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| 1 | Post-hepatectomy liver regeneration in the context of bile acid homeostasis and the gut-liver signaling axis显示文摘Background:Liver regeneration following partial hepatectomy(PHx)is a complicated process involving multiple organs and several types of signaling networks.The bile acid-activated metabolic pathways occupy an auxiliary yet important chapter in the entire biochemical story.PHx is characterized by rapid but transient bile acid overload in the liver,which constitutes the first wave of proliferative signaling in the remnant hepatocytes.Bile acids trigger hepatocyte proliferation through activation of several nuclear receptors.Following biliary passage into the intestines,enterocytes reabsorb the bile acids,which results in the activation of farnesoid X receptor(FXR),the consequent excretion of fibroblast growth factor(FGF)19/FGF15,and its release into the enterohepatic circulation.FGF19/FGF15 subsequently binds to its cognate receptor,fibroblast growth factor receptor 4(FGFR4)complexed withβ-klotho,on the hepatocyte membrane,which initiates the second wave of proliferative signaling.Because some bile acids are toxic,the remnant hepatocytes must resolve the potentially detrimental state of bile acid excess.Therefore,the hepatocytes orchestrate a bile acid detoxification and elimination response as a protective mechanism in concurrence with the proliferative signaling.The response in part results in the excretion of(biotransformed)bile acids into the canalicular system,causing the bile acids to end up in the intestines.Relevance for patients:Recently,FXR agonists have been shown to promote regeneration via the gut-liver axis.This type of pharmacological intervention may prove beneficial for patients with hepatobiliary tumors undergoing PHx.In light of these developments,the review provides an in-depth account of the pathways that underlie post-PHx liver regeneration in the context of bile acid homeostasis in the liver and the gut-liver signaling axis. | Lianne de Haan Sarah Jvan der Lely Anne-Loes K.Warps Quincy Hofsink Pim B.Olthof Mark J.de Keijzer Daniel A.Lionarons Lionel Mendes-Dias Bote G.Bruinsma Korkut Uygun Hartmut Jaeschke Geoffrey C.Farrell Narci Teoh Rowan Fvan Golen Tiangang Li Michal Heger | 2018 | Journal of Clinical & Translational Research2018，4，1： | 2 |
| 2 | The rush to novelty and high expectations in surgery: the case of ALPPS显示文摘In the editorial that accompanied the publication of the inauguralALPPS paper (associating liver partition and portalvein ligation for staged hepatectomy) [1], ALPPS was termed“the biggest technical innovation in liver surgery so far” [2].ALPPS is a two-stage hepatectomy intended to allow veryextensive liver resections in patients with very small futureliver remnants (FLR). The key element of ALPPS is that itinduces rapid and extensive hypertrophy of the FLR in the firststage of the procedure to ‘create’ an FLR sizeable enough toprovide enough liver function after an extensive resection in asecond stage, and thereby reduce the chances of post- hepatectomyliver failure. Due to the procedural and clinical complexity,ALPPS is mainly used in liver resections of borderlineresectable liver metastases. In the first step, the FLR is cleanedof tumor through one or more parenchymal sparing resections.Then the parenchyma between the part of the liver that ultimatelywill be resected and the FLR is transected. Finally, theportal vein to the liver that will be resected in the secondsstage is ligated (i.e., the liver is ‘deportalized’) and the entireportal flow directed towards the FLR. After 1 to 2 weeks theliver regenerates rapidly and the resection of the deportalizedliver can be completed in a second stage procedure [1]. | Pim B.Olthof Erik Schadde | 2016 | Journal of Clinical & Translational Research2016，2，3： | 1 |
