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Purpose Hyper activation of the JAK-STAT signaling underlies the pathophysiology of many human immune–mediated diseases. Herein, the study of 2 adult patients with SOCS1 haploinsufficiency illustrates the severe and pleomorphic consequences of its impaired regulation in the intestinal tract. Methods Two unrelated adult patients presented with gastrointestinal manifestations, one with Crohn’s disease-like ileo-colic inflammation refractory to anti-TNF and the other with lymphocytic leiomyositis causing severe chronic intestinal pseudo-occlusion. Next-generation sequencing was used to identify the underlying monogenic defect. One patient received anti-IL-12/IL-23 treatment while the other received the JAK1 inhibitor, ruxolitinib. Peripheral blood, intestinal tissues, and serum samples were analyzed before-and-after JAK1 inhibitor therapy using mass cytometry, histology, transcriptomic, and Olink assay. Results Novel germline loss-of-function variants in SOCS1 were identified in both patients. The patient with Crohn-like disease achieved clinical remission with anti-IL-12/IL-23 treatment. In the second patient with lymphocytic leiomyositis, ruxolitinib induced rapid resolution of the obstructive symptoms, significant decrease of the CD8+ T lymphocyte muscular infiltrate, and normalization of serum and intestinal cytokines. Decreased frequencies of circulating Treg cells, MAIT cells, and NK cells, with altered CD56bright:CD16lo:CD16hi NK subtype ratios were not modified by ruxolitinib. Conclusion SOCS1 haploinsufficiency can result in a broad spectrum of intestinal manifestations and need to be considered as differential diagnosis in cases of severe treatment-refractory enteropathies, including the rare condition of lymphocytic leiomyositis. This provides the rationale for genetic screening and considering JAK inhibitors in such cases.

This study aimed to investigate the prevalence, risk factors, and outcomes of colonic involvement in patients with acute mesenteric ischemia (AMI). CT scans from a prospective cohort of 114 AMI patients treated in an intestinal stroke center between 2009 and 2018 were blindly reviewed by two radiologists. Colon involvement was defined on CT scan by the presence of at least one of the following CT colonic features: wall thickening, pneumatosis, decreased wall enhancement, dilatation, or perforation. In addition, the clinical, biological, and radiological characteristics of patients with and without colonic involvement were compared to identify risk factors for colonic involvement on CT and its impact on morbidity and mortality. Colonic involvement was identified in 32/114 (28%) patients with AMI, the right colon being more frequently involved (n = 29/32, 91%). Wall thickening (n = 27/32) was the most common CT finding. Occlusion of the inferior mesenteric artery was the only statistically significant risk factor for colonic involvement (35% vs. 15%, p = 0.02). Patients with colonic involvement on CT vs. those without had more frequently transmural colonic necrosis (13% vs. 0%, p = 0.006), short bowel syndrome (16% vs. 4%, p = 0.04), need for long-term parenteral support (19% vs. 5%, p = 0.03), and death during follow-up (22% vs. 10%, p = 0.03). In patients with AMI, colonic involvement is associated with increased morbidity and mortality and should be carefully searched for during initial CT scan assessment. • In a prospective cohort of acute mesenteric ischemia patients from an intestinal stroke center, 28% had an associated colonic involvement on CT. • Colonic involvement on CT most commonly affected the right colon, and the occlusion of the inferior mesenteric artery was the only risk factor. • Colonic involvement on CT was associated with increased morbidity and mortality and should be carefully searched for during initial CT scan assessment.

