Early Postoperative Serum Phosphate Drop Predicts Sufficient Hypertrophy After Liver Surgery.
Journal
Annals of surgery
ISSN: 1528-1140
Titre abrégé: Ann Surg
Pays: United States
ID NLM: 0372354
Informations de publication
Date de publication:
01 11 2023
01 11 2023
Historique:
medline:
6
10
2023
pubmed:
19
7
2023
entrez:
19
7
2023
Statut:
ppublish
Résumé
The aim of this study was to assess the impact of postoperative hypophosphatemia on liver regeneration after major liver surgery in the scenario of Associating Liver Partition with Portal vein ligation for Staged hepatectomy (ALPPS) and living liver donation (LLD). Hypophosphatemia has been described to reflect the metabolic demands of regenerating hepatocytes. Both ALPPS and LLD are characterized by an exceptionally strong liver regeneration and may be of particular interest in the context of posthepatectomy hypophosphatemia. Serum phosphate changes within the first 7 postoperative days after ALPPS (n=61) and LLD (n=54) were prospectively assessed and correlated with standardized volumetry after 1 week. In a translational approach, postoperative phosphate changes were investigated in mice and in vitro . After ALPPS stage 1 and LLD, serum phosphate levels significantly dropped from a preoperative median of 1.08 mmol/L [interquartile range (IQR) 0.92-1.23] and 1.07 mmol/L (IQR 0.91-1.21) to a postoperative median nadir of 0.68 and 0.52 mmol/L, respectively. A pronounced phosphate drop correlated well with increased liver hypertrophy ( P <0.001). Patients with a low drop of phosphate showed a higher incidence of posthepatectomy liver failure after ALPPS (7% vs 31%, P =0.041). Like in humans, phosphate drop correlated significantly with degree of hypertrophy in murine ALPPS and hepatectomy models ( P <0.001). Blocking phosphate transporter (Slc20a1) inhibited cellular phosphate uptake and hepatocyte proliferation in vitro. Phosphate drop after hepatectomy is a direct surrogate marker for liver hypertrophy. Perioperative implementation of serum phosphate analysis has the potential to detect patients with insufficient regenerative capacity at an early stage.
Sections du résumé
OBJECTIVE
The aim of this study was to assess the impact of postoperative hypophosphatemia on liver regeneration after major liver surgery in the scenario of Associating Liver Partition with Portal vein ligation for Staged hepatectomy (ALPPS) and living liver donation (LLD).
BACKGROUND
Hypophosphatemia has been described to reflect the metabolic demands of regenerating hepatocytes. Both ALPPS and LLD are characterized by an exceptionally strong liver regeneration and may be of particular interest in the context of posthepatectomy hypophosphatemia.
METHODS
Serum phosphate changes within the first 7 postoperative days after ALPPS (n=61) and LLD (n=54) were prospectively assessed and correlated with standardized volumetry after 1 week. In a translational approach, postoperative phosphate changes were investigated in mice and in vitro .
RESULTS
After ALPPS stage 1 and LLD, serum phosphate levels significantly dropped from a preoperative median of 1.08 mmol/L [interquartile range (IQR) 0.92-1.23] and 1.07 mmol/L (IQR 0.91-1.21) to a postoperative median nadir of 0.68 and 0.52 mmol/L, respectively. A pronounced phosphate drop correlated well with increased liver hypertrophy ( P <0.001). Patients with a low drop of phosphate showed a higher incidence of posthepatectomy liver failure after ALPPS (7% vs 31%, P =0.041). Like in humans, phosphate drop correlated significantly with degree of hypertrophy in murine ALPPS and hepatectomy models ( P <0.001). Blocking phosphate transporter (Slc20a1) inhibited cellular phosphate uptake and hepatocyte proliferation in vitro.
CONCLUSION
Phosphate drop after hepatectomy is a direct surrogate marker for liver hypertrophy. Perioperative implementation of serum phosphate analysis has the potential to detect patients with insufficient regenerative capacity at an early stage.
Identifiants
pubmed: 37465990
doi: 10.1097/SLA.0000000000006013
pii: 00000658-202311000-00018
doi:
Substances chimiques
Phosphates
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
763-771Informations de copyright
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest.
Références
Michalopoulos GK, Grompe M, Theise ND. Assessing the potential of induced liver regeneration. Nat Med. 2013;19:1096–1097.
Michalopoulos GK, DeFrances MC. Liver regeneration. Science. 1997;276:60–66.
