Hypoxia and Wnt signaling inversely regulate expression of chondroprotective molecule ANP32A in articular cartilage.

OBJECTIVES: ANP32A is a key protector of cartilage health, via preventing oxidative stress and Wnt hyper-activation. We aimed to unravel how ANP32A is regulated in cartilage. METHODS: A bioinformatics pipeline was applied to identify regulators of ANP32A. Pathways of interest were targeted to study their impact on ANP32A in in vitro cultures of the human chondrocyte C28/I2 cell-line and primary human articular chondrocytes (hACs) from up to five different donors, using Wnt-activator CHIR99021, hypoxia-mimetic IOX2 and a hypoxia chamber. ANP32A was evaluated using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot. In vivo, the effect of hypoxia was examined by immunohistochemistry in mice injected intra-articularly with IOX2 after destabilization of the medial meniscus. Effects of Wnt hyper-activation were investigated using Frzb-knockout mice and wild-type mice treated intra-articularly with CHIR99021. Wnt inhibition effects were assessed upon intra-articular injection of XAV939. RESULTS: The hypoxia and Wnt signaling pathways were identified as networks controlling ANP32A expression. In vitro and in vivo experiments demonstrated increases in ANP32A upon hypoxic conditions (1.3-fold in hypoxia in C28/I2 cells with 95% confidence interval (CI) [1.11-1.54] and 1.90-fold in hACs [95% CI: 1.56-2] and 1.67-fold in ANP32A protein levels after DMM surgery with IOX2 injections [95% CI: 1.33-2.08]). Wnt hyper-activation decreased ANP32A in chondrocytes in vitro (1.23-fold decrease [95% CI: 1.02-1.49]) and in mice (1.45-fold decrease after CHIR99021 injection [95% CI: 1.22-1.72] and 1.41-fold decrease in Frzb-knockout mice [95% CI: 1.00-1.96]). Hypoxia and Wnt modulated ataxia-telangiectasia mutated serine/threonine kinase (ATM), an ANP32A target gene, in hACs (1.89-fold increase [95% CI: 1.38-2.60] and 1.41-fold decrease [95% CI: 1.02-1.96]). CONCLUSIONS: Maintaining hypoxia and limiting Wnt activation sustain ANP32A and protect against osteoarthritis.

ANP32A represses Wnt signaling across tissues thereby protecting against osteoarthritis and heart disease.

OBJECTIVES: To investigate how ANP32A, previously linked to the antioxidant response, regulates Wnt signaling as unraveled by transcriptome analysis of Anp32a-deficient mouse articular cartilage, and its implications for osteoarthritis (OA) and diseases beyond the joint. METHODS: Anp32a knockdown chondrogenic ATDC5 cells were cultured in micromasses. Wnt target genes, differentiation markers and matrix deposition were quantified. Wnt target genes were determined in articular cartilage from Anp32a-deficient mice and primary human articular chondrocytes upon ANP32A silencing, using qPCR, luciferase assays and immunohistochemistry. Co-immunoprecipitation, immunofluorescence and chromatin-immunoprecipitation quantitative PCR probed the molecular mechanism via which ANP32A regulates Wnt signaling. Anp32a-deficient mice were subjected to the destabilization of the medial meniscus (DMM) OA model and treated with a Wnt inhibitor and an antioxidant. Severity of OA was assessed by cartilage damage and osteophyte formation. Human Protein Atlas data analysis identified additional organs where ANP32A may regulate Wnt signaling. Wnt target genes were determined in heart and hippocampus from Anp32a-deficient mice, and cardiac hypertrophy and fibrosis quantified. RESULTS: Anp32a loss triggered Wnt signaling hyper-activation in articular cartilage. Mechanistically, ANP32A inhibited target gene expression via histone acetylation masking. Wnt antagonist treatment reduced OA severity in Anp32a-deficient mice by preventing osteophyte formation but not cartilage degradation, contrasting with antioxidant treatment. Dual therapy ameliorated more OA features than individual treatments. Anp32a-deficient mice also showed Wnt hyper-activation in the heart, potentially explaining the cardiac hypertrophy phenotype found. CONCLUSIONS: ANP32A is a novel translationally relevant repressor of Wnt signaling impacting osteoarthritis and cardiac disease.

[Management of complicated Barrett's esophagus. Observational study carried out in a regional hospital]. / Prise en charge de l'œsophage de Barrett compliqué. Étude observationnelle réalisée dans un centre hospitalier régional.

