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Resume Introduction L’enterite radio-induite chronique (ERC) resistante au traitement medical necessite une chirurgie. Notre etude visait a correler l’histologie des ERC a la presentation clinique et a la recidive postoperatoire. Patients et methodes Les donnees anatomopathologiques des patients operes d’une resection de l’intestin grele entre 2006 et 2017 ont ete correlees aux donnees cliniques initiales et a la recidive postoperatoire de l’ERC (occlusion, besoin de nutrition parenterale) lors d’un suivi median de 32 mois. Resultats Quarante-et-un ans patients ont ete etudies (39 femmes, âge median 62 ans lors de l’irradiation pour cancer pelvien gynecologique dans 80 % des cas). Le delai median de la chirurgie apres l’irradiation etait de 3 ans. Les resections ileo-caecales (80 %) ont retire 60 cm de grele (en mediane). Histologiquement, une arteriopathie obliterante diffuse etait presente chez 24 (59 %) patients, significativement associee a une amyotrophie, une atrophie villositaire ou des ulcerations observees chez 66, 63 et 34 % des patients respectivement (p Conclusion L’enterite radio-induite necessitant une chirurgie 13 ans en moyenne apres l’irradiation presentait une arteriopathie obliterante diffuse et des caracteristiques ischemiques en histologie. Dans notre centre, la moitie des patients ont ete gueris par la chirurgie. L’arteriopathie n’etait pas un facteur de risque de recidive postoperatoire.

Liver sinusoidal obstruction syndrome (SOS) is a well-established complication of myeloablative conditioning regimens used in hematopoietic stem cell transplantation. Hepatic venous pressure gradient (HVPG)10 mmHg was described as an accurate diagnostic tool for SOS in the 1990s. However, epidemiology and presentation of SOS have dramatically changed. Moreover, elementary histological lesions influencing HVPG are unknown.We retrospectively analyzed the charts of all patients who underwent transjugular liver biopsy with HVPG measurement for a clinical suspicion of SOS at our center. Two expert pathologists unaware of the presence or absence of SOS reviewed all liver samples and graded elementary histological lesions according to a semi-quantitative scoring definedOut of the 77 included patients, the 30 patients with SOS had higher HVPG than the 47 patients without SOS (median 14 mmHg [IQR 10-18],Even though HVPG is higher in patients with SOS, low HVPG values do not rule out SOS. Thus, HVPG cannot be used alone, and should be combined with transjugular liver biopsy, for the diagnosis of SOS.Hepatic venous pressure gradient10 mmHg has been described as an accurate tool for the diagnosis of liver sinusoidal obstruction syndrome after hematopoietic stem cell transplantation. This study shows that the sensitivity and specificity of hepatic venous pressure gradient measurement for sinusoidal obstruction syndrome are insufficient, so that liver pressure measurement should be combined with a liver biopsy in this setting.

International audience; Hepatic veno-occlusive disease (HVOD), alias sinusoidal obstruction syndrome, may develop as a complication of chemotherapy in the setting of hematopoietic stem cell transplantation. HVOD is less frequently described after exposure to chemotherapy in the nontransplant setting and can also be a complication after ingestion of toxins, such as pyrrolizidine alkaloids. Veno-occlusive disease may also affect the lungs, and it is therefore termed pulmonary veno-occlusive disease (PVOD). Similarly, PVOD can develop after exposure to chemotherapeutic agents in the treatment of solid and hematological malignancies. In addition, PVOD has also been linked to autoimmune disorders and occupational solvent exposure. Finally, the heritable form of PVOD is due to biallelic mutations of the EIF2AK4 gene. Both HVOD and PVOD share common histopathological features and pathophysiologic mechanisms. Both clinical disorders are rare complications that can appear after exposure to the common inciting trigger of chemotherapeutic agents. The present review aims to summarize the current knowledge of HVOD and PVOD and to describe both similarities as well as differences regarding both conditions.

Resume L’analyse histologique rigoureuse des biopsies coliques est indispensable pour etablir un diagnostic de colite et orienter la prise en charge du malade. Certaines colites presentent des caracteristiques histologiques specifiques permettant un diagnostic precis (colites microscopiques ou colites de type ischemique). Mais la plupart des colites inflammatoires aigues ou chroniques ne presentent pas de specificite etiologique et une confrontation clinique est necessaire prenant en compte l’aspect macroscopique des lesions (endoscopie), la duree des symptomes de diarrhee, l’anamnese, le contexte medical et les therapies en cours, la notion d’un voyage recent… Le pathologiste decrit le cadre lesionnel de la colite et propose des diagnostics en fonction des renseignements cliniques fournis. Si une discordance ou une incertitude subsiste, des biopsies iteratives a distance d’un traitement antibiotique peuvent etre recommandees. La bonne cooperation entre l’endoscopiste et le pathologiste garantit la fiabilite du diagnostic precis de colite.

