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Effect of hepatic artery embolization on liver hypertrophy response in a rabbit liver VX2tumor model

Hepatobiliary & Pancreatic Diseases International 2013年第6期12卷 622-629页

作者： Krijn P van Lienden Lisette T Hoekstra Jessica D van Trigt Joris J Roelofs Otto M van Delden Thomas M van Gulik Department of RadiologyAcademic Medical center University of Amsterdam Department of Surgery (Surgical Laboratory)Academic Medical center University of Amsterdam Department of PathologyAcademic Medical center University of Amsterdam

BACKGROUND:Portal vein embolization not only induces hypertrophy of the non-embolized liver,but also enhances tumor *** latter could be prevented by embolizing the hepatic arteries supplying the tumor-bearing liver *** study aimed to determine the effects of transcatheter arterial embolization(TAE)on tumor volume and liver regeneration in a rabbit VX2 tumor ***:Twenty-three rabbits underwent subcapsular tumor implantation with a VX2 *** weeks after implantation,18 rabbits were used for TAE experiments,5were for sham *** response and liver regeneration response of the embolized cranial and non-embolized caudal liver lobes were assessed by CT volumetry,liver to body weight index,and the amount of proliferating ***:All super-selective arterial tumor embolization procedures were performed *** embolization,the tumor volume increased after an initial steady *** tumor volume after embolization was smaller than that of the sham group,but this difference was not *** necrosis of the tumor,however,was seen after embolization,without damage of the surrounding liver *** was a significant atrophy response of the tumor bearing cranial lobe after super-selective arterial embolization of the tumor with a concomitant hypertrophy response of the non-embolized,caudal *** regeneration response was confirmed histologically by a significantly higher number of proliferating hepatocytes on the Ki-67 stained ***:Super-selective,bland arterial coil embolization causes massive necrosis of the tumor,despite increase of volume on CT *** of the tumor bearing liver lobe is seen after arterial embolization of the tumor with a concomitant hypertrophy response of the non-embolized lobe,despite absence of histological damage of the tumor-surrounding liver parenchyma.

关键词： hypertrophy liver regeneration animal model transarterial embolization hepatic artery

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CD4^(+)T cells produce IFN-I to license cDC1s for induction of cytotoxic T-cell activity in human tumors

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Cellular & Molecular immunology 2024年第4期21卷 374-392页

作者： Xin Lei Daniël C.de Groot Marij J.P.Welters Tom de Wit Ellen Schrama Hans van Eenennaam Saskia J.Santegoets Timo Oosenbrug Annemarthe van der Veen Joris L.Vos Charlotte L.Zuur Noel F.C.C.de Miranda Heinz Jacobs Sjoerd H.van der Burg Jannie Borst Yanling Xiao Department of immunology Leiden University Medical CenterLeidenThe Netherlands Oncode Institute Leiden University Medical CenterLeidenThe Netherlands Department of Tumor Biology and immunology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Medical Oncology Oncode InstituteLeiden University Medical CenterLeidenThe Netherlands IMMIOS B.V. OssThe Netherlands Division of Medical Oncology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Otorhinolaryngology Leiden University Medical center LeidenThe Netherlands Department of Pathology Leiden University Medical CenterLeidenThe Netherlands

CD4^(+)T cells can"help"or"license" conventional type 1 dendritic cells(cDC1s)to induce CD8^(+)cytotoxic T lymphocyte(CTL)anticancer responses,as proven in mouse *** recently identified cDC1s with a transcriptomic imprint of CD4^(+)T-cell help,specifically in T-cell-infiltrated human cancers,and these cells were associated with a good prognosis and response to PD-1-targeting ***,we delineate the mechanism of cDC1 licensing by CD4^(+)T cells in *** CD4^(+)T cells produce IFNβvia the STING pathway,which promotes MHC-I antigen(cross-)presentation by cDC1s and thereby improves their ability to induce CTL anticancer *** cooperation with CD40 ligand(L),IFNβalso optimizes the costimulatory and other functions of cDC1s required for CTL response ***-I-producing CD4^(+)T cells are present in diverse T-cell-infiltrated cancers and likely deliver“help”signals to CTLs locally,according to their transcriptomic profile and colocalization with“helped/licensed”cDCs and tumor-reactive CD8^(+)T *** agreement with this scenario,the presence of IFN-I-producing CD4^(+)T cells in the TME is associated with overall survival and the response to PD-1 checkpoint blockade in cancer patients.

