BACKGROUND The gluten-free diet(GFD)has limitations,and there is intense research in the development of adjuvant therapies.AIM To examine the effects of orally administered Aspergillus niger prolyl endopeptidase prote...BACKGROUND The gluten-free diet(GFD)has limitations,and there is intense research in the development of adjuvant therapies.AIM To examine the effects of orally administered Aspergillus niger prolyl endopeptidase protease(AN-PEP)on inadvertent gluten exposure and symptom prevention in adult celiac disease(CeD)patients following their usual GFD.METHODS This was an exploratory,double-blind,randomized,placebo-controlled trial that enrolled CeD patients on a long-term GFD.After a 4-wk run-in period,patients were randomized to 4 wk of two AN-PEP capsules(GliadinX;AVI Research,LLC,United States)at each of three meals per day or placebo.Outcome endpoints were:(1)Average weekly stool gluten immunogenic peptides(GIP)between the run-in and end of treatments and between AN-PEP and placebo;(2)celiac symptom index(CSI);(3)CeD-specific serology;and(4)quality of life.Stool samples were collected for GIP testing by ELISA every Tuesday and Friday during run-ins and treatments.RESULTS Forty patients were randomized for the intention-to-treat analysis,and three were excluded from the per-protocol assessment.Overall,628/640(98.1%)stool samples were collected.GIP was undetectable(<0.08μg/g)in 65.6%of samples,and no differences between treatment arms were detected.Only 0.5%of samples had GIP concentrations sufficiently high(>0.32μg/g)to potentially cause mucosal damage.Median GIP concentration in the AN-PEP arm was 44.7%lower than in the run-in period.One-third of patients exhibiting GIP>0.08μg/g during run-in had lower or undetectable GIP after AN-PEP treatment.Compared with the run-in period,the proportion of symptomatic patients(CSI>38)in the AN-PEP arm was significantly lower(P<0.03).AN-PEP did not result in changes in specific serologies.CONCLUSION This exploratory study conducted in a real-life setting revealed high adherence to the GFD.The AN-PEP treatment did not significantly reduce the overall GIP stool concentration.However,given the observation of a significantly lower prevalence of patients with severe symptoms in the AN-PEP arm,further clinical research is warranted.展开更多
The blood supply to the most of abdominal organs is provided by the branches of CT. The SMA supply caecum, ascends colon, all of the small bowels except the upper part of duodenum. Knowledge of variable anatomy of cel...The blood supply to the most of abdominal organs is provided by the branches of CT. The SMA supply caecum, ascends colon, all of the small bowels except the upper part of duodenum. Knowledge of variable anatomy of celiac axis and SMA may be useful in planning and executing radiological interventions such as celiacography and chemoembolization of hepatic and pancreatic tumors. In this study, the uncommon or low percentage cases of CT and SMA are presented in the light of clinical and embryological information. The celiac axises of a total of 30 adult corpses were examined. Dissections of abdominal region were performed in detail according to Cunningham’s manual. Angiographic images of 100 consecutive adult patients who underwent celiac MDCT angiography were evaluated. During autopsies, an incomplete celiac trunk or bifurcation of celiac trunk associated with the hepatomesenteric and gastrosplenic trunks (0.7%) and a celiacomesenteric trunk associated with high origin superior mesenteric artery and gastrosplenic trunk were detected (0.7%). During MDCT angiography, a case of total absence of celiac trunk associated with a hepatosplenomesenteric trunk (0.7%) and also a case of total absence of celiac trunk alone were observed (0.7%). The persistence or unusual development of ventral splanchnic arteries (VSAs) or ventral longitudinal anastomosis may result in variations or the unusual trunks related to celiac axis and SMA. The anomalous trunks of the CT may be result of either the persistence of some parts of the VSAs or ventral longitudinal anastomose that normally disappear or disappearance of parts that normally persist. The prevalence of unusual trunks of celiac axis and SMA in this study is quite low in literature. These abnormal vessels pose problems for surgeons and radiologists. Such vascular anomalies may cause clinical complications following surgical and radiological procedures such as resection of tumor of the pancreatic head, lymphadenectomy, coeliacography, aortic replacement with reimplantation of the trunk and coembolization of pancreatic and liver tumors.展开更多
We write a letter to the editor commenting the article“Who to screen and how to screen for celiac disease”.We discuss the present literature on cirrhosis and celiac disease(CD)and recommend screening and treating CD...We write a letter to the editor commenting the article“Who to screen and how to screen for celiac disease”.We discuss the present literature on cirrhosis and celiac disease(CD)and recommend screening and treating CD in individuals with cryptogenic cirrhosis.展开更多
BACKGROUND Celiac disease(CeD)is a multisystem immune-mediated multifactorial condition strongly associated with the intestinal microbiota.AIM To evaluate the predictive power of the gut microbiota in the diagnosis of...BACKGROUND Celiac disease(CeD)is a multisystem immune-mediated multifactorial condition strongly associated with the intestinal microbiota.AIM To evaluate the predictive power of the gut microbiota in the diagnosis of CeD and to search for important taxa that may help to distinguish CeD patients from controls.METHODS Microbial DNA from bacteria,viruses,and fungi,was isolated from mucosal and fecal samples of 40 children with CeD and 39 controls.All samples were sequenced using the HiSeq platform,the data were analyzed,and abundance and diversities were assessed.For this analysis,the predictive power of the microbiota was evaluated by calculating the area under the curve(AUC)using data for the entire microbiome.The Kruskal-Wallis test was used to evaluate the significance of the difference between AUCs.The Boruta logarithm,a wrapper built around the random forest classification algorithm,was used to identify important bacterial biomarkers for CeD.RESULTS In fecal samples,AUCs for bacterial,viral,and fungal microbiota were 52%,58%,and 67.7%respectively,suggesting weak performance in predicting CeD.However,the combination of fecal bacteria and viruses showed a higher AUC of 81.8%,indicating stronger predictive power in the diagnosis of CeD.In mucosal samples,AUCs for bacterial,viral,and fungal microbiota were 81.2%,58.6%,and 35%,respectively,indicating that mucosal bacteria alone had the highest predictive power.Two bacteria,Bacteroides intestinalis and Burkholderiales bacterium 1-1-47,in fecal samples and one virus,Human_endogenous_retrovirus_K,in mucosal samples are predicted to be“important”biomarkers,differentiating celiac from nonceliac disease groups.Bacteroides intestinalis is known to degrade complex arabinoxylans and xylan which have a protective role in the intestinal mucosa.Similarly,several Burkholderiales species have been reported to produce peptidases that hydrolyze gluten peptides,with the potential to reduce the gluten content of food.Finally,a role for Human_endogenous_retrovirus_K in immune-mediated disease such as CeD has been reported.CONCLUSION The excellent predictive power of the combination of the fecal bacterial and viral microbiota with mucosal bacteria alone indicates a potential role in the diagnosis of difficult cases of CeD.Bacteroides intestinalis and Burkholderiales bacterium 1-1-47,which were found to be deficient in CeD,have a potential protective role in the development of prophylactic modalities.Further studies on the role of the microbiota in general and Human_endogenous_retrovirus_K in particular are needed.展开更多
BACKGROUND Celiac disease(CD)has been associated with gastrointestinal malignancies.However,the magnitude of the risk of pancreatic cancer(PC)associated with CD is much less clear,and risks have not been estimated fro...BACKGROUND Celiac disease(CD)has been associated with gastrointestinal malignancies.However,the magnitude of the risk of pancreatic cancer(PC)associated with CD is much less clear,and risks have not been estimated from large populations.AIM To assess the risk of PC in CD patients.METHODS We conducted a population-based,multicenter,propensity score-matched cohort study with consecutive patients diagnosed with CD using the TriNeTx research network platform.We examined the incidence of PC in patients with CD compared with a matched cohort of patients without CD(non-CD,controls).Each patient in the main group(CD)was matched to a patient in the control group using 1:1 propensity score matching to reduce confounding effects.The incidence of PC was estimated using a Cox proportional hazards model with a hazard ratio(HR)and 95%confidence interval(CI).RESULTS A total of 389980 patients were included in this study.Among them,155877 patients had a diagnosis of CD,and the remaining 234103 individuals without CD were considered a control cohort.The mean duration of follow-up for patients in the CD and control cohorts was 5.8±1.8 and 5.9±1.1 years,respectively.During the follow-up,309 patients with CD developed PC,whereas 240 patients developed PC in the control group(HR=1.29;95%CI:1.09-1.53).In the secondary analyses in the first year after diagnosis of CD,patients with CD were at a significant increase in risk for PC;151 patients with CD had an incidence of PC compared with 96 incidences of PC among the patients in the non-CD control group(HR=1.56;95%CI:1.20-2.01)and sensitivity analysis showed similar magnitude to the one generated in the primary and secondary analysis.CONCLUSION Patients with CD are at increased risk of PC.Risk elevation persists beyond the first year after diagnosis to reference individuals without CD from the general population.展开更多