Distinction of paraganglioma (PGL) from epithelial neuroendocrine tumors (NETs) can be difficult as they can mimic each other by nested architecture and expression of neuroendocrine markers. In this study we examined differential diagnostic markers in 262 PGLs (142 adrenal pheochromocytomas and 120 extra-adrenal PGLs), 9 duodenal gangliocytic PGLs and 3 cauda equina PGLs, and 286 NETs (81 GI, 78 pancreatic, 42 thoracic, 37 medullary thyroid carcinomas, and 48 high-grade NETs including 32 small cell carcinomas of lung). While keratin expression was nearly uniform in NETs with the exception of few tumors, extensive keratin expression was seen in only one PGL (90% of PGLs but only in 2% of NETs, usually focally. Tyrosine hydroxylase (TH) was expressed in >90% of adrenal, abdominal, and thoracic PGLs but only in 37% of head and neck PGLs reflecting their variable catecholamine synthesis. Focal or occasional extensive TH-expression was detected in 10% of NETs. CDX2 was a helpful discriminator seen in 28% of pancreatic and most GI NETs but in no PGLs. SOX10 detected sustentacular cells in 85% of PGLs and 7% of NETs, while GFAP detected sustentacular cells mainly in PGLs of neck and was absent in NETs. Duodenal gangliocytic PGLs (n = 9) and all cauda equina PGLs (n = 3) expressed keratins, lacked GATA3, showed no or minimal TH expression as some NETs, and contained SOX10 and S100 protein-positive spindle cells negative for GFAP. Ganglion-like epithelioid cells were keratin-positive and negative for TH and SOX10 differing from true ganglion cells. We conclude that duodenal gangliocytic and cauda equina PGLs have a NET-like immunoprofile and differ from ordinary PGLs. NETs can be distinguished from PGLs by their expression of keratins and general lack of GATA3, TH, and GFAP-positive sustentacular cells, and sometimes by expression of CDX2 or TTF1.

The therapeutic management of malignant colorectal polyp with endoscopic resection is mainly based on specific histopathological criteria. The quality of these criteria is strongly linked to the management of the endoscopic specimen. The French Pathology Society drafted a standardized pathological report with guidelines for the macroscopic management of the endoscopic specimen and explanatory notes for each histopathological criteria. These guidelines are based on the TNM AJCC/UICC classification, 8th edition and the WHO 2010 classification of colorectal tumors, the recommendations of the French Society of Digestive Endoscopy, the synthesis of the literature and on international consensus for prognostic criteria. The pathological report of a malignant colorectal polyp must clearly mention: the histological type and the size of the polyp, the pT stage and the following five prognostic criteria: the value of the resection margins, the level of tumor invasion into the submucosa, the grade of the tumor, the absence or presence of vascular emboli and of tumor budding.

Introduction et but de l’etude Bien que l’insuffisance intestinale (II) traitee en centre expert de nutrition parenterale (NP) ait un pronostic a long terme favorable, une origine ischemique par infarctus mesenterique (IM) en constitue un facteur pronostique pejoratif independant et est toujours consideree par les medecins comme une situation dramatique. Le but de ce travail etait d’etudier les resultats a long terme de la rehabilitation intestinale des survivants a un IM. Materiel et methodes Etude de cohorte retrospective des patients consecutifs pris en charge en centre expert de NP de 2006 a 2015 apres resection intestinale pour un IM. Les patients admis pour une ischemie mesenterique evolutive ou non chirurgicale n’etaient pas inclus. Les facteurs associes a la dependance a la NP et a la recidive d’ischemie mesenterique etaient evalues par un modele multivarie de regression de Cox. Les resultats sont rapportes en Hazard Ratio (HR) avec leurs intervalles de confiance a 95 % (IC95 %). Resultats et analyse statistique Nous avons inclus 184 patients (âge median de 51 ans) admis dans notre unite apres un delai median de 3 mois apres chirurgie pour un IM. Au diagnostic, l’IM etait le premier accident vasculaire chez 53 % des patients et le taux plasmatique de lactate etait normal dans 51 % des cas. Dans le centre referent initial, le diagnostic d’IM avait ete retarde (delai diagnostique median : 2 jours) et son traitement avait ete insuffisant (taux de revascularisation : 15 %), aboutissant a une resection intestinale et une II chez tous les patients. Apres rehabilitation intestinale multidisciplinaire (nutritionnelle, vasculaire et digestive), la probabilite de survie a 3 ans etait de 86 %, sans recidive d’IM, sans stomie ni NP residuelle dans respectivement 94 %, 70 % et 47 %. En analyse multivariee, les facteurs predictifs de sevrage de la NP etaient : la revascularisation au stade initial de l’IM [HR = 2,4 ; IC95 % = 1,1–5,2 ; p = 0,02], une longueur de grele restant > 50 cm [51–150 cm : HR = 3,8 ; IC95 % = 1,8–8,0 ; > 150 cm : HR = 9,7 ; IC95 % = 3,9-23,8 ; p Conclusion Les patients en II survivants a un IM se sont initialement presente a un stade d’ischemie mesenterique precoce, potentiellement reversible, mais ont ete diagnostiques avec delai et sous-traites. Une rehabilitation intestinale multidisciplinaire en centre expert a cependant permis une survie a long terme sans NP elevee. Une reconnaissance precoce du diagnostic et une revascularisation tant au stade aigu qu’au stade de rehabilitation sont des facteurs pronostics essentiels.

