{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T12:20:04Z","timestamp":1772713204249,"version":"3.50.1"},"reference-count":48,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,7]],"date-time":"2021-08-07T00:00:00Z","timestamp":1628294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["15\/01092"],"award-info":[{"award-number":["15\/01092"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Liver resection treats primary and secondary liver tumors, though clinical applicability is limited by the remnant liver mass and quality. Herein, major hepatic resections were performed in pigs to define changes associated with sufficient and insufficient remnants and improve liver-specific outcomes with somatostatin therapy. Three experimental groups were performed: 75% hepatectomy (75H), 90% hepatectomy (90H), and 90% hepatectomy + somatostatin (90H + SST). Animals were followed for 24 h (N = 6) and 5 d (N = 6). After hepatectomy, portal pressure gradient was higher in 90H versus 75H and 90H + SST (8 (3\u201313) mmHg vs. 4 (2\u20136) mmHg and 4 (2\u20136) mmHg, respectively, p &lt; 0.001). After 24 h, changes were observed in 90H associated with stellate cell activation and collapse of sinusoidal lumen. Collagen chain type 1 alpha 1 mRNA expression was higher, extracellular matrix width less, and percentage of collagen-staining areas greater at 24 h in 90H versus 75H and 90H + SST. After 5 d, remnant liver mass was higher in 75H and 90H + SST versus 90H, and Ki-67 immunostaining was higher in 90H + SST versus 75H and 90H. As well, more TUNEL-staining cells were observed in 90H versus 75H and 90H + SST at 5 d. Perioperative somatostatin modified portal pressure, injury, apoptosis, and stellate cell activation, stemming changes related to hepatic fibrogenesis seen in liver remnants not receiving treatment.<\/jats:p>","DOI":"10.3390\/cancers13163989","type":"journal-article","created":{"date-parts":[[2021,8,8]],"date-time":"2021-08-08T21:49:41Z","timestamp":1628459381000},"page":"3989","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Somatostatin Therapy Improves Stellate Cell Activation and Early Fibrogenesis in a Preclinical Model of Extended Major Hepatectomy"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7247-5051","authenticated-orcid":false,"given":"Amelia J.","family":"Hessheimer","sequence":"first","affiliation":[{"name":"General & Digestive Surgery Service, Hospital Cl\u00ednic, 08036 Barcelona, Spain"},{"name":"CIBERehd, IDIBAPS, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5628-9876","authenticated-orcid":false,"given":"Jordi","family":"Vengohechea","sequence":"additional","affiliation":[{"name":"CIBERehd, IDIBAPS, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lilia","family":"Mart\u00ednez de la Maza","sequence":"additional","affiliation":[{"name":"General & Digestive Surgery Service, Hospital Cl\u00ednic, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"CIBERehd, IDIBAPS, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Vendrell","sequence":"additional","affiliation":[{"name":"Anesthesiology, Hospital Cl\u00ednic, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3275-2456","authenticated-orcid":false,"given":"Josep Mart\u00ed","family":"Sanahuja","sequence":"additional","affiliation":[{"name":"Anesthesiology, Hospital Cl\u00ednic, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alba","family":"Torroella","sequence":"additional","affiliation":[{"name":"General & Digestive Surgery Service, Hospital Cl\u00ednic, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farah","family":"Adel Al Shwely","sequence":"additional","affiliation":[{"name":"General & Digestive Surgery Service, Hospital Cl\u00ednic, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco","family":"Riquelme","sequence":"additional","affiliation":[{"name":"General & Digestive Surgery Service, Hospital Cl\u00ednic, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e9sar","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"General & Digestive Surgery Service, Hospital Cl\u00ednic, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roc\u00edo","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"General & Digestive Surgery Service, Hospital Cl\u00ednic, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pilar","family":"Taur\u00e1","sequence":"additional","affiliation":[{"name":"Anesthesiology, Hospital Cl\u00ednic, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6161-6824","authenticated-orcid":false,"given":"Constantino","family":"Fondevila","sequence":"additional","affiliation":[{"name":"General & Digestive Surgery Service, Hospital Cl\u00ednic, 08036 Barcelona, Spain"},{"name":"CIBERehd, IDIBAPS, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41572-021-00261-6","article-title":"Liver metastases","volume":"7","author":"Tsilimigras","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1007\/s13304-020-00854-y","article-title":"Laparoscopic versus open hemihepatectomy: Comprehensive comparison of complications and costs at 90 days using a propensity method","volume":"72","author":"Riquelme","year":"2020","journal-title":"Updates Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1097\/01.sla.0000189131.90876.9e","article-title":"The \u201d50-50 Criteria\u201d on Postoperative Day 5","volume":"242","author":"Balzan","year":"2005","journal-title":"Ann. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1111\/j.1600-6143.2005.01081.x","article-title":"Small-for-Size Syndrome After Partial Liver Transplantation: Definition, Mechanisms of Disease and Clinical Implications","volume":"5","author":"Dahm","year":"2005","journal-title":"Am. J. Transplant."