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The Journal of Allergy and Clinical... Sep 2021X-linked agammaglobulinemia (XLA) is an inherited primary immunodeficiency that usually manifests clinically with recurrent sinopulmonary infections. Gastrointestinal...
BACKGROUND
X-linked agammaglobulinemia (XLA) is an inherited primary immunodeficiency that usually manifests clinically with recurrent sinopulmonary infections. Gastrointestinal manifestations are mostly driven by acute infections and disturbed mucosal immunity, but there is a notable prevalence of inflammatory bowel disease (IBD). Differentiating between XLA-associated enteritis, which can originate from recurrent infections, and IBD can be diagnostically and therapeutically challenging.
OBJECTIVE
This study presents a critical appraisal of the clinical, radiological, endoscopic, and histological features associated with XLA-associated Crohn disease (CD)-like enteritis.
METHODS
We report 3 cases and performed a systematic review of the literature describing the diagnoses and outcomes.
RESULTS
An XLA-related enteropathy presented in adolescence with an ileocolonic CD-like phenotype without perianal disease. Abdominal pain, noninfectious diarrhea, and weight loss were the most common symptoms. Imaging and endoscopic findings closely resemble CD. However, histologically, it presents without nodular lymphoid hyperplasia and only 2 studies reported the presence of granulomas. In addition, in XLA-associated enteritis, immunohistochemistry showed the absence or marked reduction in B cells and plasma cells.
CONCLUSIONS
An XLA-associated enteritis is a distinct pathological process that presents clinically in a manner similar to ileocolonic CD. It is important to evaluate for infectious diarrhea, which is common in XLA and can mimic IBD clinically. Complete multidisciplinary evaluation is, therefore, recommended for XLA patients with persistent gastrointestinal symptoms. Although more research is needed, therapeutic selection for XLA-associated enteritis is like that of IBD, and the possible risk of drug interactions and complications from increasing immunosuppression should be considered.
Topics: Agammaglobulinaemia Tyrosine Kinase; Agammaglobulinemia; Crohn Disease; Enteritis; Genetic Diseases, X-Linked; Humans
PubMed: 34029777
DOI: 10.1016/j.jaip.2021.04.070 -
PloS One 2021A high prevalence of cryptoglandular and Crohn's perianal fistulas has been reported worldwide, and several surgical options are available for the management of anal... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
A high prevalence of cryptoglandular and Crohn's perianal fistulas has been reported worldwide, and several surgical options are available for the management of anal fistula, with varying clinical efficacy. However, currently, the available evidence for the effectiveness of these surgical approaches are lacking and of concern in terms of the credibility and strength. The purpose of this study is to evaluate the credibility of the published systematic reviews and meta-analyses that assess the efficacy and safety of the surgical options for cryptoglandular and Crohn's perianal fistulas through an umbrella review.
METHODS AND ANALYSIS
A systematic search in PubMed, Embase and Cochrane library will be performed from inception to December 2020 without any language restriction. We will include systematic reviews and meta-analyses that investigate the efficacy and safety of surgical approaches in the management of cryptoglandular and Crohn's perianal fistulas. Two reviewers will independently screen search results through reading the titles or abstracts. Relevant information will be extracted from each eligible systematic review or meta-analysis. Based on random effects model summary estimates along with their p values, 95% prediction intervals, between-study heterogeneity, small-study effects and excess significance, we will classify the evidence from convincing (class I) to weak (class IV). Findings will be summarized using quantitative synthesis combined with a narrative approach. Cryptoglandular and Crohn's perianal fistulas will be summarized separately. Two authors will independently perform the literature search, data extraction, and quality assessment of each included systematic review and meta-analysis. Any unresolved conflicts or doubts will be resolved by discussion or by consulting a senior author. The risk of bias of the systematic reviews will be assessed using a 16-item Assessment of Multiple Systematic Reviews 2 (AMSTAR2) checklist. The strength of evidence for the included systematic reviews will be classified as "high", "moderate", "low", or "critically low" quality.
