- Email: [email protected]
Relevance of the porcine model of hepatectomy for studying portal inflow modulation by splenectomy
j o u r n a l o f s u r g i c a l r e s e a r c h a p r i l 2 0 1 7 ( - ) 1 e3
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.JournalofSurgicalResearch.com
Letter to the Editor
Relevance of the porcine model of hepatectomy for studying portal inflow modulation by splenectomy To the Editor, We read with great interest the work by Athanasiou et al. who studied the efficacy of splenectomy as a method of portal inflow modulation in a porcine model of 80% hepatectomy.1 In this work, the authors demonstrated that 80% hepatectomy created the hemodynamic setting of small-for-size syndrome. They found that splenectomy after 80% hepatectomy resulted in a significant decrease in both portal vein pressure and flow, and finally, they showed that animals in the splenectomy group had improved posthepatectomy liver function and survival. Although the beneficial effects of splenectomy on splanchnic hemodynamics and postoperative outcome after extended hepatectomy have already been suggested by former studies on rats and humans,2-4 the present study is, to the best of our knowledge, the first to report such beneficial effects after extended hepatectomy in swine. The study is well designed and has included both intraoperative and postoperative data, which makes it of great relevance. However, the findings of this study are quite contradictory with data published by our group.5 In fact, we also studied the efficacy of splenectomy to modulate the portal flow in two porcine models of extended hepatectomy (Table 1), and we found that splenectomy had no significant effects on portal hemodynamics after both 70% and 90% hepatectomy (Figs. 1 and 2). In that same study, we demonstrated that the splenic vein flow represented less than one-tenth of the total portal venous flow in swine (9%), whereas it represented almost one-third of the portal flow in humans (31%,
P < 0.001). Such dramatic differences between humans and swine may explain the lack of efficacy of splenectomy to modulate portal inflow in swine, which we encountered in our study. Furthermore, it would have been interesting in the study by Athanasiou et al. to record two additional hemodynamic parameters: the hepatic venous pressure gradient and the hepatic artery flow. In fact, it is established that hepatic venous pressure gradient is a more reliable parameter than portal vein pressure to assess portal hypertension because the latter may be influenced by systemic hemodynamics. Thus, an increase in portal vein pressure after extended hepatectomy could be caused by major vascular filling, and it does not necessarily reflects acute portal hypertension. Second, when studying the process of small-for-size syndrome, it is important to measure the hepatic artery flow, which is dramatically influenced by the portal vein flow variations as a consequce of the hepatic artery buffer response.6 Such variations of the hepatic artery flow represent one of the possible causes of histologic injury and biliary lesions observed in the context of portal hyperperfusion. Nevertheless, we recognize that our former study had several limitations including the fact that we performed only intraoperative measurements and we did not study the postoperative outcome of animals, contrary to the study by Athanasiou et al., which reported data on posthepatectomy liver function and survival. Further experimental and clinical studies are warranted to confirm these promising results.
Table 1 e Additional results from the study by Darnis et al.5 70% hepatectomy (n ¼ 4)
Measured data
PVP (mmHg) HVPG (mmHg) PVF (mL/min/100g)
90% hepatectomy (n ¼ 3)
Baseline
Hepatectomy
Splenectomy
Baseline
Hepatectomy
Splenectomy
13.5 6.1 134
14.4 4.1 233
14.7 2.5 233
16.1 4.1 131
22.8 6.3 336
23.5 7.5 344
Portal vein pressure (PVP), hepatic venous pressure gradient (HVPG), and portal vein flow (PVF) at baseline, after either a 70% or 90% hepatectomy, and after splenectomy. Data after splenectomy were compared with data after hepatectomy in both groups. None were different statistically.
2
j o u r n a l o f s u r g i c a l r e s e a r c h 2 0 1 7 ( - ) 1 e3
Fig. 1 e Portal vein flow at baseline, after hepatectomy, and after splenectomy in three models of extended liver resections (70%, 80%, and 90% hepatectomy). Results by Darnis and al.5 (70% and 90% hepatectomy) and from Athanasiou and al.1 (80% hepatectomy). (Color version of figure is available online.)
Fig. 2 e Portal vein pressure at baseline, after hepatectomy, and after splenectomy in three models of extended liver resections (70%, 80%, and 90% hepatectomy). Results by Darnis and al.5 (70% and 90% hepatectomy) and from Athanasiou and al.1 (80% hepatectomy). (Color version of figure is available online.)