Patients with celiac disease(CD)have a mucosal layer that is unable to regulate the gut microbiota,leaving the host vulnerable to dangerous infections and antigens.When compared to healthy people,this dysbiosis is mar...Patients with celiac disease(CD)have a mucosal layer that is unable to regulate the gut microbiota,leaving the host vulnerable to dangerous infections and antigens.When compared to healthy people,this dysbiosis is marked by a decrease in intra-and intergeneric biodiversity,which demonstrates an imbalance between helpful bacteria and possibly harmful or proinflammatory species.The early gut microbiota is influenced by the genotype of newborns with the HLADQ2 haplotypes,and this may modify how gluten is handled in the intestinal lumen,polarize innate or adaptive immune responses,and result in glutensensitive enteropathy.The outcome of gluten digestion can vary depending on the composition of the intestinal gut bacteria and the partial conversion of gluten into peptides larger than ten amino acids in the small intestines,which can be immunogenic.In the small intestine,114 different bacterial strains belonging to 32 different species have 27 of them exhibiting peptidolytic activity.Thus,the individual risk of developing a gluten-related illness is further influenced by microbial composition and gluten degrading capacity.The conclusion that lactobacilli and Bifidobacterium spp.may be used as a probiotic supplement in CD patients is based on their shared possession of the most extensive peptidolytic and proteolytic activity thought to be engaged in the breakdown of gluten among all potential bacterial genera present in the gut microbiota.In children with CD autoimmunity,daily oral dose of Lactobacillus.plantarum HEAL9 and Lactobacillus.paracasei 8700:2 was found to modify the peripheral immune response.Bifidobacterium.breve strains have demonstrated a beneficial effect on reducing pro-inflammatory cytokine TNF-production in CD children on gluten-free diets.展开更多
AIM:To assess the feasibility of endoscopic ultrasound(EUS)guided celiac plexus neurolysis(CPN) using a poloxamer. METHODS:In this prospective evaluation,six Yorkshire pigs underwent EUS-guided CPN.Three received an i...AIM:To assess the feasibility of endoscopic ultrasound(EUS)guided celiac plexus neurolysis(CPN) using a poloxamer. METHODS:In this prospective evaluation,six Yorkshire pigs underwent EUS-guided CPN.Three received an injection of 10 mL of 0.25%Lidocaine plus methylene blue(group 1) and three received an injection of 10 mL of 0.25%Lidocaine plus blue colored poloxamer(PS137-25)(group 2) .Necropsy was performed immediately after the animals were sacrificed.The abdominal and pelvic cavities were examined for the presence of methylene blue and the blue colored poloxamer.RESULTS:EUS-guided CPN was successfully performed in all 6 pigs without immediate complication.Methylene blue was identified throughout the peritoneal and retroperitoneal cavity in group 1.The blue colored poloxamer was found in the retroperitoneal cavity immediately adjacent to the aorta,in the exact location of the celiac plexus in group 2.CONCLUSION:EUS-guided CPN using a reverse phase polymer in a non-survival porcine model was technically feasible.The presence of a poloxamer gel at the site of the celiac plexus at necropsy indicates a precise delivery of the neurolytic agent.展开更多
In the last few years, a new nomenclature has been proposed for the disease induced by the ingestion of gluten, a protein present in wheat, rice, barley and oats. Besides celiac disease and wheat allergy, the most stu...In the last few years, a new nomenclature has been proposed for the disease induced by the ingestion of gluten, a protein present in wheat, rice, barley and oats. Besides celiac disease and wheat allergy, the most studied forms of gluten-related disorders characterized by an evident immune mechanism(autoimmune in celiac disease and Ig E-mediated in wheat allergy), a new entity has been included, apparently not driven by an aberrant immune response: the non-celiac gluten sensitivity(NCGS). NCGS is characterized by a heterogeneous clinical picture with intestinal and extraintestinal symptoms arising after gluten ingestion and rapidly improving after its withdrawal from the diet. The pathogenesis of NCGS is largely unknown, but a mixture of factors such as the stimulation of the innate immune system, the direct cytotoxic effects of gluten, and probably the synergy with other wheat molecules, are clues for the complicated puzzle. In addition, the diagnostic procedures still remain problematic due to the absence of efficient diagnostic markers; thus, diagnosis is based upon the symptomatic response to a gluten-free diet and the recurrence of symptoms after gluten reintroduction with the possibility of an important involvement of a placebo effect. The temporary withdrawal of gluten seems a reasonable therapy, but the timing of gluten reintroduction and the correct patient management approach are have not yet been determined.展开更多
Currently,1% of the United States population holds a diagnosis for celiac disease(CD),however,a more recently recognized and possibly related condition,"non-celiac gluten sensitivity"(NCGS)has been suggested...Currently,1% of the United States population holds a diagnosis for celiac disease(CD),however,a more recently recognized and possibly related condition,"non-celiac gluten sensitivity"(NCGS)has been suggested to affect up to 6%of the United States public.While reliable clinical tests for CD exist,diagnosing individuals affected by NCGS is still complicated by the lack of reliable biomarkers and reliance upon a broad set of intestinal and extra intestinal symptoms possibly provoked by gluten.NCGS has been proposed to exhibit an innate immune response activated by gluten and several other wheat proteins.At present,an enormous food industry has developed to supply gluten-free products(GFP)with GFP sales in 2014 approaching$1 billion,with estimations projecting sales to reach$2 billion in the year 2020.The enormous demand for GFP also reflects a popular misconception among consumers that gluten avoidance is part of a healthy lifestyle choice.Features of NCGS and other gluten related disorders(e.g.,irritable bowel syndrome)call for a review of current distinctive diagnostic criteria that distinguish each,and identification of biomarkers selective or specific for NCGS.The aim of this paper is to review our current understanding of NCGS,highlighting the remaining challenges and questions which may improve its diagnosis and treatment.展开更多
BACKGROUND Non-responsive celiac disease(NRCD) is defined as the persistence of symptoms in individuals with celiac disease(CeD) despite being on a gluten-free diet(GFD). There is scant literature about NRCD in the pe...BACKGROUND Non-responsive celiac disease(NRCD) is defined as the persistence of symptoms in individuals with celiac disease(CeD) despite being on a gluten-free diet(GFD). There is scant literature about NRCD in the pediatric population.AIM To determine the incidence, clinical characteristics and underlying causes of NRCD in children.METHODS Retrospective cohort study performed at Boston Children’s Hospital(BCH). Children < 18 years diagnosed with CeD by positive serology and duodenal biopsies compatible with Marsh Ⅲ histology between 2008 and 2012 were identified in the BCH’s Celiac Disease Program database. Medical records were longitudinally reviewed from the time of diagnosis through September 2015. NRCD was defined as persistent symptoms at 6 mo after the initiation of a GFD and causes of NRCD as well as symptom evolution were detailed. The children without symptoms at 6 mo(responders) were compared with the NRCD group. Additionally, presenting signs and symptoms at the time of diagnosis of CeD among the responders and NRCD patients were collected and compared to identify any potential predictors for NRCD at 6 mo of GFD therapy.RESULTS Six hundred and sixteen children were included. Ninety-one(15%) met criteria for NRCD. Most were female(77%). Abdominal pain [odds ratio(OR) 1.8 95% confidence interval(CI) 1.1-2.9], constipation(OR 3.1 95%CI 1.9-4.9) and absence of abdominal distension(OR for abdominal distension 0.4 95%CI 0.1-0.98) at diagnosis were associated with NRCD. NRCD was attributed to a wide variety of diagnoses with gluten exposure(30%) and constipation(20%) being the most common causes. Other causes for NRCD included lactose intolerance(9%), gastroesophageal reflux(8%), functional abdominal pain(7%), irritable bowel syndrome(3%), depression/anxiety(3%), eosinophilic esophagitis(2%), food allergy(1%), eating disorder(1%), gastric ulcer with Helicobacter pylori(1%), lymphocytic colitis(1%), aerophagia(1%) and undetermined(13%). 64% of children with NRCD improved on follow-up.CONCLUSION NRCD after ≥ 6 mo GFD is frequent among children, especially females, and is associated with initial presenting symptoms of constipation and/or abdominal pain. Gluten exposure is the most frequent cause.展开更多