ETHICS AND DISSEMINATION
Ethics approval is not required as we will collect data from the published systematic reviews and meta-analyses without using individual patient data. The results of this umbrella review will be published in a peer-reviewed journal and will be presented at an anorectal disease conference.
PROSPERO REGISTRATION NUMBER
CRD42020200754.
Topics: Crohn Disease; Humans; Rectal Fistula; Research Design; Treatment Outcome
PubMed: 33984014
DOI: 10.1371/journal.pone.0251460 -
Cancers Mar 2021Perianal fistulizing Crohn's disease is a very disabling condition with poor quality of life. Patients with perianal fistulizing Crohn's disease are also at risk of... (Review)
Review
Perianal fistulizing Crohn's disease is a very disabling condition with poor quality of life. Patients with perianal fistulizing Crohn's disease are also at risk of perianal fistula-related squamous cell carcinoma (SCC). Cancer arising at the site of a chronic perianal fistula is rare in patients with Crohn's disease and there is a paucity of data regarding its incidence, diagnosis and management. A systematic review of the literature was undertaken using Medline, Embase, Pubmed, Cochrane and Web of Science. Several small series have described sporadic cases with perianal cancer in Crohn's disease. The incidence rate of SCC related to perianal fistula was very low (<1%). Prognosis was poor. Colorectal disease, chronic perianal disease and HPV infection were possible risk factors. Fistula-related carcinoma in CD (Chron's disease) can be very difficult to diagnose. Examination may be limited by pain, strictures and induration of the perianal tissues. HPV is an important risk factor with a particular carcinogenesis mechanism. MRI can help clinicians in diagnosis. Examination under anesthesia is highly recommended when findings, a change in symptoms, or simply long-standing disease in the perineum are present. Future studies are needed to understand the role of HPV vaccination in preventing fistula-related cancer.
PubMed: 33809997
DOI: 10.3390/cancers13061445 -
World Journal of Gastroenterology Mar 2021Although blood concentration of biologics is an important composition of disease management in inflammatory bowel disease (IBD) patients, complexity and uncertainty of...
BACKGROUND
Although blood concentration of biologics is an important composition of disease management in inflammatory bowel disease (IBD) patients, complexity and uncertainty of biological management encourage many disputes in predicting the outcome of IBD patients through blood concentration of biologics.
AIM
To verify the predictive value of blood concentration of biologics on endoscopic inactivity in IBD patients under different situations.
METHODS
We searched PubMed/MEDLINE, Embase, and Web of Science up to May 2020 and identified IBD patients as the research cohort as well as the correlations between blood concentration of biologics and endoscopic inactivity in IBD patients as the research direction.
RESULTS
A total of 23 articles with 30 clinical studies and 1939 IBD patients were included. The predictive cut-off value of blood concentration of infliximab on mucosal healing should be 2.7-10.6 μg/mL in IBD. Blood concentration of infliximab reaching 5.0-12.7 μg/mL or more increased the probability of fistula healing/closure in perianal fistulizing Crohn's disease. Blood concentration of adalimumab reaching 7.2-16.2 μg/mL or more could predict mucosal healing in IBD. The predictive cut-off value of blood concentration of adalimumab on fistula healing/closure should be 5.9-9.8 μg/mL in perianal fistulizing Crohn's disease. Blood concentration of vedolizumab surpassing 25.0 μg/mL indicated mucosal healing in ulcerative colitis patients under maintenance therapy and the predictive cut-off value of blood concentration on mucosal healing or endoscopic remission under induction therapy in IBD could be 8.0-28.9 μg/mL.
CONCLUSION
Blood concentration of biologics should not be utilized to predict endoscopic inactivity of IBD independently due to discrepancies in clinical studies, whereas conducting therapeutic drug monitoring intensively contributes to precise therapy.