The incidence of Barrett's esophagus, complication of gastroesophageal reflux disease, is rising in western countries. It is the same for esophageal adenocarcinoma, of which it is the main contributing factor. This retrospective study seeks to report the incidence of these pathologies observed in a regional hospital center and to describe their management. In 5 years, 354 Barrett's esophagus are detected and 34 of them are complicated by high-grade dysplasia or adenocarcinoma. Endoscopic resection is performed in 24 of these patients. The histological analysis of which leads to the conclusion of adenocarcinoma in 20 patients and high-grade dysplasia in the 14 others. The complications of endoscopic and surgical resections are detailed. Their frequency and severity remain low, comparable to data in the literature.

L'incidence de l'œsophage de Barrett, complication du reflux gastro-œsophagien, est en croissance dans les pays occidentaux. Il en est de même de l'adénocarcinome œsophagien dont il est le principal facteur favorisant. Cette étude rétrospective s'attache à rapporter l'incidence de ces pathologies, observées dans un centre hospitalier régional, et à détailler leur prise en charge. En 5 ans, 354 œsophages de Barrett sont détectés et 34 d'entre eux sont compliqués de dysplasie de haut grade ou d'adénocarcinome. Une résection endoscopique est réalisée chez 24 de ces malades. Les analyses histologiques permettent de conclure à un adénocarcinome chez 20 malades et une dysplasie de haut grade chez les 14 restants. Les complications des résections endoscopiques et chirurgicales sont détaillées. Leur fréquence et leur gravité restent faibles, comparables aux données de la littérature.

[Diagnosis and management of liver cysts]. / Diagnostic et traitement des kystes hépatiques.

Cystic hepatic lesions are frequent and sometimes large. They are generally asymptomatic and discovered by chance. The differential diagnosis of these lesions includes congenital, post-traumatic, benign or malignant tumors, as well as infectious pathologies. Conventional or contrast ultrasonography, abdominal computed tomography and magnetic resonance imaging can be used to characterize them. Therapeutic abstention with or without iconographic monitoring constitutes the optimal management of many benign liver cysts without clinical repercussions. Treatments for symptomatic or potentially aggressive lesions may include fenestration, puncture with sclerotherapy, or surgical resection. In this article, the authors discuss how to diagnose and treat the various hepatic cystic lesions.

Les lésions kystiques hépatiques sont fréquentes et parfois volumineuses. Elles sont généralement asymptomatiques et de découverte fortuite. Le diagnostic différentiel de ces lésions inclut des pathologies congénitales, post-traumatiques, tumorales bénignes ou malignes ainsi qu'infectieuses. L'échographie conventionnelle ou avec contraste, le scanner abdominal et la résonance magnétique nucléaire peuvent être utilisés pour les caractériser. L'abstention thérapeutique, avec ou sans surveillance iconographique, constitue la prise en charge optimale de nombreux kystes bénins sans répercussion clinique. Les traitements des lésions symptomatiques ou potentiellement agressives peuvent inclure la fenestration, la ponction avec sclérothérapie ou la résection chirurgicale. Dans cet article, les auteurs discutent des modalités de diagnostic et de traitement des diverses lésions kystiques hépatiques.

[Pre-malignant and malignant diseases of the pancreas, a centralized and multidisciplinary approach]. / Cancers et affections pré-malignes du pancréas Approche centralisée et multidisciplinaire au centre de référence de chirurgie complexe du CHU de Liège.

The incidence of pancreatic cancer has doubled during the past three decades. Pancreatic cancer is projected to become the second leading cause of cancer-related death by 2030. Overall 5-year survival is less than 10 %. It is thus of paramount importance to identify patients at risk to develop pancreatic cancer. The "pancreatic emergency route" and the weekly-organized complex surgery consultations are essential for fast and coordinated investigations for patients diagnosed of a pancreatic lesion. Pancreatic surgery, often preceded by neoadjuvant therapy, remains the only curative treatment if applicable. Implemented to decrease surgical morbidity and mortality, current centralization limits pancreatic resection surgery to a restricted numbers of expert centres in Belgium. Thanks to a close collaboration with the CHR of Liège, the CHR of Huy, the CHR of Bois de l'Abbaye, the Clinique André Renard and Vivalia, the reference centre of the CHU of Liège offers surgical, intensive, anaesthetic, oncological, gastroenterological, radiological and paramedical cares as part of a multidisciplinary approach characterized by expertise in the treatment of adenocarcinoma of the pancreas, 24 hours a day and 7 days a week.

