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Variability of anti-human transglutaminase testing in celiac disease across Mediterranean countries

World Journal of Gastroenterology 2017年第24期23卷 4437-4443页

作者： Andrea Smarrazzo Giuseppe Magazzù Mongi Ben-Hariz Maria Legarda Tamara Virtut Velmishi Elefhteria Roma Aydan Kansu Dusanka Micetic-Turk Enzo Bravi Pio Stellato Carmela Arcidiaco Luigi Greco Department of Translational Medical Sciences School of MedicineSection of PediatricsUniversity of Naples“Federico II” European Laboratory for Food Induced Diseases celiac regional centre Pediatric Gastroenterology and Cystic Fibrosis UnitUniversity of Messina Pediatric Unit Mongi SLIM’s Hospital of Tunis Paediatric Gastroenterology Unit Cruces University Hospital Service of Pediatric Gastroenterology"Mother Teresa"Hospital First Department of Pediatrics University of Athens Department of Pediatric Gastroenterology School of MedicineAnkara University University Medical centre Paediatric Department Eurospital SpA

AIM To verify the precision and accuracy of transglutaminase antibodies(TGA)assays across Mediterranean countries.METHODS This study involved 8 referral centres for celiac disease(CD)in 7 Mediterranean countries.A central laboratory prepared 8 kits of 7 blinded and randomized serum samples,with a titrated amount of Human TGA Ig A.Each sample was analysed three times on three different days,with each centre running a total of 21tests.The results were included in a blindly coded report form,which was sent to the coordinator centre.The coordinator estimated the mean coefficient of Variation(Co Var=σ/μ),the mean accuracy(Accur=Vobserved-Vreal)and the mean percent variation(Var%=[(Vobserved-Vreal)/Vreal]×100).RESULTS The analysis showed that 79.17%of the mean variation fell between-25%and+25%of the expected value,with the accuracy and precision progressively increasing with higher titres of TGA.From values 1.25 times greater than the normal cut-off,the measurements were highly reliable.CONCLUSION TGA estimation is a crucial step for the diagnosis of CD;given its accuracy and precision,clinicians could be confident in establishing a diagnosis.

关键词：腹的疾病面筋 Transglutaminase 非侵略的测试精确性精确

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Is it worth investigating splenic function in patients with celiac disease?

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World Journal of Gastroenterology 2013年第15期19卷 2313-2318页

作者： Antonio Di Sabatino Laura Brunetti Gabriella Carnevale Maffè Paolo Giuffrida Gino Roberto Corazza Department of Internal Medicine Celiac CentreS. Matteo Hospital FoundationUniversity of Pavia27100 PaviaItaly

celiac disease, an immune-mediated enteropathy induced in genetically susceptible individuals by the ingestion of gluten, is the most frequent disorder associated with splenic hypofunction or atrophy. Defective splenic function affects more than one-third of adult patients with celiac disease, and it may predispose to a higher risk of infections by encapsulated bacteria and thromboembolic and autoimmune complications, particularly when celiac patients have concomitant pre-malignant and malignant complications (refractory celiac disease, ulcerative jejunoileitis and enteropathy-associated T-cell lymphoma). However, the clinical management of patients with celiac disease does not take into account the evaluation of splenic function, and in patients with high degree of hyposplenism or splenic atrophy the prophylactic immunization with specific vaccines against the polysaccharide antigens of encapsulated bacteria is not currently recommended. We critically re-evaluate clinical and diagnostic aspects of spleen dysfunction in celiac disease, and highlight new perspectives in the prophylactic management of infections in this condition.