Objective: Celiac disease (CD) is an immune-mediated systemic disorder triggered by gluten. It has a variable combination of clinical manifestations and changes that have been occurring in recent decades however they ...Objective: Celiac disease (CD) is an immune-mediated systemic disorder triggered by gluten. It has a variable combination of clinical manifestations and changes that have been occurring in recent decades however they are not known in detail. The purpose of the article is to compare Classical and Non-Classical CD cases in terms of demographic characteristics, duodenal biopsy, extraintestinal manifestations, and associated comorbidities. Materials and Methods: A comparative retrospective cohort study from January 2008 to December 2018. Results: A total of 128 cases were included: 84 Classical (66%) and 44 Non-Classical CD (34%). The family history of CD was identified in 14% of cases without differences between groups. The age at diagnosis was distinct for Classical and Non-Classical CD (4.9 ± 4 and 8.3 ± 4 years old;p 0.001), respectively. Important changes were found within the classical presentation, including mono symptoms and a significantly higher rate of intestinal atrophy;p = 0.04. The main Non-Classical CD symptom was recurrent abdominal pain. The extraintestinal manifestations (EIM) were identified in 42% and occurred in both groups. The comparison between groups showed differences in rates of migraine and vitamin D deficiency and was higher for Non-Classical CD (p 0.05). Associated diseases occurred in 10.9%, and type 1 diabetes was significant for the Non-Classical CD group (p = 0.04). Conclusion: The classical CD was the most prevalent profile and presented a decrease in the severity of symptoms however remain a higher rate of intestinal atrophy. Recurrent abdominal pain was the main symptom of Non-Classical CD. Extraintestinal manifestations and associated diseases presented an increasing trend of occurrence among cases of Non-Classical CD.展开更多
BACKGROUND Studies in Africa,Asia,and Latin America are needed to provide a comprehensive picture of the global incidence of celiac disease(CD).AIM To describe the serology,endoscopic and histological findings in typi...BACKGROUND Studies in Africa,Asia,and Latin America are needed to provide a comprehensive picture of the global incidence of celiac disease(CD).AIM To describe the serology,endoscopic and histological findings in typical and atypical presentations of pediatric CD at a tertiary referral hospital in an African low/middle income country(LMIC).METHODS This observational study was conducted on 199 patients with CD from 2010 to 2019.The patients were divided into typical and atypical groups according to the presenting symptoms including 120 and 79 patients respectively.Serology,upper gastrointestinal endoscopy with duodenal biopsy were performed for patients who had symptoms suggestive of CD.The severity of the intestinal damage was graded according to the histo-pathologic Marsh-Oberhuber classification.RESULTS Chronic diarrhea was the main intestinal presentation in the typical group.Anemia was the most common extraintestinal symptom in both the typical and atypical group.Marsh-Oberhuber type 3b and 3c was significantly higher in the seropositive patients with a P value of 0.007.A significant correlation was observed between the histological grade of the biopsied duodenal mucosa and the clinical presentation(P<0.001).Age was significantly higher in the atypical group(P value<0.001).CONCLUSION Although typical CD was observed in 120 patients in this study,the clinical variability of the condition was frequently observed.Age only was a significant predictor for the appearance of atypical CD.Therefore,CD presentations in LMIC are not different from industrialized countries.展开更多
Cereal crops and cereal consumption have had a vital role in Mankind's history. In the recent years gluten ingestion has been linked with a range of clinical disorders. Gluten-related disorders have gradually emer...Cereal crops and cereal consumption have had a vital role in Mankind's history. In the recent years gluten ingestion has been linked with a range of clinical disorders. Gluten-related disorders have gradually emerged as an epidemiologically relevant phenomenon with an estimated global prevalence around 5%. Celiac disease, wheat allergy and non-celiac gluten sensitivity represent different gluten-related disorders. Similar clinical manifestations can be observed in these disorders, yet there are peculiar pathogenetic pathways involved in their development. Celiac disease and wheat allergy have been extensively studied, while non-celiac gluten sensitivity is a relatively novel clinical entity, believed to be closely related to other gastrointestinal functional syndromes. The diagnosis of celiac disease and wheat allergy is based on a combination of findings from the patient's clinical history and specific tests, including serology and duodenal biopsies in case of celiac disease, or laboratory and functional assays for wheat allergy. On the other hand, non-celiac gluten sensitivity is still mainly a diagnosis of exclusion, in the absence of clear-cut diagnostic criteria. A multimodal pragmatic approach combining findings from the clinical history, symptoms, serological and histological tests is required in order to reach an accurate diagnosis. A thorough knowledge of the differences and overlap in clinical presentation among gluten-related disorders, and between them and other gastrointestinal disorders, will help clinicians in the process of differential diagnosis.展开更多
AIM: To investigate celiac artery variations in gastric cancer patients and the impact on gastric cancer surgery,and also to discuss the value of the ultrasonic knife in reducing the risk caused by celiac artery varia...AIM: To investigate celiac artery variations in gastric cancer patients and the impact on gastric cancer surgery,and also to discuss the value of the ultrasonic knife in reducing the risk caused by celiac artery variations.METHODS: A retrospective analysis was conducted to investigate the difference in average operation time,intraoperative blood loss, number of harvested lymph nodes, average postoperative drainage within 3 d,and postoperative hospital stay between the group with vascular variations and no vascular variations,and between the ultrasonic harmonic scalpel and conventional electric scalpel surgery group.RESULTS: One hundred and fifty-eight cases presented with normal celiac artery, and 80 presented with celiac artery variation(33.61%). The average operation time,blood loss, average drainage within 3 d after surgery in the celiac artery variation group were significantly more than in the no celiac artery variation group(215.7 ± 32.7 min vs 204.2 ± 31.3 min, 220.0 ± 56.7mL vs 163.1 ± 52.3 mL, 193.6 ± 41.4 mL vs 175.3± 34.1 mL, respectively, P < 0.05). In celiac artery variation patients, the average operation time, blood loss, average drainage within 3 d after surgery in the ultrasonic harmonic scalpel group were significantly lower than in the conventional electric scalpel surgery group(209.5 ± 34.9 min vs 226.9 ± 29.4 min, 207.5 ±57.1 mL vs 235.6 ± 52.9 mL, 184.4 ± 38.2 mL vs 205.0± 42.9 mL, respectively, P < 0.05), and the number of lymph node dissections was significantly higher than in the conventional surgery group(25.5 ± 9.2 vs 19.9 ±7.8, P < 0.05).CONCLUSION: Celiac artery variation increases thedifficulty and risk of radical gastrectomy. Preoperative imaging evaluation and the application of ultrasonic harmonic scalpel are conducive to radical gastrectomy.展开更多
Celiac disease(CD) is a chronic immune-mediated disorder triggered by the ingestion of gluten in genetically predisposed individuals. Before activating the immune system, gluten peptides are transferred by the epithel...Celiac disease(CD) is a chronic immune-mediated disorder triggered by the ingestion of gluten in genetically predisposed individuals. Before activating the immune system, gluten peptides are transferred by the epithelial barrier to the mucosal lamina propria, where they are deamidated by intestinal tissue transglutaminase 2. As a result, they strongly bind to human leucocyte antigens(HLAs), especially HLA-DQ2 and HLA-DQ8, expressed on antigen-presenting cells. This induces an inflammatory response, which results in small bowel enteropathy. Although gluten is the main external trigger activating both innate and adaptive(specific) immunity, its presence in the intestinal lumen does not fully explain CD pathogenesis. It has been hypothesized that an early disruption of the gut barrier in genetically susceptible individuals, which would result in an increased intestinal permeability, could precede the onset of gluten-induced immune events. The intestinal barrier is a complex functional structure, whose functioning is dependent on intestinal microbiotahomeostasis, epithelial layer integrity, and the gutassociated lymphoid tissue with its intraepithelial lymphocytes(IELs). The aim of this paper was to review the current literature and summarize the role of the gut microbiota, epithelial cells and their intercellular junctions, and IELs in CD development.展开更多
