The term “Small-for-Flow” reflects the pathogenetic relevance of hepatic hemodynamics for the “Small-For-Size” syndrome and posthepatectomy liver failure. We aimed to characterize a large-animal model for studying the “Small-for-Flow” syndrome.
We performed subtotal (90%) hepatectomies in 10 female MiniPigs using a simplified transection technique with a tourniquet. Blood tests, hepatic and systemic hemodynamics, and hepatic function and histology were assessed before (Bas), 15 min (t-15 min) and 24 h (t-24 h) after the operation. Some pigs underwent computed tomography (CT) scans for hepatic volumetry (n = 4) and intracranial pressure (ICP) monitoring (n = 3). Postoperative care was performed in an intensive care unit environment.
All hepatectomies were successfully performed, and hepatic volumetry confirmed liver remnant volumes of 9.2% [6.2–11.2]. The hepatectomy resulted in characteristic hepatic hemodynamic alterations, including portal hyperperfusion, relative decrease of hepatic arterial blood flow, and increased portal pressure (PP) and portal-systemic pressure gradient. The model reproduced major diagnostic features including the development of cholestasis, coagulopathy, encephalopathy with increased ICP, ascites, and renal failure, hyperdynamic circulation, and hyperlactatemia. Two animals (20%) died before t-24 h. Histological liver damage was observed at t-15 min and at t-24 h. The degree of histological damage at t-24 h correlated with intraoperative PP (r = 0.689, p = 0.028), hepatic arterial blood flow (r = 0.655, p = 0.040), and hepatic arterial pulsatility index (r = 0.724, p = 0.066). All animals with intraoperative PP > 20 mmHg presented liver damage at t-24 h.
The present 90% hepatectomy porcine experimental model is a feasible and reproducible model for investigating the “Small-for-Flow” syndrome.
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Allard M-A, Adam R, Bucur P-O, Termos S, Cunha AS, Bismuth H, et al. Posthepatectomy portal vein pressure predicts liver failure and mortality after major liver resection on noncirrhotic liver. Ann. Surg. 2013; 258: 822–829.
Selzner M, Kashfi A, Cattral MS, Selzner N, Greig PD, Lilly L, et al. A graft to body weight ratio less than 0.8 does not exclude adult-to-adult right-lobe living donor liver transplantation. Liver Transpl. 2009; 15: 1776–1782.
Kaido T, Mori A, Ogura Y, Hata K, Yoshizawa A, Iida T, et al. Lower limit of the graft-to-recipient weight ratio can be safely reduced to 0.6% in adult-to-adult living donor liver transplantation in combination with portal pressure control. Transplant. Proc. 2011; 43: 2391–2393.
Sato Y, Yamamoto S, Oya H, Nakatsuka H, Tsukahara A, Kobayashi T, et al. Splenectomy for reduction of excessive portal hypertension after adult living-related donor liver transplantation. Hepatogastroenterology. 2002; 49: 1652–1655.
Shoreem H, Gad EH, Soliman H, Hegazy O, Saleh S, Zakaria H, et al. Small for size syndrome difficult dilemma: lessons from 10 years single centre experience in living donor liver transplantation. World J Hepatol. 2017; 9: 930–944.
Nguyen JH, Harnois DM. Incidence and outcome of small-for-size liver grafts transplanted in adult recipients. Transplant. Proc. 2018; 50: 198–201.
Nagano Y, Nagahori K, Kamiyama M, Fujii Y, Kubota T, Endo I, et al. Improved functional reserve of hypertrophied contra lateral liver after portal vein ligation in rats. J. Hepatol. 2002; 37: 72–77.
Sethi P, Thillai M, Thankamonyamma BS, Mallick S, Gopalakrishnan U, Balakrishnan D, et al. Living donor liver transplantation using small-for-size grafts: does size really matter? J Clin Exp Hepatol. 2018; 8: 125–131.
Boillot O, Delafosse B, Méchet I, Boucaud C, Pouyet M. Small-for-size partial liver graft in an adult recipient; a new transplant technique. Lancet. 2002; 359: 406–407.
Yagi S, Iida T, Hori T, Taniguchi K, Yamamoto C, Yamagiwa K, et al. Optimal portal venous circulation for liver graft function after living-donor liver transplantation. Transplantation. 2006; 81: 373–378.
Troisi R, de Hemptinne B. Clinical relevance of adapting portal vein flow in living donor liver transplantation in adult patients. Liver Transpl. 2003; 9: S36–41.