A novel histomolecular tumor of the central nervous system, the “intracranial mesenchymal tumor (IMT), FET-CREB fusion-positive” has recently been identified in the literature and will be added to the 2021 World Health Organization Classification of Tumors of the Central Nervous System. However, our latest study using DNA-methylation analyses has revealed that intracranial FET-CREB fused tumors do not represent a single molecular tumor entity. Among them, the main subgroup presented classical features of angiomatoid fibrous histiocytoma, having ultrastructural features of arachnoidal cells, for. Another tumor type with clear cell component and histopathological signs of aggressivity clustered in close vicinity with clear cell sarcoma of soft tissue. Herein, we report one case of IMT with a novel SMARCA2-CREM fusion which has until now never been described in soft tissue or the central nervous system. We compare its clinical, histopathological, immunophenotypic, genetic and epigenetic features with those previously described in IMT, FET-CREB fusion-positive. Interestingly, the current case did not cluster with IMT, FET-CREB fusion-positive but rather presented histopathological (clear cell morphology with signs of malignancy), clinical (with a dismal course with several recurrences, metastases and finally the patient’s death), genetic (fusion implicating the CREM gene), and epigenetic (DNA-methylation profiling) similarities with our previously reported clear cell sarcoma-like tumor of the central nervous system. Our results added data suggesting that different clinical and histomolecular tumor subtypes or grades seem to be included within the terminology “IMT, FET-CREB fusion-positive”, and that further series of cases are needed to better characterize them.

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.

INTRODUCTION: Magnetic resonance enterography (MRE) is useful for detecting bowel strictures, whereas a number of imaging biomarkers may reflect severity of fibrosis burden in Crohn's disease (CD). This study aimed to verify the association of MRE metrics with histologic fibrosis independent of inflammation. METHODS: This prospective European multicenter study performed MRE imaging on 60 patients with CD with bowel strictures before surgical resection. Locations of 61 histological samples were annotated on MRE examinations, followed by central readings using the Chiorean score and measurement of delayed gain of enhancement (DGE), magnetization transfer ratio, T2-weighted MRI sequences (T2R), apparent diffusion coefficient (ADC), and the magnetic resonance index of activity (MaRIA). Correlations of histology and MRE metrics were assessed. Least Absolute Shrinkage and Selection Operator and receiver operator characteristic (ROC) curve analyses were used to select composite MRE scores predictive of histology and to estimate their predictive value. RESULTS: ADC and MaRIA correlated with fibrosis (R = -0.71, P < 0.0001, and 0.59, P < 0.001) and more moderately with inflammation (R = -0.35, P < 0.01, and R = 0.53, P < 0.001). Lower or no correlations of fibrosis or inflammation were found with DGE, magnetization transfer ratio, or T2R. Least Absolute Shrinkage and Selection Operator and ROC identified a composite score of MaRIA, ADC, and DGE as a very good predictor of histologic fibrosis (ROC area under the curve = 0.910). MaRIA alone was the best predictor of histologic inflammation with excellent performance in identifying active histologic inflammation (ROC area under the curve = 0.966). DISCUSSION: MRE-based scores for histologic fibrosis and inflammation may assist in the characterization of CD stenosis and enable development of fibrosis-targeted therapies and clinical treatment of stenotic patients. ispartof: CLINICAL AND TRANSLATIONAL GASTROENTEROLOGY vol:13 issue:7 ispartof: location:United States status: published

The diagnosis of anaplastic meningioma (AM) (WHO grade III) is based on the presence of a high mitotic index (MI) and/or overt anaplasia. Only few data exist about the reproducibility and prognostic value of overt anaplasia. Additionally, the prognostic value of H3K27me3 loss in AM has not yet been demonstrated. Our objectives were to evaluate the reproducibility and prognostic value of WHO criteria and H3K27me3 loss in a multicenter series of 66 AM. Interobserver reproducibility was good for the determination of WHO grade (Kappa = 0.671) and MI (intraclass correlation coefficient [ICC] = 0.649), and fair for assessment of overt anaplasia (Kappa = 0.366). Patients with meningiomas showing high MI had significantly shorter overall survival (OS) than patients with meningiomas showing overt anaplasia without high MI (p = 0.009). OS was significantly lower in case of overt anaplasia with low MI (

Teduglutide (TED) reduces the need for parenteral support (PS) in patients with short-bowel syndrome with intestinal failure (SBS-IF). It is a glucagon-like peptide-2 analog that improves absorption, induces the expansion of the absorptive epithelium in the small intestine, and may be used in patients with SBS-IF after a 6- to 12-month adaptation period, if PS is always necessary. We described the functional and morphological effect of TED in a 40-year-old female patient with SBS-IF due to Crohn's disease who underwent terminal jejunostomy after 12 months of drug exposition. Marked hypertrophy of the villi was detected by endoscopic capsule and confirmed by histological measurements. This is the first publication demonstrating an increase in intestinal absorption in an SBS-IF patient treated with TED because of a morphological adaptation of the small bowel, with hyperplasia confirmed by capsule endoscopy and histology. The capsule endoscopy, a noninvasive exploration of the gut, could be evaluated to monitor the real efficacy of treatments with growth factors in SBS patients.

