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Meso-Rex bypass for the management of extrahepatic portal vein obstruction in adults(with video)

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Hepatobiliary & Pancreatic Diseases International 2022年第1期21卷 25-32页

作者： Martin Brichard samuele iesari Jan Lerut Raymond Reding Pierre Goffette Laurent Coubeau Service de Chirurgie et Transplantation Abdominale Cliniques Universitaires Saint-LucUniversitéCatholique de Louvain10 Avenue HippocrateBrussels 1200Belgium Pôle de Chirurgie Expérimentale et Transplantation Institut de Recherche Expérimentale et CliniqueUniversitéCatholique de LouvainBrusselsBelgium Department of Clinical Sciences and Applied Biotechnology University of L’AquilaL’AquilaItaly Department of General Surgery and Kidney Transplantation Fondazione IRCCS Ca’Granda Ospedale Maggiore PoliclinicoMilanItaly Service de Radiologie et Imagerie médicale Cliniques Universitaires Saint-LucUniversitéCatholique de LouvainBrusselsBelgium

Background:Extrahepatic portal vein obstruction(EHPVO)results in severe portal hypertension(PHT)leading to severely compromised quality of ***,pharmacological and endoscopic management is unable to solve this *** hepatic portal flow using meso-Rex bypass(MRB)may solve *** procedure,uncommon in adult patients,is considered the treatment of choice for EHPVO in ***:From 1997 to 2018,8 male and 6 female adults,with a median age of 51 years(range 22-66)underwent MRB procedure for EHPVO at the University Hospitals Saint-Luc in Brussels,***-toms of PHT were life altering in all but one patient and consisted of repetitive gastro-intestinal bleedings,sepsis due to portal biliopathy,and/or severe abdominal *** surgical technique consisted in interposition of a free venous graft or of a prosthetic graft between the superior mesenteric vein and the Rex recess of the left portal ***:Median operative time was 500 min(range 300-730).Median follow-up duration was 22 months(range 2-169).One patient died due to hemorrhagic shock following percutaneous transluminal interven-tion for early graft *** morbidity,defined as Clavien-Dindo score≥III,was 35.7%(5/14).Shunt patency at last follow-up was 64.3%(9/14):85.7%(6/7)of pure venous grafts and only 42.9%(3/7)of prosthetic *** relief was achieved in 85.7%(12/14)who became asymptomatic after ***:Adult EHPVO represents a difficult clinical condition that leads to severely compromised quality of life and possible life-threatening *** such patients,MRB represents the only and last resort to restore physiological portal vein *** successful in a majority of patients,this procedure is associated with major morbidity and mortality and should be done in tertiary centers expe-rienced with vascular liver surgery to get the best results.

关键词： Meso-Rex bypass Extrahepatic portal vein obstruction Extrahepatic portal hypertension Portal vein thrombosis Surgical procedure

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免疫抑制和肝移植

Engineering 2023年第2期21卷 175-187,M0007页

作者： Jan Lerut samuele iesari Institut de Recherche Expérimentale et Clinique Universitécatholique de LouvainBrussels 1200Belgium General Surgery and Kidney Transplantation Fondazione IRCCS Ca’Granda Ospedale Maggiore PoliclinicoMilan 20122Italy

完美的手术技术和充分的免疫抑制是确保最佳移植物和患者存活的关键。不同药物的可用性导致了一些通常由行业驱动的不同类型的临床试验,以发现理想的免疫抑制方案。然而,大量且概念不同的研究设计未能明确定义最佳免疫抑制方案。基于钙... 详细信息

完美的手术技术和充分的免疫抑制是确保最佳移植物和患者存活的关键。不同药物的可用性导致了一些通常由行业驱动的不同类型的临床试验,以发现理想的免疫抑制方案。然而,大量且概念不同的研究设计未能明确定义最佳免疫抑制方案。基于钙调神经磷酸酶抑制剂他克莫司、抗代谢药物霉酚酸酯或硫唑嘌呤和短期类固醇(除了可能的诱导外)为基础的三联免疫抑制方案仍然是目前公认的肝移植标准免疫抑制方案。然而,鉴于排斥定义的变化、免疫抑制负荷的定制以及由于慢性免疫抑制引起的长期副作用,未来的试验最好包括一个以上的终点,而不是急性T细胞介导的急性排斥(a-TCMR)或肾衰竭。相反,需要一个涵盖患者和移植物存活率以及急性和慢性排斥反应发生率的综合终点。这些免疫现象应根据一系列长期的生物学和组织学随访进行检查。临床相关a-TCMR的诊断和治疗应基于综合生物学、免疫学和组织病理学发现。这两个要素对于朝着更谨慎的免疫抑制处理和有利于临床操作耐受性的方向发展至关重要。