| 3 | Development and internal validation of the Comprehensive ALPPS Preoperative Risk Assessment(CAPRA)score:is the patient suitable for Associating Liver Partition and Portal vein ligation for Staged hepatectomy(ALPPS)?显示文摘Background:Preoperative patient selection in Associating Liver Partition and Portal vein ligation for Staged hepatectomy(ALPPS)is not always reliable with currently available scores,particularly in patients with primary liver tumor.This study aims to(I)to determine whether comorbidities and patients characteristics are a risk factor in ALPPS and(II)to create a score predicting 90-day mortality preoperatively.Methods:Thirteen high-volume centers participated in this retrospective multicentric study.A risk analysis based on patient characteristics,underlying disease and procedure type was performed to identify risk factors and model the Comprehensive ALPPS Preoperative Risk Assessment(CAPRA)score.A nonparametric receiver operating characteristic analysis was performed to estimate the predictive ability of our score against the Charlson Comorbidity Index(CCI),the age-adjusted CCI(aCCI),the ALPPS risk score before Stage 1(ALPPS-RS1)and Stage 2(ALPPS-RS2).The model was internally validated applying bootstrapping.Results:A total of 451 patients were included.Mortality was 14.4%.The CAPRA score is calculated based on the following formula:(0.1×age)−(2×BSA)+1(in the presence of primary liver tumor)+1(in the presence of severe cardiovascular disease)+2(in the presence of moderate or severe diabetes)+2(in the presence of renal disease)+2(if classic ALPPS is planned).The predictive ability was 0.837 for the CAPRA score,0.443 for CCI,0.519 for aCCI,0.693 for ALPPS-RS1 and 0.807 for ALPPS-RS2.After 1,000 cycles of bootstrapping the C statistic was 0.793.The accuracy plot revealed a cut-off for optimal prediction of postoperative mortality of 4.70.Conclusions:Comorbidities play an important role in ALPPS and should be carefully considered when planning the procedure.By assessing the patient’s preoperative condition in relation to ALPPS,the CAPRA score has a very good ability to predict postoperative mortality. | Ivan Capobianco Karl J.Oldhafer Mohammed-Hossein Fard-Aghaie Ricardo Robles-Campos Roberto Brusadin Henrik Petrowsky Michael Linecker Arianeb Mehrabi Katrin Hoffmann Jun Li Asmus Heumann Roberto Hernandez-Alejandro Mauro Enrique Tun-Abraham Elio Jovine Matteo Serenari Bergthor Bjornsson Per Sandström Ruslan Alikhanov Mikhail Efanov Paolo Muiesan Andrea Schlegel Thomas M.van Gulik Pim B.Olthof Gregor Alexander Stavrou Lina Maria Serna-Higuita Alfred Königsrainer Silvio Nadalin | 2022 | Hepatobiliary Surgery and Nutrition2022，11，1： | 1 |
| 4 | Keeping track of all ongoing colorectal cancer trials using a mobile application:Usability and satisfaction results of the Dutch Colorectal Cancer Group Trials application显示文摘Background and Aim:Both the number and complexity of medical trials are increasing vastly.To facilitate easy access to concise trial information,a freely available mobile application including all ongoing clinical trials of the Dutch Colorectal Cancer Group(DCCG)was developed.The aim of this study was to investigate the use and user satisfaction over the first 2 years.Methods:The application was launched in January 2015 on iOS and Android platforms.Google Analytics was used to monitor anonymous user data up to February 2017.In addition,an online survey regarding the use and satisfaction among health-care professionals and research affiliates active in the field of colorectal cancer in the Netherlands was conducted.Results:A total of 6173 unique users were identified,of which 1822(30%)were from the Netherlands,representing a total of 16,065 and 10,987(68%)sessions,respectively.The median session duration per day was 01:47 min(IQR 0:51–03:03).The mobile application was mostly used on Monday,Tuesday,and Thursday,and the number of sessions was highest during the following time frames:12–13 pm(9%),17–18 pm(9%),and 13–14 pm(8%).Of 121 survey responses,most were medical doctors(47%),nurses(25%),or researchers(9%),working either in a teaching(40%),academic hospital(32%),or general hospital(19%).83%of all respondents rated the application 4 or higher for satisfaction on a 5-point scale.Highest reported reasons of the use were urgent trial inquiry(57%)and usage during multi-disciplinary meetings(49%).Conclusion:The DCCG Trials application is frequently used,and the majority of users is highly satisfied.Relevance for Patients:Clustering trial information into one platform,such as DCCG trials app,has shown to be useful for medical professionals treating patients with colorectal carcinoma in the Netherlands. | Joost Huiskens Michael S.Galek-Aldridge Jean-Michel Bakker Pim B.Olthof Thomas M.van Gulik Cornelis J.A.Punt Martijn G.H.van Oijen | 2018 | Journal of Clinical & Translational Research2018，4，3： | 1 |
