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Early tacrolimus exposure does not impact long-term outcomes after liver transplantation

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World Journal of Hepatology 2021年第3期13卷 362-374页

作者： mikel gastaca Patricia Ruiz Javier Bustamante Lorea Martinez-Indart Alberto Ventoso JoséRamón Fernandez Ibone Palomares mikel Prieto Milagros Testillano Patricia Salvador Maria Senosiain Maria Jesus Suárez Andres Valdivieso Department of HPB Surgery and Liver Transplantation Unit Hospital Universitario CrucesBilbao 48903Spain Department of Hepatology Unit Hospital Universitario CrucesBilbao 48903Spain Department of Bioinformatics and Statistics Platform Biocruces Bizkaia Health Research InstituteHospital Universitario CrucesBilbao 48903Spain

BACKGROUND Tacrolimus trough levels(TTL)during the first weeks after liver transplantation(LT)have been related with long-term renal function and hepatocellular carcinoma recurrence.Nevertheless,the significance of trough levels of tacrolimus during the early post-transplant period for the long-term outcome is under debate AIM To evaluate the effect of TTL during the first month on the long-term outcomes after LT.METHODS One hundred fifty-five LT recipients treated de novo with once-daily tacrolimus were retrospectively studied.Patients with repeated LT or combined transplantation were excluded as well as those who presented renal dysfunction prior to transplantation and/or those who needed induction therapy.Patients were classified into 2 groups according to their mean TTL within the first month after transplantation:≤10(n=98)and>10 ng/mL(n=57).Multivariate analyses were performed to assess risk factors for patient mortality.RESULTS Mean levels within the first month post-transplant were 7.4±1.7 and 12.6±2.2 ng/mL in the≤10 and>10 groups,respectively.Donor age was higher in the high TTL group 62.9±16.8 years vs 45.7±17.5 years(P=0.002)whilst mycophenolate-mofetil was more frequently used in the low TTL group 32.7%vs 15.8%(P=0.02).Recipient features were generally similar across groups.After a median follow-up of 52.8 mo(range 2.8-81.1),no significant differences were observed in:Mean estimated glomerular filtration rate(P=0.69),hepatocellular carcinoma recurrence(P=0.44),de novo tumors(P=0.77),new-onset diabetes(P=0.13),or biopsy-proven acute rejection rate(12.2%and 8.8%,respectively;P=0.50).Eighteen patients died during the follow-up and were evenly distributed across groups(P=0.83).Five-year patient survival was 90.5%and 84.9%,respectively(P=0.44),while 5-year graft survival was 88.2%and 80.8%,respectively(P=0.42).Early TTL was not an independent factor for patient mortality in multivariate analyses.CONCLUSION Differences in tacrolimus levels restricted to the first month after transplant did not result in sig

关键词： Liver transplantation Tacrolimus levels Prolonged released tacrolimus Oncedaily tacrolimus Renal function Survival Outcomes

Minimally invasive liver resection for huge(≥10cm)tumors:an international multicenter matched cohort study with regression discontinuity analyses

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Hepatobiliary Surgery and Nutrition 2021年第5期10卷 587-597,I0001-I0003页

作者： Tan-To Cheung Xiaoying Wang Mikhail Efanov Rong Liu David Fuks Gi-Hong Choi Nicholas LSyn Charing CChong Iswanto Sucandy Adrian KHChiow Marco VMarino mikel gastaca Jae Hoon Lee TPeter Kingham Mathieu D’Hondt Sung Hoon Choi Robert PSutcliffe Ho-Seong Han Chung Ngai Tang Johann Pratschke Roberto ITroisi Brian KPGoh International Robotic and Laparoscopic Liver Resection Study Group Collaborators Department of Surgery Queen Mary HospitalThe University of Hong KongHong KongChina Department of Liver Surgery and Transplantation Liver Cancer InstituteZhongshan HospitalFudan UniversityShanghaiChina Department of Hepato-Pancreato-Biliary Surgery Moscow Clinical Scientific CenterMoscowRussia Faculty of Hepatopancreatobiliary Surgery The First Medical Center of Chinese People’s Liberation Army(PLA)General HospitalBeijingChina Department of Digestive Oncologic and Metabolic SurgeryInstitute Mutualiste MontsourisUniversite Paris DescartesParisFrance Division of Hepatopancreatobiliary Surgery Department of SurgerySeverance HospitalYonsei University College of MedicineSeoulKorea Department of Hepatopancreatobiliary and Transplant Surgery Singapore General Hospital and Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore Division of Hepatobiliary and Pancreatic Surgery Department of SurgeryPrince of Wales HospitalThe Chinese University of Hong KongNew TerritoriesHong KongChina AdventHealth Tampa Digestive Health InstituteTampaFLUSA Hepatopancreatobiliary Unit Department of SurgeryChangi General HospitalSingaporeSingapore General Surgery Department Azienda Ospedaliera Ospedali Riuniti Villa Sofia-CervelloPalermoItaly Oncologic Surgery Department P.Giaccone University HospitalPalermoItaly Hepatobiliary Surgery and Liver Transplantation Unit Biocruces Bizkaia Health Research InstituteCruces University HospitalUniversity of the Basque CountryBilbaoSpain Department of Surgery Division of Hepato-Biliary and Pancreatic SurgeryAsan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea Department of Surgery Memorial Sloan Kettering Cancer CenterNew YorkNew YorkUSA Department of Digestive and Hepatobiliary/Pancreatic Surgery Groeninge HospitalKortrijkBelgium Department of General Surgery CHA Bundang Medical CenterCHA University School of MedicineSeongnamKorea Department of Hepatopancreatobiliary and Liver Transplant Surgery University Ho

