Animal models for ALPPS: achievements and research development_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

YANG Xianwei ¹ , YANG Lingpeng ¹ , YANG Chuang ^1,2 , QIU Yiwen ¹ ,  WAMG Wentao ¹

1. Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;
2. Department of Hepatobiliary and Pancreatic Surgery, The Third Hospital of Mianyang City, Mianyang, Sichuan 621000, P. R. China;

Corresponding author：

WAMG Wentao, Email: wwt02@163.com

Keywords：

associating liver partition and portal vein ligation for staged hepatectomy; animal model; cirrhosis; regeneration; review

DOI：

10.7507/1007-9424.201805102

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To understand the advances in animal model and basic research of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), and to provide new ideas for basic research and clinical application of ALPPS. Methods The literatures on the basic research and animal models of ALPPS were analyzed and reviewed. Results By March 2018, there were 19 articles related to ALPPS animal models published, including 11 rat model articles, 4 mouse model articles, 2 pig model articles, 1 rabbit model article, and 1 sheep model article. These models of ALPPS were mainly simulated in normal liver background (16 articles), only 2 mouse model of colorectal liver metastasis and 1 rat model of ALPPS under the sclerotic liver background on Chinese article. In cases of rat’s models, portal blood flow deprivation of 20%–90% was finished by portal vein ligation, and the liver was localized and segmented according to the ischemic line and the ligaments of the liver, and the liver partition was mostly sutured and electrocoagulated to stop bleeding. In the above models, remnant liver hyperplasia was observed after surgery. The main causes of hyperplasia were serum cytokines-mediated ［hepatocyte growth factor (HGF), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and so on］ enhancement of proliferative gene, and secondly preservation of the portal vein lobes to increase blood volume and to accelerate liver proliferation. Conclusions The animal model is the main tool to study the safety of ALPPS and liver regeneration, but there are still few studies in the models with liver cirrhosis and liver tumors. The mechanism of liver regeneration after ALPPS is still unclear, and more basic experiments and clinical cases are needed for further study.

Citation： YANG Xianwei, YANG Lingpeng, YANG Chuang, QIU Yiwen, WAMG Wentao. Animal models for ALPPS: achievements and research development. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2018, 25(12): 1515-1520. doi: 10.7507/1007-9424.201805102 Copy

