Carcinomas in inflammatory bowel disease: a narrative review on diagnostic imaging techniques

We aimed, therefore, to review the current evidence on imaging modalities and carcinomas overlapping IBD.Patients affected by inflammatory bowel diseases (IBD) are at increased risk for developing both gastrointestinal and extra-intestinal cancers. The subtype of IBD, namely Crohn's disease or ulcerative colitis, the location, the activity, the extent, and the duration of the disease determine this risk. Standardized surveillance programs based on imaging techniques exist only for colorectal cancer, where colonoscopy is the milestone of early detection. Clarification is needed on whether different imaging modalities might be adopted in the algorithms for screening and diagnosis of cancers in IBD patients.PubMed was searched up to July 2021 to identify relevant studies investigating the accuracy of imaging techniques in identifying carcinomas in IBD patients. The following text words and corresponding Medical Subject Heading/Entree terms were used: "imaging", "computed tomography", "magnetic resonance imaging", "inflammatory bowel disease", "adenocarcinoma" and "cancer".Currently dye-chromoendoscopy (DCE) is established as the gold standard diagnostic modality for the detection of dysplasia in IBD, with a demonstrated superiority compared to white-light endoscopy. Two main radiological patterns have been described at cross-sectional imaging for both colorectal cancer and small bowel adenocarcinoma. The first subtype is characterized by a tissue mass, while the second subtype recognizes a circumferential thickening with or without the stricturing of the lumen. The diagnostic sensitivity, specificity, and accuracy of cross-sectional imaging techniques for the detection of carcinomas in the context of IBD are largely unknown and scarcely investigated. The definition of surveillance programs based on different imaging methods is warranted

Phenotypic spectrum and transcriptomic profile associated with germline variants in TRAF7

PURPOSE: Somatic variants in tumor necrosis factor receptor-associated factor 7 (TRAF7) cause meningioma, while germline variants have recently been identified in seven patients with developmental delay and cardiac, facial, and digital anomalies. We aimed to define the clinical and mutational spectrum associated with TRAF7 germline variants in a large series of patients, and to determine the molecular effects of the variants through transcriptomic analysis of patient fibroblasts. METHODS: We performed exome, targeted capture, and Sanger sequencing of patients with undiagnosed developmental disorders, in multiple independent diagnostic or research centers. Phenotypic and mutational comparisons were facilitated through data exchange platforms. Whole-transcriptome sequencing was performed on RNA from patient- and control-derived fibroblasts. RESULTS: We identified heterozygous missense variants in TRAF7 as the cause of a developmental delay-malformation syndrome in 45 patients. Major features include a recognizable facial gestalt (characterized in particular by blepharophimosis), short neck, pectus carinatum, digital deviations, and patent ductus arteriosus. Almost all variants occur in the WD40 repeats and most are recurrent. Several differentially expressed genes were identified in patient fibroblasts. CONCLUSION: We provide the first large-scale analysis of the clinical and mutational spectrum associated with the TRAF7 developmental syndrome, and we shed light on its molecular etiology through transcriptome studies

Colorectal Cancer Surveillance in Patients with Inflammatory Bowel Diseases: Chromoendoscopy or Non-Chromoendoscopy, That Is the Question

Subjects affected by ulcerative colitis and Crohn’s disease with colonic localization have an increased risk of colorectal cancer (CRC). Surveillance colonoscopy is recommended by international guidelines as it can detect early-stage CRC. Based on previous evidence, in 2015 the Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients International Consensus indicated dye chromoendoscopy (DCE) as the most effective technique for detecting dysplasia. However, advances in endoscopic technology such as high-definition colonoscopes and dye-less virtual chromoendoscopy (VCE) may change future practice. In this review, we summarize the available evidence on CRC surveillance in IBD, focusing on the emerging role of high-definition white light endoscopy (HD-WLE) and VCE over the standard DCE, and the current role of random biopsies

Ileal Pouch–Anal Anastomosis and Pouchitis: The Role of the Microbiota in the Pathogenesis and Therapy

Inflammatory bowel diseases, Crohn’s disease and ulcerative colitis, are life-long disorders characterized by the chronic relapsing inflammation of the gastrointestinal tract with the intermittent need for escalation treatment and, eventually, even surgery. The total proctocolectomy with ileal pouch–anal anastomosis (IPAA) is the surgical intervention of choice in subjects affected by ulcerative colitis (UC). Although IPAA provides satisfactory functional outcomes, it can be susceptible to some complications, including pouchitis as the most common. Furthermore, 10–20% of the pouchitis may develop into chronic pouchitis. The etiology of pouchitis is mostly unclear. However, the efficacy of antibiotics in pouchitis suggests that the dysbiosis of the IPAA microbiota plays an important role in its pathogenesis. We aimed to review the role of the microbiota in the pathogenesis and as a target therapy in subjects who develop pouchitis after undergoing the surgical intervention of total proctocolectomy with IPAA reconstruction

Sphingosine 1-Phosphate Modulation in Inflammatory Bowel Diseases: Keeping Lymphocytes Out of the Intestine

