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Expert Review of Anticancer Therapy Jun 2024APC-associated polyposis is a rare hereditary disorder characterized by the development of multiple adenomas in the digestive tract. Individuals with APC-associated... (Review)
Review
INTRODUCTION
APC-associated polyposis is a rare hereditary disorder characterized by the development of multiple adenomas in the digestive tract. Individuals with APC-associated polyposis need to be managed by specialized multidisciplinary teams in dedicated centers.
AREAS COVERED
The study aimed to review the literature on Familial adenomatous polyposis (FAP) to provide an update on diagnostic and surgical management while focusing on strategies to minimize the risk of desmoid-type fibromatosis, cancer in anorectal remnant, and postoperative complications. FAP individuals require a comprehensive approach that includes diagnosis, surveillance, preventive surgery, and addressing specific extracolonic concerns such as duodenal and desmoid tumors. Management should be personalized considering all factors: genotype, phenotype, and personal needs. Total colectomy and ileo-rectal anastomosis have been shown to yield superior QoL results when compared to Restorative Procto colectomy and ileopouch-anal anastomosis with acceptable oncological risk of developing cancer in the rectal stump if patients rigorously adhere to lifelong endoscopic surveillance. Additionally, a low-inflammatory diet may prevent adenomas and cancer by modulating systemic and tissue inflammatory indices.
EXPERT OPINION
FAP management requires a multidisciplinary and personalized approach. Integrating genetic advances, innovative surveillance techniques, and emerging therapeutic modalities will contribute to improving outcomes and quality of life for FAP individuals.
Topics: Humans; Adenomatous Polyposis Coli; Quality of Life; Colectomy; Postoperative Complications; Patient Care Team; Precision Medicine; Phenotype; Genotype; Fibromatosis, Aggressive
PubMed: 38785081
DOI: 10.1080/14737140.2024.2344649 -
Digestive and Liver Disease : Official... Oct 2023Nutritional deficiencies, including fat-soluble vitamins and minerals have been detected in many autoimmune diseases, including those involving the digestive system, but...
INTRODUCTION
Nutritional deficiencies, including fat-soluble vitamins and minerals have been detected in many autoimmune diseases, including those involving the digestive system, but have yet to be assessed in autoimmune pancreatitis (AIP). The aim of the present study was to determine the prevalence of micronutrient deficiencies in patients with AIP as well as to investigate their relationship with relapse.
PATIENTS AND METHODS
We retrospectively analysed medical records of patients treated for AIP. Demographic and clinical data were collected.
RESULTS
One hundred patients were included in the final analysis. The male-to-female ratio was 2.5:1; median age at diagnosis was 57 years (range 19-85). Median follow-up was 53 months, and during this time, 38% of patients suffered from at least one micronutrient deficiency. The most prevalent micronutrient deficiencies were vitamin D (16.1%) and zinc (25.5%). Relapse was observed in 37% of the AIP patients. Initial analysis showed that AIP relapse was associated with any micronutrient deficiency as well as zinc and vitamin D deficiency, but after stratifying for AIP type 1 and adjusting for PEI and elevated IgG4 levels, the association ceased to be statistically significant.
CONCLUSION
Zinc and vitamin D deficiencies may be common in patients with AIP, indicating that these micronutrients might play a role in the natural course of AIP. Importantly, any micronutrient deficiency may be prevalent even in the light of treated PEI, which emphasizes the potential of micronutrients as an additional tool in the workup and follow-up of AIP patients.
Topics: Humans; Male; Female; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Micronutrients; Autoimmune Pancreatitis; Retrospective Studies; Vitamins; Malnutrition; Autoimmune Diseases; Zinc; Vitamin D Deficiency; Recurrence
PubMed: 37121818
DOI: 10.1016/j.dld.2023.04.009 -
Digestive and Liver Disease : Official... Jun 2024Inflammatory Bowel Disease (IBD) is a chronic relapsing-remitting disease with a remarkable increase in incidence worldwide and a substantial disease burden. Although... (Review)
Review
Inflammatory Bowel Disease (IBD) is a chronic relapsing-remitting disease with a remarkable increase in incidence worldwide and a substantial disease burden. Although the pathophysiology is not fully elucidated yet an aberrant immune reaction against the intestinal microbiota and the gut microbial dysbiosis have been identified to play a major role. The composition of gut microbiota in IBD patients is distinct from that of healthy individuals, with certain organisms predominating over others. Differences in the microbial dysbiosis have been also observed between Crohn Disease (CD) and Ulcerative Colitis (UC). A disruption of the microbiota's balance can lead to inflammation and intestinal damage. Microbiota composition in IBD can be affected both by endogenous (i.e., interaction with the immune system and intestinal epithelial cells) and exogenous (i.e., medications, surgery, diet) factors. The complex interplay between the gut microbiota and IBD is an area of great interest for understanding disease pathogenesis and developing new treatments. The purpose of this review is to summarize the latest evidence on the role of microbiota in IBD pathogenesis and to explore possible future areas of research.