1.	Lin SM. Recent advances in radiofrequency ablation in the treatment of hepatocellular carcinoma and metastatic liver cancers. Chang Gung Med J, 2009, 32(1): 22-32.
2.	Kishi Y, Abdalla EK, Chun YS, et al. Three hundred and one consecutive extended right hepatectomies: evaluation of outcome based on systematic liver volumetry. Ann Surg, 2009, 250(4): 540-548.
3.	Shindoh J, Tzeng CW, Aloia TA, et al. Safety and efficacy of portal vein embolization before planned major or extended hepatectomy: an institutional experience of 358 patients. J Gastrointest Surg, 2014, 18(1): 45-51.
4.	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(3): 405-414.
5.	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(5): 839-846.
6.	Almau Trenard HM, Moulin LE, Padín JM, et al. Development of an experimental model of portal vein ligation associated with parenchymal transection (ALPPS) in rats. Cir Esp, 2014, 92(10): 676-681.
7.	Yao L, Li C, Ge X, et al. Establishment of a rat model of portal vein ligation combined with in situ splitting. PLoS One, 2014, 9(8): e105511.
8.	Dhar DK, Mohammad GH, Vyas S, et al. A novel rat model of liver regeneration: possible role of cytokine induced neutrophil chemoattractant-1 in augmented liver regeneration. Ann Surg Innov Res, 2015, 9: 11.
9.	Shi H, Yang G, Zheng T, et al. A preliminary study of ALPPS procedure in a rat model. Sci Rep, 2015, 5: 17567.
10.	García-Pérez R, Revilla-Nuin B, Martínez CM, et al. Associated liver partition and portal vein ligation (ALPPS) vs selective portal vein ligation (PVL) for staged hepatectomy in a rat model. Similar regenerative response? PLoS One, 2015, 10(12): e0144096.
11.	Croome KP, Mao SA, Glorioso JM, et al. Characterization of a porcine model for associating liver partition and portal vein ligation for a staged hepatectomy. HPB (Oxford), 2015, 17(12): 1130-1136.
12.	Wei W, Zhang T, Zafarnia S, et al. Establishment of a rat model: associating liver partition with portal vein ligation for staged hepatectomy. Surgery, 2016, 159(5): 1299-1307.
13.	Andersen KJ, Knudsen AR, Jepsen BN, et al. A new technique for accelerated liver regeneration: an experimental study in rats. Surgery, 2017, 162(2): 233-247.
14.	Budai A, Fulop A, Hahn O, et al. Animal models for associating liver partition and portal vein ligation for staged hepatectomy (ALPPS): achievements and future perspectives. Eur Surg Res, 2017, 58(3-4): 140-157.
15.	Sheng RF, Wang HQ, Jin KP, et al. Histogram analyses of diffusion kurtosis indices and apparent diffusion coefficient in assessing liver regeneration after ALPPS and a comparative study with portal vein ligation. J Magn Reson Imaging, 2018, 47(3): 729-736.
16.	Kawaguchi D, Hiroshima Y, Kikuchi Y, et al. Associating liver partition and portal vein occlusion, including venous congestion, induction in rats. Anticancer Res, 2017, 37(6): 2919-2925.
17.	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(3): 560-570.
18.	Liao M, Zhang T, Wang H, et al. Rabbit model provides new insights in liver regeneration after transection with portal vein ligation. J Surg Res, 2017, 209: 242-251.