关键词： CD4^(+)T-cell help cDC1 licensing IFN-I signaling CD40 costimulation (cross-)presentation CTL priming Tumor control

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Post-Mortem MRI and Histopathology in Neurologic Disease:A Translational Approach

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Neuroscience Bulletin 2019年第2期35卷 229-243页

作者： Laura E.Jonkman Boyd Kenkhuis Jeroen J.G.Geurts Wilma D.J.van de Berg Department of Anatomy and Neurosciences Amsterdam Neuroscience Amsterdam UMC Vrije Universiteit Amsterdam Department of Human Genetics Leiden University Medical Center Department of Radiology Leiden University Medical Center

In this review, combined post-mortem brain magnetic resonance imaging(MRI) and histology studies are highlighted, illustrating the relevance of translational approaches to de?ne novel MRI signatures of neuropathological lesions in neuroin?ammatory and neurodegenerative disorders. Initial studies combining post-mortem MRI and histology have validated various MRI sequences,assessing their sensitivity and speci?city as diagnostic biomarkers in neurologic disease. More recent studies have focused on de?ning new radiological(bio)markers and implementing them in the clinical(research) setting. By combining neurological and neuroanatomical expertise with radiological development and pathological validation,a cycle emerges that allows for the discovery of novel MRI biomarkers to be implemented in vivo. Examples of this cycle are presented for multiple sclerosis, Alzheimer's disease, Parkinson's disease, and traumatic brain *** applications have been shown to be successful, while others require further validation. In conclusion, there is much to explore with post-mortem MRI and histology studies, which can eventually be of high relevance for clinical practice.

关键词： MRI Histology Biomarkers Multiple sclerosis Alzheimer’s disease Parkinson’s disease

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Short-and long-term outcomes after hemihepatectomy for perihilar cholangiocarcinoma:does left or right side matter?

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Hepatobiliary Surgery and Nutrition 2021年第2期10卷 154-162,I0001,I0002页

作者： Lotte C.Franken Pim B.Olthof Joris I.Erdmann Otto M.van Delden Joanne Verheij Marc G.Besselink Olivier R.Busch Thomas M.van Gulik Department of Surgery Cancer Center AmsterdamAmsterdam UMCUniversity of AmsterdamThe Netherlands Department of Surgery Erasmus Medical CenterErasmus UniversityRotterdamThe Netherlands Department of Radiology and Nuclear Medicine Amsterdam UMCUniversity of AmsterdamAmsterdamThe Netherlands Department of Pathology Cancer Center AmsterdamAmsterdam UMCUniversity of AmsterdamAmsterdamThe Netherlands

Background:The only potentially curative option for patients with perihilar cholangiocarcinoma(PHC)is resection,typically an extrahepatic bile duct resection in combination with(extended)liver *** such as bile leakage and liver failure have been suggested to be more common after right-sided resections compared to left-sided resections,whilst superior oncological outcomes have been reported after right-sided ***,data on outcomes after right-sided or left-sided liver resections in PHC are ***,we aimed to investigate short-and long-term outcomes after left and right hemihepatectomy in patients with ***:In this retrospective study,patients undergoing major liver resection for suspected PHC in a tertiary center between 2000-2018 were *** who had undergone left-sided resections were compared to patients with right-sided resections in terms of complications(90-day mortality,overall and severe morbidity and specific complications).For long-term outcomes,only patients with pathologically proven PHC were included in the survival ***:A total of 178 patients undergoing hemihepatectomy for suspected PHC were analysed,including 76 left-sided and 102 right-sided *** 90-day mortality was 14%(24 out of 178),with no significant difference after left-sided resection(11%;8 out of 76)versus right-sided resection(16%;16 out of 102)(P=0.319).Severe morbidity(Clavein Dindo≥3)was also comparable in both groups:54%versus 61%(P=0.361).No differences in specific complications including bile leakage were observed,although liver failure appeared to occur more frequently after right hemihepatectomy(22%versus 11%,P=0.052).Five-year overall survival for pathologically proven PHC,excluding in-hospital mortality,did not differ;43.7%after left-sided resection *** 38.2%after right-sided resection(P=0.553).Conclusions:Both short-and long-term outcomes between patients undergoing left and right hemihepate