Background:The application and feasibility of minimally invasive liver resection(MILR)for huge liver tumours(≥10 cm)has not been well documented.Methods:Retrospective analysis of data on 6,617 patients who had MILR for liver tumours were gathered from 21 international centers between 2009-2019.Huge tumors and large tumors were defined as tumors with a size≥10.0 cm and 3.0-9.9 cm based on histology,respectively.1:1 coarsened exact-matching(CEM)and 1:2 Mahalanobis distance-matching(MDM)was performed according to clinically-selected variables.Regression discontinuity analyses were performed as an additional line of sensitivity analysis to estimate local treatment effects at the 10-cm tumor size cutoff.Results:Of 2,890 patients with tumours≥3 cm,there were 205 huge tumors.After 1:1 CEM,174 huge tumors were matched to 174 large tumors;and after 1:2 MDM,190 huge tumours were matched to 380 large tumours.There was significantly and consistently increased intraoperative blood loss,frequency in the application of Pringle maneuver,major morbidity and postoperative stay in the huge tumour group compared to the large tumour group after both 1:1 CEM and 1:2 MDM.These findings were reinforced in RD analyses.Intraoperative blood transfusion rate and open conversion rate were significantly higher in the huge tumor group after only 1:2 MDM but not 1:1 CEM.Conclusions:MILR for huge tumours can be safely performed in expert centers It is an operation with substantial complexity and high technical requirement,with worse perioperative outcomes compared to MILR for large tumors,therefore judicious patient selection is pivotal.

关键词： Minimally invasive liver resection(MILR) robotic-assisted liver resection huge tumours hepatocellular carcinoma laparoscopic liver resection

Robotic versus laparoscopic liver resection for huge (≥10 cm) liver tumors: an international multicenter propensity-score matched cohort study of 799 cases

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Hepatobiliary Surgery and Nutrition 2023年第2期12卷 205-215,I0005页

作者： Tan-To Cheung Rong Liu Federica Cipriani Xiaoying Wang Mikhail Efanov David Fuks Gi-Hong Choi Nicholas L.Syn Charing C.N.Chong Fabrizio Di Benedetto Ricardo Robles-Campos Vincenzo Mazzaferro Fernando Rotellar Santiago Lopez-Ben James O.Park Alejandro Mejia Iswanto Sucandy Adrian K.H.Chiow Marco V.Marino mikel gastaca Jae Hoon Lee TPeter Kingham Mathieu D’Hondt Sung Hoon Choi Robert P.Sutcliffe Ho-Seong Han Chung-Ngai Tang Johann Pratschke Roberto I.Troisi Go Wakabayashi Daniel Cherqui Felice Giuliante Davit L.Aghayan Bjorn Edwin Olivier Scatton Atsushi Sugioka Tran Cong Duy Long Constantino Fondevila Mohammad Abu Hilal Andrea Ruzzenente Alessandro Ferrero Paulo Herman Kuo-Hsin Chen Luca Aldrighetti Brian K.P.Goh International robotic and laparoscopic liver resection study group investigators Department of Surgery Queen Mary HospitalThe University of Hong KongHong Kong SARChina Faculty of Hepatopancreatobiliary Surgery The First Medical Center of Chinese People’s Liberation Army(PLA)General HospitalBeijingChina Hepatobiliary Surgery Division IRCCS San Raffaele HospitalMilanItaly Department of Liver Surgery and Transplantation Liver Cancer InstituteZhongshan HospitalFudan UniversityShanghaiChina Department of Hepato-Pancreato-Biliary Surgery Moscow Clinical Scientific CenterMoscowRussia Department of Digestive Oncologic and Metabolic SurgeryInstitute Mutualiste MontsourisUniversite Paris DescartesParisFrance Division of Hepatopancreatobiliary Surgery Department of SurgerySeverance HospitalYonsei University College of MedicineSeoulKorea Department of Hepatopancreatobiliary and Transplant Surgery Singapore General Hospital and Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore Division of Hepatobiliary and Pancreatic Surgery Department of SurgeryPrince of Wales HospitalThe Chinese University of Hong KongHong Kong SARChina HPB Surgery and Liver Transplant Unit University of Modena and Reggio EmiliaModenaItaly Department of General Visceral and Transplantation SurgeryClinic and University Hospital Virgen de la ArrixacaIMIB-ARRIXACAMurciaSpain HPB Surgery Hepatology and Liver TransplantationFondazione IRCCS Istituto Nazionale Tumori di MilanoMilanItaly HPB and Liver Transplant Unit Department of General SurgeryClinica Universidad de NavarraUniversidad de NavarraPamplonaSpain Institute of Health Research of Navarra(IdisNA) PamplonaSpain Hepatobiliary and Pancreatic Surgery Unit Department of SurgeryDr.Josep Trueta HospitalIdIBGiGironaSpain Hepatobiliary Surgical Oncology Department of SurgeryUniversity of Washington Medical CenterSeattleWAUSA The Liver Institute Methodist Dallas Medical CenterDallasTXUSA AdventHealth Tampa Digestive Health InstituteTampaFLUSA Hepatopancreatobiliary Unit Department of SurgeryChangi General

