Somatostatin Therapy Improves Stellate Cell Activation and Early Fibrogenesis in a Preclinical Model of Extended Major Hepatectomy

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 outcome...

Full description

Bibliographic Details
Main Authors: Amelia J. Hessheimer, Jordi Vengohechea, Lilia Martínez de la Maza, Javier Muñoz, Marina Vendrell, Josep Martí Sanahuja, Alba Torroella, Farah Adel Al Shwely, Francisco Riquelme, César Muñoz, Rocío García, Pilar Taurá, Constantino Fondevila
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/13/16/3989
_version_ 1797524429722353664
author Amelia J. Hessheimer
Jordi Vengohechea
Lilia Martínez de la Maza
Javier Muñoz
Marina Vendrell
Josep Martí Sanahuja
Alba Torroella
Farah Adel Al Shwely
Francisco Riquelme
César Muñoz
Rocío García
Pilar Taurá
Constantino Fondevila
author_facet Amelia J. Hessheimer
Jordi Vengohechea
Lilia Martínez de la Maza
Javier Muñoz
Marina Vendrell
Josep Martí Sanahuja
Alba Torroella
Farah Adel Al Shwely
Francisco Riquelme
César Muñoz
Rocío García
Pilar Taurá
Constantino Fondevila
author_sort Amelia J. Hessheimer
collection DOAJ
description 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 (3–13) mmHg vs. 4 (2–6) mmHg and 4 (2–6) mmHg, respectively, <i>p</i> < 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.
first_indexed 2024-03-10T08:57:16Z
format Article
id doaj.art-317cbb561fae4403bd9871306ec8fb37
institution Directory Open Access Journal
issn 2072-6694
language English
last_indexed 2024-03-10T08:57:16Z
publishDate 2021-08-01
publisher MDPI AG
record_format Article
series Cancers
spelling doaj.art-317cbb561fae4403bd9871306ec8fb372023-11-22T07:02:07ZengMDPI AGCancers2072-66942021-08-011316398910.3390/cancers13163989Somatostatin Therapy Improves Stellate Cell Activation and Early Fibrogenesis in a Preclinical Model of Extended Major HepatectomyAmelia J. Hessheimer0Jordi Vengohechea1Lilia Martínez de la Maza2Javier Muñoz3Marina Vendrell4Josep Martí Sanahuja5Alba Torroella6Farah Adel Al Shwely7Francisco Riquelme8César Muñoz9Rocío García10Pilar Taurá11Constantino Fondevila12General & Digestive Surgery Service, Hospital Clínic, 08036 Barcelona, SpainCIBERehd, IDIBAPS, University of Barcelona, 08036 Barcelona, SpainGeneral & Digestive Surgery Service, Hospital Clínic, 08036 Barcelona, SpainCIBERehd, IDIBAPS, University of Barcelona, 08036 Barcelona, SpainAnesthesiology, Hospital Clínic, University of Barcelona, 08036 Barcelona, SpainAnesthesiology, Hospital Clínic, University of Barcelona, 08036 Barcelona, SpainGeneral & Digestive Surgery Service, Hospital Clínic, 08036 Barcelona, SpainGeneral & Digestive Surgery Service, Hospital Clínic, 08036 Barcelona, SpainGeneral & Digestive Surgery Service, Hospital Clínic, 08036 Barcelona, SpainGeneral & Digestive Surgery Service, Hospital Clínic, 08036 Barcelona, SpainGeneral & Digestive Surgery Service, Hospital Clínic, 08036 Barcelona, SpainAnesthesiology, Hospital Clínic, University of Barcelona, 08036 Barcelona, SpainGeneral & Digestive Surgery Service, Hospital Clínic, 08036 Barcelona, SpainLiver 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 (3–13) mmHg vs. 4 (2–6) mmHg and 4 (2–6) mmHg, respectively, <i>p</i> < 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.https://www.mdpi.com/2072-6694/13/16/3989pigliver resectionsmall-for-size syndromepost-hepatectomy liver failure
spellingShingle Amelia J. Hessheimer
Jordi Vengohechea
Lilia Martínez de la Maza
Javier Muñoz
Marina Vendrell
Josep Martí Sanahuja
Alba Torroella
Farah Adel Al Shwely
Francisco Riquelme
César Muñoz
Rocío García
Pilar Taurá
Constantino Fondevila
Somatostatin Therapy Improves Stellate Cell Activation and Early Fibrogenesis in a Preclinical Model of Extended Major Hepatectomy
Cancers
pig
liver resection
small-for-size syndrome
post-hepatectomy liver failure
title Somatostatin Therapy Improves Stellate Cell Activation and Early Fibrogenesis in a Preclinical Model of Extended Major Hepatectomy
title_full Somatostatin Therapy Improves Stellate Cell Activation and Early Fibrogenesis in a Preclinical Model of Extended Major Hepatectomy
title_fullStr Somatostatin Therapy Improves Stellate Cell Activation and Early Fibrogenesis in a Preclinical Model of Extended Major Hepatectomy
title_full_unstemmed Somatostatin Therapy Improves Stellate Cell Activation and Early Fibrogenesis in a Preclinical Model of Extended Major Hepatectomy
title_short Somatostatin Therapy Improves Stellate Cell Activation and Early Fibrogenesis in a Preclinical Model of Extended Major Hepatectomy
title_sort somatostatin therapy improves stellate cell activation and early fibrogenesis in a preclinical model of extended major hepatectomy
topic pig
liver resection
small-for-size syndrome
post-hepatectomy liver failure
url https://www.mdpi.com/2072-6694/13/16/3989
work_keys_str_mv AT ameliajhessheimer somatostatintherapyimprovesstellatecellactivationandearlyfibrogenesisinapreclinicalmodelofextendedmajorhepatectomy
AT jordivengohechea somatostatintherapyimprovesstellatecellactivationandearlyfibrogenesisinapreclinicalmodelofextendedmajorhepatectomy
AT liliamartinezdelamaza somatostatintherapyimprovesstellatecellactivationandearlyfibrogenesisinapreclinicalmodelofextendedmajorhepatectomy
AT javiermunoz somatostatintherapyimprovesstellatecellactivationandearlyfibrogenesisinapreclinicalmodelofextendedmajorhepatectomy
AT marinavendrell somatostatintherapyimprovesstellatecellactivationandearlyfibrogenesisinapreclinicalmodelofextendedmajorhepatectomy
AT josepmartisanahuja somatostatintherapyimprovesstellatecellactivationandearlyfibrogenesisinapreclinicalmodelofextendedmajorhepatectomy
AT albatorroella somatostatintherapyimprovesstellatecellactivationandearlyfibrogenesisinapreclinicalmodelofextendedmajorhepatectomy
AT farahadelalshwely somatostatintherapyimprovesstellatecellactivationandearlyfibrogenesisinapreclinicalmodelofextendedmajorhepatectomy
AT franciscoriquelme somatostatintherapyimprovesstellatecellactivationandearlyfibrogenesisinapreclinicalmodelofextendedmajorhepatectomy
AT cesarmunoz somatostatintherapyimprovesstellatecellactivationandearlyfibrogenesisinapreclinicalmodelofextendedmajorhepatectomy
AT rociogarcia somatostatintherapyimprovesstellatecellactivationandearlyfibrogenesisinapreclinicalmodelofextendedmajorhepatectomy
AT pilartaura somatostatintherapyimprovesstellatecellactivationandearlyfibrogenesisinapreclinicalmodelofextendedmajorhepatectomy
AT constantinofondevila somatostatintherapyimprovesstellatecellactivationandearlyfibrogenesisinapreclinicalmodelofextendedmajorhepatectomy