关键词： Perihilar cholangiocarcinoma(PHC) hepatectomy outcomes mortality survival

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Functional assessment of liver regeneration after major hepatectomy

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Hepatobiliary Surgery and Nutrition 2022年第4期11卷 530-538页

作者： Fadi Rassam Pim B.Olthof Bart Takkenberg Marc G.Besselink Olivier R.Busch Joris I.Erdmann Rutger-Jan Swijnenburg Krijn Pvan Lienden Ulrich H.Beuers Roelof J.Bennink Thomas Mvan Gulik Department of Surgery Cancer Center AmsterdamAmsterdam UMCUniversity of AmsterdamThe Netherlands Department of Gastroenterology&Hepatology Amsterdam UMCUniversity of AmsterdamAmsterdamThe Netherlands Departments of Radiology and Nuclear Medicine Cancer Center AmsterdamAmsterdam UMCUniversity of AmsterdamAmsterdamThe Netherlands

Background: Liver regeneration is crucial to restore the functional liver mass after liver resection. The aim of this study was to evaluate the early postoperative changes in remnant liver function, volume and liver stiffness after major liver resection and their correlation with postoperative outcomes. Methods: Patients undergoing major liver resection (≥3 segments) between February and November 2018 underwent both functional assessment using technetium-99m mebrofenin hepatobiliary scintigraphy (HBS) and CT-volumetry of the (future) remnant liver on preoperative day 1, the 5th postoperative day, and 4-6 weeks after resection. At the same time points, patients underwent transient elastography (TE) for the assessment of liver stiffness. Severe postoperative complications (Clavien-Dindo ≥ 3A) and mortality were correlated with the functional and volumetric increases of the remnant liver. Liver failure was graded according to the International Study Group of Liver Surgery (ISGLS) criteria. Results: A total of 18 patients were included of whom 10 (56%) had severe complications and one patient (5%) developed liver failure. Function and volume of the remnant liver had increased by the 5th postoperative day from 6.9 (5.4-10.9) to 9.6 (6.7-13.8) %/min/m2, P=0.004 and from 795.5 (538.3-1,037.5) to 1,080.0 (854.0-1,283.3) mL, P<0.001, respectively. After 4-6 weeks, remnant liver volume had further increased [from 1,080.0 (854.0-1,283.3) to 1,222.0 (1,016.0-1,380.5) mL, P=0.035], however, liver function did not show any significant, further increase [from 9.6 (6.7-13.8) to 10.9 (8.8-13.6) %/min/m2, P=0.177]. Liver elasticity of the future remnant liver (FRL) increased [from 10.8 (5.7-18.7) to 17.5 (12.4-22.6) kPa, P=0.018] and gradually recovered after 4-6 weeks to a median of 10.9 (5.7-18.8) kPa (T3 vs. T4, P=0.079). Patients who had severe postoperative complications did not show a significant increase in liver function on the 5th postoperative day (P=0.203), despite increas

关键词： Hepatobiliary scintigraphy(HBS) liver resection liver regeneration posthepatectomy liver failure liver function test

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Interpatient heterogeneity in hepatic microvascular blood flow during vascular inflow occlusion (Pringle manoeuvre)

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Hepatobiliary Surgery and Nutrition 2020年第3期9卷 271-283页

作者： Lucinda Shen Zühre Uz Joanne Verheij Denise P.Veelo Yasin Ince Can Ince Thomas M.van Gulik Department of Translational Physiology Amsterdam UMCLocation Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands Department of Intensive Care Laboratory of Translational Intensive CareErasmus MCUniversity Medical CenterRotterdamThe Netherlands Department of Surgery Amsterdam UMCLocation Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands Department of Pathology Amsterdam UMCLocation Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands Department of Anesthesiology Amsterdam UMCLocation Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands

Background:Vascular inflow occlusion(VIO)during liver resections(Pringle manoeuvre)can be applied to reduce blood loss,however may at the same time,give rise to ischemia-reperfusion injury(IRI).The aim of this study was to assess the characteristics of hepatic microvascular perfusion during VIO in patients undergoing major liver ***:Assessment of hepatic microcirculation was performed using a handheld vital microscope(HVM)at the beginning of surgery,end of VIO(20 minutes)and during reperfusion after the termination of *** microcirculatory parameters assessed were:functional capillary density(FCD),microvascular flow index(MFI)and sinusoidal diameter(SinD).Results:A total of 15 patients underwent VIO;8 patients showed hepatic microvascular perfusion despite VIO(partial responders)and 7 patients showed complete cessation of hepatic microvascular perfusion(full responders).Functional microvascular parameters and blood flow levels were significantly higher in the partial responders when compared to the full responders during VIO(FCD:0.84±0.88 vs.0.00±0.00 mm/mm2,P<0.03,respectively,and MFI:0.69–0.22 vs.0.00±0.00,P<0.01,respectively).Conclusions:An interpatient heterogeneous response in hepatic microvascular blood flow was observed upon *** may explain why clinical strategies to protect the liver against IRI lacked consistency.

关键词： Liver perfusion microcirculation

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Fever without a source in children:international comparison of guidelines

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World Journal of Pediatrics 2023年第2期19卷 120-128页

作者： Sanne Graaf Maya Wietske Keuning Dasja Pajkrt Frans Berend Plötz Department of Pediatrics Tergooi HospitalRijksstraatweg 11261 ANBlaricumThe Netherlands Department of Pediatrics Amsterdam University Medical CentersLocation Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands Department of Pediatric Infectious Diseases Amsterdam University Medical CentersLocation Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands

Background Fever without a source(FWS)in children poses a diagnostic *** distinguish a self-limiting infection from a serious infection,multiple guidelines have been developed to aid physicians in the management of ***,there is no comparison of existing FWS *** This comparative review describes consistencies and differences in guideline definitions and diagnostic and therapeutic recommendations.A literature search was performed to include secondary care FWS guidelines of high-income countries,composed by national or regional pediatric or emergency care associations,available in English or *** Ten guidelines of five high-income countries were included,with varying age ranges of children with *** children younger than one month with FWS,the majority of the guidelines recommended laboratory testing,blood and urine culturing and antibiotic treatment irrespective of the clinical condition of the *** for blood culture and antibiotic treatment varied for children aged 1–3 *** children aged above three months,urine culture recommendations were inconsistent,while all guidelines consistently recommended cerebral spinal fluid testing and antibiotic treatment exclusively for children with a high risk of serious *** We found these guidelines broadly consistent,especially for children with FWS younger than one *** variation was seen most in the targeted age ranges and in recommendations for children aged 1–3 months and above three months of *** findings of the current study can assist in harmonizing guideline development and future research for the management of children with FWS.

关键词： Children Fever Guideline

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Neuron-to-astrocyte proteostatic stress signaling in response to tau pathology

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Neural Regeneration Research 2024年第3期19卷 505-506页

作者： Kevin Llewelyn Batenburg Wiep Scheper amsterdam UMC location Vrije Universiteit amsterdam Department of Human GeneticsAmsterdam Neuroscience-NeurodegenerationAmsterdamThe Netherlands Department of Functional Genomics Center for Neurogenomics and Cognitive ResearchVrije Universiteit AmsterdamAmsterdam Neuroscience-NeurodegenerationAmsterdamThe Netherlands

Maintenance of protein homeostasis or“proteostasis”is essential for the functioning and viability of *** is in particular the case for cells like neurons that cannot self-renew and acquire unique functional properties during their *** proteostatic stress responses are in place to protect cells from damage in case of proteostatic *** integrated stress response(ISR)is one of the key proteostatic stress responses in the cell(Costa-Mattioli and Walter,2020).The ISR is the downstream convergence point for the four stress-induced eIF2αkinases(EIF2AK1-4)that control stress-regulated protein translation via phosphorylation of the translation factor eIF2α.ISR activation results in a transient reduction of global translation while it concomitantly enhances the translation of specific mRNAs,including that encoding the activating transcription factor 4(ATF4).Together,the translational control mediated by the ISR results in a temporary reduction of the overall protein load and the selectively increased expression of proteins that contribute to restoration of the proteostatic balance.