19.	Schadde E, Hertl M, Breitenstein S, et al. Rat model of the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) procedure. J Vis Exp, 2017, (126): 10.
20.	Kikuchi Y, Hiroshima Y, Matsuo K, et al. Impact of associating liver partition and portal vein occlusion for staged hepatectomy on tumor growth in a mouse model of liver metastasis. Eur J Surg Oncol, 2018, 44(1): 130-138.
21.	Kambakamba P, Linecker M, Schneider M, et al. Impact of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) on growth of colorectal liver metastases. Surgery, 2018, 163(2): 311-317.
22.	Deal R, Frederiks C, Williams L, et al. Rapid liver hypertrophy after portal vein occlusion correlates with the degree of collateralization between lobes-a study in pigs. J Gastrointest Surg, 2018, 22(2): 203-213.
23.	肖遵强, 黄静, 于茜, 等. 肝硬化大鼠 ALPPS 模型的建立. 浙江医学, 2018, (5): 465-467, 550.
24.	Lainas P, Boudechiche L, Osorio A, et al. Liver regeneration and recanalization time course following reversible portal vein embolization. J Hepatol, 2008, 49(3): 354-362.
25.	Riehle KJ, Dan YY, Campbell JS, et al. New concepts in liver regeneration. J Gastroenterol Hepatol, 2011, 26(Suppl 1): 203-212.
26.	Michalopoulos GK, DeFrances MC. Liver regeneration. Science, 1997, 276(5309): 60-66.
27.	Yokoyama Y, Nagino M, Nimura Y. Mechanisms of hepatic regeneration following portal vein embolization and partial hepatectomy: a review. World J Surg, 2007, 31(2): 367-374.
28.	Lautt WW. Mechanism and role of intrinsic regulation of hepatic arterial blood flow: hepatic arterial buffer response. Am J Physiol, 1985, 249(5 Pt 1): G549-G556.
29.	Alvarez FA, Ardiles V, de Santibañes M, et al. Associating liver partition and portal vein ligation for staged hepatectomy offers high oncological feasibility with adequate patient safety: a prospective study at a single center. Ann Surg, 2015, 261(4): 723-732.
30.	de Santibañes E, Clavien PA. Playing play-doh to prevent postoperative liver failure: the " ALPPS” approach. Ann Surg, 2012, 255(3): 415-417.
31.	de Santibañes E, Alvarez FA, Ardiles V. How to avoid postoperative liver failure: a novel method. World J Surg, 2012, 36(1): 125-128.
32.	严律南. 努力加强联合肝脏分隔和门静脉结扎的二步切肝法的临床应用和研究. 中国普外基础与临床杂志, 2017, 24(12): 1425-1426.
33.	刘允怡, 刘晓欣. 对联合肝脏分隔和门静脉结扎的二步肝切除术评价—兼评洪德飞教授文章. 中国实用外科杂志, 2016, 36(1): 93-95.
34.	Hernandez-Alejandro R, Bertens KA, Pineda-Solis K, et al. Can we improve the morbidity and mortality associated with the associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) procedure in the management of colorectal liver metastases? Surgery, 2015, 157(2): 194-201.
35.	Tong YF, Meng N, Chen MQ, et al. Maturity of associating liver partition and portal vein ligation for staged hepatectomy-derived liver regeneration in a rat model. World J Gastroenterol, 2018, 24(10): 1107-1119.
36.	Matsuo K, Murakami T, Kawaguchi D, et al. Histologic features after surgery associating liver partition and portal vein ligation for staged hepatectomy versus those after hepatectomy with portal vein embolization. Surgery, 2016, 159(5): 1289-1298.