Acknowledgment Authors’ contributions: B.D., K.M., and J.-Y.M. all performed the experimental model. B.D. wrote the letter. K.M. and J.-Y.M. made several modifications to the manuscript.
references
1 Athanasiou A, Papalois A, Kontos M, et al. The beneficial role of simultaneous splenectomy after extended hepatectomy:
experimental study in pigs. J Surg Res 2017;208: 121e31. 2 Di Domenico S, Santori G, Traverso N, et al. Early effects of portal flow modulation after extended liver resection in rat. Dig Liver Dis 2011;43:814e22. 3 Sainz-Barriga M, Scudeller L, Costa MG, de Hemptinne B, Troisi RI. Lack of a correlation between portal vein flow and pressure: toward a shared interpretation of hemodynamic stress governing inflow modulation in liver transplantation. Liver Transpl 2011;17:836e48. 4 Li W, Shen S, Wu S-M, Chen Z-B, Hu C, Yan R-C. Simultaneous hepatectomy and splenectomy versus hepatectomy alone for hepatocellular carcinoma complicated by hypersplenism: a meta-analysis. Onco Targets Ther 2015;8:2129e37.
letter to the editor
5 Darnis B, Mohkam K, Schmitt Z, et al. Subtotal hepatectomy in swine for studying small-for-size syndrome and portal inflow modulation: is it reliable? HPB 2015;17:881e8. 6 Eipel C, Abshagen K, Vollmar B. Regulation of hepatic blood flow: the hepatic arterial buffer response revisited. World J Gastroenterol 2010;6:6046e57.
Benjamin Darnis, MD* Kayvan Mohkam, MD, PhD Jean-Yves Mabrut, MD, PhD Department of General Surgery and Liver Transplantation Hospices Civils de Lyon Croix-Rousse University Hospital Lyon, Cedex 04, France
3 Ecole Doctorale EDISS 205 Universite´ Lyon 1 EMR 3738, Lyon, France
*Corresponding author. Department of General Surgery and Liver Transplantation, Hospices Civils de Lyon, Croix-Rousse University Hospital, 103, Grand Rue de la Croix-Rousse, Lyon, Cedex 04, 69317, France. Tel.: þ33 472 07 11 00. E-mail address: [email protected] (B. Darnis) 0022-4804/$ e see front matter ª 2017 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jss.2017.02.074
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.JournalofSurgicalResearch.com
Letter to the Editor
Relevance of the porcine model of hepatectomy for studying portal inflow modulation by splenectomy To the Editor, We read with great interest the work by Athanasiou et al. who studied the efficacy of splenectomy as a method of portal inflow modulation in a porcine model of 80% hepatectomy.1 In this work, the authors demonstrated that 80% hepatectomy created the hemodynamic setting of small-for-size syndrome. They found that splenectomy after 80% hepatectomy resulted in a significant decrease in both portal vein pressure and flow, and finally, they showed that animals in the splenectomy group had improved posthepatectomy liver function and survival. Although the beneficial effects of splenectomy on splanchnic hemodynamics and postoperative outcome after extended hepatectomy have already been suggested by former studies on rats and humans,2-4 the present study is, to the best of our knowledge, the first to report such beneficial effects after extended hepatectomy in swine. The study is well designed and has included both intraoperative and postoperative data, which makes it of great relevance. However, the findings of this study are quite contradictory with data published by our group.5 In fact, we also studied the efficacy of splenectomy to modulate the portal flow in two porcine models of extended hepatectomy (Table 1), and we found that splenectomy had no significant effects on portal hemodynamics after both 70% and 90% hepatectomy (Figs. 1 and 2). In that same study, we demonstrated that the splenic vein flow represented less than one-tenth of the total portal venous flow in swine (9%), whereas it represented almost one-third of the portal flow in humans (31%,
P < 0.001). Such dramatic differences between humans and swine may explain the lack of efficacy of splenectomy to modulate portal inflow in swine, which we encountered in our study. Furthermore, it would have been interesting in the study by Athanasiou et al. to record two additional hemodynamic parameters: the hepatic venous pressure gradient and the hepatic artery flow. In fact, it is established that hepatic venous pressure gradient is a more reliable parameter than portal vein pressure to assess portal hypertension because the latter may be influenced by systemic hemodynamics. Thus, an increase in portal vein pressure after extended hepatectomy could be caused by major vascular filling, and it does not necessarily reflects acute portal hypertension. Second, when studying the process of small-for-size syndrome, it is important to measure the hepatic artery flow, which is dramatically influenced by the portal vein flow variations as a consequce of the hepatic artery buffer response.6 Such variations of the hepatic artery flow represent one of the possible causes of histologic injury and biliary lesions observed in the context of portal hyperperfusion. Nevertheless, we recognize that our former study had several limitations including the fact that we performed only intraoperative measurements and we did not study the postoperative outcome of animals, contrary to the study by Athanasiou et al., which reported data on posthepatectomy liver function and survival. Further experimental and clinical studies are warranted to confirm these promising results.