关键词：免疫抑制方案抗代谢药物急性排斥移植物硫唑嘌呤组织病理学临床试验肝移植

Advancing immunosuppression in liver transplantation: A narrative review

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Hepatobiliary & Pancreatic Diseases International 2024年第5期23卷 441-448页

作者： samuele iesari Francesca Laura Nava Ilaria Elena Zais Laurent Coubeau Mariano Ferraresso Evaldo Favi Jan Lerut General Surgery and Kidney Transplantation Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico15 Via della Commenda20122 MilanItaly Institut de Recherche Expérimentale et Clinique Universitécatholique de Louvain10 Avenue Hippocrate1200 BrusselsBelgium Service de Chirurgie et Transplantation Abdominale Cliniques Universitaires Saint-Luc55 Avenue Hippocrate1200 BrusselsBelgium Department of Clinical Sciences and Community Health Universitàdegli Studi di Milano19 Via della Commenda20122 MilanItaly

Immunosuppression is essential to ensure recipient and graft survivals after liver transplantation(LT). However, our understanding and management of the immune system remain suboptimal. Current immunosuppressive therapy cannot selectively inhibit the graft-specific immune response and entails a significant risk of serious side effects, i.e., among others, de novo cancers, infections, cardiovascular events, renal failure, metabolic syndrome, and late graft fibrosis, with progressive loss of graft function. Pharmacological research, aimed to develop alternative immunosuppressive agents in LT, is behind other solidorgan transplantation subspecialties, and, therefore, the development of new compounds and strategies should get priority in LT. The research trajectories cover mechanisms to induce T-cell exhaustion, to inhibit co-stimulation, to mitigate non-antigen-specific inflammatory response, and, lastly, to minimize the development and action of donor-specific antibodies. Moreover, while cellular modulation techniques are complex, active research is underway to foster the action of T-regulatory cells, to induce tolerogenic dendritic cells, and to promote the function of B-regulatory cells. We herein discuss current lines of research in clinical immunosuppression, particularly focusing on possible applications in the LT setting.

关键词： Liver transplantation Immunosuppression Drug development Long-term results Clinical operational tolerance

Insights in living-donor liver transplantation associated with two-stage total hepatectomy:First case in neuroendocrine tumor metastases and functional assessment techniques

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Hepatobiliary & Pancreatic Diseases International 2022年第4期21卷 392-395页

作者： Laurent Coubeau samuele iesari Paulina Henry Philippe D’Abadie Aude Vanbuggenhout Raymond Reding aTransplantation Abdominale Cliniques Universitaires Saint-LucUniversite catholique de LouvainBrusselsBelgium Pole de Chirurgie Experimentale et Transplantation Institut de Recherche Experimentale et CliniqueUniversite catholique de LouvainBrusselsBelgium Department of Biotechnological and Applied Clinical Sciences University of L’AquilaL’AquilaItaly Service d’anatomo-pathologie Cliniques Universitaires Saint-LucUniversite catholique de LouvainBrusselsBelgium Service de medecine nucleaire Cliniques Universitaires Saint-LucUniversite catholique de LouvainBrusselsBelgium

To the Editor:While organ shortage commonly dooms patients on waiting list,alternative options as living-donor liver transplantation(LDLT)are assiduously *** principles of liver surgery rule LDLT:there must be suffici... 详细信息

关键词： donor liver surgery

Hepatocellular carcinoma recurrence after acute liver allograft rejection treatment: A multicenter European experience

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Hepatobiliary & Pancreatic Diseases International 2019年第6期18卷 517-524页

