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Background: Alagille syndrome (ALGS) is a multisystem disorder, characterized by cholestasis. Existing outcome data are largely derived from tertiary centers and real-world data are lacking. This study aimed to elucidate the natural history of liver disease in a contemporary, international, cohort of children with ALGS. Methods: Multicenter retrospective study of children with a clinically and/or genetically confirmed ALGS diagnosis, born Jan-1997 - Aug-2019. Native liver survival (NLS) and event-free survival rates were assessed. Cox models were constructed to identify early biochemical predictors of clinically evident portal hypertension (CEPH) and NLS. Results: 1433 children (57% male) from 67 centers in 29 countries were included. 10 and 18-years NLS rates were 54.4% and 40.3%. By 10 and 18-years, 51.5% and 66.0% of ALGS children experienced ≥1 adverse liver-related event (CEPH, transplant or death). Children (>6 and ≤12 months) with median total bilirubin (TB) levels between ≥5.0 and <10.0 mg/dL had a 4.1-fold (95% CI 1.6 - 10.8) and those ≥10.0 mg/dL had an 8.0-fold (95% CI 3.4 - 18.4) increased risk of developing CEPH compared with those <5.0 mg/dL. Median TB levels between ≥5.0 and <10.0 mg/dL and >10.0 mg/dL were associated with a 4.8 (95% CI 2.4 - 9.7) and 15.6 (95% CI 8.7 - 28.2) increased risk of transplantation relative to <5.0 mg/dL. Median TB <5.0 mg/dL were associated with higher NLS rates relative to ≥5.0 mg/dL, with 79% reaching adulthood with native liver (p<0.001). Conclusions: In this large international cohort of ALGS, only 40.3% of children reach adulthood with their native liver. A TB <5.0 mg/dL between 6-and-12-months of age is associated with better hepatic outcomes. These thresholds provide clinicians with an objective tool to assist with clinical decision-making and in the evaluation of novel therapies.

Translational regulation is of paramount importance for proteome remodeling during stem cell differentiation at both the global and the transcript-specific levels. In this study, we characterized translational remodeling during hepatogenic differentiation of induced pluripotent stem cells (iPSCs) by polysome profiling. We demonstrate that protein synthesis increases during exit from pluripotency and is then globally repressed during later steps of hepatogenic maturation. This global downregulation of translation is accompanied by a decrease in the abundance of protein components of the translation machinery, which involves a global reduction in translational efficiency of terminal oligopyrimidine tract (TOP) mRNA encoding translation-related factors. Despite global translational repression during hepatogenic differentiation, key hepatogenic genes remain efficiently translated, and the translation of several transcripts involved in hepatospecific functions and metabolic maturation is even induced. We conclude that, during hepatogenic differentiation, a global decrease in protein synthesis is accompanied by a specific translational rewiring of hepatospecific transcripts.

Les néoplasies neuroendocrines sont des cancers dont la prévalence et l’incidence sont en constante augmentation. Ces tumeurs présentent entre elles des différences importantes, notamment d’un point de vue pronostique. Les facteurs pronostiques les plus importants sont de nature histomorphologiques, à savoir le grade de prolifération déterminé par le Ki67 et le degré de différenciation. La localisation, le stade TNM, l’âge et l’indice de performance du patient au diagnostic sont autant d’autres facteurs ayant un impact sur la survie. Les principaux biomarqueurs disponibles en pratique clinique présentent plusieurs limitations. L’imagerie fonctionnelle, par 68Ga-DOTA-NOC/TATE/TOC et PET-FDG, joue un rôle important dans la stratification du risque. Plusieurs biomarqueurs circulants et tissulaires sont à l’étude; à l’avenir, ils pourraient permettre une meilleure appréciation du risque et aider à la stratégie thérapeutique.

De prevalentie en de incidentie van neuro-endocriene tumoren stijgen gestaag. Er zijn grote verschillen tussen die tumoren onderling, o.a. wat de prognose betreft. De belangrijkste prognostische factoren zijn van pathologisch-anatomische aard, meer bepaald de mate van vermenigvuldiging gemeten met de Ki67-index en de mate van differentiatie. Andere factoren die invloed hebben op de overleving, zijn de ligging, het TNM-stadium, de leeftijd en de performance score van de patiënt op het ogenblik van de diagnose. We beschikken over meerdere biomarkers, maar die vertonen toch heel wat beperkingen. Functionele beeldvorming met 68Ga-DOTA-NOC/TATE/TOC en FDG-PET-scan is belangrijk bij het ramen van het risico. Er zijn meerdere biomarkers in het bloed en de weefsels in onderzoek. Mogelijk zullen die ons in de toekomst een beter idee van het risico geven en helpen bij de keuze van de behandeling.

Background: In tissues, cell-cell adhesion, barrier formation and communication are regulated by junction proteins. Interestingly, platelets express several of these proteins too. Previously, research has shown that gap junction proteins expressed by platelets form gap junctions within platelet thrombi that are necessary to control the contraction of the clots. Also, platelet activation processes are negatively regulated by endothelial cell-selective adhesion molecule (ESAM) and junctional adhesion molecule A (JAM-A), proteins that are part of the tight junctions (TJ) of endothelial cells. However, how other components of TJs -like zonula occludens 2 (ZO-2)- concentrate at platelet-platelet contacts and influence these, has not yet been described. Methods: Using transcriptomics and (phospho)proteomics databases, the expression and regulation upon platelet activation or inhibition of known tight junction proteins in platelets was investigated. Isolated human platelets were allowed to fully spread on a fibrinogen or laminin surface and were additionally activated by stimulating P2Y12, PAR1 or GPVI signaling. Fixed samples were stained to assess F-actin polymerization in relation to CD61, ZO-2 and ESAM distribution using confocal and/or super-resolution fluorescence microscopy. Platinum replica electron microscopy was applied for ultrastructural visualization of the cytoskeleton at sites of platelet-platelet interaction. Results: Confocal and super-resolution fluorescence microscopy indicated a marked redistribution and clustering of ZO-2 molecules at sites of platelet-platelet contacts, in which the colocalization of ZO-2 and ESAM was enhanced when platelets were additionally activated. Furthermore, platinum replica electron microscopy revealed that inter-platelet contacts resulted in the merging of the circumferential actin bundles between interacting platelets. These phenomena were antagonized by cAMP elevation. Conclusion: Jointly, these data point to the assembly