L'incidence de l'adénocarcinome pancréatique a doublé lors des trois dernières décennies. Il devrait devenir la deuxième cause de mortalité par cancer en 2030. La survie globale est inférieure à 10 %. Il est essentiel d'identifier les patients à risque. La route «Urgences Pancréas¼ et les réunions hebdomadaires de concertation de chirurgie complexe assurent une prise en charge rapide et coordonnée pour les patients chez qui une lésion pancréatique suspecte est découverte. La chirurgie pancréatique, généralement précédée d'un traitement néoadjuvant, est la seule option à visée curative. Afin de diminuer la morbi-mortalité liée à cette chirurgie complexe, une convention de centralisation a été imposée par l'INAMI. Grâce à une étroite collaboration médico-chirurgicale regroupant le CHR de Liège, le CHR de Huy, le Centre Hospitalier du Bois de l'Abbaye, la Clinique André Renard et l'association intercommunale Vivalia, le centre de référence du CHU de Liège offre des soins chirurgicaux, intensifs, anesthésiologiques, oncologiques, radiothérapeutiques, gastro-entérologiques, radiologiques, infirmiers et paramédicaux de qualité et ce, dans le cadre d'une approche multidisciplinaire caractérisée par une expertise en matière du traitement de l'adénocarcinome du pancréas, 24 heures sur 24 et 7 jours sur 7.

[Pre-malignant and malignant diseases of the esophagus, a centralized and multidisciplinary approach]. / Prise en charge des cancers et affections pré-malignes de l'oesophage Approche centralisée et multidisciplinaire au centre de référence de chirurgie complexe du CHU de Liège.

Esophageal cancer is the 19th most common cancer in the European Union. Its prognosis remains poor with a 5-year survival rate estimated between 15 % and 25 %. Accurate diagnosis and pre-therapeutic assessment are essential and should allow a rapid start of therapy. Current treatment is based on multimodal management of which surgery remains the cornerstone. Since 2019, Belgium has started an agreement to centralize esophageal surgery in order to improve surgical outcomes. One year after implementation of centralization, our centre shows a low rate of severe complications (Clavien-Dindo classification IIIb-V) of 20 % and a 0 % mortality rate at 30 and 90 postoperative days. Our patients have benefited from a full minimally invasive or hybrid surgical procedure, contributing to those positive results. In the future, all our efforts must be done to improve collaboration between hospitals in order to provide best medical and surgical treatments.

Le cancer de l'oesophage est le 19ème cancer le plus fréquent dans l'Union Européenne. Son pronostic reste sombre avec un taux de survie à 5 ans estimé entre 15 % et 25 %. La précocité du diagnostic et la qualité du bilan pré-thérapeutique sont essentielles et doivent permettre d'initier un traitement rapide. Le traitement repose sur une prise en charge multidisciplinaire et multimodale dont la chirurgie reste la pierre angulaire. En Belgique, le taux de mortalité à 30 et 90 jours post-opératoires étaient de 4,1 % et 9,5 %, respectivement, pour la période allant de 2008 à 2016. Dans une perspective d'amélioration de cette prise en charge, depuis 2019, la Belgique a concentré la chirurgie de l'oesophage dans 10 centres de référence, incluant le CHU de Liège. Un an après centralisation, notre centre présente un taux de complications sévères selon Clavien-Dindo (IIIb-V) de 20 % et des taux de mortalité à 30 et 90 jours de 0 %. Le bilan d'évaluation initial de chaque patient est discuté en concertation multidisciplinaire. Une prise en charge nutritionnelle est discutée avant l'instauration du traitement. Tous nos patients bénéficient d'une approche systématique totalement mini-invasive ou hybride, participant à l'amélioration des résultats sur la morbidité et la mortalité. Une collaboration croissante avec nos hôpitaux partenaires permet d'harmoniser les mises au point et les plans de traitement oncologiques pour le bénéfice des patients.

[Pregastroplasty psychological assessment at the CHU of Liege using the BIPASS]. / Le bilan psychologique prégastroplastie au CHU de Liège inspiré du BIPASS.