关键词： Hyposplenism Memory B cell Pitted red cell Pneumococcal vaccine Splenic atrophy

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Understanding celiac disease monitoring patterns and outcomes after diagnosis:A multinational,retrospective chart review study

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World Journal of Gastroenterology 2021年第20期27卷 2603-2614页

作者： Knut EA Lundin Ciaran P Kelly David S Sanders Kristina Chen Sheena Kayaniyil Sisi Wang Rajvi J Wani Caitlin Barrett Shakira Yoosuf Ellen S Pettersen Robert Sambrook Daniel A Leffler K.G.Jebsen Coeliac Disease Research centre University of OsloOslo 0450Norway Department of Gastroenterology Oslo University Hospital RikshospitaletOslo 0372Norway celiac Center Beth Israel Deaconess Medical Center Celiac Research Program Harvard Medical SchoolBostonMA 02115United States Royal Hallamshire Hospital University of SheffieldSheffield S102TNUnited Kingdom Takeda Pharmaceuticals International Co. CambridgeMA 02139United States Real World Evidence Strategy and Analytics ICON plc.TorontoON L7N 3G2Canada Real World Evidence Strategy and Analytics ICON plc.VancouverBC V6B 1P1Canada

BACKGROUND Long-term outcomes and monitoring patterns in real-world practice are largely unknown among patients with celiac disease.AIM To understand patterns of follow-up and management of patients with celiac disease,and to characterize symptoms and villous atrophy after diagnosis.METHODS A retrospective chart review study was performed using medical chart data of patients diagnosed with celiac disease.Three gastroenterology referral centers,with substantial expertise in celiac disease,participated in the United Kingdom,United States,and Norway.Demographic and clinical data were collected from medical charts.Descriptive analyses were conducted on patients with biopsyconfirmed celiac disease,diagnosed between 2008 and 2012,with at least one follow-up visit before December 31,2017.Patient demographic and clinical characteristics,biopsy/serology tests and results,symptoms,and comorbidities were captured at diagnosis and for each clinic visit occurring within the study period(i.e.,before the study end date of December 31,2017).RESULTS A total of 300 patients were included in this study[72%female;mean age at diagnosis:38.9 years,standard deviation(SD)17.2].Patients were followed-up for a mean of 29.9 mo(SD 22.1)and there were,on average,three follow-up visits per patient during the study period.Over two-thirds(68.4%)of patients were recorded as having ongoing gastrointestinal symptoms and 11.0%had ongoing symptoms and enteropathy during follow-up.Approximately 80%of patients were referred to a dietician at least once during the follow-up period.Half(50.0%)of the patients underwent at least one follow-up duodenal biopsy and 36.6%had continued villous atrophy.Patterns of monitoring varied between sites.Biopsies were conducted more frequently in Norway and patients in the United States had a longer follow-up duration.CONCLUSION This real-world study demonstrates variable follow-up of patients with celiac disease despite most patients continuing to have abnormal histology and symptoms after diagnosis.

关键词： celiac disease Outcomes research Endoscopy Real-world General practice Villous atrophy

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Effects of preoperative chemotherapy on neuroblastoma with MYCN amplification:a surgeon’s perspective

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World Journal of Pediatric Surgery 2020年第2期3卷 15-19页

作者： Chanhon Chui Surgery centre for Children Mount Elizabeth Medical CentreSingapore