Background & aims: Bile salt export pump (BSEP) deficiency frequently necessitates liver transplantation in childhood. In contrast to two predicted protein truncating mutations (PPTMs), homozygous p.D482G or p.E297G mutations are associated with relatively mild phenotypes, responsive to surgical interruption of the enterohepatic circulation (siEHC). The phenotype of patients with a compound heterozygous genotype of one p.D482G or p.E297G mutation and one PPTM has remained unclear. We aimed to assess their genotype-phenotype relationship. Methods: From the NAPPED database, we selected patients with homozygous p.D482G or p.E297G mutations (BSEP1/1; n = 31), with one p.D482G or p.E297G, and one PPTM (BSEP1/3; n = 30), and with two PPTMs (BSEP3/3; n = 77). We compared clinical presentation, native liver survival (NLS), and the effect of siEHC on NLS. Results: The groups had a similar median age at presentation (0.7-1.3 years). Overall NLS at age 10 years was 21% in BSEP1/3 vs. 75% in BSEP1/1 and 23% in BSEP3/3 (p <0.001). Without siEHC, NLS in the BSEP1/3 group was similar to that in BSEP3/3, but considerably lower than in BSEP1/1 (at age 10 years: 38%, 30%, and 71%, respectively; p = 0.003). After siEHC, BSEP1/3 and BSEP3/3 were associated with similarly low NLS, while NLS was much higher in BSEP1/1 (10 years after siEHC, 27%, 14%, and 92%, respectively; p <0.001). Conclusions: Individuals with BSEP deficiency with one p.E297G or p.D482G mutation and one PPTM have a similarly severe disease course and low responsiveness to siEHC as those with two PPTMs. This identifies a considerable subgroup of patients who are unlikely to benefit from interruption of the enterohepatic circulation by either surgical or ileal bile acid transporter inhibitor treatment. Impact and implications: This manuscript defines the clinical features and prognosis of individuals with BSEP deficiency involving the combination of one relatively mild and one very severe BSEP deficiency mutation. Until

Background Kupffer cells (KC) are embryonically derived liver resident macrophages, responsible for maintaining liver homeostasis. Apart from KCs, infiltrating mono-macrophages of bone marrow origin also make up a small proportion of the hepatic macrophage population. During chronic liver diseases, the Kupffer cell population is largely replaced by the infiltrating mono-macrophage populations. Thus, the hepatic macrophage populations differ in their origin, phenotype, and characteristics. So, maintaining a balance between the different hepatic macrophage populations determines the outcome of the progression of chronic liver diseases. Aim To study the miRNA-based epigenetic dysregulation of KCs and infiltrating macrophages during chronic liver diseases. Methods- C57BL/6 mice were intraperitoneally injected with carbon tetrachloride (CCl4) twice a week for 4 and 18 weeks to induce progressive liver damage. Enzymatic digestion of the liver using collagenase was performed to isolate non-parenchymal cell fractions (NPF). Cell sorting using specific surface antibodies was performed to isolate KCs and infiltrating mono-macrophages from the NPF of digested livers. Results The overall leukocyte cell population was found to be slightly increased in the CCl4 groups than oil-treated group. The overall frequency of the myeloid cell population remained the same between the vehicle and CCl4-treated groups. The frequency of KCs is decreased in both CCl4-treated mice liver groups (20%-25% of total myeloid cell population) in comparison to the vehicle-treated group (60% of myeloid cell population), while the frequency of mono-macrophages was found to be initially increased in the 4 weeks CCl4 treated group (25% of myeloid cells) and then decreased in the 18 weeks CCl4 treated group (10% of myeloid cells). Conclusion Our preliminary results suggest a dynamic change in the hepatic macrophage populations during chronic liver disease conditions. During the initial stage of CCl4-induced l

Cancers arising from germline DNA mismatch repair deficiency or polymerase proofreading deficiency (MMRD and PPD) in children harbour the highest mutational and microsatellite insertion-deletion (MS-indel) burden in humans. MMRD and PPD cancers are commonly lethal due to the inherent resistance to chemo-irradiation. Although immune checkpoint inhibitors (ICIs) have failed to benefit children in previous studies, we hypothesized that hypermutation caused by MMRD and PPD will improve outcomes following ICI treatment in these patients. Using an international consortium registry study, we report on the ICI treatment of 45 progressive or recurrent tumors from 38 patients. Durable objective responses were observed in most patients, culminating in a 3 year survival of 41.4%. High mutation burden predicted response for ultra-hypermutant cancers (>100 mutations per Mb) enriched for combined MMRD + PPD, while MS-indels predicted response in MMRD tumors with lower mutation burden (10-100 mutations per Mb). Furthermore, both mechanisms were associated with increased immune infiltration even in 'immunologically cold' tumors such as gliomas, contributing to the favorable response. Pseudo-progression (flare) was common and was associated with immune activation in the tumor microenvironment and systemically. Furthermore, patients with flare who continued ICI treatment achieved durable responses. This study demonstrates improved survival for patients with tumors not previously known to respond to ICI treatment, including central nervous system and synchronous cancers, and identifies the dual roles of mutation burden and MS-indels in predicting sustained response to immunotherapy.

Hereditary pancreatitis (HP) encompasses two distinct disease groups: the first manifests as congenital exocrine pancreatic insufficiency (EPI), and the second includes hereditary forms of pancreatitis. EPI represents the ultimate expression of gland function loss. Cystic fibrosis is by far the most frequent aetiology of early-onset EPI; genetics and a growing understanding of the disease mechanisms have paved the way for innovative and personalized treatment approaches. Efforts are ongoing to further decipher the pathophysiology and explore new therapies for other causes of EPI. HP occurs in patients carrying mutations in genes encoding digestive proteases or proteins playing an important role in proper pancreatic function and homeostasis. Improved sequencing techniques have led to the discovery of several causal and disease promoting genes. Most forms of HP have a paediatric onset but complications usually manifest during adulthood. Surveillance in experienced centres is mandatory to diagnose and address these complications in a timely manner.

The Hepatology Committee of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) aims to educate pediatric gastroenterologists, members of ESPGHAN and professionals from other specialties promoting an exchange of clinical expertise in the field of pediatric hepatology. Herewith we have concentrated on detailing the recent advances in acute liver failure in infants and children. The 2020 ESPGHAN monothematic three-day conference on pediatric hepatology disease, entitled "acute liver failure" (ALF), was organized in Athens, Greece. ALF is a devastating disease with high mortality and most cases remain undiagnosed. As knowledge in diagnosis and treatment of ALF in infants and children has increased in the past decades, the objective was to update physicians in the field with the latest research and developments in early recognition, curative therapies and intensive care management, imaging techniques and treatment paradigms in these age groups. In the first session, the definition, epidemiology, various causes of ALF, in neonates and older children and recurrent ALF (RALF) were discussed. The second session was dedicated to new aspects of ALF management including hepatic encephalopathy (HE), coagulopathy, intensive care interventions, acute on chronic liver failure, and the role of imaging in treatment and prognosis. Oral presentations by experts in various fields are summarized highlighting key learning points. The current report summarizes the major learning points from this meeting. It also identifies areas where there is gap of knowledge, thereby identifying the research agenda for the near future.