Background: Crohn's disease displays heterogeneity in terms of disease location, progression and response to treatment. Most patients require an intestinal resection due to complicated disease, and a majority of them will experience disease recurrence. We aimed to characterize biological pathways driving postoperative recurrence and to identify predictors which could guide therapeutic management. Methods: In this multicentre prospective study, we conducted transcriptome analysis on ileal mucosa of CD patients undergoing ileocolonic resection. Samples were collected from the most inflamed part of the ileum (n=200), from the ileal resection margin (n=149) and in the neo-terminal ileum 6 months after surgery (n=122). The primary endpoint was postoperative endoscopic recurrence at month 6. We applied a regression model to identify gene signatures predicting for endoscopic recurrence. Findings: Molecular patterns of early endoscopic recurrence significantly differed from those observed in chronic inflammation. Gene expression analysis of the inflamed area of the surgical specimens identified clusters of CD patients. However, pathway gene signatures at the ileal margin were superior to those of the inflamed area to predict postoperative outcome. Several pathways, including JAK/STAT signalling, cell adhesion molecules and extracellular matrix protein were associated with a higher risk of endoscopic recurrence. JAK/STAT pathway activation at the ileal margin predicted early postoperative endoscopic recurrence (AUC of 0*74) and was associated with a higher of clinical relapse on the long term. A significant increase of p-STAT3 levels at the ileal margin was associated with severe endoscopic recurrence (i3, i4) compared to no recurrence (i0) (p=0*02) and moderate recurrence (i1, i2) (p=0*04). Interpretation: Gene expression analysis at the ileal margin of the surgical specimen may strongly predict postoperative outcome. The inflammatory processes associated with postoperative recurrence differ from those engaged in chronic inflammation. Activation of JAK/STAT signalling at the ileal margin of the surgical specimen is predictive of postoperative recurrence and should be specifically targeted. Trial Registration: ClinicalTrials.gov (NCT03458195). Funding Statement: This work was supported by Helmsley Charitable Trust and the Institut national de sante et de la recherche biomedical (INSERM). Declaration of Interests: SN received honoraria from MSD, Abbvie, Takeda, Janssen, HAC Pharma, Tillots, Ferring, and Novartis. BP received honoraria from AbbVie, MSD, Takeda, Janssen, Bioagaran, and Ferring. AB received honoraria from MSD, Abbvie, Ferring, Takeda, Vifor Pharma, Sanofi-Aventis, Hospira, and Janssen. XT received honoraria from Abbvie, MSD, Takeda, Ferring, Norgine, and Janssen. MF received honoraria from AbbVie, MSD, Takeda, Janssen, Pfizer, Ferring, and Boehringer. PS received honoraria from Takeda, MSD, Biocodex, Ferring and Abbvie and financial support from Takeda. MA received honoraria from Janssen, Takeda, Pfizer, MSD, Abbvie, Ferring, Amgen, Biogen, Celgene, and Genentech/Roche. All other authors have no conflict of interest regarding this study. Ethics Approval Statement: All patients provided an informed written consent. The study was approved by AFFSAPS (IDRCB: 2009-A00205-52) and the French Ethic Committee (CPP 2009/17).

Inflammatory hepatocellular adenomas (IHCA), which accounts for 40% to 50% of all hepatocellular adenomas are characterized by the activation of the IL6/JAK/STAT pathway. We herein report the case of a 52-year-old woman presenting with severe multiple typical IHCA that regressed dramatically on treatment with fenofibrate, a PPAR agonist known to prevent IL6-induced inflammation experimentally and in humans. Further similar observations are needed to ascertain the potential benefit of this therapeutic approach for large or unresectable IHCA.

Resume Le traitement de l’insuffisance intestinale chronique, dont la principale cause est le syndrome de grele court, repose sur la nutrition parenterale prolongee. La maladie hepatique, par son evolution possible vers la cirrhose, est la plus menacante des complications associees a l’insuffisance intestinale chronique. Ses facteurs de risque sont associes aux modalites de la nutrition parenterale et a la maladie causale de l’insuffisance intestinale chronique. Le repos digestif et le syndrome de grele court sont des facteurs de risque de lithiases biliaires. La steatose est une lesion dont l’origine est principalement nutritionnelle (exces de glucose et/ou de lipides, nutrition parenterale continue). Les principaux facteurs de risque de cholestase sont la resection intestinale, la pullulation bacterienne intestinale et les infections, les apports d’acides gras polyinsatures a longue chaine ω-6 et de phytosterols par certaines emulsions lipidiques. L’inflammation chronique hepatique, autre facteur de risque de maladie hepatique, peut etre secondaire a des infections recidivantes, la translocation bacterienne ou toxinique, l’apport d’acides gras polyinsatures a longue chaine ω-6 (precurseurs de mediateurs de l’inflammation). La fibrose, phenomene cicatriciel predisposant a la cirrhose, peut etre compliquee d’hypertension portale et d’insuffisance hepatique ; son seul traitement est la transplantation hepato-intestinale. La prevention repose sur l’identification des patients a risque de maladie hepatique compliquee et la prise en charge optimale de la pathologie et de la nutrition parenterale. La surveillance en routine repose sur des marqueurs biologiques plus ou moins sensibles et specifiques, ainsi que sur l’echographie. La ponction-biopsie hepatique a l’aiguille est necessaire au diagnostic de fibrose, en particulier pour poser l’indication de transplantation combinee foie-intestin.