Topics: Adalimumab; Biological Products; Colitis, Ulcerative; Humans; Inflammatory Bowel Diseases; Infliximab
PubMed: 33727776
DOI: 10.3748/wjg.v27.i9.886 -
European Journal of Pediatrics Jun 2021Group A Streptococcus has been associated with a perianal infection. We conducted a systematic review of the literature on childhood streptococcal perianitis in three...
Group A Streptococcus has been associated with a perianal infection. We conducted a systematic review of the literature on childhood streptococcal perianitis in three databases: Excerpta Medica, National Library of Medicine, and Web of Science. The main purposes were to document the clinical features, the tendency to recur, the association with an asymptomatic streptococcal throat carriage, the accuracy of rapid streptococcal tests, and the mechanism possibly underlying the acquisition of this infection. More than 80% of cases are boys ≤7.0 years of age with defecation disorders, perianal pain, local itch, rectal bleeding, or fissure and a sharply demarcated perianal redness. Perianitis is associated with a streptococcal tonsillopharyngitis in about every fifth case. The time to diagnosis is ≥3 weeks in 65% of cases. Recurrences occur within 3½ months in about 20% of cases. An asymptomatic group A streptococcal throat carriage occurs in 63% of cases. As compared with perianal Streptococcus A culture, the rapid streptococcal tests have a positive predictive value of 80% and a negative predictive value of 96%. It is hypothesized that digital inoculation from nasopharynx to anus underlies perianitis. Many cases are likely caused directly by children, who are throat and nasal carriers of Streptococcus A. Some cases might occur in children, who have their bottoms wiped by caregivers with streptococcal tonsillopharyngitis or carriage of Streptococcus.Conclusion: Perianitis is an infection with a distinctive presentation and a rather long time to diagnosis. There is a need for a wider awareness of this condition among healthcare professionals. What is Known: • Group A Streptococcus may cause perianitis in childhood. • Systemic antimicrobials (penicillin V, amoxycillin, or cefuroxime) are superior to topical treatment. What is New: • The clinical presentation is distinctive (defecation disorders, perianal pain, local itch, rectal bleeding, or fissure and a sharply demarcated perianal redness). • The time to diagnosis is usually ≥3 weeks. Recurrences occur in about 20% of cases.
Topics: Amoxicillin; Anal Canal; Child; Female; Humans; Male; Pharyngitis; Streptococcal Infections; Streptococcus pyogenes
PubMed: 33532889
DOI: 10.1007/s00431-021-03965-9 -
Digestive Surgery 2021Perianal fistula is a common colorectal condition with an incidence of 9 per 100,000. Many surgical treatments exist, all aiming to eliminate symptoms with minimal risk... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Perianal fistula is a common colorectal condition with an incidence of 9 per 100,000. Many surgical treatments exist, all aiming to eliminate symptoms with minimal risk of recurrence and impact upon continence. Despite extensive evaluation of the therapeutic modalities, no clear consensus exists as to what is the gold standard approach. This systematic review aimed to examine all available evidence pertaining to the surgical management of perianal fistulas. Primary outcomes examined were recurrence and incontinence.
SUMMARY
This study was conducted according to PRISMA guidelines. Primary outcomes were analyzed for each group and expressed as pooled odds ratio with confidence intervals of 95%. 687 studies were identified from which 28 relevant studies were included. There was no significant difference in rates of incontinence identified between various surgical approaches. Glues and plugs show higher recurrence rates. Newer treatments continue to emerge with promise but lack supporting evidence of benefit over conventional therapies. Key Messages: While we await more robust randomized data, we will continue to proceed cautiously trying to offset the benefits of fistula healing against the inherent risk of altered continence.
Topics: Fecal Incontinence; Fibrin Tissue Adhesive; Humans; Rectal Fistula; Recurrence; Suture Techniques; Wound Healing
PubMed: 33503621
DOI: 10.1159/000512652 -
Biomolecules Jan 2021Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gut that can lead to severe gastrointestinal symptoms, malnutrition, and complications such as...