Alcohol use disorder (AUD) is a chronic relapsing disease associated with malnutrition, metabolic disturbances, and gut microbiota alterations that are correlated with the severity of psychological symptoms. This study aims at supplementing AUD patients with prebiotic fiber during alcohol withdrawal, in order to modulate the gut microbiota composition and to evaluate its effect on gastrointestinal tolerance, metabolism, and patient’s behavior. A randomized, double-blind, placebo-controlled study included 50 AUD patients assigned to inulin versus maltodextrin daily supplementation for 17 days. Biological measurements (fecal microbial 16S rDNA sequencing, serum biology), dietary intake, validated psychological questionnaires, and gastrointestinal tolerance assessment were performed before and after the intervention. Inulin significantly decreased the richness and evenness and induced changes of 8 genera (q < 0.1) including Bifidobacterium and Bacteroides. Prebiotic had minor effects on gastrointestinal symptoms and nutritional intakes compared to placebo. All patients showed an improvement in depression, anxiety, and craving scores during alcohol withdrawal regardless of the intervention group. Interestingly, only patients treated with inulin significantly improved the sociability score and had an increased serum level of brain-derived neurotrophic factor. This pilot study shows that inulin is well tolerated and modulates the gut microbiota and the social behavior in AUD patients, without further improving other psychological and biological parameters as compared to placebo. Gut2Brain study, clinicaltrial.gov: NCT03803709, https://clinicaltrials.gov/ct2/show/NCT03803709

Objective Immunosuppressive agents are known to interfere with T and/or B lymphocytes, which are required to mount an adequate serologic response. Therefore, we aim to investigate the antibody response to SARS-CoV- 2 in liver transplant (LT) recipients after COVID-19. Design Prospective multicentre case–control study, analysing antibodies against the nucleocapsid protein, spike (S) protein of SARS-CoV- 2 and their neutralising activity in LT recipients with confirmed SARS-CoV- 2 infection (COVID-19- LT) compared with immunocompetent patients (COVID-19- immunocompetent) and LT recipients without COVID-19 symptoms (non-COVID- 19- LT). Results Overall, 35 LT recipients were included in the COVID-19- LT cohort. 35 and 70 subjects fulfilling the matching criteria were assigned to the COVID-19- immunocompetent and non-COVID- 19- LT cohorts, respectively. We showed that LT recipients, despite immunosuppression and less symptoms, mounted a detectable antinucleocapsid antibody titre in 80% of the cases, although significantly lower compared with the COVID-19- immunocompetent cohort (3.73 vs 7.36 index level, p<0.001). When analysing anti-S antibody response, no difference in positivity rate was found between the COVID-19- LT and COVID-19- immunocompetent cohorts (97.1% vs 100%, p=0.314). Functional antibody testing showed neutralising activity in 82.9% of LT recipients (vs 100% in COVID-19- immunocompetent cohort, p=0.024). Conclusions Our findings suggest that the humoral response of LT recipients is only slightly lower than expected, compared with COVID-19 immunocompetent controls. Testing for anti-S antibodies alone can lead to an overestimation of the neutralising ability in LT recipients. Altogether, routine antibody testing against separate SARS-CoV- 2 antigens and functional testing show that the far majority of LT patients are capable of mounting an adequate antibody response with neutralising ability.

La maladie stéatosique du foie liée à une dysfonction métabolique (MAFLD) touche un quart de la population mondiale, dont certains d’entre eux évolueront vers une forme plus sévère appelée stéatohépatite non-alcoolique (NASH). Le principal facteur menant à cette pathologie est une alimentation déséquilibrée. Aucun traitement médicamenteux n’est reconnu à ce jour. Seule la prise en charge hygiénodiététique permet une amélioration des lésions histologiques de la NASH grâce à une perte de poids. Néanmoins, l’efficacité des régimes standards, la compliance des patients et la capacité à maintenir la perte de poids à long terme sont des difficultés fréquemment rencontrées. Dans cet article, nous analysons les données scientifiques récentes de différents types d’alimentation (régime méditerranéen, jeûne intermittent, régime cétogène) permettant d’apporter des bénéfices hépatiques et parfois extrahépatiques. Les inconvénients ou limites possibles sont également discutés. Le bénéfice éventuel d’autres stratégies nutritionnelles (café, acides gras oméga-3, polyphénols…) est finalement présenté. Le changement de mode alimentaire peut, dès lors, être adapté aux attentes du patient et occasionner des bénéfices indépendamment de la perte de poids., Metabolic dysfunction-associated fatty liver disease (MAFLD) affects a quarter of the world’s population,some of whom will progress to a more severe form called non-alcoholic steatohepatitis (NASH). Themain factor leading to this condition is an unbalanced diet. No drug treatment is approved to date andonly dietary management can improve the histological lesions of NASH through weight loss. However,the efficacy of standard diets, patient compliance and the ability to maintain weight loss over the longterm are common difficulties. In this review, we analyze recent scientific data on different types of diet(Mediterranean diet, intermittent fasting, ketogenic diet), which can bring benefits on general and liverhealth. Drawbacks or limitations are also listed. The possible benefit of other nutritional strategies (coffeeconsumption, omega-3, polyphenols...) is discussed. The value of dietary change could be tailored to thepatient’s needs without necessarily imposing an intense weight loss.