37.	de Santibañes M, Dietrich A, Alvarez FA, et al. Biological substrate of the rapid volumetric changes observed in the human liver during the associating liver partition and portal vein ligation for staged hepatectomy approach. J Gastrointest Surg, 2016, 20(3): 546-553.
38.	Szijártó A, Fülöp A. Triggered liver regeneration: from experimental model to clinical implications. Eur Surg Res, 2015, 54(3-4): 148-161.
39.	Braet F, Shleper M, Paizi M, et al. Liver sinusoidal endothelial cell modulation upon resection and shear stress in vitro. Comp Hepatol, 2004, 3(1): 7.
40.	van de Laarschot LF, Jansen PL, Schaap FG, et al. The role of bile salts in liver regeneration. Hepatol Int, 2016, 10(5): 733-740.
41.	de Graaf W, van Lienden KP, van den Esschert JW, et al. Increase in future remnant liver function after preoperative portal vein embolization. Br J Surg, 2011, 98(6): 825-834.
42.	Nadalin S, Testa G, Malagó M, et al. Volumetric and functional recovery of the liver after right hepatectomy for living donation. Liver Transpl, 2004, 10(8): 1024-1029.
43.	Adams RB, Haller DG, Roh MS. Improving resectability of hepatic colorectal metastases: expert consensus statement by Abdalla et al. Ann Surg Oncol, 2006, 13(10): 1281-1283.
44.	文天夫. 原发性肝癌诊疗规范(2017年版)解读. 中国普外基础与临床杂志, 2018, 25(1): 32-34.
45.	Schadde E, Raptis DA, Schnitzbauer AA, et al. Prediction of mortality after ALPPS stage-1: an analysis of 320 patients from the international ALPPS registry. Ann Surg, 2015, 262(5): 780-786.
46.	Linecker M, Björnsson B, Stavrou GA, et al. Risk adjustment in ALPPS is associated with a dramatic decrease in early mortality and morbidity. Ann Surg, 2017, 266(5): 779-786.
47.	文天夫. ALPPS 在肝细胞癌治疗中的地位. 中国普外基础与临床杂志, 2016, 23(1): 1-4.
48.	Oldhafer KJ, Donati M, Jenner RM, et al. ALPPS for patients with colorectal liver metastases: effective liver hypertrophy, but early tumor recurrence. World J Surg, 2014, 38(6): 1504-1509.
49.	Fukami Y, Kurumiya Y, Kobayashi S. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS): an analysis of tumor activity. Updates Surg, 2014, 66(3): 223-225.
50.	Petrowsky H, Györi G, de Oliveira M, et al. Is partial-ALPPS safer than ALPPS? A single-center experience. Ann Surg, 2015, 261(4): e90-e92.
51.	Dokmak S, Belghiti J. Which limits to the " ALPPS” approach? Ann Surg, 2012, 256(3): e6-e16.
52.	Chen JX, Ran HQ, Sun CQ. Associating microwave ablation and portal vein ligation for staged hepatectomy for the treatment of huge hepatocellular carcinoma with cirrhosis. Ann Surg Treat Res, 2016, 90(5): 287-291.
53.	Cai X, Tong Y, Yu H, et al. The ALPPS in the treatment of hepatitis B-related hepatocellular carcinoma with cirrhosis: a single-center study and literature review. Surg Innov, 2017, 24(4): 358-364.
54.	Levi Sandri GB, Vennarecci G, Lepiane P, et al. Associating liver partition and portal vein ligation for bleeding hepatocellular carcinoma in HBV cirrhosis: a safety strategy. Transl Gastroenterol Hepatol, 2017, 2: 20.