Obesity is a chronic disease that has become a major public health problem with a prevalence that has doubled in the past two decades in most industrialized and developing countries. Currently, bariatric surgery represents the most effective treatment for extreme or severe overweight (BMI ? 40 kg/m² or ? 35 kg/m2 with weight-related comorbidities). Pre-operative bariatric surgery psychiatric and psychological assessment is essential for various reasons. In addition to the selection of candidates for the operation, its objectives are to prepare patients for future postoperative changes as well as to optimize their psychological and psychiatric care. This article describes a standardized tool, the BIPASS (Bariatric Interprofessional Psychosocial Assessment Suitability Scale), which allows a quality assessment in the field.

L'obésité est une maladie chronique devenue un problème de santé publique majeur, avec une prévalence qui a doublé au cours des deux dernières décennies dans la majaorité des pays industrialisés et en voie de développement. Actuellement, la chirurgie bariatrique représente le traitement le plus efficace afin de remédier à cette problématique de surcharge pondérale sévère (IMC ? 40 ou ? 35 kg/m² avec complications). L'évaluation psychiatrique et psychologique préopératoire dans le cadre d'une chirurgie bariatrique s'impose pour divers enjeux. Outre la sélection des candidats à l'opération, ses objectifs sont, notamment, de préparer au mieux les patients aux changements futurs postopératoires ainsi que d'optimiser leur prise en charge psychologique et, éventuellement, psychiatrique. Cet article décrit un outil standardisé, le BIPASS (Bariatric Interprofessional Psychosocial Assessment Suitability Scale), qui permet une évaluation de qualité dans le domaine.

[Update in abdominal surgery]. / Evolution en chirurgie abdominale. Avancées techniques, collaboration intra et inter hospitalière.

During the last decade minimal invasive approach progressed in all sectors of abdominal surgery. Technological improvements allowed to perform more complex procedures laparoscopically with increased safety. The implementation of pre-, per- and postoperative protocols with an adaptation of surgical, anesthetic and analgesia methods and the patient's involvement in the healing process led to enhanced recovery after surgery. The centralization of complex esophageal and pancreatic surgery established the CHU of Liège as a tertiary referral institution for complex oncological surgery thanks to a large cooperation with regional hospitals.

La dernière décennie a vu progresser l'approche mini-invasive dans tous les domaines de la chirurgie abdominale. Les améliorations technologiques permettent de réaliser des interventions toujours plus complexes en laparoscopie avec une sécurité accrue. La systématisation de la prise en charge pré-, per- et postopératoire, avec une adaptation des techniques de chirurgie, d'anesthésie et d'analgésie, et une implication du patient dans ce processus ont abouti à une réhabilitation accélérée. La centralisation de la chirurgie complexe de l'oesophage et du pancréas a permis de créer une structure de référence en chirurgie oncologique complexe au CHU de Liège grâce à une large collaboration interhospitalière régionale.

Increased susceptibility to develop spontaneous and post-traumatic osteoarthritis in Dot1l-deficient mice.

OBJECTIVE: We earlier identified that the histone methyltransferase Disruptor of telomeric silencing 1-like (DOT1L) is as a master protector of cartilage health via limiting excessive activation of the Wnt pathway. However, cartilage-specific homozygous Dot1l knockout mice exhibited a severe growth phenotype and perinatal death, which hampered their use in induced or ageing models of osteoarthritis (OA). The aim of this study was to generate and examine haploinsufficient and inducible conditional Dot1l-deficient mouse models to evaluate the importance of DOT1L during post-traumatic or ageing-associated OA onset and progression. METHOD: We used cartilage-specific heterozygous and postnatal tamoxifen-inducible Dot1l knockout mice and performed destabilization of the medial meniscus (DMM) and ageing as OA models. Mice were examined histologically using X-rays and micro-computed tomography (µCT), and cartilage damage and osteophyte formation were assessed based on OARSI guidelines. Immunohistochemistry of DOT1L, H3K79me2, TCF1 and COLX was performed. RESULTS: Both Dot1l-deficient strains exhibit a phenotype characterized by joint remodeling with extensive osteophyte formation and ectopic ossification upon ageing, indicating accelerated development of spontaneous osteoarthritis. In the DMM-induced OA mouse model, absence of Dot1l resulted in increased cartilage damage. Wnt signalling hyper-activation and ectopic chondrocyte hypertrophy were observed in the articular cartilage of both Dot1l-deficient mice. CONCLUSIONS: This study demonstrated the functional relevance of DOT1L in vivo during the development of OA using genetically modified mice. Thus, maintaining or enhancing DOT1L activity during ageing or after trauma might prevent OA onset and progression.