关键词： translation stress Together

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Fatty acid desaturation by stearoyl-CoA desaturase-1 controls regulatory T cell differentiation and autoimmunity

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Cellular & Molecular immunology 2023年第6期20卷 666-679页

作者： Elien Grajchen Melanie Loix Paulien Baeten Beatriz F.Côrte-Real Ibrahim Hamad Sam Vanherle Mansour Haidar Jonas Dehairs Jelle Y.Broos James M.Ntambi Robert Zimmermann Rolf Breinbauer Piet Stinissen Niels Hellings Sanne G.S.Verberk Gijs Kooij Martin Giera Johannes V.Swinnen Bieke Broux Markus Kleinewietfeld Jerome J.A.Hendriks Jeroen F.J.Bogie Department of immunology and Infection Biomedical Research InstituteHasselt UniversityDiepenbeekBelgium University MS center Hasselt PeltBelgium Neuro-Immune Connections and Repair Lab Department of Immunology and InfectionBiomedical Research InstituteHasselt UniversityDiepenbeekBelgium VIB Laboratory of Translational Immunomodulation VIB Center for Inflammation ResearchHasselt UniversityDiepenbeekBelgium Department of Oncology Laboratory of Lipid Metabolism and CancerLKI–Leuven Cancer InstituteKU Leuven-University of LeuvenLeuvenBelgium Department of Molecular Cell Biology and immunology Amsterdam University Medical CenterVrije Universiteit AmsterdamAmsterdam NeuroscienceMS Center AmsterdamAmsterdamThe Netherlands center for Proteomics and Metabolomics Leiden University Medical CenterLeidenThe Netherlands Department of Biochemistry Department of Nutritional SciencesUniversity of Wisconsin-MadisonMadisonUSA Institute of Molecular Biosciences University of GrazGrazAustria BioTechMed-Graz GrazAustria Institute of Organic Chemistry Graz University of TechnologyGrazAustria Cardiovascular Research Institute Maastricht Department of Internal MedicineMaastricht UniversityMaastrichtThe Netherlands

The imbalance between pathogenic and protective T cell subsets is a cardinal feature of autoimmune disorders such as multiple sclerosis(MS).Emerging evidence indicates that endogenous and dietary-induced changes in fatty acid metabolism have a major impact on both T cell fate and *** date,however,the molecular mechanisms that underlie the impact of fatty acid metabolism on T cell physiology and autoimmunity remain poorly ***,we report that stearoyl-CoA desaturase-1(SCD1),an enzyme essential for the desaturation of fatty acids and highly regulated by dietary factors,acts as an endogenous brake on regulatory T-cell(Treg)differentiation and augments autoimmunity in an animal model of MS in a T cell-dependent *** by RNA sequencing and lipidomics analysis,we found that the absence of Scd1 in T cells promotes the hydrolysis of triglycerides and phosphatidylcholine through adipose triglyceride lipase(ATGL).ATGL-dependent release of docosahexaenoic acid enhanced Treg differentiation by activating the nuclear receptor peroxisome proliferator-activated receptor *** findings identify fatty acid desaturation by SCD1 as an essential determinant of Treg differentiation and autoimmunity,with potentially broad implications for the development of novel therapeutic strategies and dietary interventions for autoimmune disorders such as MS.

关键词： Regulatory T cells Autoimmunity Fatty acid metabolism Stearoyl-CoA desaturase-1 Multiple sclerosis

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James Hogarth Pringle and his time-honored maneuver

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Hepatobiliary Surgery and Nutrition 2024年第3期13卷 391-392页

作者： Thomas M.van Gulik Department of Surgery Amsterdam University Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands

The classical method to control blood loss during parenchymal transection of the liver is the Pringle *** his landmark article in the Annals of Surgery in 1908,James Hogarth Pringle occluded the afferent vessels to the liver by compressing the hepatoduodenal ligament between his thumb and index finger(1).He applied this maneuver in eight patients who required emergency laparotomy for major hemorrhage after severe liver *** he succeeded in controlling blood loss,the eight patients he described unfortunately all *** outcome did not prevent the Annals of Surgery from publishing his report after which James Hogarth Pringle was ready to enter the‘Hall of Fame’.Vascular inflow occlusion,applied in a continuous or intermittent fashion,became the mainstay technique for reducing blood loss during liver transection,and has remained so in the present era of laparoscopic and robotic liver resection(2).

关键词： Pringle Surgery patients

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