Pain in pancreatic cancer is often a major problem of treatment.Administration of opioids is frequently limited by side effects or insufficient analgesia.Endoscopic ultrasound-guided celiac plexus neurolysis(EUS-CPN)r...Pain in pancreatic cancer is often a major problem of treatment.Administration of opioids is frequently limited by side effects or insufficient analgesia.Endoscopic ultrasound-guided celiac plexus neurolysis(EUS-CPN)represents an alternative for the palliative treatment of visceral pain in patients with pancreatic cancer.This review focuses on the indications,technique,outcomes of EUS-CPN and predictors of pain relief.EUS-CPN should be considered as the adjunct method to standard pain management.It moderately reduces pain in pancreatic cancer,without eliminating it.Nearly all patients need to continue opioid use,often at a constant dose.The effect on quality of life is controversial and survival is not influenced.The approach could be done in the central position of the celiac axis,which is easy to perform,or in the bilateral position of the celiac axis,with similar results in terms of pain alleviation.The EUS-CPN with multiple intraganglia injection approach seems to have better results,although extended studies are still needed.Further trials are required to enable more confident conclusions regarding timing,quantity of alcohol injected and the method of choice.Severe complications have rarely been reported,and great care should be taken in choosing the site of alcohol injection.展开更多
AIM To evaluate hepatitis B virus(HBV) vaccine response and correlation with human leukocyte antigens(HLA) and/or gluten intake in celiac patients at diagnosis.METHODS Fifty-one patients affected by celiac disease, di...AIM To evaluate hepatitis B virus(HBV) vaccine response and correlation with human leukocyte antigens(HLA) and/or gluten intake in celiac patients at diagnosis.METHODS Fifty-one patients affected by celiac disease, diagnosed at the Department of Pediatrics of the University of Catania(Italy), were recruited. All patients were tested at admission for immunization against HBV, according to findings from analysis of quantitative HBV surface antibody(anti-HBs). The anti-HBs titer was measured by enzyme-linked immunosorbent assay. Following the international standards, subjects with antibody titer < 10 IU/L were defined as non-responders. The prevalence of responders and non-responders among celiac subjects and the distribution of immunization for age were examined. In addition, the prevalence of responders and non-responders was assessed for correlation to HLA and clinical features at diagnosis of celiac disease.RESULTS The entire study population was divided into three groups according to age: 24 patients aged between 0to 5.5 years(48.9%, group A); 16 aged between 5.5 and 9.5 years(30.61%, group B); 9 aged between 9.5 and 17 years(18.75%, group C). Comparison of the percentage of responders and non-responders between the youngest and the oldest age group showed no significant difference between the two groups(P > 0.05). With regard to the HLA haplotype, comparison of the distribution of vaccination response showed no statistically significant difference between the different genotypes(homozygosity for the HLADQ2 haplotype compared with HLADQ2/DQ8 heterozygosity or other haplotypes; P > 0.05). Moreover, distribution of the responders according to clinical features of celiac disease showed no statistically significant differences(P > 0.05).CONCLUSION This prospective study confirmed the lower percentage of response to HBV vaccine in celiac subjects. However, the underlying mechanism remains unclear and further studies are needed.展开更多
Pancreatic cancer is the second most common abdominal cancer in North America with an estimated 20%resectability at diagnosis,and overall 5-year survival of 5%.Pain is common in pancreatic cancer patients with 70%-80%...Pancreatic cancer is the second most common abdominal cancer in North America with an estimated 20%resectability at diagnosis,and overall 5-year survival of 5%.Pain is common in pancreatic cancer patients with 70%-80%suffering substantial pain.Celiac plexus neurolysis(CPN)is a technique that can potentially improve pain control in pancreatic cancer while preventing further escalation of opioid consumption.CPN is performed by injecting absolute alcohol into the celiac plexus neural network of ganglia.This review sets out to explore the current status of CPN in non-resectable pancreatic cancer.We will examine:(1)the efficacy and safety of percutaneous-CPN and endoscopic ultrasound guided-CPN;(2)specific technique modifications including bilateral(vs central)injections and celiac ganglia neurolysis;and(3)the issue of CPN timing,early at pancreatic cancer diagnosis vs traditional late use as salvage therapy.展开更多
BACKGROUND Celiac Disease(CD)is an immune-mediated disorder,in which the HLA immunogenetic background(DQ2 and DQ8 heterodimers)and environmental trigger(gluten)are well established.Indeed,both factors are necessary–b...BACKGROUND Celiac Disease(CD)is an immune-mediated disorder,in which the HLA immunogenetic background(DQ2 and DQ8 heterodimers)and environmental trigger(gluten)are well established.Indeed,both factors are necessary–but not sufficient–to develop CD.However,it is very likely that CD is underdiagnosed in both developing and developed countries,due to several aspects,including the fact that a lot of patients present mild and/or atypical symptoms,without the presence of any recognized risk factors.Therefore,the possibility and feasibility of widened screening strategies to identify CD patients are debated.AIM To provide further evidence of the main epidemiological importance of HLADQB1*02 allele in the population of CD patients.METHODS We performed a systematic search in PubMed,EMBASE,Cochrane,Web of Science and Scopus databases,in order to produce a systematic review assessing the carrier frequency of HLA-DQB1*02 allele in the celiac population.Following the PRISMA guidelines,we retrieved all the original articles describing CD patients’HLA-DQB1 genotype in such a way that could allow to assess the HLADQB1*02 carrier frequency among CD patients,along with the evidence of the appropriate diagnostic work-up to achieve a correct and final diagnosis of CD.RESULTS The final output of this systematic search in the medical literature consisted of 38 studies providing the appropriate HLA-DQB1 genotype information of the respective CD population.According to this systematic review,including a pool of 4945 HLA-DQ genotyped CD patients,the HLA-DQB1*02 carrier frequency was 94.94%,meaning that only 5.06%of CD patients were completely lacking this allelic variant.Interestingly,if we consider only the studies whereby the prevalence of CD patients affected with type 1 diabetes mellitus was supposed or clearly established to be very low,the frequency of non-HLA-DQB1*02 carriers among CD patients dropped to 3.65%.CONCLUSION Such a high carrier frequency of the HLA-DQB1*02 allelic variant(which is>95%-96%in CD patients without risk factors,like type 1 diabetes mellitus comorbidity)might be exploited to consider a cost-effective and widened screening approach.If a sustainable strategy could be implemented through a low-cost targeted genetic test to detect the individual presence of HLA-DQB1*02 allele,an appropriate algorithm for serological screening in individuals resulting to be genetically predisposed to CD,might be considered.展开更多
AIM: To establish the diagnostic performance of sev-eral serological tests, individually and in combination, for diagnosing celiac disease (CD) in patients with different pretest probabilities, and to explore potentia...AIM: To establish the diagnostic performance of sev-eral serological tests, individually and in combination, for diagnosing celiac disease (CD) in patients with different pretest probabilities, and to explore potential se- rological algorithms to reduce the necessity for biopsy. METHODS: We prospectively performed duodenal biopsy and serology in 679 adults who had either high risk (n = 161) or low risk (n = 518) for CD. Blood samples were tested using six assays (enzyme-linked immunosorbent assay) that detected antibodies to tissue transglutaminase (tTG) and deamidated gliadin peptide (DGP). RESULTS: CD prevalence was 39.1% in the high-risk population and 3.3% in the low-risk group. In high-risk patients, all individual assays had a high diagnostic efficacy [area under receiving operator characteristic curves (AU ROC): 0.968 to 0.999]. In contrast, assays had a lower diagnostic efficacy (AU ROC: 0.835 to 0.972) in the low-risk group. Using assay combinations, it would be possible to reach or rule out diagnosis of CD without biopsy in 92% of cases in both pretest populations. We observed that the new DGP/tTG Screen assay resulted in a surplus compared to more conventional assays in any clinical situation. CONCLUSION: The DGP/tTG Screen assay could be considered as the best initial test for CD. Combinations of two tests, including a DGP/tTG Screen, might be able to diagnose CD accurately in different clinical scenarios making biopsy avoidable in a high proportion of subjects.展开更多
基金Supported by the Asociación de Celíacos y Sensibles al Gluten de Madrid,No.ACM2020)and Research Committee Argentine Society of Gastroenterology,No.2020.