Table 1 e Additional results from the study by Darnis et al.5 70% hepatectomy (n ¼ 4)
Measured data
PVP (mmHg) HVPG (mmHg) PVF (mL/min/100g)
90% hepatectomy (n ¼ 3)
Baseline
Hepatectomy
Splenectomy
Baseline
Hepatectomy
Splenectomy
13.5 6.1 134
14.4 4.1 233
14.7 2.5 233
16.1 4.1 131
22.8 6.3 336
23.5 7.5 344
Portal vein pressure (PVP), hepatic venous pressure gradient (HVPG), and portal vein flow (PVF) at baseline, after either a 70% or 90% hepatectomy, and after splenectomy. Data after splenectomy were compared with data after hepatectomy in both groups. None were different statistically.
2
j o u r n a l o f s u r g i c a l r e s e a r c h 2 0 1 7 ( - ) 1 e3
Fig. 1 e Portal vein flow at baseline, after hepatectomy, and after splenectomy in three models of extended liver resections (70%, 80%, and 90% hepatectomy). Results by Darnis and al.5 (70% and 90% hepatectomy) and from Athanasiou and al.1 (80% hepatectomy). (Color version of figure is available online.)
Fig. 2 e Portal vein pressure at baseline, after hepatectomy, and after splenectomy in three models of extended liver resections (70%, 80%, and 90% hepatectomy). Results by Darnis and al.5 (70% and 90% hepatectomy) and from Athanasiou and al.1 (80% hepatectomy). (Color version of figure is available online.)
Acknowledgment Authors’ contributions: B.D., K.M., and J.-Y.M. all performed the experimental model. B.D. wrote the letter. K.M. and J.-Y.M. made several modifications to the manuscript.
references
1 Athanasiou A, Papalois A, Kontos M, et al. The beneficial role of simultaneous splenectomy after extended hepatectomy:
experimental study in pigs. J Surg Res 2017;208: 121e31. 2 Di Domenico S, Santori G, Traverso N, et al. Early effects of portal flow modulation after extended liver resection in rat. Dig Liver Dis 2011;43:814e22. 3 Sainz-Barriga M, Scudeller L, Costa MG, de Hemptinne B, Troisi RI. Lack of a correlation between portal vein flow and pressure: toward a shared interpretation of hemodynamic stress governing inflow modulation in liver transplantation. Liver Transpl 2011;17:836e48. 4 Li W, Shen S, Wu S-M, Chen Z-B, Hu C, Yan R-C. Simultaneous hepatectomy and splenectomy versus hepatectomy alone for hepatocellular carcinoma complicated by hypersplenism: a meta-analysis. Onco Targets Ther 2015;8:2129e37.
letter to the editor
5 Darnis B, Mohkam K, Schmitt Z, et al. Subtotal hepatectomy in swine for studying small-for-size syndrome and portal inflow modulation: is it reliable? HPB 2015;17:881e8. 6 Eipel C, Abshagen K, Vollmar B. Regulation of hepatic blood flow: the hepatic arterial buffer response revisited. World J Gastroenterol 2010;6:6046e57.
Benjamin Darnis, MD* Kayvan Mohkam, MD, PhD Jean-Yves Mabrut, MD, PhD Department of General Surgery and Liver Transplantation Hospices Civils de Lyon Croix-Rousse University Hospital Lyon, Cedex 04, France
3 Ecole Doctorale EDISS 205 Universite´ Lyon 1 EMR 3738, Lyon, France
*Corresponding author. Department of General Surgery and Liver Transplantation, Hospices Civils de Lyon, Croix-Rousse University Hospital, 103, Grand Rue de la Croix-Rousse, Lyon, Cedex 04, 69317, France. Tel.: þ33 472 07 11 00. E-mail address: [email protected] (B. Darnis) 0022-4804/$ e see front matter ª 2017 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jss.2017.02.074