[Parietal surgery in the cirrhotic patient. A litterature review]. / La chirurgie pariétale chez le patient cirrhotique - Revue de la littérature.

The prevalence of liver cirrhosis progresses due to an increased occurrence of hepatitis C viral infection and of Non Alcoholic SteatoHepatopathy (NASH) related to the metabolic syndrome. Cirrhosis is a known risk factor for the development of hernia. The peri-operative morbidity and mortality after abdominal wall surgery is higher in the cirrhotic patient because of postoperative organ failure. The optimal timing for surgery and the method of repair remain controversial, but growing evidence orientates towards elective rather than emergency treatment regardless of the Child-Pugh score.

La prévalence de la cirrhose hépatique augmente du fait de l'élévation de la fréquence de l'infection par le virus C et des hépatopathies liées au syndrome métabolique. La cirrhose favorise la survenue de hernies et d'éventrations. La morbi-mortalité péri-opératoire des patients cirrhotiques est élevée en raison des défaillances d'organes associées à cette pathologie. Le timing et la modalité de la prise en charge chirurgicale des hernies et éventrations restent controversés, mais de plus en plus d'études démontrent un bénéfice à intervenir en électif plutôt qu'en urgence, quel que soit le score de Child-Pugh.

[Comprehensive therapeutic strategy for localized esophageal cancer. Second part : interest of multimodal approaches with or without surgery]. / Comment je traite... les cancers localisés de l'œsophage. Etat actuel des données et stratégie thérapeutique. 2ème partie : l'intérêt des approches multimodales avec ou sans chirurgie.

In recent years, the treatment of esophagus cancer has been completely changed, thus competing the dogma of surgery as the cornerstone treatment. Multimodality treatments as radio-chemotherapy directly followed by surgery, or delayed surgery, significantly improve patient survival compared to surgery alone. Neoadjuvant radiochemotherapy is associated with a higher complete pathologic response rate and improved survival compared to chemotherapy alone. Immediate surgery after radio-chemotherapy is challenged for patients who present a complete clinical response, especially in case of squamous cell carcinoma. Indeed, systematic resection is associated with a significant postoperative mortality rate and has not proven any survival advantage in complete clinical responders as opposed to delayed resection in case of locally persistent or recurrent disease. In squamous cell carcinoma, this could lead to organ preservation, thus avoiding the mortality and durable functional impairment of esophagectomy. This review will discuss the positioning of the multimodality treatment strategy with neoadjuvant radiochemotherapy and chemotherapy and also the strategy of organ preservation.

Depuis quelques années, le traitement du cancer de l'œsophage est en pleine mutation, bousculant ainsi le grand dogme de la chirurgie comme pierre angulaire du traitement. Par rapport à la chirurgie seule, les traitements multimodaux de radiochimiothérapie suivis, directement ou de façon différée, par la chirurgie améliorent significativement les chances de survie prolongée des patients. Comparée à la chimiothérapie néodjuvante, la radiochimiothérapie néoadjuvante démontre un taux de réponse pathologique complet plus élevé qui résulte en une survie prolongée. Chez les très bons répondeurs cliniques, la question de la place de la résection chirurgicale d'emblée est remise en question, surtout pour les carcinomes épidermoïdes. Chez ces patients, la résection systématique par rapport à un acte différé n'offre pas d'avantage en survie, expose le patient à un risque de mortalité significatif alors qu'un certain nombre de patients n'auront jamais à être opérés. Le seul bénéfice actuellement démontré de la résection est une amélioration du contrôle local; or, le devenir du patient est principalement lié à la récidive métastatique. Dans cette revue, nous positionnons et discutons la place des différents traitements multimodaux, chimiothérapie et radiochimiothérapie néoadjuvantes, ainsi que la place de la préservation d'organe par rapport à une chirurgie d'emblée après une radiochimiothérapie.

[Comprehensive therapeutic strategy for localized esophageal cancer]. / Comment je traite... les cancers localisés de l'œsophage. Etat actuel des données et stratégie thérapeutique. 1ère partie : le point sur les approches chirurgicales et non chirurgicales.