Background & Aims The aim of this study was to evaluate the specificity of the infiltration of digestive tract mucosa by immunoglobulin (Ig) G4–positive plasma cells in patients with autoimmune pancreatitis (AIP), as compared with normal or inflammatory mucosa. Methods Plasma cell infiltration, CD138 and IgG4 immunostaining of digestive biopsies were compared in 4 groups of patients: AIP type 1 (n = 19); AIP type 2 (n = 4) with inflammatory bowel disease (IBD); IBD without pancreatic disorders (n = 20); and controls (n = 26). Results With AIP type 1 versus controls, more plasma cells were present in the gastric mucosa of AIP (P = .02) without difference concerning IgG4+ plasma cells at any biopsy site. With AIP type 1 versus IBD, colonic mucosa was more often abnormal (P = .004), and more CD138 (P = .02) and IgG4 plasma cells (P = .0002) were counted in the colon biopsies of IBD. With AIP type 2 versus IBD, no difference for plasma cell and IgG4 infiltration was found. Conclusions IgG4-positive plasma cells are not more numerous in the digestive mucosa of AIP patients than in controls, but they are more abundant in the colon of IBD patients than in AIP patients.

The ability to predict response after chemoradiotherapy in rectal adenocarcinoma may allow selecting patients to whom less invasive surgical treatment could be proposed. Tumor hypoxia has been implicated in the mechanisms of resistance to chemoradiotherapy in several malignancies. The aim was to identify morphological criteria and molecular markers of hypoxia associated with chemoradiotherapy response. Clinicopathologic data from 61 patients (35 male, 60.5 ± 10 years) undergoing rectal cancer resection after neoadjuvant chemoradiotherapy were collected. Pretreatment biopsies, available for 40 patients, were immunostained for hypoxia markers (carbonic anhydrase 9, glucose transporter 1, chemokine receptor 4) and microvascular density determination. Mean tumor size was 2.7 ± 1.6 cm. Twenty-one patients (34%) were considered as responders, that is, having significant or complete primary tumor regression without lymph node metastasis. Compared to other patients, responders had significantly more often flat tumors with or without ulceration (57% versus 18%, P = .01) and less vascular and/or neural invasions (9% versus 65%, P < .0001) or tumor necrosis (9% versus 41%, P < .01), respectively. Regarding pretreatment biopsies, carbonic anhydrase 9 expression was significantly lower in responders (7% versus 46%, P = .012). This study showed that tumor necrosis as an overexpression of carbonic anhydrase 9 was an effective molecular marker of postchemoradiotherapy response. This might suggest a key role of hypoxia in resistance mechanisms of chemoradiotherapy in rectal adenocarcinoma. This study highlighted the importance of predictive criteria to chemoradiotherapy response in proposing to selected patients an alternative treatment (eg, local resection) to more radical surgery.

Background & Aims Ulcerative colitis (UC) is a chronic inflammatory disorder that affects the colonic epithelium. Epidemiology studies indicate an environmental component is involved in pathogenesis, although the primary changes in the digestive epithelium that cause an uncontrolled inflammatory response are not known. Animal studies have shown that altered endoplasmic reticulum (ER) stress response initiates intestinal inflammation in epithelial tissues, but abnormalities associated with ER stress have not been identified in patients with UC. Methods Using immunoblotting, real-time polymerase chain reaction, immunohistochemistry, and immunofluorescence analyses, we assessed ER stress signaling in uninflammed colonic mucosa from patients with UC and controls. Genome-wide microarray analysis of actively translated polysome-bound messenger RNA was performed using samples of unaffected mucosa from patients with UC, and data were compared with those from controls. Results Inositol-requiring kinase and activating transcription factor signaling pathways were activated in inactive colonic epithelium from patients with UC; these mediate proinflammatory and regenerative responses. Blocking phosphorylation of the translation initiation factor 2 (eIF2α), which mediates the integrated stress response, deregulated initiation of translation and reduced the numbers of stress granules in colonic epithelial cells from patients with UC. Genome-wide microarray analysis of actively translated, polysome-bound messenger RNA from patients revealed changes in protein translation that altered colonic epithelial barrier function (levels of detoxification and antioxidant enzymes and proteins that regulate the cell cycle, cell-cell adhesion, and secretion), compared with controls. Conclusions Colonic mucosa samples from patients with UC have defects in the eIF2α pathway that controls protein translation and the cell stress response. This pathway might be investigated to identify new therapeutic targets for patients with UC.