作者： Quirino Lai samuele iesari Armin Finkenstedt Maria Hoppe-Lotichius Maxime Foguenne Konrad Lehner Gerd Otto Jan Lerut Starzl Unit of Abdominal Transplantation University Hospitals Saint LucUniversitécatholique LouvainBrusselsBelgium Hepato-biliary Surgery and Liver Transplantation Unit Sapienza University of RomeUmberto I HospitalRomeItaly Department of Bio-technological and Applied Clinical Sciences University of L’AquilaL’AquilaItaly Department of Internal Medicine I Innsbruck Medical UniversityInnsbruckAustria Department of Transplantation and Hepatobiliary Surgery University of MainzMainzGermany

Background:During the last decades,several risk factors for the recurrence of hepatocellular carcinoma(HCC)after liver transplantation(LT)have been ***,the impact of two important drivers of oncogenesis,namely the immunosuppression and the treatment of acute cellular rejection(ACR)have been marginally *** study aimed at investigating the impact of ACR treatment on the incidence of tumor recurrence in a large European HCC-LT ***:Seven hundred and eighty-one adult patients transplanted between February 1,1985 and June 30,2016 were retrospectively *** propensity score match,116 patients treated for ACR using steroid boluses were compared with 115 patients who did not present any ACR or a histologic but clinical irrelevant ***:Steroid boluses treated patients had a 18-fold higher overall incidence of HCC recurrence than those non-treated patients(16.4%vs.0.9%;P<0.0001).At multivariate Cox regression analysis,steroid boluses used to treat ACR were an independent risk factor for HCC recurrence(HR=14.2;95%CI:1.8–110.4;P=0.010).Conclusions:The decision to treat ACR as well as to reinforce immunosuppression load should be cautiously taken in view of the presented *** studies are needed to further elucidate the clinical impact of immunosuppression on HCC recurrence after transplantation.

关键词： Liver transplantation Recurrence Steroid biopsy Acute rejection

Secondary non-resectable liver tumors:A single-center living-donor and deceased-donor liver transplantation case series

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Hepatobiliary & Pancreatic Diseases International 2019年第5期18卷 412-422页

作者： Jan Lerut samuele iesari Gaetan Vandeplas Tiziana Fabbrizio Kevin Ackenine Milton Eduardo Inostroza Nunez Mina Komuta Laurent Coubeau Olga Ciccarelli Eliano Bonaccorsi-Riani BrusselsBelgium Department of Biotechnological and Applied Clinical Sciences University of L’AquilaL’AquilaItaly Starzl Abdominal Transplant Unit University Hospitals Saint-LucUniversité catholique de LouvainBrusselsBelgium Hepatobilio-pancreatic Unit Las Higueras HospitalTalcahuanoChile Department of Pathology University Hospitals Saint-LucUniversite catholique de LouvainBrusselsBelgium

Background: During the last decades, deceased-donor liver transplantation (DDLT) has gained a place in the therapeutic algorithm of well-selected patients harbouring non-resectable secondary liver tumors. Living-donor LT (LDLT) might represent a valuable means to further expand this indication for LT. Methods: Between 1985 and 2016, twenty-two adults were transplanted because of neuroendocrine ( n = 18, 82%) and colorectal metastases ( n = 4, 18%);50% received DDLT and 50% LDLT. In LDLT, 4 (36%) right and 7 (64%) left grafts were used;the median graft-to-recipient-weight ratios (GRWR) were 1.03%(IQR 0.86%- 1.30%) and 0.59%(IQR 0.51%- 0.91%), respectively. Median post-LT follow-up was 64 months (IQR 17–107) in the DDLT group and 40 months (IQR 35–116) in the LDLT group. DDLT and LDLT recipients were compared in terms of overall survival, graft survival, postoperative complications and recurrence. Results: The 1- and 5-year actuarial patient survivals were 82% and 55% after DDLT, 100% and 100% after LDLT, respectively ( P < 0.01). One- and 5-year actuarial graft survivals were 73% and 36% after DDLT, 91% and 91% after LDLT ( P < 0.01). The outcomes of right or left LDLT were comparable. Donor hepatectomy proved safe, and one donor experienced a Clavien IIIb complication. Bilirubin peak was significantly lower after left hepatectomy compared with that after right hepatectomy [1.3 (IQR 1.2–2.2) vs. 3.3 (IQR 2.3–5.2) mg/dL;P = 0.02]. Conclusions: The more recent LDLT series compared favorably to our DDLT series in the treatment of secondary liver malignancies. The absence of portal hypertension and the use of smaller left grafts make recipient and donor surgeries safe. The safety of the procedures and lack of interference with the scarce allograft pool are expected to lead to a more frequent use of LDLT in the field of transplant oncology.

