Top

Published in:

Open Access 01-12-2017 | Research

ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) does not affect proliferation, apoptosis, or angiogenesis as compared to standard liver resection for colorectal liver metastases

Authors: Katharina Joechle, Christian Moser, Petra Ruemmele, Katharina M. Schmidt, Jens M. Werner, Edward K. Geissler, Hans J. Schlitt, Sven A. Lang

Published in: World Journal of Surgical Oncology | Issue 1/2017

Abstract

Background

ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) is a novel two-stage strategy to induce rapid hypertrophy of the future liver remnant (FLR) when patients are in danger of postoperative liver failure due to insufficient FLR. However, the effects of ALPPS on colorectal liver metastases (CRLM) are not clear so far. The aim of our study was to determine whether ALPPS induces proliferation, apoptosis, or vascularization compared to standard (one-stage) liver resection.

Methods

Six patients who underwent ALPPS were matched with 12 patients undergoing standard liver resection regarding characteristics of the metastases (size, number), time of appearance (syn-/metachronous), preoperative chemotherapy, primary tumor (localization, TNM stage, grading), and patient variables (gender, age). The largest resected metastasis was used for the analyses. Tissue was stained for tumor cell proliferation (Ki67), apoptosis (TUNEL, caspase-3), vascularization (CD31), and pericytes (αSMA).

Results

Vascularization (CD31; p = 0.149), proliferation (Mib-1; p = 0.244), and αSMA expression (p = 0.205) did not significantly differ between the two groups, although a trend towards less proliferation and αSMA expression was observed in patients undergoing ALPPS. Concerning apoptosis, caspase-3 staining showed significantly fewer apoptotic cells upon ALPPS (p < 0.0001), but this was not confirmed by TUNEL staining (p = 0.7344).

Conclusions

ALPPS does not induce proliferation, apoptosis, or vascularization of CRLM when compared to standard liver resection.

Ariizumi S, Kotera Y, Katagiri S, Nakano M, Nakanuma Y, Saito A, et al. Long-term survival of patients with cholangiolocellular carcinoma after curative hepatectomy. Ann Surg Oncol. 2014;21 Suppl 3:S451–458.CrossRefPubMed

Hackl C, Neumann P, Gerken M, Loss M, Klinkhammer-Schalke M, Schlitt HJ. Treatment of colorectal liver metastases in Germany: a ten-year population-based analysis of 5772 cases of primary colorectal adenocarcinoma. BMC Cancer. 2014;14:810.CrossRefPubMedPubMedCentral

Sadot E, Groot Koerkamp B, Leal JN, Shia J, Gonen M, Allen PJ, et al. Resection margin and survival in 2368 patients undergoing hepatic resection for metastatic colorectal cancer: surgical technique or biologic surrogate? Ann Surg. 2015;262:476–85.CrossRefPubMedPubMedCentral

Zhong JH, Ke Y, Gong WF, Xiang BD, Ma L, Ye XP, et al. Hepatic resection associated with good survival for selected patients with intermediate and advanced-stage hepatocellular carcinoma. Ann Surg. 2014;260:329–40.CrossRefPubMed

Abdalla EK, Adam R, Bilchik AJ, Jaeck D, Vauthey JN, Mahvi D. Improving resectability of hepatic colorectal metastases: expert consensus statement. Ann Surg Oncol. 2006;13:1271–80.CrossRefPubMed

Mohammad WM, Martel G, Mimeault R, Fairfull-Smith RJ, Auer RC, Balaa FK. Evaluating agreement regarding the resectability of colorectal liver metastases: a national case-based survey of hepatic surgeons. HPB (Oxford). 2012;14:291–7.CrossRef

Rocha FG, Helton WS. Resectability of colorectal liver metastases: an evolving definition. HPB (Oxford). 2012;14:283–4.CrossRef

Kishi Y, Abdalla EK, Chun YS, Zorzi D, Madoff DC, Wallace MJ, et al. Three hundred and one consecutive extended right hepatectomies: evaluation of outcome based on systematic liver volumetry. Ann Surg. 2009;250:540–8.PubMed

Vauthey JN, Chaoui A, Do KA, Bilimoria MM, Fenstermacher MJ, Charnsangavej C, et al. Standardized measurement of the future liver remnant prior to extended liver resection: methodology and clinical associations. Surgery. 2000;127:512–9.CrossRefPubMed

10.