Alcohol-related liver disease (ALD) ranges from never-decompensated ALD (ndALD) to the life-threatening decompensated phenotype, known as alcohol-related hepatitis (AH). A multidimensional study of the clinical, histological and molecular features of these subtypes is lacking. Two large cohorts of patients were recruited in an international, observational multicentre study: a retrospective cohort of patients with ndALD (n=110) and a prospective cohort of patients with AH (n=225). Clinical, analytical, immunohistochemistry and hepatic RNA microarray analysis of both disease phenotypes were performed. Age and mean alcohol intake were similar in both groups. AH patients had greater aspartate amino transferase/alanine amino transferase ratio and lower gamma-glutamyl transferase levels than in ndALD patients. Patients with AH demonstrated profound liver failure and increased mortality. One-year mortality was 10% in ndALD and 50% in AH. Histologically, steatosis grade, ballooning and pericellular fibrosis were similar in both groups, while advanced fibrosis, Mallory-Denk bodies, bilirubinostasis, severe neutrophil infiltration and ductular reaction were more frequent among AH patients. Transcriptome analysis revealed a profound gene dysregulation within both phenotypes when compare to controls. While ndALD was characterised by deregulated expression of genes involved in matrisome and immune response, the development of AH resulted in a marked deregulation of genes involved in hepatocyte reprogramming and bile acid metabolism. Despite comparable alcohol intake, AH patients presented with worse liver function compared with ndALD patients. Bilirubinostasis, severe fibrosis and ductular reaction were prominent features of AH. AH patients exhibited a more profound deregulation of gene expression compared with ndALD patients.

The platelet transmembrane receptor GPVI can be assessed together with other platelet membrane markers in a whole blood multicolor flow cytometry panel. The advantage of combining multiple antibodies in a single tube is the possibility of distinguishing multiple platelet subgroups. In this short communication, we describe an activation problem encountered with anti-GPVI, clone HY101. Activation of platelets was seen after the addition of anti-GPVI in a flow cytometry panel, highlighted by the expression of the activation markers CD62P, PAC-1, CD63, and CD107a. This was also confirmed by platelet aggregation studies.

Purpose: Metabolic dysfunction-associated fatty liver disease-related cirrhosis is possible at the time of bariatric surgery, complicated by further liver decompensation. Hepatic decompensation can also occur in the absence of cirrhosis but the presentation is less clear. Methods: We analyze the clinical characteristics, histological findings, and management of patients without cirrhosis who developed hepatic decompensation after bariatric surgery in our single tertiary-care hospital. Results: From 2014 to 2019, 6 patients underwent a transvenous liver biopsy for liver decompensation after bariatric surgery. Mean age at diagnosis was 44 years. The time between bariatric surgery and the onset of symptoms varied widely (min. 8 months, max. 17 years). Mean % of weight loss was high at 43%. The clinical presentation was as follows: fatigue and jaundice (5/6), leg edema (3/6), and ascites (1/6). Blood test showed increased transaminases (mean ALT 53 UI/L, mean AST 130 UI/L), bilirubin (mean 6 mg/dL), and INR (mean 1.5) with a low albumin level (mean 27 mg/dL). The hepatic venous pressure gradient was high (mean 10 mmHg). Histology revealed steatosis, hepatocyte ballooning but also portal inflammation with polymorphonuclear cells, and bile duct alterations. Mean fibrosis score was 2. The clinical course was favorable with nutritional support with a mean follow-up of 36 months. Conclusion: Liver decompensation in the absence of cirrhosis can occur after bariatric surgery with a highly variable delay. A special histological signature is present with the coexistence of steatosis, bile duct alterations, and portal inflammation. Substantial clinical improvement with appropriate nutritional support seems to be effective.

L’année 2021 a comporté plusieurs mises au point et avancées en hépato-gastro-entérologie, notamment à destination du médecin traitant généraliste. Des moyens non-invasifs simples sont à sa disposition et validés par la société scientifique européenne de l’étude du foie pour rechercher la présence d’une fibrose hépatique chez les individus à risque (syndrome métabolique ou alcool). Les critères de remboursement de certaines médications contre le virus de l’hépatite B ont été revus. Ils ne comportent plus la réalisation d’une biopsie hépatique systématique et ciblent plus de patients à risque. Concernant la maladie stéatosique métabolique, plusieurs études scientifiques ont été réalisées avec différents types de régimes alimentaires permettant une régression de la maladie. Leurs avantages et inconvénients potentiels sont décrits. Ces régimes peuvent donc être proposés par le médecin traitant. Un domaine de l’endoscopie moins connu est également présenté avec l’utilisation de l’entéroscopie spiralée motorisée qui fait son apparition aux Cliniques universitaires Saint-Luc et qui permettra d’améliorer l’exploration et la prise en charge des maladies de l’intestin grêle. Enfin, les praticiens sont souvent confrontés à la maladie hémorroïdaire. Des recommandations de sa prise en charge ont été rédigées et publiées par un groupe de proctologues experts belges.

We believe that it is essential to determine the presence of alcoholic steatohepatitis (ASH) on a histological basis not only for cases of diagnostic uncertainty but in all patients with severe (clinical) alcoholic hepatitis (AH) before starting corticosteroid treatment. In the absence of histological confirmation of ASH (10%–20% of cases), such treatment should not be initiated.

Unlike simple obesity, Madelung's disease (MD) is a rare disease characterized by symmetric accumulation of massive adipose tissue on the neck, the superior part of the trunk and limbs, leading to a pathognomonic cosmetic deformity. Here, we report an extremely rare case of MD associated with bilateral gynecomastia in a 61-year-old man, with a history of recent liver transplantation for alcoholic liver disease (ALD).

Brieuc Van Nieuwenhuyse1, Dimitri Van der Linden1,2, Olga Chatzis2, Cédric Lood3,4, Jeroen Wagemans3, Rob Lavigne4, Catherine de Magnée5, Étienne Sokal1,6, Hector Rodriguez-Villalobos7, Sarah Djebara8, Maya Merabishvili9, Patrick Soentjens8, Jean-Paul Pirnay9. 1Institute of Experimental and Clinical Research's Pediatric department, UCLouvain, Brussels, Belgium; 2Pediatric Infectious Diseases, General Pediatrics Department, Cliniques universitaires Saint-Luc, Brussels, Belgium; 3Department of Biosystems, Laboratory of Gene Technology, KULeuven, Leuven, Belgium; 4Department of Microbial and Molecular Systems, Centre of Microbial and Plant Genetics, KULeuven, Leuven, Belgium; 5Pediatric and Transplantation Surgery, Cliniques universitaires Saint-Luc, Brussels, Belgium; 6Pediatric Hepatology and Gastro-enterology, Cliniques universitaires Saint-Luc, Brussels, Belgium; 7Department of Microbiology, Cliniques universitaires Saint-Luc, Brussels, Belgium; 8Center for Infectious Diseases, Queen Astrid Military Hospital, Brussels, Belgium; 9Laboratory for Molecular and Cellular Technology, Queen Astrid Military Hospital, Brussels, Belgium A 14-month old boy undergoes a first liver transplantation (LT) (Day 0), from an ABO-incompatible living donor. On D+20, we detect a fecal carriage of an extensively drug-resistant (XDR) Pseudomonas aeruginosa (Pa) strain. Besides intermediate susceptibility to aztreonam and colistin and susceptibility to gentamycin, the strain is resistant to all other antibiotics. On D+53, the child enters a severe septic state due to a bacteremia with the same Pa strain. New antibiogram suggests a resistance to colistin. Liver bilomas' drainage material is cultured and grows the same Pa strain. Admission to the pediatric intensive care unit and adjunction of intravenous (IV) aztreonam, gentamycin, and colistin led to no improvement on the microbiological or clinical levels during the next four days. By collaborating with Queen Astrid Military Hospital (Bru