关键词： Colorectal cancer Living-donor liver transplantation Liver metastasis Neuroendocrine tumor Secondary liver tumors

Adult-to-adult living-donor liver transplantation: The experience of the Université catholique de Louvain

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Hepatobiliary & Pancreatic Diseases International 2019年第2期18卷 132-142页

作者： samuele iesari Milton Eduardo Inostroza Nú?ez Juan Manuel Rico Juri Olga Ciccarelli Eliano Bonaccorsi-Riani Laurent Coubeau Pierre-Fran?ois Laterre Pierre Goffette Chantal De Reyck Beno?t Lengelé Pierre Gianello Jan Lerut Starzl Abdominal Transplant Unit Cliniques Universitaires Saint-Luc Institut de Recherche Expérimentale et Clinique Université catholique de Louvain Department of Biotechnological and Applied Clinical Sciences University of L’Aquila Hepatobiliopancreatic Unit Las Higueras Hospital Cirugía de Trasplantes Centro Médico Imbanaco Department of Intensive Care Cliniques Universitaires Saint-Luc Université catholique de Louvain Department of Radiology Cliniques Universitaires Saint-Luc Université catholique de Louvain Department of Plastic and Reconstructive Surgery Cliniques Universitaires Saint-Luc Université catholique de Louvain P?le de Chirurgie Expérimentale et Transplantation Institut de Recherche Expérimentale et Clinique Université catholique de Louvain

Background: Liver transplantation is the treatment for end-stage liver diseases and well-selected malignancies. The allograft shortage may be alleviated with living donation. The initial UCLouvain experience of adult living-donor liver transplantation(LDLT) is presented. Methods: A retrospective analysis of 64 adult-to-adult LDLTs performed at our institution between 1998 and 2016 was conducted. The median age of 29(45.3%) females and 35(54.7%) males was 50.2 years(interquartile range, IQR 32.9–57.5). Twenty-two(34.4%) recipients had no portal hypertension. Three(4.7%) patients had a benign and 33(51.6%) a malignant tumor [19(29.7%) hepatocellular cancer, 11(17.2%) secondary cancer and one(1.6%) each hemangioendothelioma, hepatoblastoma and embryonal liver sarcoma]. Median donor and recipient follow-ups were 93 months(IQR 41–159) and 39 months(22–91), respectively. Results: Right and left hemi-livers were implanted in 39(60.9%) and 25(39.1%) cases, respectively. Median weights of right-and left-liver were 810 g(IQR 730–940) and 454 g(IQR 394–534), respectively. Graft-to-recipient weight ratios(GRWRs) were 1.17%(right, IQR 0.98%-1.4%) and 0.77%(left, 0.59%-0.95%). One-and five-year patient survivals were 85% and 71%(right) vs. 84% and 58%(left), respectively. Oneand five-year graft survivals were 74% and 61%(right) vs. 76% and 53%(left), respectively. The patient and graft survival of right and left grafts and of very small( < 0.6%), small(0.6%–0.79%) and large( ≥0.8%) GRWR were similar. Survival of very small grafts was 86% and 86% at 3-and 12-month. No donor died while five(7.8%) developed a Clavien–Dindo complication IIIa, IIIb or IV. Recipient morbidity consisted mainly of biliary and vascular complications; three(4.7%) recipients developed a small-for-size syndrome according to the Kyushu criteria. Conclusions: Adult-to-adult LDLT is a demanding procedure that widens therapeutic possibilities of many hepatobiliary diseases. The donor procedure can be done safely

关键词： Liver transplantation Living-donor Hepatocellular cancer Secondary liver tumor Small-for-size syndrome Small-for-size graft

