From metaplasia over dysplasia to early cancer : the pathologist’s view. What do clinicians need to know?

Introduction : L’incidence de l’adénocarcinome de l’oesophage est en croissance exponentielle dans les pays occidentaux. Depuis longtemps, l’oesophage de Barrett est considéré comme une lésion prénéoplasique. Il peut graduellement progresser vers la cancérisation en passant par différentes étapes morphologiquement identifiables correspondant aux lésions de dysplasie. Il faut toutefois noter que le diagnostic histopathologique de l’oesophage de Barrett et de la dysplasie pose certains problèmes spécifiques. Cette revue a pour but d’informer les cliniciens des difficultés et dès lors des moyens que le pathologiste utilise pour poser un diagnostic correct et utile à la clinique. Matériel et méthodes : Ce texte est fondé sur des articles sélectionnés (peer review publications) publiés sur l’évaluation microscopique des biopsies du bas oesophage prélevées dans un contexte de reflux. Toutes les références peuvent être consultées dans la base de données Pubmed. Résultats : Les sujets suivants sont discutés : 1) définitions de l’oesophage de Barrett utilisées dans la littérature et leurs implications cliniques ; 2) méthodes alternatives de comptes rendus utilisables par le pathologiste ; 3) problème du diagnostic différentiel et possibilités de solutions ; 4) concept de la dysplasie dans l’oesophage de Barrett ; 5) critères morphologiques de gradation de la dysplasie ; 6) techniques complémentaires morphologiques ou autres appliquées pour grader le risque de cancérisation de l’oesophage de Barrett. Conclusion : Les pathologistes jouent un rôle essentiel dans le diagnostic, le pronostic et le suivi des lésions précurseurs de l’adénocarcinome. Ils jouent également un rôle majeur dans l’évaluation des nouvelles techniques proposées comme complémentaires à l’histologie standard.Introduction: The incidence of esophageal adenocarcinoma is rapidly increasing in the Western world. Barrett’s esophagus has since long been recognized as the precursor lesion. It may show a stepwise neoplastic progression with a morphologically identifiable correlate: dysplasia. The histopathological diagnosis of Barrett’s esophagus and dysplasia poses particular problems. This review aims at informing clinicians about these hurdles and the ways how the pathologist can overcome them to arrive at a clinically meaningful diagnosis. Material and methods: The text is based on selected peerreviewed articles pertaining to microscopic evaluation of lower esophageal biopsies taken in a context of reflux disease. All references are accessible via the PubMed database. Results: The following subjects are discussed: 1) various definitions of Barrett’s esophagus and their clinical implications; 2) alternative ways of reporting which can be used by the pathologist; 3) differential diagnostic problems and suggested solutions; 4) the concept of dysplasia in Barrett’s esophagus; 5) morphologic criteria appropriate to each category of dysplasia; and 6) advanced morphologic or other techniques applied to risk stratification in Barrett’s esophagus. Conclusion: Pathologists play an essential role in the diagnosis, prognostication and follow-up of precursor lesions to esophageal adenocarcinoma. They are also indispensable in the evaluation of new techniques proposed as adjunctives to standard histolog

Assessment of the Microbiota in Microdissected Tissues of Crohn's Disease Patients

The microbiota of the gastrointestinal tract is frequently mentioned as one of the key players in the etiopathogenesis of Crohn's disease (CD). Four hypotheses have been suggested: the single, still unknown bacterial pathogen, an abnormal overall composition of the bowel microbiota (“dysbiosis”), an abnormal immunological reaction to an essentially normally composed microbiota, and increased bacterial translocation. We propose that laser capture microdissection of selected microscopic structures, followed by broad-range 16S rRNA gene sequencing, is an excellent method to assess spatiotemporal alterations in the composition of the bowel microbiota in CD. Using this approach, we demonstrated significant changes of the composition, abundance, and location of the gut microbiome in this disease. Some of these abnormal findings persisted even after macroscopic mucosal healing. Further investigations along these lines may lead to a better understanding of the possible involvement of the bowel bacteria in the development of clinical Crohn's disease

Mucosal Gene Expression of Antimicrobial Peptides in Inflammatory Bowel Disease Before and After First Infliximab Treatment