Background Preoperative chemotherapy plays an important role in the surgical management of unresectable neuroblastoma.Its response to chemotherapy has been variable due to the tumor’s heterogeneity.We aimed to evaluate the effects of preoperative chemotherapy on MYCN-amplified(MYCNA)neuroblastoma that would impact on surgical resection.Methods Patients with MYCNA neuroblastoma who received preoperative chemotherapy followed by surgical resection performed at our center were included.The tools of response evaluated included tumor volume reduction(TVR),reduction in image-defined risk factors(IDRFs),percentage tumor necrosis(Nec),and surgical complications.Results Among 62 patients evaluated,mean age was 3.0(range,0.9-11.8)years,and primary tumors were distributed in the abdomen(n=59),pelvis(n=2),and thorax(n=1).The patients were in stages L2(n=14)and M(n=48).Surgery was performed after median of 4(range,2-10)cycles of chemotherapy.On completion of preoperative chemotherapy,41(66.1%)patients had TVR>65%,24(42.9%)responded with reduced IDRFs,47(75.8%)tumors had Nec>50%,and 27 patients suffered 31 surgical complications.Majority(83.9%)continued to have IDRFs at surgery.IDRFs commonly encountered were encasement of renal pedicles(n=50),superior mesenteric artery(n=46),celiac axis(n=45),and aorta/vena cava(n=44),and most remained refractory to resolution.Patients with TVR>65%were associated with Nec>50%(87.5%vs 54.5%,p=0.004)and reduced IDRFs(46.3%vs 19%,p=0.035),but not with the incidence of surgical complications.Conclusions Majority of MYCNA neuroblastomas were highly chemosensitive as they experienced high TVR,reduced IDRFs,and high Nec,and hence created favorable conditions for surgical resection.Poor responders and persistent IDRFs that were commonly refractory to preoperative chemotherapy remained a surgical challenge.

关键词： neuroblastoma MYCN Surgery

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Role of capsule endoscopy in suspected celiac disease: A European multi-centre study

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World Journal of Gastroenterology 2017年第4期23卷 703-711页

作者： Marisol Luján-Sanchis Enrique Pérez-Cuadrado-Robles Javier Garcia-Lledo José-Francisco Juanmartinena Fernandez Luca Elli Victoria-Alejandra Jiménez-García Juan Egea-Valenzuela Julio Valle-Munoz Cristina Carretero-Ribón Ignacio Fernández-Urién-Sainz Antonio López-Higueras Noelia Alonso-Lazaro Mileidis Sanjuan-Acosta Francisco Sanchez-Ceballos Bruno Rosa Santiago González-Vázquez Federica Branchi Lucía Ruano-Díaz César Prieto-de-Frías Vicente Pons-Beltrán Pilar Borque-Barrera Begona González-Suárez Sofía Xavier Federico Argüelles-Arias Juan-Manuel Herrerías-Gutiérrez Enrique Pérez-Cuadrado-Martínez Javier Sempere-García-Argüelles Digestive Diseases Unit General University Hospital of Valencia Small Bowel Unit Hospital Morales Meseguer Digestive Diseases Unit General University Gregorio Maranón Unit of Gastroenterology and Endoscopy Complejo Hospitalario de Navarra Center for prevention and Diagnosis of celiac Disease Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico Unit of Gastroenterology and Endoscopy University Hospital Virgen Macarena Gastroenterology department Hospital Virgen de la Arrixaca Department of Gastroenterology Complejo Hospitalario de Toledo Department of Gastroenterology University of Navarra Clinic1 Endoscopy Digestive Unit Digestive Diseases AreaUniversitari i Politècnic La Fe Hospital1 Digestive Diseases Unit University Hospital Nuestra Senora de Candelaria1 Digestive Diseases Unit Clinical Hospital San Carlos1 Digestive Diseases Unit Hospital da Senhora da Oliveira-Guimaraes1 Endoscopy Digestive Unit Hospital Clinic de Barcelona