Objectifs : L’hépatite auto-immune (HAI) est une maladie inflammatoire chronique qui peut mener à la cirrhose chez les patients réfractaires au traitement conventionnel. Les traitements de seconde ligne actuels ont une efficacité variable et un niveau de recommandation faible. Dans ce contexte, l’utilisation des inhibiteurs du mammalian target of rapamycin (mTOR) s’est récemment développée dans l’HAI réfractaire au traitement. L'everolimus a montré des résultats prometteurs dans une série limitée chez l'adulte, mais aucun rapport n’a été publié dans l’HAI pédiatrique à ce jour. L’objectif de notre travail était de partager notre expérience de l’everolimus comme thérapie de deuxième ou de troisième ligne dans l’HAI pédiatrique. Méthodes : Les patients âgés de 0 à 18 ans atteints d’HAI et non transplantés ayant reçu de l’everolimus entre 2014 et 2021 ont été identifiés rétrospectivement dans la base de données d’hépatologie pédiatrique des Cliniques Universitaires Saint-Luc (Bruxelles, Belgique). Tous les patients ont été soumis à un dosage régulier des taux plasmatiques d’everolimus afin d’éviter la toxicité et d’évaluer la compliance thérapeutique. Une attention particulière a été portée à la survenue d’effets secondaires cliniques et biochimiques attribuables à l’everolimus. Résultats : Six patients atteints d’HAI ont été traités par everolimus dans notre centre pour une durée comprise entre 8 et 48 mois (médiane 28 mois). Aucun effet secondaire n’a été rapporté lorsque les taux plasmatiques d’everolimus se situaient dans les normes thérapeutiques. Les transaminases hépatiques se sont améliorées chez 5/6 patients à l’instauration de l’everolimus et ont diminué significativement à la fin du suivi (p<0.05). Aucun patient n’est entré en rémission biochimique au sens strict au cours du suivi et 3/6 patients ont admis avoir une compliance suboptimale au traitement. Conclusions : Nos données préliminaires présentent l’everolimus comme une option thérapeutique de deuxième

BACKGROUND: Dietary interventions targeting the gut microbiota have been proposed as innovative strategies to improve obesity-associated metabolic disorders. Increasing physical activity (PA) is considered as a key behavioral change for improving health. We have tested the hypothesis that changing the PA status during a nutritional intervention based on prebiotic supplementation can alter or even change the metabolic response to the prebiotic. We confirm in obese subjects and in high-fat diet fed mice that performing PA in parallel to a prebiotic supplementation is necessary to observe metabolic improvements upon inulin. METHODS: A randomized, single-blinded, multicentric, placebo-controlled trial was conducted in obese participants who received 16 g/day native inulin versus maltodextrin, coupled to dietary advice to consume inulin-rich versus -poor vegetables for 3 months, respectively, in addition to dietary caloric restriction. Primary outcomes concern the changes on the gut microbiota composition, and secondary outcomes are related to the measures of anthropometric and metabolic parameters, as well as the evaluation of PA. Among the 106 patients who completed the study, 61 patients filled a questionnaire for PA before and after intervention (placebo: n = 31, prebiotic: n = 30). Except the dietitian (who provided dietary advices and recipes book), all participants and research staff were blinded to the treatments and no advices related to PA were given to participants in order to change their habits. In parallel, a preclinical study was designed combining both inulin supplementation and voluntary exercise in a model of diet-induced obesity in mice. RESULTS: Obese subjects who increased PA during a 3 months intervention with inulin-enriched diet exhibited several clinical improvements such as reduced BMI (- 1.6 kg/m2), decreased liver enzymes and plasma cholesterol, and improved glucose tolerance. Interestingly, the regulations of Bifidobacterium, Dialister, and C

Objectives: The Hepatology Committee of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) aims to educate pediatric gastroenterologists, members of ESPGHAN and professionals from other specialties promoting an exchange of clinical expertise in the field of pediatric hepatology. Methods: The 2020 single topic ESPGHAN monothematic 3-day conference on pediatric liver disease, was organized in Athens, Greece and was entitled " Acute Liver Failure" (ALF). ALF is a devastating disease with high mortality and in a considerable fraction of patients, the cause remains unresolved. As knowledge in diagnosis and treatment of ALF in infants and children has increased in the past decades, the objective was to update physicians in the field with developments in medical therapy and indications for liver transplantation (LT) and to identify areas for future research in clinical and neurocognitive outcomes in ALF. Results: We recently reported the epidemiology, diagnosis, and initial intensive care management issues in separate manuscript. Herewith we report on the medical treatment, clinical lessons arising from pediatric studies, nutritional and renal replacement therapy (RRT), indications and contraindications for LT, neurocognitive outcomes, new techniques used as bridging to LT, and areas for future research. Oral presentations by experts in various fields are summarized highlighting key learning points. Conclusions: The current report summarizes the current insights in medical treatment of pediatric ALF and the directions for future research.