Esophageal cancers represent a highly heterogeneous entity mixing two different tumour types : AdenoCarcinoma (ADC) and Squamous Cell Carcinoma (SSC). Developing in the same organ, they are very often considered as a unique pathology and, consequently, the same therapeutic strategy is indiscriminately applied. Esophageal cancer treatments are particularly complex and require a multidisciplinary approach. Despite impressive advances in the tumour statidifaction, surgery, radiotherapy and chemotherapy, the overall prognosis remains grim even at an early stage of the disease. In order to improve the treatment of esophageal cancers and the patient’s survival, we need to consider that ADC and SCC represent two different pathologies requiring specific therapeutic strategies. This review in two parts will present recent data from clinical trials under the scope of tumour histology to set up dedicated therapeutic strategies. In this first part, we explain the restricted role of surgical resection, the prognostic factors and the results of exclusive combined chemotherapy and radiation in localized esophageal cancer.

Les cancers de l'œsophage concernent deux entités d'histologie et de pathogenèse différentes : les carcinomes épidermoïdes (CE) et les adénocarcinomes (ADC). Ils se développent dans un même organe et sont souvent considérés comme une seule et unique maladie avec, comme conséquence, une stratégie thérapeutique identique. Leur traitement est complexe et requiert une prise en charge multidisciplinaire. Bien que les techniques de mise au point de la pathologie, de traitement par chirurgie, de radiothérapie et de chimiothérapie se soient améliorées, le pronostic de la maladie reste péjoratif, même à un stade précoce. L'amélioration de la prise en charge et de la survie des patients nécessite de considérer les CE et les ADC comme deux pathologies distinctes, impliquant des approches thérapeutiques qui leur soient spécifiquement dédiées. Cette revue en deux parties analyse les différents aspects thérapeutiques des cancers de l'œsophage sous l'angle de l'histologie et permet de dégager des stratégies spécifiques. Cette première partie est consacrée aux limites de la résection chirurgicale, aux facteurs pronostiques et aux résultats des traitements par radio-chimiothérapie exclusive des cancers localisés.

[Incidence and treatment of complications observed after endoscopic mucosal resection of superficial digestive tumours in a regional general hospital]. / Incidence et traitement des complications observées après résections endoscopiques muqueuses des tumeurs digestives superficielles dans un Centre Hospitalier Régional.

Superficial digestive tumours resection by endoscopic mucosal resection and sub-mucosal dissection causes very few complications according to the results obtained in expert centers. This work reports the rate of complications observed in a regional hospital, also comparing the results of their therapeutic management. The first 100 patients treated by endoscopic mucosal resection and sub-mucosal dissection, conducted by conventional techniques, were studied. The usual complications (stenosis, bleeding, perforation) were identified and details of their treatment reported. The overall complication rate was 16 %. Symptomatic stenoses are observed in 4 % of patients. Secondary bleeding occurs in 5 % of cases. Endoscopic management of these complications is effective in all cases, when it is attempted. Perforations complicate 7 % of the procedures. Two patients were assigned to surgery, successfully, the other 5 patients were treated by endoscopic sutures without damage. The complication rates observed in our department are comparable with results reported by the reference western centers. Their endoscopic management is usually successful and rescue surgery is unfrequent.

La résection par mucosectomie et dissection sous-muqueuse des tumeurs digestives superficielles n'entraîne que très peu de complications selon les résultats obtenus dans les centres experts. Ce travail rapporte le taux de complications observé dans un centre hospitalier régional, comparant également les résultats de leur prise en charge. Les 100 premiers patients ayant été traités par mucosectomie et dissection sous-muqueuse, effectuées selon les techniques classiques, ont été étudiés. Les complications habituelles (sténoses, hémorragies et perforations) ont été répertoriées ainsi que les détails de leur traitement. Le taux global de complications est de 16 %. Les sténoses symptomatiques affectent 4 % des patients. Les hémorragies secondaires surviennent dans 5 % des cas. La prise en charge endoscopique de ces complications est efficace dans tous les cas, lorsqu'elle est tentée. Les perforations compliquent 7 % des procédures. Deux patients ont été confiés à la chirurgie, avec succès, les 5 autres patients ont été traités par sutures endoscopiques sans séquelle. Le taux de complications observé dans notre service est comparable aux résultats rapportés par les centres occidentaux de référence. Leur prise en charge endoscopique est régulièrement efficace et le recours à la chirurgie est peu fréquent.

Solid pseudopapillary tumor of the pancreas: a report of six cases.