Topics: Humans; Dysbiosis; Inflammatory Bowel Diseases; Gastrointestinal Microbiome; Crohn Disease; Colitis, Ulcerative; Probiotics; Microbiota
PubMed: 38008696
DOI: 10.1016/j.dld.2023.11.015 -
Clinical Gastroenterology and... Dec 2023The available risk stratification indices for hepatocellular cancer (HCC) have limited applicability. We developed and externally validated an HCC risk stratification...
BACKGROUND & AIMS
The available risk stratification indices for hepatocellular cancer (HCC) have limited applicability. We developed and externally validated an HCC risk stratification index in U.S. cohorts of patients with cirrhosis.
METHODS
We used data from 2 prospective U.S. cohorts to develop the risk index. Patients with cirrhosis were enrolled from 8 centers and followed until development of HCC, death, or December 31, 2021. We identified an optimal set of predictors with the highest discriminatory ability (C-index) for HCC. The predictors were refit using competing risk regression and its predictive performance was evaluated using the area under the receiver-operating characteristic curve (AUROC). External validation was performed in a cohort of 21,550 patients with cirrhosis seen in the U.S Veterans Affairs system between 2018 and 2019 with follow-up through 2021.
RESULTS
We developed the model in 2431 patients (mean age 60 years, 31% women, 24% cured hepatitis C, 16% alcoholic liver disease, and 29% nonalcoholic fatty liver disease). The selected model had a C-index of 0.77 (95% confidence interval [CI], 0.73-0.81), and the predictors were age, sex, smoking, alcohol use, body mass index, etiology, α-fetoprotein, albumin, alanine aminotransferase, and platelet levels. The AUROCs were 0.75 (95% CI, 0.65-0.85) at 1 year and 0.77 (95% CI, 0.71-0.83) at 2 years, and the model was well calibrated. In the external validation cohort, the AUROC at 2 years was 0.70 with excellent calibration.
CONCLUSION
The risk index, including objective and routinely available risk factors, can differentiate patients with cirrhosis who will develop HCC and help guide discussions regarding HCC surveillance and prevention. Future studies are needed for additional external validation and refinement of risk stratification.
Topics: Humans; Female; Middle Aged; Male; Liver Neoplasms; Carcinoma, Hepatocellular; Prospective Studies; Liver Cirrhosis; Risk Factors; Risk Assessment
PubMed: 37390101
DOI: 10.1016/j.cgh.2023.04.019 -
World Journal of Gastroenterology Dec 2023The etiology of upper gastrointestinal bleeding (UGIB) varies by age, from newborns to adolescents, with some of the causes overlapping between age groups. While... (Review)
Review
The etiology of upper gastrointestinal bleeding (UGIB) varies by age, from newborns to adolescents, with some of the causes overlapping between age groups. While particular causes such as vitamin K deficiency and cow's milk protein allergy are limited to specific age groups, occurring only in neonates and infants, others such as erosive esophagitis and gastritis may be identified at all ages. Furthermore, the incidence of UGIB is variable throughout the world and in different hospital settings. In North America and Europe, most UGIBs are non-variceal, associated with erosive esophagitis, gastritis, and gastric and duodenal ulcers. In recent years, the most common causes in some Middle Eastern and Far Eastern countries are becoming similar to those in Western countries. However, variceal bleeding still predominates in certain parts of the world, especially in South Asia. The most severe hemorrhage arises from variceal bleeding, peptic ulceration, and disseminated intravascular coagulation. Hematemesis is a credible indicator of a UGI source of bleeding in the majority of patients. Being familiar with the most likely UGIB causes in specific ages and geographic areas is especially important for adequate orientation in clinical settings, the use of proper diagnostic tests, and rapid initiation of the therapy. The fundamental approach to the management of UGIB includes an immediate assessment of severity, detecting possible causes, and providing hemodynamic stability, followed by early endoscopy. Unusual UGIB causes must always be considered when establishing a diagnosis in the pediatric population because some of them are unique to children. Endoscopic techniques are of significant diagnostic value, and combined with medicaments, may be used for the management of acute bleeding. Finally, surgical treatment is reserved for the most severe bleeding.