Common sites of colorectal breast carcinoma metastasis are bones, lungs, the central nervous system and the liver. Metastases in the gastrointestinal (GI) tract are rare and especially involve the stomach rather than the colon. Clinical or radiological features usually cannot differentiate them from a primary colorectal tumor, resulting in inappropriate treatment. In some cases, this lesion suggests multifocal spread of breast cancer with peritoneal carcinomatosis. Colorectal breast cancer metastasis is a rare finding and there is no consensus on the management of these lesions. The present case report describes a 69-year-old female with metastatic breast cancer presenting as an obstructive tumor of the transverse colon.

Resume Objectif La panniculite mesenterique (PM), la mesenterite sclerosante (MS) et la lipodystrophie mesenterique (LM) sont les trois formes histopathologiques d’une meme maladie inflammatoire rare du mesentere. Sa pathogenie est mal connue ; l’hypothese d’un trouble dysimmunitaire est evoquee. Le but de notre travail etait de rechercher des arguments histologiques pour appuyer cette hypothese. Materiel et methodes Tous les patients avec un diagnostic de maladie inflammatoire mesenterique porte a l’hopital Beaujon ont ete retrospectivement analyses. L’etude comportait une relecture histologique et une etude immunohistochimique avec les anticorps IgG4, CD3 et CD8. La nature dysimmunitaire de la maladie etait definie par : un contingent plasmocytaire superieur ou egal a 30 %, des polynucleaires eosinophiles superieur ou egal a 10 %, un rapport de lymphocytes T CD8/CD3 superieur ou egal a 30 % et un nombre de plasmocytes IgG4+ superieur ou egal a 30 au champ × 400. Les cas ont ete classes selon le composant cellulaire predominant en PM (infiltrat lymphoide/plasmocytaire), MS (fibrose), LM (necrose du tissu adipeux). Resultats Treize patients (sept hommes, six femmes) ont ete etudies, d’âge moyen de 57 ans (21–80 ans) ; on disposait d’un bloc paraffine pour dix d’entre eux. Le diagnostic etait fait par biopsie chirurgicale chez neuf des 13 patients. Les presentations cliniques et histologiques etaient heterogenes : une masse mesenterique etait le mode de revelation le plus frequent (six sur 13 patients) et les formes histologiques etaient toutes representees avec trois, cinq et cinq cas de PM, MS et LM, respectivement. L’etude histologique notait de nombreux polynucleaires eosinophiles (> 10 %) dans trois cas sur 13 (23 %, repondant tous a une MS) et de nombreux plasmocytes (> 30 %) dans six cas/13 (46 %). L’immunohistochimie (realisee sur dix sur 13 cas) montrait une forte composante de lymphocytes T CD8+ (CD8/CD3 > 30 %) dans huit cas (80 %) et un taux eleve de plasmocytes dans quatre cas soit dans 31 % des maladies inflammatoires du mesentere (IgG4+ > 30/× 400). Conclusion Nos resultats montrent que les maladies inflammatoires du mesentere sont heterogenes : une forte composante plasmocytaire, eosinophile ou lymphocytaire T CD8+ etait presente dans 46, 23 et 80 % des cas, respectivement ; les eosinophiles n’etaient visibles que dans les formes sclerosantes. Seuls 31 % des cas comportaient un taux eleve de plasmocytes IgG4+, suggerant une pathogenie differente des maladies a IgG4.

Background & Aims: Because there is a low risk of malignancy for intraductal papillary and mucinous neoplasms of the pancreas (IPMNs) confined to branch ducts (BD), patient follow-up evaluation without surgery is possible. The aim of this study was to assess time-related morphologic changes and risk of progress to malignancy in patients with BD IPMN. A prospective design was used in an academic tertiary referral center. Methods: All consecutive patients seen from 1999 to 2005 with highly suspected IPMNs confined to BD without criteria suggesting a malignant development (mural nodule, cyst wall thickness >2 mm, BD diameter >30 mm, or main pancreatic duct involvement) were followed up prospectively using computerized tomography, magnetic resonance cholangiopancreatography, and endoscopic ultrasonography. Results: A total of 121 patients (median age, 63 y) were included. After a median follow-up period of 33 months, no morphologic changes had occurred in 88 patients. The size of the cyst increased in 30 of the 33 remaining patients, and 12 developed criteria suggesting a malignant development. Surgery, performed in 8 of 12 patients, found 4 IPMN-adenomas, 1 borderline-IPMN, and 4 IPMN carcinoma in situ. The 4 remaining patients did not undergo surgery because of severe comorbid conditions in 2, change in reference hospital in 1, and a mural nodule considered being sequelae of previous fine-needle aspiration in 1 patient. The only factor associated with signs suggesting malignant development was an increase in cyst size to more than 5 mm during the follow-up evaluation. Conclusions: In patients with IPMNs confined to BD, morphologic changes are rare events, justifying a nonsurgical approach. Careful follow-up evaluation remains necessary, particularly in patients with an increase in BD size.