BACKGROUND: Solid pseudopapillary tumor of the pancreas (SPTP) is a rare pancreatic neoplasm. The aim of this study was to discuss the clinical presentation, management, and outcome of patients with this kind of tumor. MATERIALS AND METHODS: A retrospective review was performed in 6 patients with SPTP surgically treated between January 2004 and September 2011 in our hospital. RESULTS: All the 6 patients were female. The mean age of the patients was 39 years (range, 18 to 67 years). The main clinical presentation was abdominal pain or discomfort, however a third of the patients were asymptomatic. The mean size of the tumor was 9.7 cm (range, 2.5 to 18 cm). Three tumors had a well defined capsule, 3 tumors extended in the pancreas. Four of the 6 tumors had a cystic component, and calcifications were observed in one tumor. No lymph node involvement, no lymphatic invasion and no nerve invasion were observed. One tumor showed an infiltration of the splenic vein, and another patient had a liver metastasis with complete resection. Distal pancreatectomy (n = 3), local resection (n = 1), cephalic duodenopancreatectomy (n = 1), and distal pancreatectomy associated with a right hepatectomy (n = 1) were performed. The main postoperative complication in the short-term was bleeding (n = 1), and long-term the development of an insulin-requiring diabetes (n = 2). No patient received adjuvant therapy. Overall mortality rate was 0%. All patients were still alive without recurrent disease with a median follow up of 36.2 months. CONCLUSION: Patients with SPTP have an excellent prognosis after its complete removal, even if it is a minimized resection.

[Metabolic surgery: an increasing place in the management of diabetes]. / Chirurgie métabolique: une place croissante dans le traitement du diabète.

Bariatric surgery becomes more and more important in the management of the obese patient with type 2 diabetes, especially in case of failure of medical approaches. Metabolic improvement results not only from weight loss and the subsequent reduction in insulin resistance, but also from modifications of digestive hormones (especially incretins) that contribute to promote insulin secretion. This new paradigm, moving from bariatric surgery to metabolic surgery, opens new perspectives. The present article briefly describes innovative surgical techniques focusing on endocrine and metabolic improvement rather than on weight loss, the preliminary results of metabolic surgery in patients with type 2 diabetes and a body mass index <35 kg/m2 and, finally, some data regarding the surgical management of obese patients with type I diabetes not well treated with classical medical means.

Esophageal cancer surgery in patients older than 75: long term results.

PURPOSE: The purpose of this study was to evaluate short and long term results after esophageal cancer resection in patients older than 75. METHODS: We retrospectively analyzed the database of esophageal cancer surgically treated in our department between January 2003 and December 2009 to identify patients older than 75. The preoperative, operative, postoperative and long term characteristics were analyzed. RESULTS: Among 137 patient, 23 were older than 75. The histological subtype was adenocarcinoma in 100%. The surgical techniques were a "Lewis-Santy" procedure in 43%, a trans-hiatal resection in 22%, a "Sweet" procedure in 13%, a stripping in 13% and a McKeown procedure in 9%. The in-hospital postoperative mortality was 13%. The in-hospital postoperative morbidity (Dindo-Clavien Grade >2, deceased patients included) was 26%. In univariate analysis, no statistically significant risk factor of morbidity was found. A Charlson Comorbidity Index >2 was, in univariate analysis, the sole risk factor of postoperative mortality (p = 0.0362). The mean hospital stay was 22 +/- 12 days. The median survival was 24.2 months. The 5-year overall survival was 39% and the 5-year disease free survival was 26%.57% of long-term deaths were not cancer related. CONCLUSION: Esophageal surgery performed in selected patients older than 75 has an acceptable morbidity and mortality but when a severe complication occurs, it leads to death in half of the cases. Surgery enables a long term survival benefit. This study confirmed our attitude of not considering age as a contra-indication for esophageal surgery but rather considering general status, self-reliance and associated comorbidities for patients' selection.

[Metabolic surgery: an evolution (or revolution) of bariatric surgery?]. / La chirurgie métabolique, vers une (r)evolution de la chirurgie bariatrique?

Bariatric surgery has proven its efficacy to obtain a marked and sustained weight loss and dramatically improves metabolic control in obese patients. The frequently observed remission of type 2 diabetes occurs very early, before any marked weight reduction. Increasing evidence suggests that this favourable effect results from profound changes in gut hormones involved in the regulation of energy intake behaviour and glucose homeostasis rather than simply from mechanical food restriction or malabsorption imposed by the surgical procedure. The better knowledge of these pathophysiological mechanisms, especially well studied with Roux-en Y gastric bypass, resulted in recent innovation in the technical procedures leading to a shift from bariatric surgery to metabolic surgery. Such type of surgery is currently evaluated in patients with type 2 diabetes, but with only a moderate obesity (BMI < 35 kg/m2), or even without obesity (BMI < 30 kg/m2). The Belgian Metabolic Intervention (BMI) Study Group would like to contribute very soon to this evaluation in a multidisciplinary approach.