1. Lin SM. Recent advances in radiofrequency ablation in the treatment of hepatocellular carcinoma and metastatic liver cancers. Chang Gung Med J, 2009, 32(1): 22-32.
2. Kishi Y, Abdalla EK, Chun YS, et al. Three hundred and one consecutive extended right hepatectomies: evaluation of outcome based on systematic liver volumetry. Ann Surg, 2009, 250(4): 540-548.
3. Shindoh J, Tzeng CW, Aloia TA, et al. Safety and efficacy of portal vein embolization before planned major or extended hepatectomy: an institutional experience of 358 patients. J Gastrointest Surg, 2014, 18(1): 45-51.
4. 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(3): 405-414.
5. 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(5): 839-846.
6. Almau Trenard HM, Moulin LE, Padín JM, et al. Development of an experimental model of portal vein ligation associated with parenchymal transection (ALPPS) in rats. Cir Esp, 2014, 92(10): 676-681.
7. Yao L, Li C, Ge X, et al. Establishment of a rat model of portal vein ligation combined with in situ splitting. PLoS One, 2014, 9(8): e105511.
8. Dhar DK, Mohammad GH, Vyas S, et al. A novel rat model of liver regeneration: possible role of cytokine induced neutrophil chemoattractant-1 in augmented liver regeneration. Ann Surg Innov Res, 2015, 9: 11.
9. Shi H, Yang G, Zheng T, et al. A preliminary study of ALPPS procedure in a rat model. Sci Rep, 2015, 5: 17567.
10. García-Pérez R, Revilla-Nuin B, Martínez CM, et al. Associated liver partition and portal vein ligation (ALPPS) vs selective portal vein ligation (PVL) for staged hepatectomy in a rat model. Similar regenerative response? PLoS One, 2015, 10(12): e0144096.
11. Croome KP, Mao SA, Glorioso JM, et al. Characterization of a porcine model for associating liver partition and portal vein ligation for a staged hepatectomy. HPB (Oxford), 2015, 17(12): 1130-1136.
12. Wei W, Zhang T, Zafarnia S, et al. Establishment of a rat model: associating liver partition with portal vein ligation for staged hepatectomy. Surgery, 2016, 159(5): 1299-1307.
13. Andersen KJ, Knudsen AR, Jepsen BN, et al. A new technique for accelerated liver regeneration: an experimental study in rats. Surgery, 2017, 162(2): 233-247.
14. Budai A, Fulop A, Hahn O, et al. Animal models for associating liver partition and portal vein ligation for staged hepatectomy (ALPPS): achievements and future perspectives. Eur Surg Res, 2017, 58(3-4): 140-157.
15. Sheng RF, Wang HQ, Jin KP, et al. Histogram analyses of diffusion kurtosis indices and apparent diffusion coefficient in assessing liver regeneration after ALPPS and a comparative study with portal vein ligation. J Magn Reson Imaging, 2018, 47(3): 729-736.
16. Kawaguchi D, Hiroshima Y, Kikuchi Y, et al. Associating liver partition and portal vein occlusion, including venous congestion, induction in rats. Anticancer Res, 2017, 37(6): 2919-2925.
17. 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(3): 560-570.
18. Liao M, Zhang T, Wang H, et al. Rabbit model provides new insights in liver regeneration after transection with portal vein ligation. J Surg Res, 2017, 209: 242-251.
19. Schadde E, Hertl M, Breitenstein S, et al. Rat model of the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) procedure. J Vis Exp, 2017, (126): 10.
20. Kikuchi Y, Hiroshima Y, Matsuo K, et al. Impact of associating liver partition and portal vein occlusion for staged hepatectomy on tumor growth in a mouse model of liver metastasis. Eur J Surg Oncol, 2018, 44(1): 130-138.
21. Kambakamba P, Linecker M, Schneider M, et al. Impact of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) on growth of colorectal liver metastases. Surgery, 2018, 163(2): 311-317.
22. Deal R, Frederiks C, Williams L, et al. Rapid liver hypertrophy after portal vein occlusion correlates with the degree of collateralization between lobes-a study in pigs. J Gastrointest Surg, 2018, 22(2): 203-213.
23. 肖遵强, 黄静, 于茜, 等. 肝硬化大鼠 ALPPS 模型的建立. 浙江医学, 2018, (5): 465-467, 550.
24. Lainas P, Boudechiche L, Osorio A, et al. Liver regeneration and recanalization time course following reversible portal vein embolization. J Hepatol, 2008, 49(3): 354-362.
25. Riehle KJ, Dan YY, Campbell JS, et al. New concepts in liver regeneration. J Gastroenterol Hepatol, 2011, 26(Suppl 1): 203-212.
26. Michalopoulos GK, DeFrances MC. Liver regeneration. Science, 1997, 276(5309): 60-66.
27. Yokoyama Y, Nagino M, Nimura Y. Mechanisms of hepatic regeneration following portal vein embolization and partial hepatectomy: a review. World J Surg, 2007, 31(2): 367-374.
28. Lautt WW. Mechanism and role of intrinsic regulation of hepatic arterial blood flow: hepatic arterial buffer response. Am J Physiol, 1985, 249(5 Pt 1): G549-G556.