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gut that can lead to severe gastrointestinal symptoms, malnutrition, and complications such as fistulas and cancer. Mesenchymal stem/stromal cells (MSCs) are being investigated as a novel therapy for IBD and have been demonstrated to be safe and effective for perianal fistulizing Crohn's disease (PFCD). This systematic review aims to present the most recent studies on the safety and efficacy of MSC therapy in IBD. A detailed search strategy of clinical trials on MSCs and IBD was performed on PubMed, with 32 studies selected for inclusion in this review. The newest studies on local MSC injection for PFCD continue to support long-term efficacy while maintaining a favorable safety profile. The evidence for systemic MSC infusion in luminal IBD remains mixed due to marked methodological heterogeneity and unclear safety profiles. Although further studies are needed to better establish the role of this novel treatment modality, MSCs are proving to be a very exciting addition to the limited therapies available for IBD.
Topics: Crohn Disease; Humans; Inflammatory Bowel Diseases; Injections; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells
PubMed: 33440772
DOI: 10.3390/biom11010082 -
Stem Cell Research & Therapy Jan 2021Fistulas have puzzled us all the time and stem cell therapy for it is still in its infancy. We conducted a meta-analysis and systematic review to evaluate the efficacy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Fistulas have puzzled us all the time and stem cell therapy for it is still in its infancy. We conducted a meta-analysis and systematic review to evaluate the efficacy of stem cells and its potential mechanisms in the management of Crohn's fistula.
METHODS
Electronic databases were searched comprehensively for studies reporting the efficacy and safety of stem cells in patients with any form of Crohn's fistula. A random-effects model was used, and all outcomes were calculated by SPSS 24.0.
RESULTS
Twenty-nine articles with 1252 patients were included. It showed that stem cell group had a higher rate of fistula healing compared to placebo group in patients of Crohn's fistula (61.75% vs 40.46%, OR 2.21, 95% CI 1.19 to 4.11, P < 0.05). 3 × 10 cells/mL stem cell (SC) group had an advantage in fistula healing rate with 71.0% compared to other doses group of stem cells (RR 1.3, 95% CI 0.76 to 2.22). And the healing rates of patients with perianal and transsphincteric fistulas (77.95%, 76.41%) were higher than those with rectovaginal fistulas. It was an amazing phenomenon that CDAI and PDAI scores occurred an obviously transient rise with the use of stem cells after 1 month (both of P < 0.05), while they returned to the baseline level by giving stem cells 3 months later. Furthermore, the incidence rate of treatment-related adverse events in the stem cell group was significantly lower than in the placebo group (RR 0.58, 95% CI 0.30 to 1.14).
CONCLUSIONS
Our study has highlighted that stem cells was a promising method in the treatment of Crohn's fistula based on its higher efficacy and lower incidence of adverse events, especially ADSCs and Cx601. While it also needs more clinical and pre-clinical studies to strengthen evidences in the future.
Topics: Crohn Disease; Female; Fistula; Humans; Stem Cell Transplantation; Treatment Outcome
PubMed: 33413661
DOI: 10.1186/s13287-020-02095-7 -
Chirurgia (Bucharest, Romania : 1990) 2020Lung cancer is the most frequent cancer, accounting for over 2 million new cases per year worldwide. In Romania, the cancers with the highest incidence are lung cancer...