Background and Aims The prognosis of lymphoma that occurs in patients with inflammatory bowel disease [IBD] is poorly known. Methods A multicentre retrospective cohort analysis was done in seven French tertiary centres from 1999 to 2019. Only lymphoma occurring in patients with previous established diagnosis of IBD were analysed. The primary outcome was progression-free survival at 3 years. Results A total of 52 patients [male 65%, Crohn’s disease 79%, median age 48.3 years, median duration of IBD 10.1 years] were included, of whom 37 had been previously exposed to immunosuppressants and/or biologics for at least 3 months and 20 had primary intestinal lymphomas. The lymphoma histological types were: diffuse large B cell lymphomas [N = 17], Hodgkin lymphomas [N = 17], indolent B cell lymphomas [N = 12], and others including T cell lymphomas, mantle cell lymphomas, and unclassifiable B cell lymphoma [N = 6]. The median follow-up after lymphoma was 5.1 years (interquartile range [IQR] 4–7.8). Progression-free survival at 3 years was 85% in the overall population (95% confidence interval [CI] 75%–96%) with no significant difference between the exposed and unexposed group, 79% for patients exposed to immunosuppressants and/or biologics [95% CI 67%–94%], and 83% for patients diagnosed with primary intestinal lymphoma [95% CI 67%–100%]. No relapse of IBD has been observed during chemotherapy. The IBD relapse rate at the end of the last chemotherapy cycle was 23% at 3 years [95% CI 11%-39%] in the overall population. Conclusions In this large cohort, the prognosis for lymphomas occurring in IBD appears to be good and similar to what is expected, irrespective of the exposure to biologics and/or immunosuppressants.

International audience; Middle ear adenomatous neuroendocrine tumours are extremely rare causes of middle ear masses. Differential diagnosis is of primary importance to decide on the correct management since they require surgery whereas other lesions can be actively watched.CT and MRI show a non‐hypervascular lesion, differentiating it from paraganglioma. It is a mesotympanic lesion that usually encases the ossicles without bone erosion and it can invade the retrotympanum and Eustachian tube.Radical surgery is the treatment of choice. Since middle ear adenomatous neuroendocrine tumours adhere to adjacent structures and lack a tumour capsule, gross total resection is challenging.Late recurrences may be observed and complicated by the development of middle ear cholesteatoma, emphasising the importance of a long follow‐up.Recurrence can be associated with neural and intracranial invasion, lymph node or distant metastasis, highlighting the malignant potential of middle ear adenomatous neuroendocrine tumours.

ObjectivePeritoneal or mesenteric tumours may correspond to several tumour types or tumour-like conditions, some of them being represented by histiocytosis. This rare condition often poses diagnostic difficulties that can lead to important time delay in targeted therapies. Our aim was to describe main features of histiocytoses with mesenteric localisation that can improve the diagnostic process.DesignWe performed a retrospective study on 22 patients, whose peritoneal/mesenteric biopsies were infiltrated by histiocytes.ResultsAbdominal pain was the revealing symptom in 10 cases, and 19 patients underwent surgical biopsies. The diagnosis of histiocytosis was proposed by initial pathologists in 41% of patients. The other initial diagnoses were inflammation (n=7), sclerosing mesenteritis (n=4) and liposarcoma (n=1). The CD163/CD68+CD1a- histiocytes infiltrated subserosa and/or deeper adipose tissues in 16 and 14 cases, respectively. A BRAFV600E mutation was detected within the biopsies in 11 cases, and two others were MAP2K1 mutated. The final diagnosis was histiocytosis in 18 patients, 15 of whom had Erdheim-Chester disease. The median diagnostic delay of histiocytosis was 9 months. Patients treated with BRAF or MEK inhibitors showed a partial response or a stable disease. One patient died soon after surgery, and five died by the progression of the disease.ConclusionDiagnosis of masses arising in the mesentery should be carefully explored as one of the possibilities in histiocytosis. This diagnosis is frequently missed on mesenteric biopsies. Molecular biology for detecting the mutations in BRAF or in genes of the MAP kinase pathway is a critical diagnostic tool.