AIM To analyze the diagnostic yield(DY), therapeutic impact(TI) and safety of capsule endoscopy(CE).METHODS This is a multi-centre, observational, analytical, retrospective study. A total of 163 patients with suspicion of celiac disease(CD)(mean age = 46.4 ± 17.3 years, 68.1% women) who underwent CE from 2003 to 2015 were included. Patients were divided into four groups: seronegative CD with atrophy(Group-Ⅰ, n = 19), seropositive CD without atrophy(Group-Ⅱ, n = 39), contraindication to gastroscopy(Group-Ⅲ, n = 6), seronegative CD without atrophy, but with a compatible context(Group-Ⅳ, n = 99). DY, TI and the safety of CE were analysed.RESULTS The overall DY was 54% and the final diagnosis was villous atrophy(n = 65, 39.9%), complicated CD(n = 12, 7.4%) and other enteropathies(n = 11, 6.8%; 8 Crohn's). DY for groups Ⅰ to Ⅳ was 73.7%, 69.2%, 50% and 44.4%, respectively. Atrophy was located in duodenum in 24 cases(36.9%), diffuse in 19(29.2%), jejunal in 11(16.9%), and patchy in 10 cases(15.4%). Factors associated with a greater DY were positive serology(68.3% vs 49.2%, P = 0.034) and older age(P = 0.008). On the other hand, neither sex nor clinical presentation, family background, positive histology or HLA status were associated with DY. CE resultschanged the therapeutic approach in 71.8% of the cases. Atrophy was associated with a greater TI(92.3% vs 45.3%, P < 0.001) and 81.9% of the patients responded to diet. There was one case of capsule retention(0.6%). Agreement between CE findings and subsequent histology was 100% for diagnosing normal/other conditions, 70% for suspected CD and 50% for complicated CD.CONCLUSION CE has a high DY in cases of suspicion of CD and it leads to changes in the clinical course of the disease. CE is safe procedure with a high degree of concordance with histology and it helps in the differential diagnosis of CD.

关键词：囊内视镜检查法腹的疾病 Anti-transglutaminase 抗体没有面筋的饮食非腹的面筋敏感

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Atypical hematological manifestation of celiac disease:A case report of aplastic anemia in a 2-year-old child and review of the literature

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Pediatric Investigation 2021年第2期5卷 159-162页

作者： Thea von Graffenried Mattia Rizzi Michel Russo Andreas Nydegger Simon Kayemba-Kay’s Pediatric Gastroenterology Unit Department of PediatricsUniversity of LausanneCentre Hospitalier Universitaire VaudoisLausanneSwitzerland Hemato-Oncology Unit Department of PediatricsUniversity of LausanneSwitzerland Department of Pediatrics Centre Hospitalier du Valais RomandSionSwitzerland Department of Pediatrics Centre Hospitalier des Pays de MorlaixFrance

Introduction celiac disease typically presents with symptoms of malabsorption,but extraintestinal manifestations are increasingly reported.Aplastic anemia as the mode of celiac disease presentation is extremely rare in children.Case presentation We report a 2-year-old boy who presented with loose stools,loss of appetite,and bicytopenia with severe aregenerative normocytic anemia.Investigations,including bone marrow aspirate and biopsy,revealed aplastic anemia.Screening for malabsorption showed increased plasma concentrations of anti-transglutaminase and anti-gliadin antibodies.A duodenal biopsy confirmed the histologic features of celiac disease.The child received a packed red cell transfusion and was started on a gluten-free diet,with a very good prognosis and normalization of both his blood and histological parameters.To the best of our knowledge,our report is the sixth pediatric case in the literature.Conclusion Screening for celiac disease should be performed in children with unexplained hematological abnormalities such as aplastic anemia with or without gastrointestinal symptoms.

关键词： Aplastic anemia celiac disease Child Gluten-free diet

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Median arcuate ligament syndrome often poses a diagnostic challenge: A literature review with a scope of our own experience

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World Journal of Gastrointestinal Surgery 2023年第6期15卷 1048-1055页

作者： Alexandros Giakoustidis Stavros Moschonas Gregory Christodoulidis Danae Chourmouzi Anna Diamantidou Sophia Masoura Eleni Louri Vasileios N Papadopoulos Dimitrios Giakoustidis Department of Surgery General Hospital PapageorgiouAristotle University of ThessalonikiThessaloniki 56429Greece Fifth Department of Surgery Interbalkan European Medical CentreThessaloniki 55535Greece Department of General Surgery University Hospital of LarissaLarissa 41110Greece