Lung cancer is the most frequent cancer, accounting for over 2 million new cases per year worldwide. In Romania, the cancers with the highest incidence are lung cancer for men and breast cancer for women. Cancer-related deaths follow the same pattern. More than 50% of the patients with lung cancers have distant metastases at the time of diagnosis. Metastases from lung cancer occur mainly in the brain, bones, liver, and adrenals. Anal metastases from primary lung cancer are extremely uncommon. As far as we know there are only 12 cases reported in the literature until now. Case report: Case report and systematic review. We performed a systematic literature search in PubMed using the following MeSH terms: "lung cancer metastasis" AND "anal" OR "anus" OR "perianal". The search was conducted from the beginning of the database onwards. No language exclusion criteria were used. We report the case of a patient with advanced lung adenocarcinoma presenting with a painful, ulcerated and bleeding anal tumor. The anal tumor was excised with primary wound closure in spinal anesthesia. The pathology report and the immunohistochemistry of the specimen revealed metastasis of the lung adenocarcinoma. The review included 12 papers reporting 12 cases. The male/female ratio was 3/1. The average age was 62,16 years. Among these 12 patients, one had a SCLC. From the remaining 11 cases with NSCLC, 4 were adenocarcinomas, 4 squamous cell carcinomas, two anaplastic carcinomas and one mucoepidermoid carcinoma. The anal metastases were synchronous in 4 cases and metachronous in the rest of 8 cases. Since 2006 immuno-histochemistry plays an important role in the diagnosis of these metastases. Our patient presented an anal metastasis of a lung adenocarcinoma that was masquerading as a complicated hemorrhoidal disease. Because anal masses can be easily misdiagnosed, patients with lung cancers and anal or perianal complaints should be evaluated for metastatic disease. Medical teams that are managing such cases must be aware of this rare but possible situation. Immunohistochemistry plays an important role in establishing the diagnosis for the anal or perianal tumours in patients with lung cancer.
Topics: Adenocarcinoma; Anus Neoplasms; Diagnosis, Differential; Hemorrhoids; Humans; Lung Neoplasms
PubMed: 33138907
DOI: 10.21614/chirurgia.115.5.681 -
Gastroenterology Jan 2021A better understanding of prognostic factors within the heterogeneous spectrum of pediatric Crohn's disease (CD) should improve patient management and reduce... (Meta-Analysis)
Meta-Analysis
Predicting Outcomes in Pediatric Crohn's Disease for Management Optimization: Systematic Review and Consensus Statements From the Pediatric Inflammatory Bowel Disease-Ahead Program.
BACKGROUND & AIMS
A better understanding of prognostic factors within the heterogeneous spectrum of pediatric Crohn's disease (CD) should improve patient management and reduce complications. We aimed to identify evidence-based predictors of outcomes with the goal of optimizing individual patient management.
METHODS
A survey of 202 experts in pediatric CD identified and prioritized adverse outcomes to be avoided. A systematic review of the literature with meta-analysis, when possible, was performed to identify clinical studies that investigated predictors of these outcomes. Multiple national and international face-to-face meetings were held to draft consensus statements based on the published evidence.
RESULTS
Consensus was reached on 27 statements regarding prognostic factors for surgery, complications, chronically active pediatric CD, and hospitalization. Prognostic factors for surgery included CD diagnosis during adolescence, growth impairment, NOD2/CARD15 polymorphisms, disease behavior, and positive anti-Saccharomyces cerevisiae antibody status. Isolated colonic disease was associated with fewer surgeries. Older age at presentation, small bowel disease, serology (anti-Saccharomyces cerevisiae antibody, antiflagellin, and OmpC), NOD2/CARD15 polymorphisms, perianal disease, and ethnicity were risk factors for penetrating (B3) and/or stenotic disease (B2). Male sex, young age at onset, small bowel disease, more active disease, and diagnostic delay may be associated with growth impairment. Malnutrition and higher disease activity were associated with reduced bone density.
CONCLUSIONS
These evidence-based consensus statements offer insight into predictors of poor outcomes in pediatric CD and are valuable when developing treatment algorithms and planning future studies. Targeted longitudinal studies are needed to further characterize prognostic factors in pediatric CD and to evaluate the impact of treatment algorithms tailored to individual patient risk.
Topics: Adolescent; Child; Child, Preschool; Consensus; Crohn Disease; Female; Humans; Infant; Infant, Newborn; Male; Outcome Assessment, Health Care; Predictive Value of Tests; Prognosis
PubMed: 32979356
DOI: 10.1053/j.gastro.2020.07.065