Background and study aims: The role of malnutrition on the prognosis of hospitalized cirrhotic patients is incompletely studied. Our aim was to determine the prevalence of malnutrition, functional scores and their impact on prognosis of hospitalized cirrhotic patients. Patients and methods: This retrospective study included all patients with cirrhosis hospitalized in the gastroenterology unit at Saint-Luc university hospital, Brussels between April 2014 and September 2014. Nutritional status was evaluated according to minimum clinical summary diagnostic criteria. Cirrhosis-related complications or death occurrence were analysed in a one-year follow-up. Results: 95 cirrhotic patients were assessed for nutritional status and outcomes. Malnutrition affected 45.3% of patients and was more frequent with the severity of cirrhosis: 29% in Child-Pugh A, 48.8% in Child-Pugh B and 72.2% in Child-Pugh C patients. 58.9% of patients developed cirrhosis-related complications (60.7% in the malnutrition group vs. 39.3%, p<0.001, OR 5.06, IC95 1.90-14.58) and 33.7% of patients died (68.75% vs. 31.25%, p=0.002, OR 4.33, IC95 1.62-12.28). Adjusting for age, sodium, MELD, Charlson index, hepatocellular carcinoma, platelets, diabetes, prognostic nutritional index and Braden scale, malnutrition was significantly associated with higher mortality and morbidity rates with an OR of 3.56 (CI95 1.55-8.16) and 2.09 (CI95 1.16-3.77) respectively. Braden scale was significantly associated with higher mortality (p=0.027, OR 1.25, CI95 1.03-1.52) whereas prognostic nutritional index was associated with higher morbidity (p=0.001, OR 0.94, CI95 0.900.98). Conclusion: Malnutrition is highly prevalent in hospitalized cirrhotic patients. Malnutrition, low prognostic nutritional index and low Braden scale are associated with poor outcomes in cirrhosis. (Acta gastroenterol. belg., 2022, 85, 1-9).

Background: This case report describes a child born with both cystic fibrosis (CF) and alpha-1 antitrypsin deficiency (A1ATD). Both are autosomal recessive inherited diseases, mainly affecting the lungs and the liver. The combination of both diseases together is rare and may lead to a fulminant disease with limited life span. To the best of our knowledge, no case has been reported of a patient born with both diseases. Case presentation: After an uneventful pregnancy, a male baby was born with meconium ileus. The suspected diagnosis of CF was confirmed based on the sweat test and genetic analysis. The child developed persisting cholestasis, too severe to be likely caused by CF alone and indicating an associated problem. The diagnosis of A1ATD was established based on clinical suspicion (persisting cholestasis), decreased serum alpha-1 antitrypsin and genetic analysis. Supportive therapy was started, however the boy evolved to rapidly progressive liver disease leading to liver failure which necessitated an infant liver transplantation. Conclusions: This case illustrates the complexity of care in case of two severe inherited diseases as well as post solid organ transplant care.

No abstract available

Data on procedural outcome and quality of endoscopic retrograde cholangiopancreatography (ERCP) in Belgian practice are scarce. The aim of this study is to assess current status of ERCP-performance in Belgium. National multi-institutional survey (online questionnaire) among members of the Belgian Society of Gastrointestinal Endoscopy (BSGIE), conducted in the period June-August 2018. The RIZIV/INAMI provided real-life data on the total number of ERCPs performed in Belgium. Forty-five responders completed the survey (for 43 centers performing ERCP), providing information for 8368 ERCPs performed in 45% (43/95) of institutions performing ERCP in Belgium. Fifty-eight percent of centers performed > 100 ERCPs/year and 7% of centers (n=3) performed < 50 ERCPs/year. According to the RIZIV/INAMI data, low case-volume centers are underrepresented in this survey. The most common ERCPindication was stone extraction (52%). 74% of endoscopists had more than 10 years of experience in performing ERCP. The majority of centers had their own written protocol (84%) for microbiological duodenoscope surveillance. Monitoring of cannulation rate and post-ERCP pancreatitis (PEP) was only performed in a minority of centers (30%). The majority of centers (76%) provided verbal informed consent relating to the ERCP-procedure ; a minority also requested a written informed consent (23%). 65% of centers systematically use NSAIDs for PEP prophylaxis. This is the first survey of ERCP performance in Belgium. There were wide variations in practice. Adherence to key performance measures and measurement and evaluation of ERCP performance in daily practice at center and endoscopist level are not uniformly widespread.

Obinutuzumab and lenalidomide (referred to as the GALEN combination) is an active immunomodulatory combination with a manageable safety profile in multiple types of lymphoma. We report efficacy and safety results for the phase 2 GALEN study in previously untreated patients with advanced follicular lymphoma (FL). Eligible patients aged ≥18 years had an Eastern Cooperative Oncology Group performance status ≤2 and high-tumor burden, grade 1 to 3a FL. Induction treatment was obinutuzumab (1000 mg IV, days 8, 15, and 22, cycle 1; day 1, cycles 2-6) plus lenalidomide (20 mg/d, days 1-21, cycle 1; days 2-22, cycles 2-6) for six 28-day cycles. Maintenance included obinutuzumab (1000 mg every 2 cycles) plus lenalidomide (10 mg, days 2-22) for ≤12 cycles (year 1) followed by obinutuzumab (1000 mg every 56 days) for 6 cycles (year 2). The primary end point was complete response rate (CRR) after induction per the 1999 International Working Group criteria. From October 2015 to February 2017, a total of 100 patients were enrolled. CRR after induction was 47%, and the overall response rate (ORR) was 92%. Post hoc analyses per the 2014 Lugano classification, including patients with missing bone marrow assessments, identified an additional 13 patients fulfilling CRR criteria, resulting in a complete metabolic response of 80% and an ORR of 94%. At a median follow-up of 3.7 years, 3-year progression-free survival and overall survival were 82% and 94%, respectively. The most common adverse event was neutropenia (48% any grade; 47% grade ≥3). Only 2% of patients presented with febrile neutropenia; others were mainly grade ≤2. No other specific grade ≥3 toxicity occurred at a frequency >3%. Overall, these results showed promising clinical efficacy for the chemotherapy-free GALEN backbone in previously untreated patients with high tumor burden FL. Except for neutropenia, the safety profile of the combination is remarkable. The study was registered at clinicaltrials.gov as #NCT01582776.

