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Validation of a surgical model for posthepatectomy liver failure in rats

Animal Models and Experimental Medicine 2023年第3期6卷 266-273页

作者： Andrea Lund Michelle Meier Kasper Jarlhelt Andersen Marie Ingemann Pedersen Anders Riegels Knudsen Jakob Kirkegård Frank Viborg Mortensen Aarhus University Hospital Department of Upper Gastrointestinal and Hepato-Pancreato-Biliary SurgeryAarhus NDenmark

Background:The upper limit for liver resections in rats is approximately 90%.In the early postoperative phase,mortality increases.The aim of the present study was to validate the rat model of 90%partial hepatectomy(PH)as a model of post-hepatectomy liver failure(PHLF).Further,we wanted to test a quantitative scoring system as a detector of lethal outcomes caused by PHLF in rats.Methods:Sixty-eight rats were randomized to 90%PH,sham operation,or no sur-gery.Further,block randomization was performed based on time of euthanization:12,24,or 48 h after surgery.A general distress score(GDS)≥10 during the day or≥6 at midnight prompted early euthanization and classification as nonsurvivor.Animals euthanized as planned were classified as survivors.During euthanization,blood and liver tissue were collected,and liver-specific biochemistry was evaluated.Results:Based on the biochemical results,all animals subjected to 90%PH expe-rienced PHLF.Seventeen rats were euthanized due to irreversible PHLF.The GDS increased for nonsurvivors within 12–18 h after surgery.The mean time for euthaniza-tion was 27 h after surgery.Conclusion:Based on the GDS and liver-specific biochemistry,we concluded that the model of 90%PH seems to be a proper model for investigating PHLF in rats.As a high GDS is associated with increased mortality,the GDS appears to be valuable in detect-ing lethal outcomes caused by PHLF in rats.

关键词： 90%liver resection general distress score liver failure post-hepatectomy liver failure rats

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Preserved liver regeneration capacity after partial hepatectomy in rats with non-alcoholic steatohepatitis

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World Journal of Hepatology 2018年第1期10卷 8-21页

作者： David Haldrup Sara Heeboll Karen Louise Thomsen Kasper Jarlhelt Andersen Michelle Meier Frank Viborg Mortensen Jens Randel Nyengaard Stephen Hamilton-Dutoit Henning Gronbaek Department of Hepatology and Gastroenterology Aarhus University HospitalAarhus C DK-8000Denmark Department of Internal Medicine Randers Regional HospitalRanders NO DK-8930Denmark Department of Surgical Gastroenterology Aarhus University HospitalAarhus C DK-8000Denmark Stereology and Electron Microscopy Laboratory Centre for Stochastic Geometry and Advanced BioimagingAarhus University HospitalAarhus C DK-8000Denmark Institute of Pathology Aarhus University HospitalAarhus C DK-8000Denmark

AIM To evaluate the liver regeneration capacity(LRC) after partial hepatectomy(PH) in experimental non-alcoholic steatohepatitis(NASH).METHODS Fifty-four female rats were fed a high-fat, high-cholesterol diet(HFCD, 65% fat, 1% cholesterol) or standard diet(STD) for 16 wk. A 70% PH was performed and the animals were euthanised before PH or 2 or 5 d postPH. LRC was evaluated using: The total number of Ki-67 positive hepatocytes in the caudate lobe, N(Ki-67, lobe) evaluated in a stereology-based design, the regenerated protein ratio(RPR), prothrombin-proconvertin ratio(PP), and m RNA expression of genes related to regeneration.RESULTS The HFCD NASH model showed significant steatosis with ballooning and inflammation, while no fibrosis was present. Mortality was similar in HFCD and STD animals following PH. HFCD groups were compared to respective STD groups and HFCD animals had a significantly elevated alanine transaminase at baseline(P < 0.001), as well as a significantly elevated bilirubin at day 2 after PH(P < 0.05). HFCD animals had a higher N(Ki-67, lobe) at baseline,(P < 0.0001), day 2 after PH(P = 0.06) and day 5 after PH(P < 0.025). We found no significant difference in RPR or PP neither 2 or 5 d post-PH. Expression of liver regeneration genes(e.g., hepatic growth factor) was higher at both day 2 and 5 post-PH in HFCD groups(P < 0.05).CONCLUSION NASH rats had a preserved LRC after hepatectomy when compared to STD rats. The methods and models of NASH are essential in understanding and evaluating LRC.