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.

Context The origin of tumor deposit in colorectal cancer is still unknown, and currently there is no single morphological feature to distinguish a metastatic lymph node from a tumor deposit. Histologically, the normal lymph node capsule and trabeculae contain a smooth muscular layer, which when present in extramural deposits would strongly suggest their lymph node origin. Objective We analyze the value of the smooth muscular layer criterion in reclassifying tumor deposit into metastatic lymph node. Design A total of 458 colo-rectal carcinomas surgical specimens treated or not by neoadjuvant (radio)chemotherapy were retrospectively included. Harvested tumor deposits were analyzed by Hematoxylin and Eosin and elastin staining on 10 consecutive serial sections and by α- smooth muscle actin immunostaining. Results A total of 129 tumor deposits were identified. 77 (60%) tumor deposits were reclassified into metastatic lymph node, of which 63 (49%) presented a smooth muscular layer on the initial Hematein Eosin staining and/or after serial tissue sections, confirmed by positive α-smooth muscle actin immunostaining in 43 out of 45 cases (90%). Fourteen (18%) additional tumor deposits were reclassified into metastatic lymph node by the appearance of lymphoid tissue after serial sections. Conclusions The presence of a smooth muscular layer in a presumable tumor deposit is helpful in pointing out its lymph node origin in patients with colo-rectal carcinomas. This criterion could improve the inter-observer agreement of tumor deposit identification, allowing accurate nodal staging and better assessment of patient's prognosis.

International audience; Glomus tumors (GTs) are perivascular tumors mostly occurring in the distal extremities. Rare cases arise in the digestive tract and may be misdiagnosed with neuroendocrine or gastrointestinal stromal tumors. We aimed to specify the features of GT of the upper digestive tract. Clinical, histological, phenotypic, and molecular features of 16 digestive GTs were analyzed, of whom two underwent whole exome and RNA sequencing to search for gene alterations. RNA-sequencing disclosed a t(1:5)(p13;q32) translocation, which resulted in the fusion of CARMN and NOTCH2 in two GTs. The fusion gene encoded a protein sequence corresponding to the NOTCH2 intracellular domain that functions as transcription factor. These finding was supported by high expression of genes targeted by NOTCH. The CARMN-NOTCH2 translocation was detected in 14 out of 16 (88%) GTs of the upper digestive tract; but in only in two out of six cutaneous GTs (33%). Most digestive GT arose from the stomach (n = 13), and the others from duodenal (2) or oesophagous (1). Nuclear expression of NOTCH2 was detected in the 14 cases containing the fusion transcripts. The CARMN-NOTCH2 fusion transcript may contribute to activation of the NOTCH2 pathway in GT and drive tumor development. The high frequency of this translocation in GT of the upper digestive track suggest that detection of nuclear NOTCH2 expression may be useful diagnostic biomarker of these tumors.

INTRODUCTION To investigate the factors associated with a delayed diagnosis (DD) of acute mesenteric ischemia (AMI). METHODS An observational cohort study from an intestinal failure center. The primary outcome was DD >24 hours. RESULTS Between 2006 and 2015, 74 patients with AMI were included and 39 (53%) had a DD. Plasma lactate