The median arcuate ligament syndrome(MALS)is recognized as a rare clinical entity,characterized by chronic post-prandial abdominal pain,nausea,vomiting,and unintentional weight loss.Due to its vague symptomatology,it is mainly regarded as a diagnosis of exclusion.Patients can often be misdiagnosed for several years before a correct diagnosis is established,also due to a medical team’s clinical suspicion.We present a case series of two patients who suffered from MALS and were treated successfully.The first patient is a 32-year-old woman,presenting with post-prandial abdominal pain and weight loss that have lasted for the past ten years.The second patient,a 50-year-old woman,presented with similar symptomatology,with the symptoms lasting for the last five years.Both cases were treated by laparoscopic division of the median arcuate ligament fibers,which alleviated extrinsic pressure from the celiac artery.Previous cases of MALS were retrieved from PubMed,to assemble a better diagnostic algorithm and propose a treatment method of choice.The literature review suggests an angiography with a respiratory variation protocol as the diagnostic modality of choice,along with the laparoscopic division of the median arcuate ligament fibers as the proposed treatment of choice.

关键词： Median arcuate ligament syndrome Dunbar syndrome celiac trunk compression syndrome celiac artery compression syndrome Case series Review

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Information seeking and anxiety among colonoscopy-na?ve adults: direct-to-colonoscopy vs traditional consult-first pathways

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World Journal of Gastrointestinal Endoscopy 2016年第19期8卷 701-708页

作者： Jocelyn A Silvester Harmandeep Kalkat Lesley A Graff John R Walker Harminder Singh Donald R Duerksen Faculty of Health Sciences College of MedicineUniversity of Manitoba celiac Research Program Boston Children’s Hospital and Beth Israel Deaconess Medical CenterHarvard Medical School

AIM To investigate the effects of direct to colonoscopy pathways on information seeking behaviors and anxiety among colonoscopy-na?ve patients.METHODS Colonoscopy-na?ve patients at two tertiary care hospitals completed a survey immediately prior to their scheduled outpatient procedure and before receiving sedation.Survey items included clinical pathway(direct or consult),procedure indication(cancer screening or symptom investigation),telephone and written contact from the physician endoscopist office,information sources,and pre-procedure anxiety.Participants reported pre-procedure anxiety using a 10 point scale anchored by "very relaxed"(1) and "very nervous"(10).At least three months following the procedure,patient medical records were reviewed to determine sedative dose,procedure indications and any adverse events.The primary comparison was between the direct and consult pathways.Given the very different implications,a secondary analysis considering the patient-reported indication for the procedure(symptoms or screening).Effects of pathway(direct vs consult) were compared both within and between the screening and symptom subgroups.RESULTS Of 409 patients who completed the survey,34% followed a direct pathway.Indications for colonoscopy were similar in each group.The majority of the participants were women(58%),married(61%),and internet users(81%).The most important information source was family physicians(Direct) and specialist physicians(Consult).Use of other information sources,including the internet(20% vs 18%) and Direct family and friends(64% vs 53%),was similar in the Direct and Consult groups,respectively.Only 31% of the 81% who were internet users accessed internet health information.Most sought fundamental information such as what a colonoscopy is or why it is done.Pre-procedure anxiety did not differ between care pathways.Those undergoing colonoscopy for symptoms reported greater anxiety [mean 5.3,95%CI: 5.0-5.7(10 point Likert scale)] than those for screening colonoscopy(4.3,95%CI: 3.9-4.7).CONCLUSIO

关键词： Direct access colonoscopy Colonoscopy/ utilization Information seeking behavior Referral and consultation Health care delivery Anxiety

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Epidemiology of cancer of the small intestine

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World Journal of Gastrointestinal Oncology 2011年第3期3卷 33-42页

作者： Howard Morrison Science Integration Division Centre for Chronic Disease Prevention and ControlPublic Health Agency of Canada