Background:The use of laparoscopic(LLR)and robotic liver resections(RLR)has been safely performed in many institutions for liver tumours.A large scale international multicenter study would provide stronger evidence and insight into application of these techniques for huge liver tumours≥10 cm.Methods:This was a retrospective review of 971 patients who underwent LLR and RLR for huge(≥10 cm)tumors at 42 international centers between 2002-2020.Results:One hundred RLR and 699 LLR which met study criteria were included.The comparison between the 2 approaches for patients with huge tumors were performed using 1:3 propensity-score matching(PSM)(73 vs.219).Before PSM,LLR was associated with significantly increased frequency of previous abdominal surgery,malignant pathology,liver cirrhosis and increased median blood.After PSM,RLR and LLR was associated with no significant difference in key perioperative outcomes including media operation time(242 vs.290 min,P=0.286),transfusion rate rate(19.2%vs.16.9%,P=0.652),median blood loss(200 vs.300 mL,P=0.694),open conversion rate(8.2%vs.11.0%,P=0.519),morbidity(28.8%vs.21.9%,P=0.221),major morbidity(4.1%vs.9.6%,P=0.152),mortality and postoperative length of stay(6 vs.6 days,P=0.435).Conclusions:RLR and LLR can be performed safely for selected patients with huge liver tumours with excellent outcomes.There was no significant difference in perioperative outcomes after RLR or LLR.

关键词： Laparoscopic liver resection(LLR) robotic liver resection(RLR) hepatocellular carcinoma colorectal liver metastases huge

Thiosemicarbazones Synthesized from Acetophenones: Tautomerism, Spectrometric Data, Reactivity and Theoretical Calculations

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International Journal of Analytical Mass Spectrometry and Chromatography 2019年第2期7卷 19-34页

作者： Belén gastaca Hernán Rubén Sánchez Fiorella Menestrina Maricel Caputo María de las Mercedes Schiavoni Jorge Javier Pedro Furlong Laboratory of Organic Compounds Studies (LADECOR) Department of Chemistry Facultad de Ciencias Exactas National University of La Plata La Plata Argentina Institute of Physics of Liquids and Biological Systems (IFLySIB CONICET) National University of La Plata La Plata Argentina Laboratory of Research and Development of Analytical Methods (LIDMA) Department of Chemistry Facultad de Ciencias Exactas National University of La Plata La Plata Argentina

Tautomeric forms of Thiosemicarbazones have been investigated by spectrometric methods, their chemical reactivity and theoretical calculations of the relative tautomers stabilities. The mass spectral fragmentation of thiosemicarbazones synthesized from acetophenones has been studied by CG/MS. The analysis of the corresponding spectra shows not only the regular fragmentation mechanisms but homolytic ruptures from even-electron species. 1H NMR spectra exhibit signals for the most intense open thioketo tautomeric structure, although when using TFA a ring structure is observed in the corresponding tautomeric equilibrium. Density Functional Theory calculations (DFT) also provide evidence to support the experimental observations by GC-MS and 1H NMR. Methylation reactions give support to the occurrence of the thioenol tautomeric form which would be the second most abundant according to the Density Functional Theoretical calculations.

关键词： Thiosemicarbazones Tautomerism MS NMR Theoretical Calculations

GC/MS Analyses of Thiosemicarbazones Synthesized from Acetophenones: Thermal Decay and Mass Spectra Features

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International Journal of Analytical Mass Spectrometry and Chromatography 2015年第1期3卷 1-13页

作者： Belén gastaca Gastón Galletti Hernán Rubén Sánchez Reinaldo Pis Diez María de las Mercedes Schiavoni Jorge Javier Pedro Furlong Laboratorio de Estudio de Compuestos Orgánicos (LADECOR) Departamento de Química Facultad de Ciencias Exactas Universidad Nacional de La Plata La Plata Argentina CEQUINOR Centro de Química Inorgánica (CONICET UNLP) Facultad de Ciencias Exactas UNLP La Plata Argentina

The mass spectral fragmentation of thiosemicarbazones synthesized from acetophenones has been studied by CG/MS. These carbonyl compounds exhibit chromatographic peaks which are not observed in aliphatic analogues or those synthesized from aldehydes. The analysis of the corresponding spectra has allowed structural assignment to the dimerization of gas phase neutral fragments. Theoretical calculations (DFT level) also provide evidence to support the experimental observations.

关键词： Thiosemicarbazones Mass Spectrometry Analyses Dimerization of Thiosemicarbazones