文摘BACKGROUND The gluten-free diet(GFD)has limitations,and there is intense research in the development of adjuvant therapies.AIM To examine the effects of orally administered Aspergillus niger prolyl endopeptidase protease(AN-PEP)on inadvertent gluten exposure and symptom prevention in adult celiac disease(CeD)patients following their usual GFD.METHODS This was an exploratory,double-blind,randomized,placebo-controlled trial that enrolled CeD patients on a long-term GFD.After a 4-wk run-in period,patients were randomized to 4 wk of two AN-PEP capsules(GliadinX;AVI Research,LLC,United States)at each of three meals per day or placebo.Outcome endpoints were:(1)Average weekly stool gluten immunogenic peptides(GIP)between the run-in and end of treatments and between AN-PEP and placebo;(2)celiac symptom index(CSI);(3)CeD-specific serology;and(4)quality of life.Stool samples were collected for GIP testing by ELISA every Tuesday and Friday during run-ins and treatments.RESULTS Forty patients were randomized for the intention-to-treat analysis,and three were excluded from the per-protocol assessment.Overall,628/640(98.1%)stool samples were collected.GIP was undetectable(<0.08μg/g)in 65.6%of samples,and no differences between treatment arms were detected.Only 0.5%of samples had GIP concentrations sufficiently high(>0.32μg/g)to potentially cause mucosal damage.Median GIP concentration in the AN-PEP arm was 44.7%lower than in the run-in period.One-third of patients exhibiting GIP>0.08μg/g during run-in had lower or undetectable GIP after AN-PEP treatment.Compared with the run-in period,the proportion of symptomatic patients(CSI>38)in the AN-PEP arm was significantly lower(P<0.03).AN-PEP did not result in changes in specific serologies.CONCLUSION This exploratory study conducted in a real-life setting revealed high adherence to the GFD.The AN-PEP treatment did not significantly reduce the overall GIP stool concentration.However,given the observation of a significantly lower prevalence of patients with severe symptoms in the AN-PEP arm,further clinical research is warranted.
文摘The blood supply to the most of abdominal organs is provided by the branches of CT. The SMA supply caecum, ascends colon, all of the small bowels except the upper part of duodenum. Knowledge of variable anatomy of celiac axis and SMA may be useful in planning and executing radiological interventions such as celiacography and chemoembolization of hepatic and pancreatic tumors. In this study, the uncommon or low percentage cases of CT and SMA are presented in the light of clinical and embryological information. The celiac axises of a total of 30 adult corpses were examined. Dissections of abdominal region were performed in detail according to Cunningham’s manual. Angiographic images of 100 consecutive adult patients who underwent celiac MDCT angiography were evaluated. During autopsies, an incomplete celiac trunk or bifurcation of celiac trunk associated with the hepatomesenteric and gastrosplenic trunks (0.7%) and a celiacomesenteric trunk associated with high origin superior mesenteric artery and gastrosplenic trunk were detected (0.7%). During MDCT angiography, a case of total absence of celiac trunk associated with a hepatosplenomesenteric trunk (0.7%) and also a case of total absence of celiac trunk alone were observed (0.7%). The persistence or unusual development of ventral splanchnic arteries (VSAs) or ventral longitudinal anastomosis may result in variations or the unusual trunks related to celiac axis and SMA. The anomalous trunks of the CT may be result of either the persistence of some parts of the VSAs or ventral longitudinal anastomose that normally disappear or disappearance of parts that normally persist. The prevalence of unusual trunks of celiac axis and SMA in this study is quite low in literature. These abnormal vessels pose problems for surgeons and radiologists. Such vascular anomalies may cause clinical complications following surgical and radiological procedures such as resection of tumor of the pancreatic head, lymphadenectomy, coeliacography, aortic replacement with reimplantation of the trunk and coembolization of pancreatic and liver tumors.
文摘We write a letter to the editor commenting the article“Who to screen and how to screen for celiac disease”.We discuss the present literature on cirrhosis and celiac disease(CD)and recommend screening and treating CD in individuals with cryptogenic cirrhosis.
基金Supported by the Deanship of Scientific Research,King Saud University,No.RGP-1441-007.
文摘BACKGROUND Celiac disease(CeD)is a multisystem immune-mediated multifactorial condition strongly associated with the intestinal microbiota.AIM To evaluate the predictive power of the gut microbiota in the diagnosis of CeD and to search for important taxa that may help to distinguish CeD patients from controls.METHODS Microbial DNA from bacteria,viruses,and fungi,was isolated from mucosal and fecal samples of 40 children with CeD and 39 controls.All samples were sequenced using the HiSeq platform,the data were analyzed,and abundance and diversities were assessed.For this analysis,the predictive power of the microbiota was evaluated by calculating the area under the curve(AUC)using data for the entire microbiome.The Kruskal-Wallis test was used to evaluate the significance of the difference between AUCs.The Boruta logarithm,a wrapper built around the random forest classification algorithm,was used to identify important bacterial biomarkers for CeD.RESULTS In fecal samples,AUCs for bacterial,viral,and fungal microbiota were 52%,58%,and 67.7%respectively,suggesting weak performance in predicting CeD.However,the combination of fecal bacteria and viruses showed a higher AUC of 81.8%,indicating stronger predictive power in the diagnosis of CeD.In mucosal samples,AUCs for bacterial,viral,and fungal microbiota were 81.2%,58.6%,and 35%,respectively,indicating that mucosal bacteria alone had the highest predictive power.Two bacteria,Bacteroides intestinalis and Burkholderiales bacterium 1-1-47,in fecal samples and one virus,Human_endogenous_retrovirus_K,in mucosal samples are predicted to be“important”biomarkers,differentiating celiac from nonceliac disease groups.Bacteroides intestinalis is known to degrade complex arabinoxylans and xylan which have a protective role in the intestinal mucosa.Similarly,several Burkholderiales species have been reported to produce peptidases that hydrolyze gluten peptides,with the potential to reduce the gluten content of food.Finally,a role for Human_endogenous_retrovirus_K in immune-mediated disease such as CeD has been reported.CONCLUSION The excellent predictive power of the combination of the fecal bacterial and viral microbiota with mucosal bacteria alone indicates a potential role in the diagnosis of difficult cases of CeD.Bacteroides intestinalis and Burkholderiales bacterium 1-1-47,which were found to be deficient in CeD,have a potential protective role in the development of prophylactic modalities.Further studies on the role of the microbiota in general and Human_endogenous_retrovirus_K in particular are needed.