Hallet J, Karanicolas PJ, Zih FS, et al. Hypophosphatemia and recovery of post-hepatectomy liver insufficiency. Hepatobiliary Surg Nutr. 2016;5:217–224.
Kambakamba P, Stocker D, Reiner CS, et al. Liver kinetic growth rate predicts postoperative liver failure after ALPPS. HPB (Oxford). 2016;18:800–805.
Keushkerian S, Wade T. Hypophosphatemia after major hepatic resection. Curr Surg. 1984;41:12–14.
Zakian KL, Koutcher JA, Malhotra S, et al. Liver regeneration in humans is characterized by significant changes in cellular phosphorus metabolism: assessment using proton-decoupled 31P-magnetic resonance spectroscopic imaging. Magn Reson Med. 2005;54:264–271.
Michalopoulos GK. Liver regeneration after partial hepatectomy: critical analysis of mechanistic dilemmas. Am J Pathol. 2010;176:2–13.
Schnitzbauer AA, Lang SA, Goessmann H, et al. Right portal vein ligation combined with in situ splitting induces rapid left lateral liver lobe hypertrophy enabling 2-staged extended right hepatic resection in small-for-size settings. Ann Surg. 2012;255:405–414.
de Santibanes E, Clavien PA. Playing Play-Doh to prevent postoperative liver failure: the “ALPPS” approach. Ann Surg. 2012;255:415–417.
Eshmuminov D, Tschuor C, Raptis DA, et al. Rapid liver volume increase induced by associating liver partition with portal vein ligation for staged hepatectomy (ALPPS): is it edema, steatosis, or true proliferation? Surgery. 2017;161:1549–1552.
Croome KP, Hernandez-Alejandro R, Parker M, et al. Is the liver kinetic growth rate in ALPPS unprecedented when compared with PVE and living donor liver transplant? A multicentre analysis. HPB (Oxford). 2015;17:477–484.
Petrowsky H, Gyori G, de Oliveira M, et al. Is partial-ALPPS safer than ALPPS? A single-center experience. Ann Surg. 2015;261:e90–e92.
Nadalin S, Capobianco I, Panaro F, et al. Living donor liver transplantation in Europe. Hepatobiliary Surg Nutr. 2016;5:159–175.
Clavien PA, Barkun J, de Oliveira ML, et al. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009;250:187–196.
Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240:205–213.
Balzan S, Belghiti J, Farges O, et al. The “50-50 criteria” on postoperative day 5: an accurate predictor of liver failure and death after hepatectomy. Ann Surg. 2005;242:824–828; discussion 828-829.
Rahbari NN, Garden OJ, Padbury R, et al. Posthepatectomy liver failure: a definition and grading by the International Study Group of Liver Surgery (ISGLS). Surgery. 2011;149:713–724.
Ribero D, Chun YS, Vauthey JN. Standardized liver volumetry for portal vein embolization. Semin Intervent Radiol. 2008;25:104–109.
Vauthey JN, Chaoui A, Do KA, et al. Standardized measurement of the future liver remnant prior to extended liver resection: methodology and clinical associations. Surgery. 2000;127:512–519.
Shindoh J, Truty MJ, Aloia TA, et al. Kinetic growth rate after portal vein embolization predicts posthepatectomy outcomes: toward zero liver-related mortality in patients with colorectal liver metastases and small future liver remnant. J Am Coll Surg. 2013;216:201–209.
Schadde E, Ardiles V, Robles-Campos R, et al. Early survival and safety of ALPPS: first report of the International ALPPS Registry. Ann Surg. 2014;260:829–836; discussion 836-828.
Linecker M, Kambakamba P, Reiner CS, et al. How much liver needs to be transected in ALPPS? A translational study investigating the concept of less invasiveness. Surgery. 2017;161:453–464.
Schlegel A, Lesurtel M, Melloul E, et al. ALPPS: from human to mice highlighting accelerated and novel mechanisms of liver regeneration. Ann Surg. 2014;260:839–846.
Lehmann K, Tschuor C, Rickenbacher A, et al. Liver failure after extended hepatectomy in mice is mediated by a p21-dependent barrier to liver regeneration. Gastroenterology. 2012;143:1609–1619 e1604.
Martins PN, Theruvath TP, Neuhaus P. Rodent models of partial hepatectomies. Liver Int. 2008;28:3–11.