The SADAL study evaluated oral selinexor in patients with relapsed and/or refractory diffuse large B-cell lymphoma (DLBCL) after at least 2 prior lines of systemic therapy. In this post-hoc analysis, we analyzed the outcomes of the SADAL study by DLBCL subtype to determine the effects of DLBCL subtypes on efficacy and tolerability of selinexor. Data from 134 patients in SADAL were analyzed by DLBCL subtypes for overall response rate (ORR), overall survival (OS), duration of treatment response, progression-free survival, and adverse events rate. ORR in the entire cohort was 29.1%, and similar in patients with germinal center (GCB) versus non-GCB DLBCL (31.7% vs. 24.2%, P = 0.45); transformed DLBCL showed a trend towards higher ORR than de novo DLBCL: 38.7% vs. 26.2% (P = 0.23). Despite similar prior treatment regimens and baseline characteristics, patients with DLBCL and normal C-MYC/BCL-2 protein expression levels had a significantly higher ORR (46.2% vs.14.8%, P = 0.012) and significantly longer OS (medians 13.7 vs. 5.1 months, hazard ratio 0.43 [95% CI, 0.23-0.77], P = 0.004) as compared with those whose DLBCL had C-MYC and BCL-2 overexpression. Among patients who had normal expression levels of either C-MYC or BCL-2 and baseline hemoglobin levels ≥ 10g/dL, ORR was 51.5% (n = 47), with median OS of 15.5 months and median PFS of 4.6 months. Similar rates of adverse events were noted in all subgroups. Overall, single agent oral selinexor showed strong responses in patients with limited treatment alternatives regardless of germinal center B-cell type or disease origin.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the evidence of steatosis in the setting of a metabolic risk condition such as type 2 diabetes mellitus (T2DM). Indeed, T2DM and liver steatosis share common pathophysiological mechanisms, and one can lead to the other. MAFLD can progress from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis as well as hepatocellular carcinoma (HCC). Because of the lack / disparity of guidelines for MAFLD screening, which is asymptomatic in its early stages, it is not rare that diabetic patients are belatedly diagnosed with NASH cirrhosis or HCC. We therefore recommend systematic non-invasive tests (NITs) that calculate an estimate of the risk based on readily available anthropometric and biological parameters. These include the fatty liver index (FLI) for steatosis detection and at least one of the following for fibrosis: non-alcoholic fatty liver disease fibrosis score (NFS), fibrosis-4 index (FIB-4) or Hepamet fibrosis score (HFS). Indeed, NFS and FIB-4 are the best predictors of liver-related events, while FIB-4 and HFS correlate with overall mortality. Systematic literature review found only few retrospective or cross-sectional studies using NITs for systematic steatosis and fibrosis screening in T2DM patients, with a crucial need for prospective studies. This screening strategy will allow targeted patients to be referred for further liver investigation (e.g. ultrasound, elastometry) and care. Current treatment modalities of MAFLD in T2DM patients range from lifestyle and dietary interventions to specific glucose-lowering drugs that recently showed some benefits regarding MAFLD, such as pioglitazone, glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors. Other treatments are currently under investigation.

Appendiceal neuroendocrine neo-plasms (aNENs) are a diverse group of malignant neoplasms of varying biological behavior for which information about manage-ment and outcome is sparse, with the majority of available studies being retrospective, including only a limited number of patients, and therefore not necessarily reflecting the reality in the community. In the present study clinical, epidemiological and pathological data of appendiceal neuroendocrine neoplasms in Belgium is provided and compared with current literature. A population-based study was conducted by linking data of the Belgian Cancer Registry with medical procedures in the Belgian Health Insurance database for patients diagnosed with aNEN between 2010 and 2015. We found an aNEN incidence of 0.97/100.000 person years in Belgium. Neuroendocrine carcinoma of the appendix are rare. Most appendiceal neuroendocrine tumors (aNETs) are small G1 tumors. Positive lymph nodes are often found in tumors larger than 2cm, especially aNET G2. A rapid uptake of changing classifications was seen in the community. However, systematic reporting of risk factors for small aNEN can still be improved and should be stimulated. In 9% of cases, reclassifications had to be made, pointing out that in a retrospective analysis, original pathological reports should be checked for specific parameters, before reliable conclusions can be drawn.

No abstract available

Background and Aims: The prevalence of insulin resistance (IR) and type 2 diabetes mellitus (T2DM) is higher in patients with cirrhosis, compared to control patients without liver disease. The exact mechanism for this is unknown but could include liver inflammation. In this study, we investigate whether cirrhosis is the primum movens of IR or if impaired insulin sensitivity is already present in non-cirrhotic patients with chronic liver diseases. Method: Patients were recruited and divided into three groups: control (CTL), active chronic liver disease without cirrhosis (CLD) and cirrhosis (CIR). In patients not taking pharmacological treatment for T2DM, IR was quantified using the homeostasis model assessment of insulin resistance (HOMA-IR). The proportion of patients treated for T2DM was recorded in each group. Additionally, HOMA-IR levels among different disease etiologies were compared. The study was approved by the local ethics committee. Results: 422 patients were included in our study, 16 were controls, 278 had a CLD and 128 were cirrhotic (CIR). The causes of liver disease were as follows: metabolic-dysfunction associated fatty liver disease (MAFLD, n=206), alcoholic liver disease (ALD, n=117), active chronic hepatitis C (HCV, n=59), other cause (n=24). IR, represented by a HOMA-IR value exceeding 2.5, is already present in patients with non-cirrhotic CLD (median HOMA-IR 4.0). HOMA-IR levels lie between those seen in CTL (median HOMA-IR 1.3) and CIR patients (median HOMA-IR 5.7), with a statistically significant difference between the three groups (p-value <0.001). Median glycemia in the CLD and CIR groups is the same (98 mg/dL and 99 mg/dL respectively) but insulinemia is different (101.5 pmol/L and 132.3 pmol/L respectively) resulting in distinct HOMA-IR values in CLD and CIR patients (p=0.018). Compared to CLD patients, patients in the CIR group are also characterised by a higher age, higher AST levels and a lower platelet count consistent with portal hype

No abstract available

Vedolizumab (VDZ) is a gutselective integrin inhibitor used to treat Crohn's disease (CD) and ulcerative colitis (UC). This retrospective study assessed effectiveness and treatment persistence of VDZ in a Belgian reallife cohort of CD and UC patients. CD and UC patients from 15 Belgian centers, who started VDZ between 01/09/2015 and 31/06/2016 and attended ≥1 visit after the first VDZ infusion, were included. Data were collected before first infusion, at week (W)10, W14 (CD patients only), month (M)6 and last follow-up. Treatment response and remission rates (changes in disease activity scores) and treatment persistence (Kaplan-Meier analysis) were assessed. Of the 348 patients receiving at least one dose of VDZ, 325 (202 CD, 45 biologic-naïve; and 123 UC, 42 biologic-naïve) patients were included in data analyses. At M6, 87.6% (176/201) of CD and 86.1% (105/122) of UC patients were still on VDZ treatment, 75.6% (34/45) and 83.9% (26/31) achieved clinical response, and 66.7% (44/66) and 42.9% (15/35) were in remission. At M6 remission rates was significantly higher while response rates tended to be higher among biologic-naïve versus biologic-failure CD patients. VDZ offers an effective treatment option in real-life settings and treatment effectiveness appears higher in biologic-naïve versus biologic-failure CD patients. (Acta gastroenterol. belg., 2020, 83, 15-23).