Background Chronic intestinal pseudo-obstruction (CIPO) is a rare condition that is not commonly associated with Crohn’s disease (CD). We performed a cohort study aiming at identifying clinical, immunological and genetic features as well as response to conventional CD treatments of patients co-affected with CIPO and CD. Methods We conducted an observational retrospective cohort study in two tertiary CIPO and IBD centers. Patients with parenteral nutrition-dependent CIPO and features of CD including large intestinal or perianal ulcers, strictures, abscesses and fistula with pathology findings compatible with CD, were included. We used flow-cytometry and targeted-next generation sequencing to identify immune defects and monogenic causes in 129 predefined genes responsible for monogenic enteropathies Results Eight unrelated patients were studied. 5 had a myogenic phenotype and 3 had a neurogenic form with histological exam for all patients. CD involved small bowel in all cases whereas one patient had ileocolonic involvement. Two patients had perianal complex fistula. Seven patients had a stricturing form and 1 had an inflammatory-only behavior. No patient had a penetrating form. All patients were diagnosed with CIPO prior to CD. Median age at CIPO diagnosis was 11.5 years old (IQR 0,31.5) while it was 22.5 (IQR 19,29) at CD diagnosis. At CD diagnosis, mean fecal calprotectin level was 551 ug/g (range 390 - 1200) and citrulline averaged 23.6 umol/l (range 15–35 umol/l). Histopathological analyses of intestinal specimens revealed ulcerations for half of the patients, increase in intraepithelial lymphocytes in 3, granuloma and cryptitis in 1 patient. Abnormalities in peripheral lymphocytes’ subsets were found in 2 patients. 5 patients were ultimately diagnosed with monogenic forms of enteropathy: 2 in ACTG2, with an autosomal dominant inheritance, 1 with a STAT1gain of function, (GOF) and two with recessive inheritance: TYMP. All patients received steroids with clinical response in 2. 6 patients received antiTNF, with only one sustained remission. Two patients received vedolizumab and 2 were treated with ustekinumab. Except for antiTNF in 1 patient, common CD treatments did not lead to any improvement. Of note, antiJAK therapy in a patient with STAT1GOF failed to induce remission. Conclusion Herein is described the first cohort of extensively genetically and immunologically explored patients co-affected with CIPO and CD. Immune defects were common and monogenic forms were found with a high prevalence. Rates of response to biologic treatment were very low. Identification of monogenic cause through immunological and genetic explorations is warranted in patient with CIPO-CD association as it could lead to targeted therapy and genetic counseling.

Background Teduglutide (TED), a GLP2 agonist, have been shown to exert anti-inflammatory effects on the intestinal mucosa in murine preclinical models and evaluated with a positive trend in a phase 2a randomized controlled trial in non-short bowel syndrome (SBS) Crohn’s disease (CD) patients. TED showed efficacy in reducing parenteral nutrition and or intravenous (PN/IV) dependence in SBS with intestinal failure (SBS-IF). However, limited data exists on its specific effect on the natural history of IBD in SBS patients treated with TED. Therefore, we aimed to assess the efficacy and safety of TED in patients with IBD-associated SBS as well as the effect of TED on the course of IBD. Methods We conducted an observational retrospective study. Adult patients SBS-IF due to IBD and who were treated with TED were enrolled. Response was defined as a decrease of at least 20% in total volume of PN. Active IBD was defined based on morphologic and histologic data (CT-scan, colonoscopy and/or enteroMRI). Patients were followed until last news or TED discontinuation. Results We enrolled 14 IBD patients, including 2 patients with ulcerative colitis, with a median follow-up of 4.2 ± 4 years. Of the 12 CD patients, 11 had ileocolonic involvement and 1 had only small bowel involvement. 11 patients had type-1 SBS and 3 had type-2 SBS. 7 patients were only receiving intravenous fluid and 7 were on PN/IV. Patients were in average receiving PN/IV for 9.1 years at TED initiation. Regarding IBD, 4 patients had active disease at inclusion, 3 with a structuring behavior and 1 with a fistulizing behavior. 5 patients were on biologic treatment (antiTNF or ustekinumab) at inclusion. At month 3 (M3), 9 of 14 patients were responders. 3 were weaned from any iv supplementation. 3 of 7 patients initially on TPN were weaned from caloric input, including one still receiving iv fluids. Caloric input was in average at 7330 kcal/week at baseline versus 4615 at M3. Mean total parenteral volume went from 11849 ml/week at M0 to 8223 at M3. 2 of 4 patients with active disease at baseline showed improvement in disease activity while on TED. The latter 2 patients were totally weaned off PN/IV.Six patients withdrew TED during follow-up. 2 patients stopped after a diagnosis of cancer (1 melanoma and 1 chronic myeloid leukemia). Survival without TED discontinuation was estimated at 85.7 % IC95(69.2–100) at 1 year, 78.6% IC95(59.8–100) at 2 years and at 64.3% IC95(43.5–95) at 5 years Conclusion TED appears effective and safe in IBD-associated SBS-IF patients. In specific cases, it may impact positively the inflammatory course of the disease. Further prospective studies are warranted to specifically evaluate TED in IBD-associated SBS, including patients with active IBD.