Liver transplant donation after cardiac death: experience at the University of Liege.

OBJECTIVE: Donation after cardiac death (DCD) has been proposed to overcome in part the organ donor shortage. In liver transplantation, the additional warm ischemia time associated with DCD procurement may promote higher rates of primary nonfunction and ischemic biliary lesions. We reviewed the results of liver transplantation from DCD. PATIENTS AND METHODS: From 2003 to 2007, we consecutively performed 13 controlled DCD liver transplantations. The medical records of all donors and recipients were retrospectively reviewed, evaluating in particular the outcome and occurrence of biliary complications. Mean follow-up was 25 months. RESULTS: Mean donor age was 51 years, and mean intensive care unit stay was 5.4 days. Mean time between ventilation arrest and cardiac arrest was 9.3 minutes. Mean time between cardiac arrest and arterial flushing was 7.7 minutes. No-touch period was 2 to 5 minutes. Mean graft cold ischemia time was 295 minutes, and mean suture warm ischemia time was 38 minutes. Postoperatively, there was no primary nonfunction. Mean peak transaminase level was 2546 UI/mL. Patient and graft survival was 100% at 1 year. Two of 13 patients (15%) developed main bile duct stenosis and underwent endoscopic management of the graft. No patient developed symptomatic intrahepatic bile duct strictures or needed a second transplantation. CONCLUSIONS: Our experience confirms that controlled DCD donors may be a valuable source of transplantable liver grafts in cases of short warm ischemia at procurement and minimal cold ischemia time.

Organ procurement after euthanasia: Belgian experience.

Euthanasia was legalized in Belgium in 2002 for adults under strict conditions. The patient must be in a medically futile condition and of constant and unbearable physical or mental suffering that cannot be alleviated, resulting from a serious and incurable disorder caused by illness or accident. Between 2005 and 2007, 4 patients (3 in Antwerp and 1 in Liège) expressed their will for organ donation after their request for euthanasia was granted. Patients were aged 43 to 50 years and had a debilitating neurologic disease, either after severe cerebrovascular accident or primary progressive multiple sclerosis. Ethical boards requested complete written scenario with informed consent of donor and relatives, clear separation between euthanasia and organ procurement procedure, and all procedures to be performed by senior staff members and nursing staff on a voluntary basis. The euthanasia procedure was performed by three independent physicians in the operating room. After clinical diagnosis of cardiac death, organ procurement was performed by femoral vessel cannulation or quick laparotomy. In 2 patients, the liver, both kidneys, and pancreatic islets (one case) were procured and transplanted; in the other 2 patients, there was additional lung procurement and transplantation. Transplant centers were informed of the nature of the case and the elements of organ procurement. There was primary function of all organs. The involved physicians and transplant teams had the well-discussed opinion that this strong request for organ donation after euthanasia could not be waived. A clear separation between the euthanasia request, the euthanasia procedure, and the organ procurement procedure is necessary.

[Treatment of (unresectable) hepatocellular carcinoma at an intermediate or advanced stage]. / Straitement des carcinomes hépatocellulaires à un stade intermédiaire ou avancé.

Hepatocellular carcinoma is the main primitive tumor of the liver. It occurs in the setting of liver cirrhosis in more than 90% of the cases in developing countries. The prognosis depends on the size, number and extension of the tumor as well as on the severity of the underlying liver disease. The Barcelona Clinic Classification takes into account these different parameters and helps the clinician in the therapeutic decision. Some patients (around 25%) are amenable to therapy with a curative intent (liver transplantation, resection, destruction by radiofrequency). In patients with hepatocellular carcinoma at an intermediate stage, lipiodolized chemoembolization gives a survival advantage in comparison with placebo. No conventional regimen of chemotherapy has a proven survival benefit. In patients with a hepatocellular carcinoma at an advanced stage, sorafenib, an oral multi-targeted kinase inhibitor, is the first compound to demonstrate a significant effect on survival free of disease progression in a selected group of patients. Its toxicity profile is particularly favourable. Combination of surgical and medical therapies should be properly evaluated in clinical trials in the near future.