29. Alvarez FA, Ardiles V, de Santibañes M, et al. Associating liver partition and portal vein ligation for staged hepatectomy offers high oncological feasibility with adequate patient safety: a prospective study at a single center. Ann Surg, 2015, 261(4): 723-732.
30. de Santibañes E, Clavien PA. Playing play-doh to prevent postoperative liver failure: the " ALPPS” approach. Ann Surg, 2012, 255(3): 415-417.
31. de Santibañes E, Alvarez FA, Ardiles V. How to avoid postoperative liver failure: a novel method. World J Surg, 2012, 36(1): 125-128.
32. 严律南. 努力加强联合肝脏分隔和门静脉结扎的二步切肝法的临床应用和研究. 中国普外基础与临床杂志, 2017, 24(12): 1425-1426.
33. 刘允怡, 刘晓欣. 对联合肝脏分隔和门静脉结扎的二步肝切除术评价—兼评洪德飞教授文章. 中国实用外科杂志, 2016, 36(1): 93-95.
34. Hernandez-Alejandro R, Bertens KA, Pineda-Solis K, et al. Can we improve the morbidity and mortality associated with the associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) procedure in the management of colorectal liver metastases? Surgery, 2015, 157(2): 194-201.
35. Tong YF, Meng N, Chen MQ, et al. Maturity of associating liver partition and portal vein ligation for staged hepatectomy-derived liver regeneration in a rat model. World J Gastroenterol, 2018, 24(10): 1107-1119.
36. Matsuo K, Murakami T, Kawaguchi D, et al. Histologic features after surgery associating liver partition and portal vein ligation for staged hepatectomy versus those after hepatectomy with portal vein embolization. Surgery, 2016, 159(5): 1289-1298.
37. de Santibañes M, Dietrich A, Alvarez FA, et al. Biological substrate of the rapid volumetric changes observed in the human liver during the associating liver partition and portal vein ligation for staged hepatectomy approach. J Gastrointest Surg, 2016, 20(3): 546-553.
38. Szijártó A, Fülöp A. Triggered liver regeneration: from experimental model to clinical implications. Eur Surg Res, 2015, 54(3-4): 148-161.
39. Braet F, Shleper M, Paizi M, et al. Liver sinusoidal endothelial cell modulation upon resection and shear stress in vitro. Comp Hepatol, 2004, 3(1): 7.
40. van de Laarschot LF, Jansen PL, Schaap FG, et al. The role of bile salts in liver regeneration. Hepatol Int, 2016, 10(5): 733-740.
41. de Graaf W, van Lienden KP, van den Esschert JW, et al. Increase in future remnant liver function after preoperative portal vein embolization. Br J Surg, 2011, 98(6): 825-834.
42. Nadalin S, Testa G, Malagó M, et al. Volumetric and functional recovery of the liver after right hepatectomy for living donation. Liver Transpl, 2004, 10(8): 1024-1029.
43. Adams RB, Haller DG, Roh MS. Improving resectability of hepatic colorectal metastases: expert consensus statement by Abdalla et al. Ann Surg Oncol, 2006, 13(10): 1281-1283.
44. 文天夫. 原发性肝癌诊疗规范(2017年版)解读. 中国普外基础与临床杂志, 2018, 25(1): 32-34.
45. Schadde E, Raptis DA, Schnitzbauer AA, et al. Prediction of mortality after ALPPS stage-1: an analysis of 320 patients from the international ALPPS registry. Ann Surg, 2015, 262(5): 780-786.
46. Linecker M, Björnsson B, Stavrou GA, et al. Risk adjustment in ALPPS is associated with a dramatic decrease in early mortality and morbidity. Ann Surg, 2017, 266(5): 779-786.
47. 文天夫. ALPPS 在肝细胞癌治疗中的地位. 中国普外基础与临床杂志, 2016, 23(1): 1-4.
48. Oldhafer KJ, Donati M, Jenner RM, et al. ALPPS for patients with colorectal liver metastases: effective liver hypertrophy, but early tumor recurrence. World J Surg, 2014, 38(6): 1504-1509.
49. Fukami Y, Kurumiya Y, Kobayashi S. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS): an analysis of tumor activity. Updates Surg, 2014, 66(3): 223-225.
50. Petrowsky H, Györi G, de Oliveira M, et al. Is partial-ALPPS safer than ALPPS? A single-center experience. Ann Surg, 2015, 261(4): e90-e92.
51. Dokmak S, Belghiti J. Which limits to the " ALPPS” approach? Ann Surg, 2012, 256(3): e6-e16.
52. Chen JX, Ran HQ, Sun CQ. Associating microwave ablation and portal vein ligation for staged hepatectomy for the treatment of huge hepatocellular carcinoma with cirrhosis. Ann Surg Treat Res, 2016, 90(5): 287-291.
53. Cai X, Tong Y, Yu H, et al. The ALPPS in the treatment of hepatitis B-related hepatocellular carcinoma with cirrhosis: a single-center study and literature review. Surg Innov, 2017, 24(4): 358-364.
54. Levi Sandri GB, Vennarecci G, Lepiane P, et al. Associating liver partition and portal vein ligation for bleeding hepatocellular carcinoma in HBV cirrhosis: a safety strategy. Transl Gastroenterol Hepatol, 2017, 2: 20.

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Animal models for ALPPS: achievements and research development

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