文摘BACKGROUND Celiac disease(CD)has been associated with gastrointestinal malignancies.However,the magnitude of the risk of pancreatic cancer(PC)associated with CD is much less clear,and risks have not been estimated from large populations.AIM To assess the risk of PC in CD patients.METHODS We conducted a population-based,multicenter,propensity score-matched cohort study with consecutive patients diagnosed with CD using the TriNeTx research network platform.We examined the incidence of PC in patients with CD compared with a matched cohort of patients without CD(non-CD,controls).Each patient in the main group(CD)was matched to a patient in the control group using 1:1 propensity score matching to reduce confounding effects.The incidence of PC was estimated using a Cox proportional hazards model with a hazard ratio(HR)and 95%confidence interval(CI).RESULTS A total of 389980 patients were included in this study.Among them,155877 patients had a diagnosis of CD,and the remaining 234103 individuals without CD were considered a control cohort.The mean duration of follow-up for patients in the CD and control cohorts was 5.8±1.8 and 5.9±1.1 years,respectively.During the follow-up,309 patients with CD developed PC,whereas 240 patients developed PC in the control group(HR=1.29;95%CI:1.09-1.53).In the secondary analyses in the first year after diagnosis of CD,patients with CD were at a significant increase in risk for PC;151 patients with CD had an incidence of PC compared with 96 incidences of PC among the patients in the non-CD control group(HR=1.56;95%CI:1.20-2.01)and sensitivity analysis showed similar magnitude to the one generated in the primary and secondary analysis.CONCLUSION Patients with CD are at increased risk of PC.Risk elevation persists beyond the first year after diagnosis to reference individuals without CD from the general population.
文摘Patients with celiac disease(CD)have a mucosal layer that is unable to regulate the gut microbiota,leaving the host vulnerable to dangerous infections and antigens.When compared to healthy people,this dysbiosis is marked by a decrease in intra-and intergeneric biodiversity,which demonstrates an imbalance between helpful bacteria and possibly harmful or proinflammatory species.The early gut microbiota is influenced by the genotype of newborns with the HLADQ2 haplotypes,and this may modify how gluten is handled in the intestinal lumen,polarize innate or adaptive immune responses,and result in glutensensitive enteropathy.The outcome of gluten digestion can vary depending on the composition of the intestinal gut bacteria and the partial conversion of gluten into peptides larger than ten amino acids in the small intestines,which can be immunogenic.In the small intestine,114 different bacterial strains belonging to 32 different species have 27 of them exhibiting peptidolytic activity.Thus,the individual risk of developing a gluten-related illness is further influenced by microbial composition and gluten degrading capacity.The conclusion that lactobacilli and Bifidobacterium spp.may be used as a probiotic supplement in CD patients is based on their shared possession of the most extensive peptidolytic and proteolytic activity thought to be engaged in the breakdown of gluten among all potential bacterial genera present in the gut microbiota.In children with CD autoimmunity,daily oral dose of Lactobacillus.plantarum HEAL9 and Lactobacillus.paracasei 8700:2 was found to modify the peripheral immune response.Bifidobacterium.breve strains have demonstrated a beneficial effect on reducing pro-inflammatory cytokine TNF-production in CD children on gluten-free diets.
基金Supported by A grant from Generalitat de Catalunya(AGAUR,BE-100022)
文摘AIM:To assess the feasibility of endoscopic ultrasound(EUS)guided celiac plexus neurolysis(CPN) using a poloxamer. METHODS:In this prospective evaluation,six Yorkshire pigs underwent EUS-guided CPN.Three received an injection of 10 mL of 0.25%Lidocaine plus methylene blue(group 1) and three received an injection of 10 mL of 0.25%Lidocaine plus blue colored poloxamer(PS137-25)(group 2) .Necropsy was performed immediately after the animals were sacrificed.The abdominal and pelvic cavities were examined for the presence of methylene blue and the blue colored poloxamer.RESULTS:EUS-guided CPN was successfully performed in all 6 pigs without immediate complication.Methylene blue was identified throughout the peritoneal and retroperitoneal cavity in group 1.The blue colored poloxamer was found in the retroperitoneal cavity immediately adjacent to the aorta,in the exact location of the celiac plexus in group 2.CONCLUSION:EUS-guided CPN using a reverse phase polymer in a non-survival porcine model was technically feasible.The presence of a poloxamer gel at the site of the celiac plexus at necropsy indicates a precise delivery of the neurolytic agent.
文摘In the last few years, a new nomenclature has been proposed for the disease induced by the ingestion of gluten, a protein present in wheat, rice, barley and oats. Besides celiac disease and wheat allergy, the most studied forms of gluten-related disorders characterized by an evident immune mechanism(autoimmune in celiac disease and Ig E-mediated in wheat allergy), a new entity has been included, apparently not driven by an aberrant immune response: the non-celiac gluten sensitivity(NCGS). NCGS is characterized by a heterogeneous clinical picture with intestinal and extraintestinal symptoms arising after gluten ingestion and rapidly improving after its withdrawal from the diet. The pathogenesis of NCGS is largely unknown, but a mixture of factors such as the stimulation of the innate immune system, the direct cytotoxic effects of gluten, and probably the synergy with other wheat molecules, are clues for the complicated puzzle. In addition, the diagnostic procedures still remain problematic due to the absence of efficient diagnostic markers; thus, diagnosis is based upon the symptomatic response to a gluten-free diet and the recurrence of symptoms after gluten reintroduction with the possibility of an important involvement of a placebo effect. The temporary withdrawal of gluten seems a reasonable therapy, but the timing of gluten reintroduction and the correct patient management approach are have not yet been determined.
文摘Currently,1% of the United States population holds a diagnosis for celiac disease(CD),however,a more recently recognized and possibly related condition,"non-celiac gluten sensitivity"(NCGS)has been suggested to affect up to 6%of the United States public.While reliable clinical tests for CD exist,diagnosing individuals affected by NCGS is still complicated by the lack of reliable biomarkers and reliance upon a broad set of intestinal and extra intestinal symptoms possibly provoked by gluten.NCGS has been proposed to exhibit an innate immune response activated by gluten and several other wheat proteins.At present,an enormous food industry has developed to supply gluten-free products(GFP)with GFP sales in 2014 approaching$1 billion,with estimations projecting sales to reach$2 billion in the year 2020.The enormous demand for GFP also reflects a popular misconception among consumers that gluten avoidance is part of a healthy lifestyle choice.Features of NCGS and other gluten related disorders(e.g.,irritable bowel syndrome)call for a review of current distinctive diagnostic criteria that distinguish each,and identification of biomarkers selective or specific for NCGS.The aim of this paper is to review our current understanding of NCGS,highlighting the remaining challenges and questions which may improve its diagnosis and treatment.