Background Considering that pediatric high-grade gliomas (HGGs) are biologically distinct from their adult counterparts, the objective of this study was to define the landscape of HGGs in adolescents and young adults (AYAs). Methods We performed a multicentric retrospective study of 112 AYAs from adult and pediatric Ile-de-France neurosurgical units, treated between 1998 and 2013 to analyze their clinicoradiological and histomolecular profiles. The inclusion criteria were age between 15 and 25 years, histopathological HGG diagnosis, available clinical data, and preoperative and follow-up MRI. MRI and tumoral samples were centrally reviewed. Immunohistochemistry and complementary molecular techniques such as targeted/next-generation sequencing, whole exome sequencing, and DNA-methylation analyses were performed to achieve an integrated diagnosis according to the 2016 World Health Organization (WHO) classification. Results Based on 80 documented AYA patients, HGGs constitute heterogeneous clinicopathological and molecular groups, with a predominant representation of pediatric subtypes (histone H3-mutants, 40%) but also adult subtypes (isocitrate dehydrogenase [IDH] mutants, 28%) characterized by the rarity of oligodendrogliomas, IDH mutants, and 1p/19q codeletion and the relative high frequency of “rare adult IDH mutations” (20%). H3G34-mutants (14%) represent the most specific subgroup in AYAs. In the H3K27-mutant subgroup, non-brainstem diffuse midline gliomas are more frequent (66.7%) than diffuse intrinsic pontine gliomas (23.8%), contrary to what is observed in children. We found that WHO grade has no prognostic value, but molecular subgrouping has major prognostic importance. Conclusions HGGs in AYAs could benefit from a specific classification, driven by molecular subtyping rather than age group. Collaborative efforts are needed from pediatric and adult neuro-oncology teams to improve the management of HGGs in AYAs.

Background Ileal pouch-anal anastomosis (IPAA) is the standard of care after total proctocolectomy for ulcerative colitis (UC). However, inflammation often develops in the pouch, leading to acute or recurrent/chronic pouchitis (R/CP). MicroRNAs (miRNA) are used as accurate diagnostic and predictive biomarkers in many human diseases, including inflammatory bowel diseases. Therefore, we aimed to identify an miRNA-based biomarker to predict the occurrence of R/CP in patients with UC after colectomy and IPAA. Methods We conducted a retrospective study in 3 tertiary centers in France. We included patients with UC who had undergone IPAA with or without subsequent R/CP. Paraffin-embedded biopsies collected from the terminal ileum during the proctocolectomy procedure were used for microarray analysis of miRNA expression profiles. Deep neural network–based classifiers were used to identify biomarkers predicting R/CP using miRNA expression and relevant biological and clinical factors in a discovery cohort of 29 patients. The classification algorithm was tested in an independent validation cohort of 28 patients. Results A combination of 11 miRNA expression profiles and 3 biological/clinical factors predicted the outcome of R/CP with 88% accuracy (area under the curve = 0.94) in the discovery cohort. The performance of the classification algorithm was confirmed in the validation cohort with 88% accuracy (area under the curve = 0.90). Apoptosis, cytoskeletal regulation by Rho GTPase, and fibroblast growth factor signaling were the most dysregulated targets of the 11 selected miRNAs. Conclusions We developed and validated a computational miRNA-based algorithm for accurately predicting R/CP in patients with UC after IPAA.

The department of neuropathology of Sainte-Anne Hospital uses zinc-formalin as the fixative agent for its samples. No publication referenced in Pubmed has proven the validity of this fixative agent. In the context of the accreditation of our standard staining (HPS for Hemalun-Phloxin-Saffron), we started a file for the validation of this method in which the fixative agent constitutes an « interfering » substance which can modify the quality of the technique. The aim of this study was to prove that the use of zinc-formalin as a fixative agent is as suitable as the fixation with 4 % buffered formalin.A cohort of samples fixed by zinc-formalin and by 4 % buffered formalin was performed on fresh samples, then cut and stained by HPS. The slides were interpreted by three pathologists (one of them was outside our centre) ``blind '' to the fixative agent and they evaluated four criteria (general quality of the staining, components of the extracellular matrix, cytoplasmic details, and nuclear details) and scored them (from 0 to 3) according to the Association française en assurance qualité (AFAQAP) recommendations.The cohort included 43 samples. The results of the analysis showed that for samples fixed by zinc-formalin, three of the four criteria obtained significantly a better score than the samples fixed by classical formalin.Our results show that the zinc-formalin fixative does not constitute an ``interfering '' agent for the quality of the HPS staining for neuropathological samples.