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1111\/j.1478-3231.2008.01777.x","article-title":"Liver failure after partial hepatic resection: Definition, pathophysiology, risk factors and treatment","volume":"28","author":"Broek","year":"2008","journal-title":"Liver Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.surg.2010.10.001","article-title":"Posthepatectomy liver failure: A definition and grading by the International Study Group of Liver Surgery (ISGLS)","volume":"149","author":"Rahbari","year":"2011","journal-title":"Surgery"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1053\/jlts.2003.50128","article-title":"Relationship between portal venous flow and liver regeneration in patients after living donor right-lobe liver transplantation","volume":"9","author":"Eguchi","year":"2003","journal-title":"Liver Transplant."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1097\/00007890-200301150-00018","article-title":"Factors influencing liver regeneration following living-donor liver transplantation of the right hepatic lobe","volume":"75","author":"Maetani","year":"2003","journal-title":"Transplantation"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1097\/SLA.0b013e3181ffb2d7","article-title":"Decompression of the Portal Bed and Twice-Baseline Portal Inflow Are Necessary for the Functional Recovery of a \u201cSmall-for-Size\u201d Graft","volume":"253","author":"Hessheimer","year":"2011","journal-title":"Ann. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1097\/00007890-199505270-00005","article-title":"Evidence that portal vein decompression improves survival of canine quarter orthotopic liver transplantation","volume":"59","author":"Ku","year":"1995","journal-title":"Transplantation"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1097\/00000658-199610000-00012","article-title":"Functional Analysis of Grafts from Living Donors","volume":"224","author":"Emond","year":"1996","journal-title":"Ann. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1111\/j.1600-6143.2005.00850.x","article-title":"Effects of Hemi-Portocaval Shunts For Inflow Modulation on the Outcome of Small-for-Size Grafts in Living Donor Liver Transplantation","volume":"5","author":"Troisi","year":"2005","journal-title":"Am. J. Transplant."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1002\/lt.21989","article-title":"Portal hyperperfusion: Mechanism of injury and stimulus for regeneration in porcine small-for-size transplantation","volume":"16","author":"Fondevila","year":"2010","journal-title":"Liver Transplant."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1806","DOI":"10.1111\/ajt.12758","article-title":"Somatostatin Therapy Protects Porcine Livers in Small-for-Size Liver Transplantation","volume":"14","author":"Hessheimer","year":"2014","journal-title":"Am. J. Transplant."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1111\/j.1600-6143.2010.03150.x","article-title":"Deceleration of Regenerative Response Improves the Outcome of Rat with Massive Hepatectomy","volume":"10","author":"Ninomiya","year":"2010","journal-title":"Am. J. Transplant."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Hessheimer, A.J., Mart\u00ednez de la Maza, L., Adel Al Shwely, F., Espinoza, A.S., Ausania, F., and Fondevila, C. (2019). Somatostatin and the \u201csmall-for-size\u201d. Liver Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20102512"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1002\/bjs.4053","article-title":"Segmental nature of the porcine liver and its potential as a model for experimental partial hepatectomy","volume":"90","author":"Court","year":"2003","journal-title":"Br. J. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.jss.2003.08.007","article-title":"Subtotal hepatectomy: A porcine model for the study of liver regeneration","volume":"116","author":"Court","year":"2004","journal-title":"J. Surg. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1002\/jhbp.396","article-title":"Porcine models for the study of small-for-size syndrome and portal inflow modulation: Literature review and proposal for a standardized nomenclature","volume":"23","author":"Mohkam","year":"2016","journal-title":"J. Hepato Biliary Pancreat. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1097\/00007890-199112000-00008","article-title":"The beneficial effect of a prostaglandin 12 analog on ischemic rat liver","volume":"52","author":"Suzuki","year":"1991","journal-title":"Transplantation"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e20003","DOI":"10.1097\/MD.0000000000020003","article-title":"Liver fibrosis is a major risk factor for liver regeneration","volume":"99","author":"Aierken","year":"2020","journal-title":"Medicine"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3534","DOI":"10.1245\/s10434-020-08828-5","article-title":"Fibrosis-4 Index, a Noninvasive Fibrosis Marker, Predicts Survival Outcomes after Hepatectomy for Colorectal Cancer Liver Metastases","volume":"27","author":"Akiyama","year":"2020","journal-title":"Ann. Surg. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.jhep.2020.04.032","article-title":"A nomogram based on liver stiffness predicts postoperative complications in patients with hepatocellular carcinoma","volume":"73","author":"Serenari","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1172\/JCI24282","article-title":"Science in medicine Liver fibrosis","volume":"115","author":"Bataller","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1002\/hep.26053","article-title":"A novel murine model to deplete hepatic stellate cells uncovers their role in amplifying liver damage in mice","volume":"57","author":"Puche","year":"2013","journal-title":"Hepatology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s12072-015-9613-5","article-title":"New cellular and molecular targets for the treatment of portal hypertension","volume":"9","author":"Bosch","year":"2015","journal-title":"Hepatol. Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1007\/s00595-020-02088-2","article-title":"Issues to be considered to address the future liver remnant prior to major hepatectomy","volume":"51","author":"Kishi","year":"2021","journal-title":"Surg. Today"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.ejso.2020.09.001","article-title":"Post hepatectomy liver failure (PHLF) \u2013 Recent advances in prevention and clinical management","volume":"47","author":"Deshpande","year":"2021","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1111\/hpb.12424","article-title":"Reductions in post-hepatectomy liver failure and related mortality after implementation of the LiMAx algorithm in preoperative work-up: A single-centre analysis of 1170 hepatectomies of one or more segments","volume":"17","author":"Jara","year":"2015","journal-title":"HPB"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1080\/00365521.2018.1501604","article-title":"The impact of post-hepatectomy liver failure on mortality: A population-based study","volume":"53","author":"Gilg","year":"2018","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1001\/archsurg.2011.771","article-title":"Improvement in Perioperative and Long-term Outcome After Surgical Treatment of Hilar Cholangiocarcinoma","volume":"147","author":"Nuzzo","year":"2012","journal-title":"Arch. Surg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1097\/SLA.0b013e3182708b57","article-title":"Evolution of surgical treatment for perihilar cholangiocarcinoma: A single-center 34-year review of 574 consecutive resections","volume":"258","author":"Nagino","year":"2013","journal-title":"Ann. Surg."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1016\/j.surg.2019.01.010","article-title":"Morbidity and mortality after major liver resection in patients with perihilar cholangiocarcinoma: A systematic review and meta-analysis","volume":"165","author":"Franken","year":"2019","journal-title":"Surgery"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1007\/s00268-013-2401-2","article-title":"ALPPS for Patients with Colorectal Liver Metastases: Effective Liver Hypertrophy, but Early Tumor Recurrence","volume":"38","author":"Oldhafer","year":"2014","journal-title":"World J. Surg."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1002\/bjs.10256","article-title":"Outcome after associating liver partition and portal vein ligation for staged hepatectomy and conventional two-stage hepatectomy for colorectal liver metastases","volume":"103","author":"Adam","year":"2016","journal-title":"BJS"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/0022-4804(91)90079-2","article-title":"Inhibitory effects of somatostatin on rat hepatocyte proliferation are mediated by cyclic AMP","volume":"51","author":"Kokudo","year":"1991","journal-title":"J. Surg. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/0002-9610(92)90271-R","article-title":"Inhibition of DNA synthesis by somatostatin in rat hepatocytes stimulated by hepatocyte growth factor or epidermal growth factor","volume":"163","author":"Kokudo","year":"1992","journal-title":"Am. J. Surg."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1002\/jcb.240590214","article-title":"Preferential suppression of insulin-stimulated proliferation of cultured hepatocytes by somatostatin: Evidence for receptor-mediated growth regulation","volume":"59","author":"Kothary","year":"1995","journal-title":"J. Cell. Biochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1126\/science.276.5309.60","article-title":"Liver Regeneration","volume":"276","author":"Michalopoulos","year":"1997","journal-title":"Science"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1038\/nrm1489","article-title":"Liver regeneration: From myth to mechanism","volume":"5","author":"Taub","year":"2004","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1007\/s12192-018-0929-7","article-title":"Somatostatin analogue, Octreotide, improves restraint stress-induced liver injury by ameliorating oxidative stress, inflammatory response, and activation of hepatic stellate cells","volume":"23","author":"Aziz","year":"2018","journal-title":"Cell Stress Chaperon"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.intimp.2018.08.005","article-title":"Octreotide attenuates hepatic fibrosis and hepatic stellate cells proliferation and activation by inhibiting Wnt\/\u03b2-catenin signaling pathway, c-Myc and cyclin D1","volume":"63","author":"Zhang","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.3892\/mmr.2013.1385","article-title":"The mechanism through which octreotide inhibits hepatic stellate cell activity","volume":"7","author":"Wang","year":"2013","journal-title":"Mol. Med. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/sj.bjp.0706298","article-title":"Somatostatin at nanomolar concentration reduces collagen I and III synthesis by, but not proliferation of activated rat hepatic stellate cells","volume":"146","author":"Reynaert","year":"2005","journal-title":"Br. J. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1097\/SLA.0000000000003062","article-title":"Somatostatin as inflow modulator in liver-transplant recipients with severe portal hypertension: A randomized trial","volume":"269","author":"Troisi","year":"2019","journal-title":"Ann. Surg."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e101","DOI":"10.1097\/SLA.0000000000002601","article-title":"Portal Inflow Modulation by Somatostatin After Major Liver Resection","volume":"267","author":"Rhaiem","year":"2018","journal-title":"Ann. Surg."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2201","DOI":"10.1016\/j.ejso.2021.03.256","article-title":"Somatostatin perfusion and modulation of portal inflow after major liver resection: Response to \u201cPost hepatectomy liver failure (PHLF)-Recent advances in prevention and clinical management\u201d","volume":"47","author":"Rhaiem","year":"2021","journal-title":"Eur. J. Surg. Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/16\/3989\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:42:11Z","timestamp":1760164931000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/16\/3989"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,7]]},"references-count":48,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["cancers13163989"],"URL":"https:\/\/doi.org\/10.3390\/cancers13163989","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,7]]}}}