC within the Milan criteria, no significant difference of HCC recurrence (P 5 0.82) and patient survival (P 5 0.95) was found based on GRWR. However, for patients with HCC beyond the Milan criteria, 1-, 3-, and 5-year recurrence-free survival rates were 52.4%, 49.3%, and 49.3%, respectively, for patients with GRWR < 0.8%, and 76.5%, 68.3%, and 64.3%, respectively, for patients with GRWR 0.8% (P 5 0.049). The former group exhibited poor patient survival rates (P 5 0.047). In conclusion, for patients with HCC within the Milan criteria, no significant difference in oncologic outcomes was found based on liver graft size. However, among the patients with HCC beyond the Milan criteria, SFSG recipients showed poor oncologic outcomes. Because extended criteria are frequently used in LDLT for HCC, a recipient's prognosis can be improved if a liver graft of appropriate size is carefully selected during donor selection. Liver Transplantation 24 35-43 2018 AASLD.Received May 24, 2017; accepted August 27, 2017. Although living donor liver transplantation (LDLT) was initiated because of the shortage of deceased donor livers, it was accepted as an established method of treatment for end-stage liver diseases in the 1990s. The first LDLT was performed to transplant the left lateral section of the liver from a mother to a child with biliary atresia in 1989. (1)(2)(3) After the mid-1990s, right lobe LDLT started to be performed on adult recipients with high metabolic demands, and significant improvements in the outcomes were observed.A major limitation of LDLT is the size of the liver graft that can be obtained safely from living donors. Small-for-size grafts (SFSGs) cannot appropriately deal with the portal flow in the recipient due to decreased liver volume. Shear stress caused by transient portal hypertension can cause acute mechanical injury, which then induces severe inflammatory responses to negatively affect the outcomes of liver transpla...

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 93%

Small‐for‐size grafts increase recurrence of hepatocellular carcinoma in liver transplantation beyond milan criteria

et al. 2017

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“…Increased tumor growth in the remnant liver after partial liver resection in rats is a phenomenon that has been described by several groups. [24][25][26][27] Thus, we felt it was relevant to study the expression of growth factors and their receptors on primary colorectal carcinomas and their liver metastases in relation to clinicopathological variables and survival. In the present study, patients were selected on the basis of the presence of liver metastases of colorectal carcinomas, in which preoperative investigations did not reveal signs of extrahepatic metastases.…”

Section: Discussionmentioning

confidence: 99%

Clinical relevance of transforming growth factor ?, epidermal growth factor receptor, p53, and Ki67 in colorectal liver metastases and corresponding primary tumors

et al. 1998

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To determine whether the expression of transforming growth factor ␣ (TGF-␣), its receptor (epidermal growth factor receptor [EGFr]), p53 nuclear protein, and proliferation influences prognosis of patients with liver metastases, a study was performed in 45 liver metastases and 33 corresponding primary colorectal carcinomas in patients referred for liver surgery. The expression of TGF-␣, EGFr, p53 nuclear protein, and proliferation rate was correlated with clinicopathological characteristics and survival after partial liver resection. In liver metastases, TGF-␣ expression was low in 42%, intermediate in 35%, and high in 23%. TGF-␣ expression was higher in liver metastases derived from lymph node-positive primary carcinomas, in synchronous and in irresectable liver metastases compared with those derived from lymph node-negative primary carcinomas, metachronous, and resectable liver metastases. Nuclear p53 expression was found in 83% of primary tumors and 71% of liver metastases. p53 expression did not correlate with the various clinicopathological characteristics. Ki67 expression was not associated with clinicopathological characteristics in primary and metastatic tumors. In the 38 patients in whom a partial liver resection was performed, median survival was 25 months in patients with a higher TGF-␣ expression in the metastasis than in the primary tumor and 60 months in patients with comparable or lower TGF-␣ expression in the metastasis than in the primary tumor (P ‫؍‬ .036). Median survival after liver resection was 21 months in patients with p53-negative liver metastases and 58 months in patients with p53-positive metastases (P ‫؍‬ .043). By multivariate analysis, p53 and EGFr expression on liver metastases were the best predictors of diseasefree survival after partial liver resection, with relative risks of 2.38 and 3.33, respectively. In patients with colorectal liver metastases, referred for liver surgery, a higher TGF-␣ expression is associated with unfavorable tumor characteristics, whereas p53 and absence of EGFr expression is associated with a better survival after partial liver resection. (HEPATOLOGY 1998;28:971-979.)Colorectal carcinoma is the second-leading cause of cancer deaths in the Western community. Of all colorectal cancer patients, about 50% will die within 5 years after diagnosis. 1 At the time of initial diagnosis, 15% to 25% of patients present with synchronous liver metastases. 1 It is estimated that overall, only 5% of patients who develop liver metastases of colorectal carcinomas are amenable to partial liver resection. 2 Despite intentionally curative liver resections, only 20% to 30% of these patients have a disease-free 5-year survival. [3][4][5] Furthermore, in patients with recurrences after liver resection, these recurrences often appear early after liver surgery, with the liver being a frequent site of initial failure. 5,6 In the animal model, tumor growth can be influenced by growth factors produced by the tumor cells and by growth factors generated by the organ that harbors the m...