Truant S, Oberlin O, Sergent G, Lebuffe G, Gambiez L, Ernst O, et al. Remnant liver volume to body weight ratio > or =0.5%: A new cut-off to estimate postoperative risks after extended resection in noncirrhotic liver. J Am Coll Surg. 2007;204:22–33.CrossRefPubMed

11.

Lam VW, Laurence JM, Johnston E, Hollands MJ, Pleass HC, Richardson AJ. A systematic review of two-stage hepatectomy in patients with initially unresectable colorectal liver metastases. HPB (Oxford). 2013;15:483–91.CrossRef

12.

Shimada H, Tanaka K, Matsuo K, Togo S. Treatment for multiple bilobar liver metastases of colorectal cancer. Langenbecks Arch Surg. 2006;391:130–42.CrossRefPubMed

13.

Shindoh J, Tzeng CW, Aloia TA, Curley SA, Zimmitti G, Wei SH, et al. Portal vein embolization improves rate of resection of extensive colorectal liver metastases without worsening survival. Br J Surg. 2013;100:1777–83.CrossRefPubMed

14.

Yang C, Rahbari NN, Mees ST, Schaab F, Koch M, Weitz J, et al. Staged resection of bilobar colorectal liver metastases: surgical strategies. Langenbecks Arch Surg. 2015;400:633–40.CrossRefPubMed

15.

Hemming AW, Reed AI, Howard RJ, Fujita S, Hochwald SN, Caridi JG, et al. Preoperative portal vein embolization for extended hepatectomy. Ann Surg. 2003;237:686–91. discussion 691-683.PubMedPubMedCentral

16.

Jaeck D, Oussoultzoglou E, Rosso E, Greget M, Weber JC, Bachellier P. A two-stage hepatectomy procedure combined with portal vein embolization to achieve curative resection for initially unresectable multiple and bilobar colorectal liver metastases. Ann Surg. 2004;240:1037–49. discussion 1049-1051.CrossRefPubMedPubMedCentral

17.

Schnitzbauer AA, Lang SA, Goessmann H, Nadalin S, Baumgart J, Farkas SA, 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;255:405–14.CrossRefPubMed

18.

Lang SA, Loss M, Benseler V, Glockzin G, Schlitt HJ. Long-term results after in-situ split (ISS) liver resection. Langenbecks Arch Surg. 2015;400:361–9.CrossRefPubMed

19.

Schadde E, Ardiles V, Slankamenac K, Tschuor C, Sergeant G, Amacker N, et al. ALPPS offers a better chance of complete resection in patients with primarily unresectable liver tumors compared with conventional-staged hepatectomies: results of a multicenter analysis. World J Surg. 2014;38:1510–9.CrossRefPubMed

20.

de Graaf W, van den Esschert JW, van Lienden KP, van Gulik TM. Induction of tumor growth after preoperative portal vein embolization: is it a real problem? Ann Surg Oncol. 2009;16:423–30.CrossRefPubMed

21.

Ardito F, Vellone M, Barbaro B, Grande G, Clemente G, Giovannini I, et al. Right and extended-right hepatectomies for unilobar colorectal metastases: impact of portal vein embolization on long-term outcome and liver recurrence. Surgery. 2013;153:801–10.CrossRefPubMed

22.

Hoekstra LT, van Lienden KP, Doets A, Busch OR, Gouma DJ, van Gulik TM. Tumor progression after preoperative portal vein embolization. Ann Surg. 2012;256:812–7. discussion 817-818.CrossRefPubMed

23.

Simoneau E, Hassanain M, Shaheen M, Aljiffry M, Molla N, Chaudhury P, et al. Portal vein embolization and its effect on tumour progression for colorectal cancer liver metastases. Br J Surg. 2015;102:1240–9.CrossRefPubMed

24.

Yamashita S, Hasegawa K, Takahashi M, Inoue Y, Sakamoto Y, Aoki T, et al. One-stage hepatectomy following portal vein embolization for colorectal liver metastasis. World J Surg. 2013;37:622–8.CrossRefPubMed

25.