Resume La maladie exostosante est une maladie a transmission autosomique dominante caracterisee par la survenue de tumeurs osseuses metaphysaires recouvertes de cartilage. Ces exostoses siegent generalement au niveau des membres et sont le plus souvent benignes. La complication majeure de ces exostoses est leur possible degenerescence maligne, notamment en osteochondrosarcome. Nous rapportons un phenotype rare de la maladie : un patient dont la transformation maligne d’une exostose lombaire a ete revelee par une symptomatologie digestive obstructive.

Resume Les tumeurs secretant du vasoactive intestinal peptide (VIP) sont essentiellement d’origine epitheliale. Les tumeurs derivees du tissu sympathique, exceptionnelles chez l’adulte, peuvent egalement synthetiser cette hormone. Nous rapportons l’observation d’une malade âgee de 40 ans ayant un ganglioneuroblastome metastatique revele par un syndrome de Verner-Morrison. La diarrhee a disparu apres resection chirurgicale de la tumeur primitive et des metastases hepatiques. La prise en charge de ces tumeurs n’est pas codifiee chez l’adulte du fait de leur rarete.

Background/Aims Endoplasmic reticulum (ER)-related unfolded protein response (UPR) is mediated by PKR-like ER kinase (PERK), ATF6 and IRE1. PERK phosphorylates eukaryotic translation initiation factor-2α (eIF2α) to attenuate protein synthesis, including in NF-κB-dependent antiapoptotic proteins. We hypothesized that an altered UPR in the liver may sensitize cirrhotic livers to LPS-induced, TNFα-mediated apoptosis. Thus, we examined in vivo UPR and NF-κB activity in livers from cirrhotic and normal LPS-challenged rats. Methods Livers were harvested in rats that did or did not receive LPS. Results Under baseline conditions, no UPR was found in normal livers while PERK/eIF2α and ATF6 pathways were activated in cirrhotic livers. After LPS, in normal livers, the PERK/eIF2α pathway was transiently activated. ATF6 and IRE1 were activated. In cirrhotic livers, the PERK/eIF2α pathway remained elevated. ATF6 and IRE1 pathways were altered. LPS-induced, NF-κB-dependent antiapoptotic proteins increased in normal livers whereas their expression was blunted at the posttranscriptional level in cirrhotic livers. Conclusions Cirrhotic livers exhibit partial UPR activation in the basal state and full UPR, although altered, after LPS challenge. Sustained eIF2α phosphorylation, a hallmark of cirrhotic liver UPR, is associated with a lack of LPS-induced accumulation of NF-κB-dependent antiapoptotic proteins which may sensitize cirrhotic livers to LPS/TNFα-mediated apoptosis.

Resume Nous rapportons l’observation d’une malade âgee de 75 ans ayant des metastases hepatiques d’un carcinome des voies urinaires avec elevation marquee du CA 19-9 serique sans cholestase. Les mecanismes d’elevation du taux de ce marqueur, dans les tumeurs urinaires, semblent similaires a ceux des affections biliaires.

The DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) corresponds to a drug reaction generally including cutaneous eruption, fever, hematologic abnormalities such as eosinophilia and atypical lymphocytosis and one or more specific visceral lesions specially in the liver. We report a case of drug hypersensitivity syndrome or DRESS associated with intra and extra-hepatic biliary lesions. This syndrome was associated with sulfasalazine and naproxene therapy. A reactivation of HHV6 was documented in the continuations of the DRESS and could play a role in the symptomms.

We report the case of a 32-year-old Indian man with symptoms suggesting Zollinger-Ellison syndrome including abdominal pain, esaphagitis, duodenal stenosis that did not improve with antisecretory medication, elevated fasting gastrin serum levels that increased after intravenous secretin injections, elevated chromogranin A serum levels and tumoral aspect of pancreatic uncus on CT scan examination. A pancreaticoduodenectomy was performed. Histological examination of the resected specimen showed that there was no endocrine tumour of the pancreas or the duodenum, but identified marked lesions of follicular and caseous tuberculosis. The final diagnosis retained pseudo Zollinger-Ellison syndrome due to gastric outlet obstruction caused by duodenal stenosis of a tuberculosis origin.

Background & Aims: Arterial vasodilation plays a role in the pathogenesis of the complications of cirrhosis. This vasodilation is caused by the overproduction of arterial nitric oxide (NO). Bacterial translocation may be involved in NO synthase (NOS) up-regulation by activating both endothelial NOS (eNOS) and inducible NOS (iNOS). The prevention of intestinal gram-negative translocation by norfloxacin administration corrects systemic circulatory changes by decreasing NO production in cirrhosis. However, the signaling mechanisms for NO overproduction from bacterial translocation are unknown. In this study, we investigated the signal transduction pathway of bacterial translocation-induced aortic NOS up-regulation in cirrhotic rats. Methods: Proinflammatory cytokine levels, Akt and NOS activities, eNOS phosphorylation, and NOS expressions were assessed in aorta from norfloxacin-treated and untreated cirrhotic rats. Norfloxacin was administered to reduce intestinal bacterial translocation. Results: Aortic eNOS and iNOS protein expressions, Akt activity, and eNOS phosphorylation by Akt at serine 1177 were up-regulated in cirrhotic rats. Norfloxacin administration significantly decreased the incidence of gram-negative translocation and proinflammatory cytokine (tumor necrosis factor-α, interferon-γ, and interleukin-6) levels; norfloxacin also decreased aortic Akt activity, eNOS phosphorylation, and NOS expressions and activities. The decrease in aortic Akt activity and NOS expressions also was obtained after colistin or anti-tumor necrosis factor-α antibody administration to cirrhotic rats. Conclusions: This study identifies a signaling pathway in which bacterial translocation induces aortic NOS up-regulation and thus NO overproduction in cirrhotic rats. These results strongly suggest that bacterial translocation and proinflammatory cytokines play a role in systemic NO overproduction in cirrhosis by the Akt pathway.