基金Supported by Boston Children’s Hospital and the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health,No. P30DK034854, No. K23DK119584 and No. T32DK07760DG Kinnear Award from the Association Quebecoise des。
文摘BACKGROUND Non-responsive celiac disease(NRCD) is defined as the persistence of symptoms in individuals with celiac disease(CeD) despite being on a gluten-free diet(GFD). There is scant literature about NRCD in the pediatric population.AIM To determine the incidence, clinical characteristics and underlying causes of NRCD in children.METHODS Retrospective cohort study performed at Boston Children’s Hospital(BCH). Children < 18 years diagnosed with CeD by positive serology and duodenal biopsies compatible with Marsh Ⅲ histology between 2008 and 2012 were identified in the BCH’s Celiac Disease Program database. Medical records were longitudinally reviewed from the time of diagnosis through September 2015. NRCD was defined as persistent symptoms at 6 mo after the initiation of a GFD and causes of NRCD as well as symptom evolution were detailed. The children without symptoms at 6 mo(responders) were compared with the NRCD group. Additionally, presenting signs and symptoms at the time of diagnosis of CeD among the responders and NRCD patients were collected and compared to identify any potential predictors for NRCD at 6 mo of GFD therapy.RESULTS Six hundred and sixteen children were included. Ninety-one(15%) met criteria for NRCD. Most were female(77%). Abdominal pain [odds ratio(OR) 1.8 95% confidence interval(CI) 1.1-2.9], constipation(OR 3.1 95%CI 1.9-4.9) and absence of abdominal distension(OR for abdominal distension 0.4 95%CI 0.1-0.98) at diagnosis were associated with NRCD. NRCD was attributed to a wide variety of diagnoses with gluten exposure(30%) and constipation(20%) being the most common causes. Other causes for NRCD included lactose intolerance(9%), gastroesophageal reflux(8%), functional abdominal pain(7%), irritable bowel syndrome(3%), depression/anxiety(3%), eosinophilic esophagitis(2%), food allergy(1%), eating disorder(1%), gastric ulcer with Helicobacter pylori(1%), lymphocytic colitis(1%), aerophagia(1%) and undetermined(13%). 64% of children with NRCD improved on follow-up.CONCLUSION NRCD after ≥ 6 mo GFD is frequent among children, especially females, and is associated with initial presenting symptoms of constipation and/or abdominal pain. Gluten exposure is the most frequent cause.
文摘Objective: Celiac disease (CD) is an immune-mediated systemic disorder triggered by gluten. It has a variable combination of clinical manifestations and changes that have been occurring in recent decades however they are not known in detail. The purpose of the article is to compare Classical and Non-Classical CD cases in terms of demographic characteristics, duodenal biopsy, extraintestinal manifestations, and associated comorbidities. Materials and Methods: A comparative retrospective cohort study from January 2008 to December 2018. Results: A total of 128 cases were included: 84 Classical (66%) and 44 Non-Classical CD (34%). The family history of CD was identified in 14% of cases without differences between groups. The age at diagnosis was distinct for Classical and Non-Classical CD (4.9 ± 4 and 8.3 ± 4 years old;p 0.001), respectively. Important changes were found within the classical presentation, including mono symptoms and a significantly higher rate of intestinal atrophy;p = 0.04. The main Non-Classical CD symptom was recurrent abdominal pain. The extraintestinal manifestations (EIM) were identified in 42% and occurred in both groups. The comparison between groups showed differences in rates of migraine and vitamin D deficiency and was higher for Non-Classical CD (p 0.05). Associated diseases occurred in 10.9%, and type 1 diabetes was significant for the Non-Classical CD group (p = 0.04). Conclusion: The classical CD was the most prevalent profile and presented a decrease in the severity of symptoms however remain a higher rate of intestinal atrophy. Recurrent abdominal pain was the main symptom of Non-Classical CD. Extraintestinal manifestations and associated diseases presented an increasing trend of occurrence among cases of Non-Classical CD.
文摘BACKGROUND Studies in Africa,Asia,and Latin America are needed to provide a comprehensive picture of the global incidence of celiac disease(CD).AIM To describe the serology,endoscopic and histological findings in typical and atypical presentations of pediatric CD at a tertiary referral hospital in an African low/middle income country(LMIC).METHODS This observational study was conducted on 199 patients with CD from 2010 to 2019.The patients were divided into typical and atypical groups according to the presenting symptoms including 120 and 79 patients respectively.Serology,upper gastrointestinal endoscopy with duodenal biopsy were performed for patients who had symptoms suggestive of CD.The severity of the intestinal damage was graded according to the histo-pathologic Marsh-Oberhuber classification.RESULTS Chronic diarrhea was the main intestinal presentation in the typical group.Anemia was the most common extraintestinal symptom in both the typical and atypical group.Marsh-Oberhuber type 3b and 3c was significantly higher in the seropositive patients with a P value of 0.007.A significant correlation was observed between the histological grade of the biopsied duodenal mucosa and the clinical presentation(P<0.001).Age was significantly higher in the atypical group(P value<0.001).CONCLUSION Although typical CD was observed in 120 patients in this study,the clinical variability of the condition was frequently observed.Age only was a significant predictor for the appearance of atypical CD.Therefore,CD presentations in LMIC are not different from industrialized countries.
文摘Cereal crops and cereal consumption have had a vital role in Mankind's history. In the recent years gluten ingestion has been linked with a range of clinical disorders. Gluten-related disorders have gradually emerged as an epidemiologically relevant phenomenon with an estimated global prevalence around 5%. Celiac disease, wheat allergy and non-celiac gluten sensitivity represent different gluten-related disorders. Similar clinical manifestations can be observed in these disorders, yet there are peculiar pathogenetic pathways involved in their development. Celiac disease and wheat allergy have been extensively studied, while non-celiac gluten sensitivity is a relatively novel clinical entity, believed to be closely related to other gastrointestinal functional syndromes. The diagnosis of celiac disease and wheat allergy is based on a combination of findings from the patient's clinical history and specific tests, including serology and duodenal biopsies in case of celiac disease, or laboratory and functional assays for wheat allergy. On the other hand, non-celiac gluten sensitivity is still mainly a diagnosis of exclusion, in the absence of clear-cut diagnostic criteria. A multimodal pragmatic approach combining findings from the clinical history, symptoms, serological and histological tests is required in order to reach an accurate diagnosis. A thorough knowledge of the differences and overlap in clinical presentation among gluten-related disorders, and between them and other gastrointestinal disorders, will help clinicians in the process of differential diagnosis.
文摘AIM: To investigate celiac artery variations in gastric cancer patients and the impact on gastric cancer surgery,and also to discuss the value of the ultrasonic knife in reducing the risk caused by celiac artery variations.METHODS: A retrospective analysis was conducted to investigate the difference in average operation time,intraoperative blood loss, number of harvested lymph nodes, average postoperative drainage within 3 d,and postoperative hospital stay between the group with vascular variations and no vascular variations,and between the ultrasonic harmonic scalpel and conventional electric scalpel surgery group.RESULTS: One hundred and fifty-eight cases presented with normal celiac artery, and 80 presented with celiac artery variation(33.61%). The average operation time,blood loss, average drainage within 3 d after surgery in the celiac artery variation group were significantly more than in the no celiac artery variation group(215.7 ± 32.7 min vs 204.2 ± 31.3 min, 220.0 ± 56.7mL vs 163.1 ± 52.3 mL, 193.6 ± 41.4 mL vs 175.3± 34.1 mL, respectively, P < 0.05). In celiac artery variation patients, the average operation time, blood loss, average drainage within 3 d after surgery in the ultrasonic harmonic scalpel group were significantly lower than in the conventional electric scalpel surgery group(209.5 ± 34.9 min vs 226.9 ± 29.4 min, 207.5 ±57.1 mL vs 235.6 ± 52.9 mL, 184.4 ± 38.2 mL vs 205.0± 42.9 mL, respectively, P < 0.05), and the number of lymph node dissections was significantly higher than in the conventional surgery group(25.5 ± 9.2 vs 19.9 ±7.8, P < 0.05).CONCLUSION: Celiac artery variation increases thedifficulty and risk of radical gastrectomy. Preoperative imaging evaluation and the application of ultrasonic harmonic scalpel are conducive to radical gastrectomy.
基金Supported by the Children’s Memorial Health Institute Grants,No.236/15,No.243/16 and No.S147/2016
文摘Celiac disease(CD) is a chronic immune-mediated disorder triggered by the ingestion of gluten in genetically predisposed individuals. Before activating the immune system, gluten peptides are transferred by the epithelial barrier to the mucosal lamina propria, where they are deamidated by intestinal tissue transglutaminase 2. As a result, they strongly bind to human leucocyte antigens(HLAs), especially HLA-DQ2 and HLA-DQ8, expressed on antigen-presenting cells. This induces an inflammatory response, which results in small bowel enteropathy. Although gluten is the main external trigger activating both innate and adaptive(specific) immunity, its presence in the intestinal lumen does not fully explain CD pathogenesis. It has been hypothesized that an early disruption of the gut barrier in genetically susceptible individuals, which would result in an increased intestinal permeability, could precede the onset of gluten-induced immune events. The intestinal barrier is a complex functional structure, whose functioning is dependent on intestinal microbiotahomeostasis, epithelial layer integrity, and the gutassociated lymphoid tissue with its intraepithelial lymphocytes(IELs). The aim of this paper was to review the current literature and summarize the role of the gut microbiota, epithelial cells and their intercellular junctions, and IELs in CD development.