| 5 | IL-23 and IL-17A are not involved in hepatic/ischemia reperfusion injury in mouse and man显示文摘Background:Hepatic ischemia and reperfusion(I/R)is common in liver surgery and transplantation and compromises postoperative liver function.Hepatic I/R injury is characterized by sterile inflammation that contributes to hepatocellular necrosis.Many immune cells and cytokines have been implicated in hepatic I/R injury.However,the role and relevance of IL-23 and IL-17A remains controversial in literature.Aim:To determine whether the IL-23/IL-17A signaling axis is activated in hepatic I/R using a triple-level experimental approach(in vitro,in vivo,and clinical).Methods:IL-23 and IL-17A were assayed by ELISA in the supernatant fractions of cultured murine(RAW 264.7)macrophages that were activated by supernatant fractions of necrotic cultured mouse(AML12)hepatocytes.Similarly,levels of these cytokines were determined in plasma samples and liver tissue of mice(N=85)subjected to partial(70%)liver I/R.Finally,IL-23 and IL-17A were assayed in plasma samples obtained from a controlled cohort of liver resection patients who were either subjected to I/R(N=27)or not(N=13).Results:Activated macrophages did not produce IL-23 in response to supernatant of necrotic AML12 hepatocytes.IL-23 and IL-17A were not elevated in mice subjected hepatic I/R and were not elevated in serum from patients subjected to I/R during liver resection.Conclusion:IL-23 and IL-17A are not involved in hepatic I/R injury in mouse and man.Relevance for patients:If IL-23 and IL-17A were to mediate hepatocellular injury following I/R,these cytokines would constitute potential therapeutic targets.Since this study has revealed that IL-23 and IL-17A do not play a role in hepatic I/R,other pathways and therapeutic targets should be considered when developing modalities aimed at reducing hepatic I/R injury. | Pim B.Olthof Rowan F.van Golen Megan J.Reiniers Milan Kos Lindy K.Alles Martinus A.Maas Joanne Verheij Thomas M.van Gulik Michal Heger | 2015 | Journal of Clinical & Translational Research2015，1，3： | 0 |
| 6 | Short-and long-term outcomes after hemihepatectomy for perihilar cholangiocarcinoma:does left or right side matter?显示文摘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 resection.Complications 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 resections.However,data on outcomes after right-sided or left-sided liver resections in PHC are scarce.Therefore,we aimed to investigate short-and long-term outcomes after left and right hemihepatectomy in patients with PHC.Methods:In this retrospective study,patients undergoing major liver resection for suspected PHC in a tertiary center between 2000-2018 were included.Patients 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 analysis.Results:A total of 178 patients undergoing hemihepatectomy for suspected PHC were analysed,including 76 left-sided and 102 right-sided resections.Overall 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 vs.and 38.2%after right-sided resection(P=0.553).Conclusions:Both short-and long-term outcomes between patients undergoing left and right hemihepatectomy for PHC were comparable.Post-hepatectomy liver failure was more common after right-sided resection. | 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 | 2021 | Hepatobiliary Surgery and Nutrition2021，10，2： | 0 |
| 7 | Functional assessment of liver regeneration after major hepatectomy显示文摘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 increase of volume (P<0.01). Conclusions: Functional regeneration of the remnant liver predominantly occurs during the first 5 days after resection. In case of severe complications, functional regeneration is delayed, in contrast to volume increase. | 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 | 2022 | Hepatobiliary Surgery and Nutrition2022，11，4： | 0 |
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