Cancer of the small intestine is very uncommon.There are 4 main histological subtypes:adenocarcinomas,carcinoid tumors,lymphoma and sarcoma.The incidence of small intestine cancer has increased over the past several decades with a four-fold increase for carcinoid tumors,less dramatic rises for adenocarcinoma and lymphoma and stable sarcoma rates.Very little is known about its etiology.An increased risk has been noted for individuals with Crohn's disease,celiac disease,adenoma,familial adenomatous polyposis and Peutz-Jeghers syndrome.Several behavioral risk factors including consumption of red or smoked meat,saturated fat,obesity and smoking have been suggested.The prognosis for carcinomas of the small intestine cancer is poor(5 years relative survival < 30%),better for lymphomas and sarcomas,and best for carcinoid tumors.There has been no signif icant change in longterm survival rates for any of the 4 histological subtypes.Currently,with the possible exceptions of obesity and cigarette smoking,there are no established modifiable risk factors which might provide the foundation for a prevention program aimed at reducing the incidence and mortality of cancers of the small intestine.More research with better quality and sufficient statistical power is needed to get better understanding of the etiology and biology of this cancer.In addition,more studies should be done to assess not only exposures of interest,but also host susceptibility.

关键词： Cancer of the small intestine Histology Incidence Risk factors Survival

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Consumption of gluten with gluten-degrading enzyme by celiac patients: A pilot-study

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World Journal of Gastroenterology 2013年第35期19卷 5837-5847页

作者： Greetje J Tack Jolanda MW van de Water Maaike J Bruins Engelina MC Kooy-Winkelaar Jeroen van Bergen Petra Bonnet Anita CE Vreugdenhil Ilma Korponay-Szabo Luppo Edens B Mary E von Blomberg Marco WJ Schreurs Chris J Mulder Frits Koning Department of Gastroenterology and Hepatology VU University Medical Centre DSM Biotechnology centre Department of Immunohematology and Blood Transfusion Leiden University Medical Centre Department of Pathology VU University Medical Centre Department of Paediatrics University Hospital Maastricht Department of Paediatrics University of Debrecen Paediatric Research centre University of Tampere

AIM:To assesses the safety and efficacy of Aspergillus niger prolyl endoprotease(AN-PEP)to mitigate the im-munogenic effects of gluten in celiac patients.METHODS:Patients with initial diagnosis of celiac disease as confirmed by positive serology with subtotal or total villous atrophy on duodenal biopsies who adhere to a strict gluten-free diet(GFD)resulting in normalised antibodies and mucosal healing classified as Marsh 0 orⅠwere included.In a randomised double-blind placebo-controlled pilot study,patients consumed toast(approximately 7 g/d gluten)with AN-PEP for 2 wk(safety phase).After a 2-wk washout period with adherence of the usual GFD,14 patients were randomised to gluten intake with either AN-PEP or placebo for 2 wk(efficacy phase).Measurements at baseline included complaints,quality-of-life,serum antibodies,immunophenotyping of T-cells and duodenal mucosa immunohistology.Furthermore,serum and quality of life questionnaires were collected during and after the safety,washout and efficacy phase.Duodenal biopsies were collected after the safety phase and after the efficacy phase.A change in histological evaluation according to the modified Marsh classification was the primary endpoint.RESULTS:In total,16 adults were enrolled in the study.No serious adverse events occurred during the trial and no patients withdrew during the trial.The mean score for the gastrointestinal subcategory of the celiac disease quality(CDQ)was relatively high throughout the study,indicating that AN-PEP was well tolerated.In the efficacy phase,the CDQ scores of patients consuming gluten with placebo or gluten with AN-PEP did not significantly deteriorate and moreover no differences between the groups were observed.During the efficacy phase,neither the placebo nor the AN-PEP group developed significant antibody titers.The IgA-EM concentrations remained negative in both groups.Two patients were excluded from entering the efficacy phase as their mucosa showed an increase oftwo Marsh steps after the safety phase,yet with undetectable seru

关键词： celiac disease Gluten Enzyme Prolyl endoprotease Aspergillus niger prolyl endoprotease Treatment Adverse events efficacy IgA-tTG intestinal deposits

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