Topics: Child; Infant, Newborn; Adolescent; Animals; Cattle; Female; Infant; Humans; Gastrointestinal Hemorrhage; Esophageal and Gastric Varices; Peptic Ulcer; Esophagitis; Gastritis; Age Factors
PubMed: 38186684
DOI: 10.3748/wjg.v29.i47.6095 -
Frontiers in Immunology 2023The brain-gut axis link has attracted increasing attention, with observational studies suggesting that the relationship between common mental disorders and inflammatory...
BACKGROUND
The brain-gut axis link has attracted increasing attention, with observational studies suggesting that the relationship between common mental disorders and inflammatory bowel disease (IBD) may run in both directions. However, so far, it is not clear whether there is causality and in which direction.
METHODS
We conducted a bidirectional 2-sample Mendelian randomization study to investigate the relationship between IBD, including Crohn's disease (CD) and ulcerative colitis (UC), and mental disorders, using summary-level GWAS data. The main analysis was the inverse variance weighted method. IBD (including CD and UC), and nine mental disorders were used as both exposures and outcomes.
RESULTS
We found that UC could significantly lead to obsessive-compulsive disorder, attention deficit hyperactivity disorder, and autism spectrum disorder, with odds ratio (OR) of 1.245 (95% confidence intervals [CI]: 1.069-1.450; =0.008), 1.050 (95%CI: 1.023-1.077; =2.42×10), and 1.041 (95%CI: 1.015-1.068; =0.002) respectively. In addition, we found that bipolar disorder and schizophrenia could increase the odds of IBD, with OR values of 1.138 (95%CI: 1.084-1.194; =1.9×10), and 1.115 (95%CI: 1.071-1.161; =1.12×10), respectively. Our results also indicate that obsessive-compulsive disorder could lead to IBD, especially for UC, with OR values of 1.091 (95%CI: 1.024-1.162; =0.009), and 1.124 (95%CI: 1.041-1.214; =0.004), respectively.
CONCLUSIONS
Our findings indicate that the brain-gut axis involves the association between IBD, especially UC, and some mental disorders, which guides the targeted prevention, management, and mechanism exploration of these diseases.
Topics: Humans; Autism Spectrum Disorder; Mendelian Randomization Analysis; Inflammatory Bowel Diseases; Mental Disorders; Colitis, Ulcerative; Crohn Disease; Ascomycota
PubMed: 37901213
DOI: 10.3389/fimmu.2023.1267834 -
Immunology and Allergy Clinics of North... May 2024Eosinophilic gastrointestinal disorder (EGID) is an umbrella term encompassing a group of chronic, immune-mediated disorders characterized by eosinophil-rich... (Review)
Review
Eosinophilic gastrointestinal disorder (EGID) is an umbrella term encompassing a group of chronic, immune-mediated disorders characterized by eosinophil-rich inflammation affecting one or more segments of the gastrointestinal tract. A recent consensus in nomenclature and emerging data made possible through multi-center consortia are beginning to unravel the molecular and cellular underpinnings of EGIDs below the esophagus. These emerging findings are revealing both overarching commonalities related to a food allergen-driven, chronic, Th2-mediated immune response as well as location-specific nuances in the pathophysiology of the collective EGIDs. Altogether, these advances offer promise for improved diagnoses and more efficacious interventional strategies.
Topics: Humans; Enteritis; Gastritis; Eosinophilia; Eosinophilic Esophagitis
PubMed: 38575225
DOI: 10.1016/j.iac.2024.01.003 -
United European Gastroenterology Journal Oct 2023Gastroparesis (GP) is characterized by delayed gastric emptying in the absence of mechanical obstruction. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Gastroparesis (GP) is characterized by delayed gastric emptying in the absence of mechanical obstruction.
OBJECTIVE
Genetic predisposition may play a role; however, investigation at the genome-wide level has not been performed.
METHODS
We carried out a genome-wide association study (GWAS) meta-analysis on (i) 478 GP patients from the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium (GpCRC) compared to 9931 population-based controls from the University of Michigan Health and Retirement Study; and (ii) 402 GP cases compared to 48,340 non-gastroparesis controls from the Michigan Genomics Initiative. Associations for 5,811,784 high-quality SNPs were tested on a total of 880 GP patients and 58,271 controls, using logistic mixed models adjusted for age, sex, and principal components. Gene mapping was obtained based on genomic position and expression quantitative trait loci, and a gene-set network enrichment analysis was performed. Genetic associations with clinical data were tested in GpCRC patients. Protein expression of selected candidate genes was determined in full thickness gastric biopsies from GpCRC patients and controls.