Surgery is required in patients with symptoms of chronic radiation-induced enteritis (CRE) resistant to medical therapy. The study aimed to correlate histopathologic features of CRE to the clinical presentation and the postoperative recurrence.All patients with small bowel resection performed for CRE between 2006 and 2017 were studied. Histological data were retrospectively correlated to initial clinical data and to postoperative recurrence of CRE (occlusion, need for parenteral nutrition) observed during a median follow-up of 32 months.Forty-one patients were studied (39 women and 2 men, median age 62 yo at time of radiation for pelvic cancer, 80% gynecologic). Median time to surgery after radiation was 3 years. Ileocaecal resections (80% of patients) removed 60cm (median length). Histologically, a diffuse obliterative arteriopathy was present in 24 (59%) patients, highly associated to amyotrophy, villous atrophy and ulceration observed in 66, 63 and 34% of patients respectively (P.05). Diffuse arteriopathy was uncorrelated with patient's age and vascular risk factor (tobacco, diabetes, hypertension, dyslipidemia). Median time to surgery after radiation was longer in patients presenting with obliterative arteriopathy (13 years vs. 2.6 years, P=0.0002). During follow-up, half of the patients had a recurrence of CRE, uncorrelated to the arteriopathy.Radiation-induced enteritis requiring late surgery after radiation presented histologically with a diffuse obliterative arteriopathy and ischemic features. In our center, half of the patients were cured by surgery. The arterial injury was not a risk factor for postoperative recurrence.

Background 1p/19q-codeleted anaplastic gliomas have variable clinical behavior. We have recently shown that the common 9p21.3 allelic loss is an independent prognostic factor in this tumor type. The aim of this study is to identify less frequent genomic copy number variations (CNVs) with clinical importance that may shed light on molecular oncogenesis of this tumor type. Materials and Methods A cohort of 197 patients with anaplastic oligodendroglioma was collected as part of the French POLA network. Clinical, pathological, and molecular information was recorded. CNV analysis was performed using single-nucleotide polymorphism arrays. Computational biology and feature selection based on the random forests method were used to identify CNV events associated with overall survival and other clinical-pathological variables. Results Recurrent chromosomal events were identified in chromosomes 4, 9, and 11. Forty-six focal amplification events and 22 focal deletion events were identified. Twenty-four focal CNV areas were associated with survival, and five of them were significantly associated with survival after multivariable analysis. Nine out of 24 CNV events were validated using an external cohort of The Cancer Genome Atlas. Five of the validated events contain a cancer-related gene or microRNA: CDKN2A deletion, SS18L1 amplification, RHOA/MIR191 copy-neutral loss of heterozygosity, FGFR3 amplification, and ARNT amplification. The CNV profile contributes to better survival prediction compared with clinical-based risk assessment. Conclusion Several recurrent CNV events, detected in anaplastic oligodendroglioma, enable better survival prediction. More importantly, they help in identifying potential genes for understanding oncogenesis and for personalized therapy. Implications for Practice Genomic analysis of 197 anaplastic oligodendroglioma tumors reveals recurrent somatic copy number variation areas that may help in understanding oncogenesis and target identification for precision medicine. A machine learning multivariable model built using this genomic information enables better survival prediction.

The components of the hepatic vascular system (hepatic arteries, portal and hepatic veins, sinusoids, and lymphatics) can be damaged by various types of injury. Each of the resulting conditions is rare, which has limited knowledge and awareness. In the last two decades, international collaborations have allowed to reach critical masses of data, which has driven significant progresses in understanding and management of vascular disorders of the liver. The present paper discusses definitions, denominations, and diagnosis of such vascular disorders with the exception of those affecting hepatic arteries. Evolving pathogenic or pathophysiologic views relevant to the clinical aspects are also overviewed.