Summary Situs ambiguous is a rare anomaly, which includes various abnormalities of position and development of trunk organs and results in diagnostic and therapeutic problems during major abdominal intervention. We report the case of a woman with peripheral papillary cholangiocarcinoma and hilar extension, developed on situs ambiguous associated with the following abnormalities: agenesis of the retrohepatic vena cava, preduodenal portal vein, a variant of the hepatic arteries, truncated pancreas, polysplenia, and mesenteric malrotation. After complete anatomical assessment, resection of segments 4 to 8 extended to the common bile duct with lymphadenectomy and reconstruction by hepaticojejunostomy was performed with no surgical complications. The patient was alive with no signs of recurrence at 18 month follow-up. The specificities of situs ambiguous must be identified by anatomical assessment but do not prevent complex abdominal surgery.

Resume Les tumeurs a cellules geantes osteoclastiques sont des tumeurs osseuses de l’adulte considerees comme benignes selon l’OMS mais localement agressives. Des tumeurs strictement identiques sont decrites dans le pancreas sans localisation osseuse concomitante. Nous rapportons l’observation d’une femme de 62 ans ayant une tumeur a cellules geantes osteoclastiques du pancreas gauche, sans contingent epithelial identifiable, dont le diagnostic n’a ete fait qu’apres exerese, et sans recidive avec un recul de 24 mois. Ces tumeurs pancreatiques sont exceptionnelles, d’histogenese imprecise et souvent confondues avec les carcinomes pleomorphes ou indifferencies pancreatiques avec composante a cellules geantes osteoclastiques, de pronostic tres sombre. Ces tumeurs pancreatiques a cellules geantes osteoclastiques se presentent comme de volumineuses formations kystiques. L’exerese chirurgicale complete assure dans certains cas une survie prolongee.

A metastatic hepatic process, generally arising from a primary tumor of the gastrointestinal tract, is a common cause of multinodular and/or multicystic liver. If the primary tumor remains unknown in spite of complete and exhaustive explorations, it might be useful to re-evaluate the benign nature of previously resected tumors. We report the case of a 37 year-old woman who presented a multicystic metastatic liver related to a nasal cylindrical cell carcinoma resected 4 years earlier and diagnosed initially "inverted papilloma". Cylindrical cell carcinoma also called "transitional carcinoma" or "schneiderian carcinoma" is rare with only a few cases reported in the literature. Metastases occur generally in the lungs and no previous reported cases mention secondary hepatic location.

Biliary papillomatosis is a papillary adenomatosis of the biliary mucosa of the extra- and the intrahepatic biliary tree. It is a rare neoplasm difficult to manage, characterized by extensive lesions and a great potential for malignant transformation. We report a case of a 75 year-old man, who presented with malignant papillomatosis of the common bile duct without involvement of the intrahepatic biliary ducts. Duodenopancreatectomy enabled the diagnosis of papillomatosis lined 5.5 cm of the common bile duct which displayed an invasive 1.5 cm papillary carcinoma located in the distal portion of the choledocus. Immunohistochemistry showed strong expression of p53 in the distally located invasive carcinoma and in distant dysplastic lesions. MUC5AC was exclusively detected in both malignant and dysplastic lesions without detection of MUC1 or MUC2. Detection of p53 expression on biliary brush samples could be interesting for the follow-up and the prediction of malignant progression in multifocal biliary papillomatosis.