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no abstract available

Endoscopic ultrasound-guided digestive anastomosis (EUS-A) is a new alternative under evaluation in patients presenting with afferent limb syndrome (ALS) after Whipple surgery. The aim of the present study is to analyze the safety and effectiveness of EUS-A in ALS. This is an observational multicenter study. All patients ≥18 years old with previous Whipple surgery presenting with ALS who underwent an EUS-A using a lumen-apposing metal stent (LAMS) between 2015 and 2021 were included. The primary outcome was clinical success, defined as resolution of the ALS or ALS-related cholangitis. Furthermore, technical success, adverse event rate, and mortality were evaluated. Forty-five patients (mean age: 65.5 ± 10.2 years; 44.4% male) were included. The most common underlying disease was pancreatic cancer (68.9%). EUS-A was performed at a median of 6 weeks after local tumor recurrence. The most common approach used was the direct/freehand technique (66.7%). Technical success was achieved in 95.6%, with no differences between large (≥15 mm) and small LAMS (97.4% vs. 100%, P = 0.664). Clinical success was retained in 91.1% of patients. A complementary treatment by dilation of the stent followed by endoscopic retrograde cholangiopancreatography through the LAMS was performed in three cases (6.7%). There were six recurrent episodes of cholangitis (14.6%) and two procedure-related adverse events (4.4%) after a median follow-up of 4 months. Twenty-six patients (57.8%) died during the follow-up due to disease progression. EUS-A is a safe and effective technique in the treatment of malignant ALS, achieving high clinical success with an acceptable recurrence rate.

Despite efforts from various endoscopy societies, reporting in the field of endoscopy remains extremely heterogeneous. Harmonisation of clinical practice in endoscopy has been highlighted by application of many clinical practice guidelines and standards pertaining to the endoscopic procedures and reporting are underlined. The aim of the proposed "standardised reporting" is to (1) facilitate recognition of gastrointestinal neuroendocrine neoplasms (NEN) on initial endoscopy, (2) to enable interdisciplinary decision making for treatment by a multidisciplinary team, (3) to provide a basis for a standardised endoscopic follow-up which allows detection of recurrence or progression reliably, (4) to make endoscopic reports on NEN comparable between different units, and (5) to allow research collaboration between NEN centres in terms of consistency of their endoscopic data. The ultimate goal is to improve disease management, patient outcome and reduce the diagnostic burden on the side of the patient by ensuring the highest possible diagnostic accuracy and validity of endoscopic exams and possibly interventions.

no abstract available

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EUS has evolved into a therapeutic modality for gastrointestinal disorders. Simulators, ex vivo models, and phantoms are the current teaching methods for therapeutic EUS (TEUS). We create and evaluate a high-fidelity simulated live animal model (HiFi SAM) for teaching endoscopists TEUS. Designing a curriculum that uses HiFi SAM and enables trainees to perform realistic procedures with expert mentors. Twenty-seven trainees participated in a 3-day program with 6 h of theoretical and 14 h of hands using life HiFi SAM. Eighteen experts participated. Twenty-two (20-25) TEUS were defined for each HiFi SAM, and 616 were performed in all. Of 616/264 (43%) were evaluated with a mean of 88 per course (ranging between 80 and 95). Ninety-one percent (240/264) of the procedures were completed successfully. In 24, success was not achieved due to technical and/or model problems. Student rating of HiFi SAM was: 71% excellent rating (scale 8-10) and 95% excellent/good. The HiFi SAM procedure evaluation was (scale 1-5): fine-needle biopsy: 4.79, radiofrequency: 4.76, common bile duct and gallbladder drainage: 4.75, cystic drainages: 4.72, neurolysis: 4.55, microbiopsy: 4.50, and hepatogastric drainage: 4.04, with an overall satisfaction rate of 4.56 (91%). A short survey showed: 83% would recommend absolutely (17% most likely), 33% think that ITEC training was sufficient for their practice, and 66% would like additional training, especially more practice in specific techniques rather than more clinical case discussion. Regarding impact on their practice, 66% of the trainees started a new procedure and/or noted improvement in previous ones. HiFi SAM is a complex model; however, experts and trainees are satisfied with the training this new curriculum provided.

Acrometastasis is an uncommon metastatic location appearing in the small bones of hands and feet (1). Its low incidence, around 0,1% of all bone metastases, may be due to the subclinical presentation and the lack of attention to the extremities in routine examination (1- 5). However, it sometimes represents the first expression of an occult malignancy (1-4). The symptoms are aspecific and may mimic a local infection, an inflammatory disease (arthritis, tenosynovitis) or a dermatologic lesion (1-5). The correct diagnosis of this atypical entity is important to draw the attention of the clinicians to the metastatic dissemination of the disease, to initiate adequate treatment and reduce patient morbidity.

Selective internal radiation therapy (SIRT) is part of the treatment strategy for hepatocellular carcinoma (HCC). Strong clinical data demonstrated the effectiveness of this therapy in HCC with a significant improvement in patient outcomes. Recent studies demonstrated a strong correlation between the tumor response and the patient outcome when the tumor-absorbed dose was assessed by nuclear medicine imaging. Dosimetry plays a key role in predicting the clinical response and can be optimized using a personalized method of activity planning (multi-compartmental dosimetry). This paper reviews the main clinical results of SIRT in HCC and emphasizes the central role of dosimetry for improving it effectiveness. Moreover, some patient and tumor characteristics predict a worse outcome, and toxicity related to SIRT treatment of advanced HCC patient selection based on the performance status, liver function, tumor characteristics, and tumor targeting using technetium-99m macro-aggregated albumin scintigraphy can significantly improve the clinical performance of SIRT.

Pancreatic exocrine insufficiency (PEI) is a common condition in patients with pancreatic cancer (PC). PEI can be due to the tumor, which, if located in the head, causes obstruction of the pancreatic duct with subsequent atrophy of the pancreatic parenchyma, or it can be the consequence of pancreatic surgical resection. The standard treatment of PEI is pancreatic enzyme replacement therapy (PERT). Clinical data to support the use of PERT in PC are however limited. There are very few randomized clinical trials that evaluated PERT in PC. Most data come from observational studies. Despite this limited clinical evidence, PERT treatment for PEI is an essential part of supportive therapy to ensure optimal nutritional status in PC patients who will receive surgery, neoadjuvant/adjuvant or palliative treatment. The objective of this review is to increase the awareness about PEI in PC patients and to provide expert recommendations on the use of PERT in resected, borderline resectable and unresectable patients, based on clinical experience and literature review.