Generating soil thickness maps by means of geomorphological-empirical approach and random forest algorithm in Wanzhou County,Three Gorges Reservoir

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Geoscience Frontiers 2023年第2期14卷 47-58页

作者： Ting Xiao samuele Segoni Xin Liang Kunlong Yin Nicola Casagli Key Laboratory of Metallogenic Prediction of Nonferrous Metals and Geological Environment Monitoring Ministry of EducationSchool of Geosciences and Info-PhysicsCentral South UniversityChangsha 410083China Faculty of Engineering China University of GeosciencesWuhan 430074China Department of Earth Sciences University of FlorenceFlorence 50121Italy

Soil thickness,intended as depth to bedrock,is a key input parameter for many environmental ***,it is often difficult to obtain a reliable spatially exhaustive soil thickness map in widearea applications,and existing prediction models have been extensively applied only to test sites with shallow soil *** study addresses this limitation by showing the results of an application to a section of Wanzhou County(Three Gorges Reservoir Area,China),where soil thickness varies from 0 to40 *** different approaches were used to derive soil thickness maps:a modified version of the geomorphologically indexed soil thickness(GIST)model,purposely customized to better account for the peculiar setting of the test site,and a regression performed with a machine learning algorithm,i.e.,the random forest,combined with the geomorphological parameters of GIST(GIST-RF).Additionally,the errors of the two models were quantified,and validation with geophysical data was carried *** results showed that the GIST model could not fully contend with the high spatial variability of soil thickness in the study area:the mean absolute error was 10.68 m with the root-mean-square error(RMSE)of 12.61 m,and the frequency distribution residuals showed a tendency toward *** contrast,GIST-RF returned a better performance with the mean absolute error of 3.52 m and RMSE of 4.56 *** derived soil thickness map could be considered a critical fundamental input parameter for further analyses.

关键词： Soil thickness Soil thickness mapping Geomorphologically indexed soil thickness Random forest

Altered pattern of tumor necrosis factor-alpha production in peripheral blood monocytes from Crohn's disease

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World Journal of Gastroenterology 2016年第41期22卷 9117-9126页

作者： Claudia Loganes Alessia Pin samuele Naviglio Martina Girardelli Anna Monica Bianco Stefano Martelossi Alberto Tommasini Elisa Piscianz Department of Medicine Surgery and Health Sciences University of Trieste Department of Pediatrics Institute for Maternal and Child Health IRCCS "Burlo Garofolo"

AIM To evaluate the inflammatory state in Crohn's disease(CD) patients and correlate it with genetic background and microbial *** By means of flow cytometry, production of tumor necrosis factor-alpha(TNF-α) was measured in peripheral blood monocytes from patients suffering from CD, ulcerative colitis(UC) and in healthy subjects after stimulation of the NOD2 and TLR pathways. CD patients were genotyped for the three most common NOD2 variants(R702W, G908 R and L1007Pfs*2) and basal production of TNF-α was correlated to NOD2 genotype. Also, production of TNF-α was correlated to plasmatic levels of LPS Binding Protein(LBP), soluble(s) CD14 and to the activity state of the *** The patients with CD were characterized by a significantly higher monocyte basal expression of TNF-αcompared with healthy subjects and UC patients, and after stimulation with Pam3CSK4(ligand of TLR2/1) and MDP-L18(ligand of NOD2) this difference was maintained, while other microbial stimuli(LPS, ligand of TLR4 and Poly I:C, ligand of TLR3) induced massive activation in CD monocytes as well as in UC and in healthy control cells. There was no significant difference in the production of TNF- α between patients who carried CD-associated heterozygous or homozygous variants in NOD2 and patients with wild type NOD2 genotype. Although serum LBP levels have been shown to correlate positively with the state of activity of the disease, TNF-α production did not show a clear correlation with either LBP or s CD14 levels in plasma. Moreover, no clear correlation was seen between TNF-α production and activity indices in either CD or *** Peripheral monocytes from CD express higher basal and stimulated TNF-α than controls, regardless of NOD2 genotype and without a clear correlation with disease activity.

关键词： Crohn’s disease Ulcerative colitis Tumor necrosis factor-α NOD2 variants Toll like receptors Dysbiosis Activity index LPS-binding protein