Clavien PA, Petrowsky H, DeOliveira ML, et al. Strategies for safer liver surgery and partial liver transplantation. N Engl J Med. 2007;356:1545–1559.
Collins JF, Bai L, Ghishan FK. The SLC20 family of proteins: dual functions as sodium-phosphate cotransporters and viral receptors. Pflugers Arch. 2004;447:647–652.
Kachaylo E, Tschuor C, Calo N, et al. PTEN down-regulation promotes beta-oxidation to fuel hypertrophic liver growth after hepatectomy in mice. Hepatology. 2017;66:908–921.
Langiewicz M, Schlegel A, Saponara E, et al. Hedgehog pathway mediates early acceleration of liver regeneration induced by a novel two-staged hepatectomy in mice. J Hepatol. 2017;66:560–570.
Findling R, Foreman JW, Krummel TM. Hypophosphatemia in a pediatric patient after major hepatic resection. J Pediatr Surg. 1989;24:1165–1166.
George R, Shiu MH. Hypophosphatemia after major hepatic resection. Surgery. 1992;111:281–286.
Squires MH III, Dann GC, Lad NL, et al. Hypophosphataemia after major hepatectomy and the risk of post-operative hepatic insufficiency and mortality: an analysis of 719 patients. HPB (Oxford). 2014;16:884–891.
Smyrniotis V, Kostopanagiotou G, Katsarelias D, et al. Changes of serum phosphorus levels in hepatic resections and implications on patients’ outcomes. Int Surg. 2003;88:100–104.
Ove P, Takai SI, Umeda T, et al. Adenosine triphosphate in liver after partial hepatectomy and acute stress. J Biol Chem. 1967;242:4963–4971.
Mann DV, Lam WW, Hjelm NM, et al. Metabolic control patterns in acute phase and regenerating human liver determined in vivo by 31-phosphorus magnetic resonance spectroscopy. Ann Surg. 2002;235:408–416.
Kooby DA, Zakian KL, Challa SN, et al. Use of phosphorous-31 nuclear magnetic resonance spectroscopy to determine safe timing of chemotherapy after hepatic resection. Cancer Res. 2000;60:3800–3806.
Nomura K, Tatsumi S, Miyagawa A, et al. Hepatectomy-related hypophosphatemia: a novel phosphaturic factor in the liver-kidney axis. J Am Soc Nephrol. 2014;25:761–772.
Nafidi O, Lapointe RW, Lepage R, et al. Mechanisms of renal phosphate loss in liver resection-associated hypophosphatemia. Ann Surg. 2009;249:824–827.
Salem RR, Tray K. Hepatic resection-related hypophosphatemia is of renal origin as manifested by isolated hyperphosphaturia. Ann Surg. 2005;241:343–348.
Tatsumi S, Katai K, Kaneko I, et al. NAD metabolism and the SLC34 family: evidence for a liver-kidney axis regulating inorganic phosphate. Pflugers Arch. 2019;471:109–122.
Riauka R, Ignatavicius P, Barauskas G. Hypophosphatemia as a prognostic tool for post-hepatectomy liver failure: a systematic review. World J Gastrointest Surg. 2023;15:249–257.
Buell JF, Berger AC, Plotkin JS, et al. The clinical implications of hypophosphatemia following major hepatic resection or cryosurgery. Arch Surg. 1998;133:757–761.
Giovannini I, Chiarla C, Nuzzo G. Pathophysiologic and clinical correlates of hypophosphatemia and the relationship with sepsis and outcome in postoperative patients after hepatectomy. Shock. 2002;18:111–115.
Yuan D, Wei YG, Chen K, et al. Hepatectomy-related hypophosphatemia may predict donor liver dysfunction in live-donor liver transplantation. Transplant Proc. 2010;42:4548–4551.
Serrano OK, Mongin SJ, Berglund D, et al. Clinical utility of postoperative phosphate recovery profiles to predict liver insufficiency after living donor hepatectomy. Am J Surg. 2019;218:374–379.
Margonis GA, Amini N, Buettner S, et al. Impact of perioperative phosphorus and glucose levels on liver regeneration and long-term outcomes after major liver resection. J Gastrointest Surg. 2016;20:1305–1316.
Olthof PB, Tomassini F, Huespe PE, et al. Hepatobiliary scintigraphy to evaluate liver function in associating liver partition and portal vein ligation for staged hepatectomy: Liver volume overestimates liver function. Surgery. 2017;162:775–783.