Background: Antimicrobial peptides (AMPs) protect the host intestinal mucosa against microorganisms. Abnormal expression of defensins was shown in inflammatory bowel disease (IBD), but it is not clear whether this is a primary defect. We investigated the impact of anti-inflammatory therapy with infliximab on the mucosal gene expression of AMPs in IBD. Methodology/Principal Findings: Mucosal gene expression of 81 AMPs was assessed in 61 IBD patients before and 4-6 weeks after their first infliximab infusion and in 12 control patients, using Affymetrix arrays. Quantitative real-time reverse-transcription PCR and immunohistochemistry were used to confirm microarray data. The dysregulation of many AMPs in colonic IBD in comparison with control colons was widely restored by infliximab therapy, and only DEFB1 expression remained significantly decreased after therapy in the colonic mucosa of IBD responders to infliximab. In ileal Crohn's disease (CD), expression of two neuropeptides with antimicrobial activity, PYY and CHGB, was significantly decreased before therapy compared to control ileums, and ileal PYY expression remained significantly decreased after therapy in CD responders. Expression of the downregulated AMPs before and after treatment (DEFB1 and PYY) correlated with villin 1 expression, a gut epithelial cell marker, indicating that the decrease is a consequence of epithelial damage. Conclusions/Significance: Our study shows that the dysregulation of AMPs in IBD mucosa is the consequence of inflammation, but may be responsible for perpetuation of inflammation due to ineffective clearance of microorganisms

Portal hypertension after combined liver and intestinal transplantation, a diagnostic and therapeutic challenge?

A widely accepted technique to transplant the liver-bowel bloc is first to perform a piggyback anastomosis of the donor suprahepatic vena cava to the recipient vena cava; second to restore the arterial blood supply through an aortic interposition graft; and third to ensure venous drainage of the native foregut. The venous drainage of the native foregut can be restored through an end-to-end portocaval anastomosis between the donor infrahepatic vena cava and the recipient portal vein. Stenosis of this anastomosis can lead to portal hypertension presenting with upper GI congestion, bleeding, and hypersplenism. We report the successful treatment of this complication using an e-PTFE-covered stent inserted following balloon angioplasty

Elective nodal radiotherapy in prostate cancer

In patients with prostate cancer who have a high risk of pelvic nodal disease, the use of elective whole pelvis radiotherapy is still controversial. Two large, randomised, controlled trials (RTOG 9413 and GETUG-01) did not show a benefit of elective whole pelvis radiotherapy over prostate-only radiotherapy. In 2020, the POP-RT trial established the role of elective whole pelvis radiotherapy in patients who have more than a 35% risk of lymph node invasion (known as the Roach formula). POP-RT stressed the importance of patient selection. In patients with cN1 (clinically node positive) disease or pN1 (pathologically node positive) disease, the addition of whole pelvis radiotherapy to androgen deprivation therapy significantly improved survival compared with androgen deprivation therapy alone, as shown in large, retrospective studies. This patient population might increase in the future because use of the more sensitive prostate-specific membrane antigen PET-CT will become the standard staging procedure. Additionally, the SPORTT trial suggested a benefit of whole pelvis radiotherapy in biochemical recurrence-free survival in the salvage setting. A correct definition of the upper field border, which should include the bifurcation of the abdominal aorta, is key in the use of pelvic radiotherapy. As a result of using modern radiotherapy technology, severe late urinary and intestinal toxic effects are rare and do not seem to increase compared with prostate-only radiotherapy

Osteoprotegerin is a new regulator of inflammation and angiogenesis in proliferative diabetic retinopathy

Osteoprotegerin (OPG) is a novel regulator of endothelial cell function, angiogenesis, and vasculogenesis. We correlated expression levels of OPG with those of the angiogenic and inflammatory factors vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1 (MCP-1/CCL2) in proliferative diabetic retinopathy (PDR). We also examined expression of OPG in retinas from diabetic rats and diabetic patients and measured production of OPG by human retinal microvascular endothelial cells (HRMEC) and investigated its angiogenic activity.status: publishe

人型ロボットのための物理的制約に基づいた時間的ならびに空間的動作スタイルの模倣

学位の種別: 課程博士審査委員会委員 : (主査)東京大学教授 相澤 清晴, 東京大学教授 池内 克史, 東京大学教授 佐藤 洋一, 東京大学教授 苗村 健, 東京大学准教授 大石 岳史, 東京大学准教授 山崎 俊彦University of Tokyo(東京大学

Magnetic Resonance Enterography and Histology in Patients With Fibrostenotic Crohn's Disease: A Multicenter Study

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