关键词： Rat Non-alcoholic fatty liver Non-alcoholic steatohepatitis Liver regeneration Hepatectomy Ki-67 Gene expression

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Impact of palliative therapies in metastatic esophageal cancer patients not receiving chemotherapy

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World Journal of Gastrointestinal Surgery 2020年第9期12卷 377-389页

作者： Sungjin Kim Timothy P DiPeri michelle Guan Veronica R Placencio-Hickok Haesoo Kim Jar-Yee Liu Andrew Hendifar Samuel J Klempner Ryan Nipp Alexandra Gangi Miguel Burch Kevin Waters May Cho Joseph Chao Katelyn Atkins Mitchell Kamrava Richard Tuli Jun Gong Biostatistics and Bioinformatics Research Center Samuel Oschin Comprehensive Cancer InstituteCedars-Sinai Medical CenterLos AngelesCA 90048United States Division of Surgical Oncology Department of SurgerySamuel Oschin Comprehensive Cancer InstituteCedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Medicine Division of Hematology and OncologySamuel Oschin Comprehensive Cancer InstituteCedars Sinai Medical CenterLos AngelesCA 90048United States Department of Medicine Massachusetts General Hospital Cancer CenterHarvard Medical SchoolBostonMA 02114United States Department of Pathology and Laboratory Medicine Cedars-Sinai Medical CenterLos AngelesCA 90048United States Division of Hematology and Oncology Department of MedicineUniversity of CaliforniaDavisSacramentoCA 95817United States Department of Medical Oncology and Therapeutics Research City of Hope Comprehensive Cancer CenterDuarteCA 91010United States Department of Radiation Oncology Cedars Sinai Medical CenterLos AngelesCA 90048United States Department of Radiation Oncology Memorial Sloan Kettering Cancer CenterNew YorkNY 10065United States

BACKGROUND Palliative therapy has been associated with improved overall survival(OS)in several tumor types.Not all patients with metastatic esophageal cancer receive palliative chemotherapy,and the roles of other palliative therapies in these patients are limited.AIM To investigate the impact of other palliative therapies in patients with metastatic esophageal cancer not receiving chemotherapy.METHODS The National Cancer Database was used to identify patients between 2004-2015.Patients with M1 disease who declined chemotherapy and had known palliative therapy status[palliative therapies were defined as surgery,radiotherapy(RT),pain management,or any combination thereof]were included.Cases with unknown chemotherapy,RT,or nonprimary surgery status were excluded.Kaplan-meier estimates of OS were calculated.Cox proportional hazards regression models were employed to examine factors influencing survival.RESULTS Among 140234 esophageal cancer cases,we identified 1493 patients who did not receive chemotherapy and had complete data.Median age was 70 years,most(66.3%)had a Charlson Comorbidity Index(CCI)of 0,and 37.1%were treated at an academic center.The majority(72.7%)did not receive other palliative therapies.On both univariate and multivariable analyses,there was no difference in OS between those receiving other palliative therapy(median 2.83 mo,95%CI:2.53-3.12)vs no palliative therapy(2.37 no,95%CI:2.2-2.56;multivariable P=0.290).On univariate,but not multivariable analysis,treatment at an academic center was predictive of improved OS[Hazard ratio(HR)0.90,95%CI:0.80-1.00;P=0.047].On multivariable analysis,female sex(HR 0.81,95%CI:0.71-0.92)and non-black,other race compared to white race(HR 0.72,95%CI:0.56-0.93)were associated with reduced mortality,while South geographic region relative to West region(HR 1.23,95%CI:1.04-1.46)and CCI of 1 relative to CCI of 0(HR 1.17,95%CI:1.03-1.32)were associated with increased mortality.Higher histologic grade and T-stage were also associated with worse OS(P<0.05).CONCLUSION Pallia

关键词： Esophageal cancer Metastatic Palliative Chemotherapy Radiotherapy Survival

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