Tanaka K, Matsuo K, Murakami T, Kawaguchi D, Hiroshima Y, Koda K, et al. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS): short-term outcome, functional changes in the future liver remnant, and tumor growth activity. Eur J Surg Oncol. 2015;41:506–12.CrossRefPubMed

26.

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;66:223–5.CrossRefPubMed

27.

Krause P, Flikweert H, Monin M, Seif Amir Hosseini A, Helms G, Cantanhede G, et al. Increased growth of colorectal liver metastasis following partial hepatectomy. Clin Exp Metastasis. 2013;30:681–93.CrossRefPubMedPubMedCentral

28.

Maggiori L, Bretagnol F, Sibert A, Paradis V, Vilgrain V, Panis Y. Selective portal vein ligation and embolization induce different tumoral responses in the rat liver. Surgery. 2011;149:496–503.CrossRefPubMed

29.

Hoekstra LT, van Lienden KP, Verheij J, van der Loos CM, Heger M, van Gulik TM. Enhanced tumor growth after portal vein embolization in a rabbit tumor model. J Surg Res. 2013;180:89–96.CrossRefPubMed

30.

Pamecha V, Levene A, Grillo F, Woodward N, Dhillon A, Davidson BR. Effect of portal vein embolisation on the growth rate of colorectal liver metastases. Br J Cancer. 2009;100:617–22.CrossRefPubMedPubMedCentral

31.

Schadde E, Tsatsaris C, Swiderska-Syn M, Breitenstein S, Urner M, Schimmer R, et al. Hypoxia of the growing liver accelerates regeneration. Surgery. 2017;161:666-79.

32.

Giglio MC, Giakoustidis A, Draz A, Jawad ZA, Pai M, Habib NA, et al. Oncological outcomes of major liver resection following portal vein embolization: a systematic review and meta-analysis. Ann Surg Oncol. 2016;23:3709–17.CrossRefPubMed

33.

Oldhafer KJ, Donati M, Jenner RM, Stang A, Stavrou GA. ALPPS for patients with colorectal liver metastases: effective liver hypertrophy, but early tumor recurrence. World J Surg. 2014;38:1504–9.CrossRefPubMed

34.

Schadde E, Ardiles V, Robles-Campos R, Malago M, Machado M, Hernandez-Alejandro R, et al. Early survival and safety of ALPPS: first report of the International ALPPS Registry. Ann Surg. 2014;260:829–36. discussion 836-828.CrossRefPubMed

35.

Alvarez FA, Ardiles V, de Santibanes M, Pekolj J, de Santibanes E. 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;261:723–32.CrossRefPubMed

36.

Lim C, Farges O. Portal vein occlusion before major hepatectomy in patients with colorectal liver metastases: rationale, indications, technical aspects, complications and outcome. J Visc Surg. 2012;149:e86–96.CrossRefPubMed

37.

Jones RP, Jackson R, Dunne DF, Malik HZ, Fenwick SW, Poston GJ, et al. Systematic review and meta-analysis of follow-up after hepatectomy for colorectal liver metastases. Br J Surg. 2012;99:477–86.CrossRefPubMed

Title: ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) does not affect proliferation, apoptosis, or angiogenesis as compared to standard liver resection for colorectal liver metastases
Authors: Katharina Joechle
Christian Moser
Petra Ruemmele
Katharina M. Schmidt
Jens M. Werner
Edward K. Geissler
Hans J. Schlitt
Sven A. Lang
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: World Journal of Surgical Oncology / Issue 1/2017
Electronic ISSN: 1477-7819
DOI: https://doi.org/10.1186/s12957-017-1121-8

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) does not affect proliferation, apoptosis, or angiogenesis as compared to standard liver resection for colorectal liver metastases

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2017

Oncofertility in patients with stage I epithelial ovarian cancer: fertility-sparing surgery in young women of reproductive age

Outcome of colon cancer initially presenting as colon perforation and obstruction

An acetabular-preserving procedure for pelvic giant cell tumor involving partial acetabulum

Morbidity and oncologic outcome after saphenous vein-sparing inguinal lymphadenectomy in melanoma patients

Influence of tumor extent on central lymph node metastasis in solitary papillary thyroid microcarcinomas: a retrospective study of 1092 patients

Liver necrosis shortly after pancreaticoduodenectomy with resection of the replaced left hepatic artery