RESULTS
While no SNP associations were detected at strict significance (p ≤ 5 × 10 ), nine independent genomic loci were associated at suggestive significance (p ≤ 1 × 10 ), with the strongest signal (rs9273363, odds ratio = 1.4, p = 1 × 10 ) mapped to the human leukocyte antigen region. Computational annotation of suggestive risk loci identified 14 protein-coding candidate genes. Gene-set network enrichment analysis revealed pathways potentially involved in immune and motor dysregulation (p ≤ 0.05). The GP risk allele rs6984536A (Peroxidasin-Like; PXDNL) was associated with increased abdominal pain severity scores (Beta = 0.13, p = 0.03). Gastric muscularis expression of PXDNL also positively correlated with abdominal pain in GP patients (r = 0.8, p = 0.02). Dickkopf WNT Signaling Pathway Inhibitor 1 showed decreased expression in diabetic GP patients (p = 0.005 vs. controls).
CONCLUSION
We report preliminary GWAS findings for GP, which highlight candidate genes and pathways related to immune and sensory-motor dysregulation. Larger studies are needed to validate and expand these findings in independent datasets.
Topics: Humans; Genome-Wide Association Study; Gastroparesis; Genetic Predisposition to Disease; Abdominal Pain
PubMed: 37688361
DOI: 10.1002/ueg2.12453 -
Gastrointestinal Endoscopy Clinics of... Jul 2024
Topics: Humans; Pancreatic Diseases; Endoscopy, Digestive System; Cholangiopancreatography, Endoscopic Retrograde; Biliary Tract Diseases
PubMed: 38796301
DOI: 10.1016/j.giec.2024.03.001 -
Journal of Crohn's & Colitis Nov 2023Autoimmune pancreatitis [AIP] is rarely associated with inflammatory bowel disease [IBD]. The long-term outcomes of AIP and IBD in patients with coexisting AIP-IBD and...
BACKGROUND
Autoimmune pancreatitis [AIP] is rarely associated with inflammatory bowel disease [IBD]. The long-term outcomes of AIP and IBD in patients with coexisting AIP-IBD and predictors of complicated AIP course have rarely been reported.
METHODS
An ECCO COllaborative Network For Exceptionally Rare case reports project [ECCO-CONFER] collected cases of AIP diagnosed in patients with IBD. Complicated AIP was defined as a composite of endocrine and/or exocrine pancreatic insufficiency, and/or pancreatic cancer. We explored factors associated with complicated AIP in IBD.
RESULTS
We included 96 patients [53% males, 79% ulcerative colitis, 72% type 2 AIP, age at AIP diagnosis 35 ± 16 years]. The majority of Crohn's disease [CD] cases [78%] had colonic/ileocolonic involvement. In 59%, IBD preceded AIP diagnosis, whereas 18% were diagnosed simultaneously. Advanced therapy to control IBD was used in 61% and 17% underwent IBD-related surgery. In total, 82% of patients were treated with steroids for AIP, the majority of whom [91%] responded to a single course of treatment. During a mean follow-up of 7 years, AIP complications occurred in 25/96 [26%] individuals. In a multivariate model, older age at AIP diagnosis was associated with a complicated AIP course (odds ratio [OR] = 1.05, p = 0.008), whereas family history of IBD [OR = 0.1, p = 0.03], and CD diagnosis [OR = 0.2, p = 0.04] decreased the risk of AIP complications. No IBD- or AIP-related deaths occurred.
CONCLUSIONS
In this large international cohort of patients with concomitant AIP-IBD, most patients have type 2 AIP and colonic IBD. AIP course is relatively benign and long-term outcomes are favourable, but one-quarter develop pancreatic complications. Age, familial history of IBD, and CD may predict uncomplicated AIP course.
Topics: Male; Humans; Young Adult; Adult; Middle Aged; Female; Autoimmune Pancreatitis; Pancreatitis; Retrospective Studies; Autoimmune Diseases; Inflammatory Bowel Diseases; Colitis, Ulcerative; Crohn Disease
PubMed: 37283545
DOI: 10.1093/ecco-jcc/jjad097