Background/Aims: Combined hepatocellular-cholangiocarcinoma (HCC-CC) show dual hepatocellular and biliary epithelial differentiation. To better understand the relations between cholangiocarcinoma (CC), HCC-CC and hepatocellular carcinoma (HCC), we screened for genetic alterations. Methods: A series of nine CC, 15 HCC-CC and three separated HCC and CC lesions (‘collision tumors’) were screened for loss of heterozygosity (LOH) using 400 microsatellite markers and for p53 and b-catenin mutations. A comparison with a previously characterized series of 137 HCC was performed. Results: In six cases of CC and HCC-CC, we identified TP53 gene mutations. A CTNNB1/b-catenin was identified in two patients presenting collision tumors, but no mutations were found in CC or in HCC-CC. A high level of chromosome instability in both CC and HCC-CC was found. Recurrent specific LOH were identified at 3p and 14q in more than 50% of the CC and the HCC-CC cases, whereas these chromosomal regions were deleted in less than 10% of the HCC cases ( P< 10 25 ). Minimal common regions of deletion (MCRD) were defined at 3p24-p14 and 14q24-q32, respectively. Conclusions: These results suggest that combined HCC-CC are genetically closer to CC than HCC and common carcinogenesis pathways may be altered in HCC-CC and CC. q 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Cholestatic liver diseases leading to progressive destruction of intra-hepatic bile ducts and ductopenia encompass multiple etiologies. Pathophysiology and natural history of drug-induced cholangiopathies remain unclear. We report a case of prolonged ductopenia attributed to Tenoxicam (Tilcotil o--a non-steroidal anti-inflammatory drug of the oxicam family) ingested at therapeutic dose. A 36 year-old male patient was admitted for jaundice and Lyell syndrome starting 1 week after the ingestion of Tenoxicam. Liver biopsy showed cholestasis, non-suppurative cholangitis and polymorphous inflammatory infiltrate of the portal tracts (round cells, macrophages an eosinophils). Treatment with ursodesoxycholic acid and cholestyramine was instituted and the patient was asymptomatic 1 year after. Three years later mild biological cholestasis persisted and ductopenia was evidenced on liver biopsy. In this report we found that: (1) The toxicity of tenoxicam was probably mediated by an immunoallergic mechanism (Lyell syndrome and eosinophils on histology); (2) ductopenia was secondary to inflammatory cholangitis. Factors responsible for this chronic evolution are still unknown (genetic predisposition, vascular factors, etc.); and (3) the presence of ductopenia contrasted with the "clinical recovery" of the disease suggesting accessory bile drainage by cholangioles or partial reconstruction of the biliary tree.

La Presse Medicale - In Press.Proof corrected by the author Available online since jeudi 4 juin 2015

L'adenocarcinome hepatoide de l'estomac est une entite rare associant une proliferation adenocarcinomateuse primitive de l'estomac ayant une differenciation hepatocytaire et inconstamment une elevationde l'alpha-fœtoproteine (AFP) serique [1, 2]. Cette tumeur represente, avec les dysembryomes malins, les plus frequentes causes tumorales d'elevation du taux de l'AFP serique non liees au carcinome hepatocellulaire [3, 4]. La localisation oesophagienne de l'adenocarcinome hepatoide n'a, a notre connaissance, ete decrite que deux fois [5, 6]. Nous rapportons ici une observation d'adenocarcinome hepatoide de l'oesophage associe a une elevation importante du taux de l'AFP serique.

Objectives Portal hypertension (PHT) is the main complication of cystic fibrosis liver disease (CFLD) but severe liver dysfunction occurred only in 0.5% of the patients. The early diagnosis of CFLD is elusive and a gold standard for diagnosis of liver disease is lacking. The aim of this study was to evaluate liver stiffness measurement (LSM) and CT with IV injected contrast medium in CF adult patients. Median LSM in 241 CF patients was 5.9 kPa. Methods 57 CF patients (28F, 33 yrs −18; 51) had LSM and CT done for lung transplant assessement or after lung transplantation. Results LSM was obtained in 53 patients (92%). PHT was evident on CT in 25 patients (portosystemic collaterals 12, splenomegaly 19, proeminent portal vein 25). PHT was present in 60% of the patients when LSM was >5.9 and in 12% when LSM was Conclusion CFLD with PHT could be present in patient with low LSM. Decompensation of PHT is unfrequent even in adults with end stage pulmonary disease or after lung transplantation. Portal venopathy without cirrhosis could explain PHT. The mechanism remains obscure but could explain the rare occurence of hepatocellular deficiency in CFLD.

The prevalence of CF related liver disease (CFLD) ranges from 26% to 45%. The pathogenesis is allegedly related to small bile duct obstruction leading to focal biliary cirrhosis and cirrhosis. Portal hypertension (PHT) without hepatocellular insufficiency is the main presentation of CFLD. The aim of this study was to establish the pathologic pattern in CFLD patients with severe PHT. Patients and Methods In 2 CF centers, all consecutive patients who underwent liver transplantation were retrospectively analysed. Results Eight patients (7 males; 14–32 y) were analysed. All presented with severe PHT: esophageal varices more than grade 2 (bleeding in 2 patients), splenomegaly 18–30 cm, collaterals or ascites. None had signs of hepatocellular insufficiency. Liver tests were less than 1.5 times elevated. Macroscopically, all explants (mean weight 1.6 kg) were dysmorphic with left atrophy and irregular macronodular aspect. There was no thrombosis of the large veins and large bile ducts were normal. Microscopically, all explants showed septal fibrosis without cirrhosis (F2 or F3 Metavir Score, n = 4 each). Diffuse obliterative portal venopathy with sinusoidal dilatation and regenerative nodular hyperplasia was observed in all, associated with frequent ductopenia in small portal tracts, without cholestasis or inflammation. Biliary plugs with ductular reaction were scarce, medium or large biliary ducts were normal. Conclusion According to histological examination of the native livers, CFLD with PHT is not related to biliary cirrhosis but responds to vascular damages as observed in idiopathic non-cirrhotic PHT. The mechanism leading to vascular lesion in CF is unknown.