BACKGROUND: Following recent studies underlining the differences between de novo and secondary anaplastic meningiomas and the prognostic value of telomerase reverse transcriptase (TERT) promoter mutation, we decided to conduct a multicenter retrospective study to address these questions and determine specific prognostic factors in each of these 2 anaplastic meningioma subgroups. METHODS: Among the 68 meningioma cases initially selected, only 57 were confirmed as anaplastic meningiomas after centralized pathological review. TERT promoter mutation analysis was performed in all cases. RESULTS: Median overall survival was 2.6 years and 5-year survival rate was 10%. This study confirmed the better prognosis of de novo anaplastic meningiomas (28 tumors) compared with secondary anaplastic meningiomas (29 tumors) (P = 0.02). In the “de novo” group, meningiomas diagnosed on histological anaplasia alone had a better prognosis than those in patients with a high number of mitoses with or without anaplasia (P = 0.01). In the “secondary” group, tumors demonstrate very heterogeneous clinical courses leading to malignant transformation, and time to first relapse as a low-grade tumor was a strong predictor of overall survival (P = 0.0007). TERT promoter mutation in anaplastic meningiomas was rare (14%) and did not influence overall survival but was associated with a shorter recurrence-free survival in the secondary anaplastic meningioma subgroup (P = 0.02). The absence of TERT promoter methylation, although rare (3/33 cases), may be associated with prolonged overall survival (P = 0.02). CONCLUSION: This study highlights the different prognoses of de novo and secondary anaplastic meningiomas with specific prognostic factors in each subgroup. The analysis of TERT mutation and methylation could provide additional prognostic insights.

BACKGROUND Considering that paediatric high-grade gliomas (HGGs) are biologically distinct from their adult counterparts, the objective of this study was to define the landscape of HGGs in adolescents and young adults (AYAs). METHODS We performed a multicentric retrospective study of 112 AYAs from adult and paediatric Ile-de-France neurosurgical units, treated between 1998 and 2013 to analyse their clinicoradiological and histomolecular profiles. The inclusion criteria were age between 15 and 25-years, histopathological HGG diagnosis, available clinical data, pre-operative and follow-up MRI. MRI and tumoral samples were centrally reviewed. Immunohistochemistry and complementary molecular techniques such as targeted/next generation sequencing, whole exome sequencing and DNA-methylation analyses were performed to achieve an integrated diagnosis according to the 2016 WHO classification. RESULTS Based on 80 documented AYA patients, HGGs constitute heterogeneous clinicopathological and molecular groups, with a predominant representation of paediatric-subtypes (Histone H3-mutants, 40%) but also adult-subtypes (IDH-mutants, 28%) characterized by the rarity of oligodendrogliomas, IDH-mutant and 1p/19q co-deleted and the relative high frequency of “rare adult IDH mutations” (20%). H3G34-mutants (14%) represent the most specific subgroup in AYAs. In the H3K27-mutant subgroup, the non-brainstem diffuse midline gliomas are more frequent (66.7%) than diffuse intrinsic pontine gliomas (23.8%), contrary to children. We found that WHO grade has no prognostic value, but molecular subgrouping has major prognostic importance. CONCLUSIONS HGGs in AYAs could benefit from a more personalized neuro-oncological management, driven by molecular subtyping rather than age group. Collaborative efforts are needed from paediatric and adult neuro-oncology teams to improve the management of HGGs in AYAs.

Background & aims Intestinal failure-associated liver disease is rare in adults and risk factors are unclear. The aim of this study was to determine risk factors of liver fibrosis in adults receiving home parenteral nutrition (HPN) for intestinal failure and its impact on survival. Methods We retrospectively analyzed patients with irreversible intestinal failure who underwent a liver biopsy between 2000 and 2013. Significant liver fibrosis was defined as ≥F2 according to NASH-CRN score. Results Thirty-two patients [46 years (29-60)] underwent liver biopsy 55 months (9-201) after beginning parenteral nutrition. Twenty-six patients (81%) had a short bowel (gut < 200cm), including 12 (37%) with an ultra-short bowel (gut