Troisi R, Ricciardi S, Smeets P, Petrovic M, Van Maele G, Colle I, et al. Effects of hemi-portocaval shunts for inflow modulation on the outcome of small-for-size grafts in living donor liver transplantation. Am. J. Transplant. 2005; 5: 1397–1404.
Asencio JM, Vaquero J, Olmedilla L, García Sabrido JL. “Small-for-flow” syndrome: shifting the “size” paradigm. Med. Hypotheses. 2013; 80: 573–577.
Court FG, Wemyss-Holden SA, Morrison CP, Teague BD, Laws PE, Kew J, et al. Segmental nature of the porcine liver and its potential as a model for experimental partial hepatectomy. Br J Surg. 2003; 90: 440–444.
Golriz M, Fonouni H, Nickkholgh A, Hafezi M, Garoussi C, Mehrabi A. Pig kidney transplantation: an up-to-date guideline. Eur Surg Res. 2012; 49: 121–129.
Fondevila C, Hessheimer AJ, Taurá P, Sánchez O, Calatayud D, de Riva N, et al. Portal hyperperfusion: mechanism of injury and stimulus for regeneration in porcine small-for-size transplantation. Liver Transpl. 2010; 16: 364–374.
Asencio JM, García-Sabrido JL, López-Baena JA, Olmedilla L, Peligros I, Lozano P, et al. Preconditioning by portal vein embolization modulates hepatic hemodynamics and improves liver function in pigs with extended hepatectomy. Surgery. 2017; 161: 1489–1501.
Asencio JM, García Sabrido JL, Olmedilla L. How to expand the safe limits in hepatic resections? J Hepatobiliary Pancreat Sci. 2014; 21: 399–404.
Mohkam K, Darnis B, Mabrut J-Y. Porcine models for the study of small-for-size syndrome and portal inflow modulation: literature review and proposal for a standardized nomenclature. J Hepatobiliary Pancreat Sci. 2016; 23: 668–680.
Xia Q, Lu T-F, Zhou Z-H, Hu L-X, Ying J, Ding D-Z, et al. Extended hepatectomy with segments I and VII as resection remnant: a simple model for small-for-size injuries in pigs. HBPD INT. 2008; 7: 601–607.
Kahn D, Hickman R, Terblanche J, von Sommoggy S. Partial hepatectomy and liver regeneration in pigs--the response to different resection sizes. J. Surg. Res. 1988; 45: 176–180.
Kaiser GM, Frühauf NR. Method of intracranial pressure monitoring and cerebrospinal fluid sampling in swine. Lab. Anim. 2007; 41: 80–85.
Frühauf NR, Radunz S, Grabellus F, Laube T, Uerschels AK, Kaiser GM. Neuromonitoring in a porcine model of acute hepatic failure. Lab. Anim. 2011; 45: 174–178.
Dahm F, Georgiev P, Clavien P-A. Small-for-size syndrome after partial liver transplantation: definition, mechanisms of disease and clinical implications. Am. J. Transplant. 2005; 5: 2605–2610.
Rahbari NN, Garden OJ, Padbury R, Brooke-Smith M, Crawford M, Adam R, et al. Posthepatectomy liver failure: a definition and grading by the International Study Group of Liver Surgery (ISGLS). Surgery. 2011; 149: 713–724.
Qadan M, Garden OJ, Corvera CU, Visser BC. Management of postoperative hepatic failure. J. Am. Coll. Surg. 2016; 222: 195–208.
Demetris AJ, Kelly DM, Eghtesad B, Fontes P, Wallis Marsh J, Tom K, et al. Pathophysiologic observations and histopathologic recognition of the portal hyperperfusion or small-for-size syndrome. Am. J. Surg. Pathol. 2006; 30: 986–993.
Kelly DM, Demetris AJ, Fung JJ, Marcos A, Zhu Y, Subbotin V, et al. Porcine partial liver transplantation: a novel model of the “small-for-size” liver graft. Liver Transpl. 2004; 10: 253–263.
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: 836–848.
This study is supported by a grant of the Sociedad Española de Trasplante Hepático (SETH) to J.M.A. J.V. was supported by a grant from ISCIII-Fondos FEDER “Una manera de hacer Europa” (PI15/1083) from Spain.
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Orue-Echebarria, M.I., Vaquero, J., Lisbona, C.J. et al. Comprehensive Characterization of a Porcine Model of The “Small-for-Flow” Syndrome. J Gastrointest Surg 23, 2174–2183 (2019). https://doi.org/10.1007/s11605-019-04130-2
- Posthepatectomy liver failure