文摘Pain in pancreatic cancer is often a major problem of treatment.Administration of opioids is frequently limited by side effects or insufficient analgesia.Endoscopic ultrasound-guided celiac plexus neurolysis(EUS-CPN)represents an alternative for the palliative treatment of visceral pain in patients with pancreatic cancer.This review focuses on the indications,technique,outcomes of EUS-CPN and predictors of pain relief.EUS-CPN should be considered as the adjunct method to standard pain management.It moderately reduces pain in pancreatic cancer,without eliminating it.Nearly all patients need to continue opioid use,often at a constant dose.The effect on quality of life is controversial and survival is not influenced.The approach could be done in the central position of the celiac axis,which is easy to perform,or in the bilateral position of the celiac axis,with similar results in terms of pain alleviation.The EUS-CPN with multiple intraganglia injection approach seems to have better results,although extended studies are still needed.Further trials are required to enable more confident conclusions regarding timing,quantity of alcohol injected and the method of choice.Severe complications have rarely been reported,and great care should be taken in choosing the site of alcohol injection.
文摘AIM To evaluate hepatitis B virus(HBV) vaccine response and correlation with human leukocyte antigens(HLA) and/or gluten intake in celiac patients at diagnosis.METHODS Fifty-one patients affected by celiac disease, diagnosed at the Department of Pediatrics of the University of Catania(Italy), were recruited. All patients were tested at admission for immunization against HBV, according to findings from analysis of quantitative HBV surface antibody(anti-HBs). The anti-HBs titer was measured by enzyme-linked immunosorbent assay. Following the international standards, subjects with antibody titer < 10 IU/L were defined as non-responders. The prevalence of responders and non-responders among celiac subjects and the distribution of immunization for age were examined. In addition, the prevalence of responders and non-responders was assessed for correlation to HLA and clinical features at diagnosis of celiac disease.RESULTS The entire study population was divided into three groups according to age: 24 patients aged between 0to 5.5 years(48.9%, group A); 16 aged between 5.5 and 9.5 years(30.61%, group B); 9 aged between 9.5 and 17 years(18.75%, group C). Comparison of the percentage of responders and non-responders between the youngest and the oldest age group showed no significant difference between the two groups(P > 0.05). With regard to the HLA haplotype, comparison of the distribution of vaccination response showed no statistically significant difference between the different genotypes(homozygosity for the HLADQ2 haplotype compared with HLADQ2/DQ8 heterozygosity or other haplotypes; P > 0.05). Moreover, distribution of the responders according to clinical features of celiac disease showed no statistically significant differences(P > 0.05).CONCLUSION This prospective study confirmed the lower percentage of response to HBV vaccine in celiac subjects. However, the underlying mechanism remains unclear and further studies are needed.
文摘Pancreatic cancer is the second most common abdominal cancer in North America with an estimated 20%resectability at diagnosis,and overall 5-year survival of 5%.Pain is common in pancreatic cancer patients with 70%-80%suffering substantial pain.Celiac plexus neurolysis(CPN)is a technique that can potentially improve pain control in pancreatic cancer while preventing further escalation of opioid consumption.CPN is performed by injecting absolute alcohol into the celiac plexus neural network of ganglia.This review sets out to explore the current status of CPN in non-resectable pancreatic cancer.We will examine:(1)the efficacy and safety of percutaneous-CPN and endoscopic ultrasound guided-CPN;(2)specific technique modifications including bilateral(vs central)injections and celiac ganglia neurolysis;and(3)the issue of CPN timing,early at pancreatic cancer diagnosis vs traditional late use as salvage therapy.
基金the Nazarbayev University Faculty Development Competitive Research Grant 2020-2022,No.240919FD3912.
文摘BACKGROUND Celiac Disease(CD)is an immune-mediated disorder,in which the HLA immunogenetic background(DQ2 and DQ8 heterodimers)and environmental trigger(gluten)are well established.Indeed,both factors are necessary–but not sufficient–to develop CD.However,it is very likely that CD is underdiagnosed in both developing and developed countries,due to several aspects,including the fact that a lot of patients present mild and/or atypical symptoms,without the presence of any recognized risk factors.Therefore,the possibility and feasibility of widened screening strategies to identify CD patients are debated.AIM To provide further evidence of the main epidemiological importance of HLADQB1*02 allele in the population of CD patients.METHODS We performed a systematic search in PubMed,EMBASE,Cochrane,Web of Science and Scopus databases,in order to produce a systematic review assessing the carrier frequency of HLA-DQB1*02 allele in the celiac population.Following the PRISMA guidelines,we retrieved all the original articles describing CD patients’HLA-DQB1 genotype in such a way that could allow to assess the HLADQB1*02 carrier frequency among CD patients,along with the evidence of the appropriate diagnostic work-up to achieve a correct and final diagnosis of CD.RESULTS The final output of this systematic search in the medical literature consisted of 38 studies providing the appropriate HLA-DQB1 genotype information of the respective CD population.According to this systematic review,including a pool of 4945 HLA-DQ genotyped CD patients,the HLA-DQB1*02 carrier frequency was 94.94%,meaning that only 5.06%of CD patients were completely lacking this allelic variant.Interestingly,if we consider only the studies whereby the prevalence of CD patients affected with type 1 diabetes mellitus was supposed or clearly established to be very low,the frequency of non-HLA-DQB1*02 carriers among CD patients dropped to 3.65%.CONCLUSION Such a high carrier frequency of the HLA-DQB1*02 allelic variant(which is>95%-96%in CD patients without risk factors,like type 1 diabetes mellitus comorbidity)might be exploited to consider a cost-effective and widened screening approach.If a sustainable strategy could be implemented through a low-cost targeted genetic test to detect the individual presence of HLA-DQB1*02 allele,an appropriate algorithm for serological screening in individuals resulting to be genetically predisposed to CD,might be considered.
基金Supported by (in part) A Grant from the Consejo de Investig-ación en Salud del Ministerio de Salud del Gobierno Autónomo de la Ciudad de Buenos Aires, Argentina
文摘AIM: To establish the diagnostic performance of sev-eral serological tests, individually and in combination, for diagnosing celiac disease (CD) in patients with different pretest probabilities, and to explore potential se- rological algorithms to reduce the necessity for biopsy. METHODS: We prospectively performed duodenal biopsy and serology in 679 adults who had either high risk (n = 161) or low risk (n = 518) for CD. Blood samples were tested using six assays (enzyme-linked immunosorbent assay) that detected antibodies to tissue transglutaminase (tTG) and deamidated gliadin peptide (DGP). RESULTS: CD prevalence was 39.1% in the high-risk population and 3.3% in the low-risk group. In high-risk patients, all individual assays had a high diagnostic efficacy [area under receiving operator characteristic curves (AU ROC): 0.968 to 0.999]. In contrast, assays had a lower diagnostic efficacy (AU ROC: 0.835 to 0.972) in the low-risk group. Using assay combinations, it would be possible to reach or rule out diagnosis of CD without biopsy in 92% of cases in both pretest populations. We observed that the new DGP/tTG Screen assay resulted in a surplus compared to more conventional assays in any clinical situation. CONCLUSION: The DGP/tTG Screen assay could be considered as the best initial test for CD. Combinations of two tests, including a DGP/tTG Screen, might be able to diagnose CD accurately in different clinical scenarios making biopsy avoidable in a high proportion of subjects.