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“…Previous studies suggest that removal of the primary tumour can be associated with an enhanced tumour growth of residual micro-metastases (1). Experimental animal data show that metastatic growth after liver resection is significantly accelerated in the course of hepatic regeneration (2)(3)(4)(5). However, the exact mechanism of this enhanced tumour growth remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Increased growth factor expression after hepatic and pancreatic resection

Justinger

Schlüter²,

Oliviera-Frick³

et al. 1994

Oncol Rep

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Abstract. Removal of the primary tumour is suggested to associate with an enhanced tumour growth of residual micrometastases. Recent data focus on growth factors that may be released in response to surgery-stimulating receptors of residual tumour cells. Vascular endothelial (VEGF) and hepatocyte growth factor (HGF) are potent inducers of angiogenesis. The two factors are necessary for wound healing and the promotion of tumour growth. This study was designed to determine growth factor serum levels in patients before, during and after major abdominal surgery. It was recently shown that simultaneous hepatic and pancreatic resection led to poor liver regeneration. As growth factors may be involved in these findings we compared the growth factor levels after liver resection with the levels in patients after pancreatic resection. Forty patients were accrued before hepatopancreatic surgery (hepatic resection n=20 and pancreatic resection n=20). Blood samples were taken from each patient immediately prior to surgery, during the operation and on the postoperative days (POD) 1-3, 5 and 10. To examine the wound fluid, liquid from the wound drains was collected on POD 3. Using ELISA the concentration of the angiogenic cytokines HGF and VEGF 165 was determined. After the liver and pancreatic resections, circulating HGF and VEGF 165 were increased. We found significantly higher levels of HGF on POD 1-3 (p<0.01), compared to preoperative results with a peak on POD 2. After measuring the postoperative VEGF 165 levels we found significantly higher levels of circulating VEGF 165 on POD 1-5 (p<0.01) compared to the preoperative levels. On comparing liver with pancreatic resection we did not detect significantly different levels of the two growth factors in the two groups. VEGF 165 and HGF concentrations measured during the operation demonstrated no change. HGF and VEGF 165 levels detected in the wound fluid on POD 3 were ~10 times higher than the preoperative serum levels, respectively. In summary, our data show increased VEGF 165 and HGF levels after hepatopancreatic surgery. Notably, the lack of an impact of the type of organ resection on the concentration-time curve of the two growth factors suggest that high postoperative growth factor levels are part of normal wound healing and systemic inflammation. Thus, the proangiogenetic potential of growth factors may account for accelerated tumour growth when residual tumour cells are exposed to high levels of VEGF 165 and HGF.

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The effect of partial hepatectomy on tumor growth in rats:In vivo andin vitro studies

Cited by 59 publications

References 66 publications

Small‐for‐size grafts increase recurrence of hepatocellular carcinoma in liver transplantation beyond milan criteria

Small‐for‐size grafts increase recurrence of hepatocellular carcinoma in liver transplantation beyond milan criteria

Clinical relevance of transforming growth factor ?, epidermal growth factor receptor, p53, and Ki67 in colorectal liver metastases and corresponding primary tumors

Increased growth factor expression after hepatic and pancreatic resection

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