Inflammatory bowel diseases (IBDs) are chronic and disabling conditions that, uncontrolled, lead to irreversible bowel damage and associated comorbidities. Despite the new era of biological therapies, IBDs remain not curative. The treatment purpose is to induce endoscopic remission, reduce the progression of the disease and improve the quality of life. Optimal and early treatment could enable the prevention of their complications. Small molecules, administrated as oral agents, have the capacity of overcoming the limitations of biologic agents (i.e., parenteral administration, rapidity of action and primary and secondary non-responsiveness). Of special interest are results from the use of oral sphingosine 1-phosphate (S1P) receptor modulators (ozanimod, etrasimod, fingolimod and laquinimod), based on S1P activities to target lymphocyte recirculation in the mucosa, acting as immunosuppressive agents. Most S1P modulators are reported to be safe and effective in the treatment of both UC and CD. High and satisfactory rates of clinical remission as well as endoscopic improvement and remission can be achieved with these molecules. Safety alarms remain rather low, although the S1P binding to two of its G protein-coupled receptors, 2 and 3 (S1PR2 and S1PR3), may be associated with cardiovascular risks. Cost-effectiveness studies and head-to-head trials are needed to better define their place in therapy. This review summarizes these emerging data published by PubMed and EMBASE databases and from ongoing clinical trials on the safety and efficacy of selectivity of S1P modulators in the treatment of IBD

Colorectal Cancer Surveillance in Patients with Inflammatory Bowel Diseases: Chromoendoscopy or Non-Chromoendoscopy, That Is the Question

Subjects affected by ulcerative colitis and Crohn’s disease with colonic localization have an increased risk of colorectal cancer (CRC). Surveillance colonoscopy is recommended by international guidelines as it can detect early-stage CRC. Based on previous evidence, in 2015 the Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients International Consensus indicated dye chromoendoscopy (DCE) as the most effective technique for detecting dysplasia. However, advances in endoscopic technology such as high-definition colonoscopes and dye-less virtual chromoendoscopy (VCE) may change future practice. In this review, we summarize the available evidence on CRC surveillance in IBD, focusing on the emerging role of high-definition white light endoscopy (HD-WLE) and VCE over the standard DCE, and the current role of random biopsies

Management of Post-Operative Crohn’s Disease: Knowns and Unknowns

Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract characterized by relapsing–remission phases. CD often requires surgical intervention during its course, mainly ileo-cecal/ileo-colonic resection. However, surgery in CD is not curative and post-operative recurrence (POR) can happen. The management of CD after surgery presents challenges. Ensuring timely, effective, and safe therapy to prevent POR is essential but difficult, considering that approximately 20–30% of subjects may not experience endoscopic POR and that 40–50% will only exhibit intermediate lesions, which carry a low risk of mid- and long-term clinical and surgical POR. Currently, there are two accepted intervention strategies: early post-operative prophylactic therapy (systematically or based on the patient’s risk of recurrence) or starting therapy after confirming endoscopic POR 6–12 months after surgery (endoscopy-driven prophylactic therapy). The risk of overtreatment lies in exposing patients to undesired adverse events, along with the costs associated with medications. Conversely, undertreatment may lead to missed opportunities to prevent bowel damage and the necessity for additional surgery. This article aims to perform a comprehensive review regarding the optimal strategy to reduce the risk of POR in CD patients and the current therapeutic options

Prosthesis design based on virtual prototyping techniques

Lower limb prosthesis for above or lower knee amputees are still designed and manufactured almost completely in a manual way, deeply relying on the experience and manual skills of orthopaedic technicians. Such a nonrepeatable non-deterministic procedure is poorly efficient and time consuming and patients may have to wait for a considerable amount of time before getting a new, hopefully better, prosthesis. The proposed paper shows the main features characterizing the working prototype of a virtual environment developed to assist the technicians in the creation and test of the virtual prosthesis. To reach the ambitious goal of replacing the manual process with a virtual one several issues have been considered and addressed: the capture and formalization of process knowledge of orthopaedic technicians, the acquisition of patient’s information and digital data also by means of diagnostic instruments, the development of integrated solution to design and test standard and custom-fit components and the use of digital human techniques to simulate the way the prosthesis will behave during walking. The architecture of the integrated environment will be described in the paper and the main tools will be briefly introduced in order to illustrate the most important steps creating an uninterrupted path going from patient’s history and MRI data to the creation of his/her avatar wearing the new digital prosthesis, virtually trying it, setting it up and passing data for automatic production

Prevalence of Gastrointestinal Symptoms and Fecal Viral Shedding in Patients With Coronavirus Disease 2019 A Systematic Review and Meta-analysis

Importance Coronavirus disease 2019 (COVID-19) is a global pandemic and can involve the gastrointestinal (GI) tract, including symptoms like diarrhea and shedding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in feces. Objective To provide a pooled estimate of GI symptoms, liver enzyme levels outside reference ranges, and fecal tests positive for SARS-CoV-2 among patients with COVID-19. Data Sources An electronic literature search was performed for published (using MEDLINE/PubMed and Embase) and preprint (using bioRxiv and medRxiv) studies of interest conducted from November 1, 2019, to March 30, 2020. Search terms included "COVID-19," "SARS-Cov-2," and/or "novel coronavirus." Study Selection Eligible studies were those including patients with SARS-CoV-2 infection who reported GI symptoms. Data Extraction and Synthesis Data on patients with GI symptoms (ie, diarrhea, nausea, or vomiting), liver enzyme level changes, and fecal shedding of virus were extracted. Quality of studies was examined using methodological index for nonrandomized studies. Pooled estimates (%) were reported with 95% CIs with level of heterogeneity (I-2). Main Outcomes and Measures Study and patient characteristics with pooled detection rates for diarrhea, nausea or vomiting, liver enzyme levels outside reference ranges, and SARS-CoV-2 positivity in feces tests were analyzed. Results Of 1484 records reviewed, 23 published and 6 preprint studies were included in the analysis, with a total of 4805 patients (mean [SD] age, 52.2 [14.8] years; 1598 [33.2%] women) with COVID-19. The pooled rates were 7.4% (95% CI, 4.3%-12.2%) of patients reporting diarrhea and 4.6% (95% CI, 2.6%-8.0%) of patients reporting nausea or vomiting. The pooled rate for aspartate aminotransferase levels outside reference ranges was 20% (95% CI, 15.3%-25.6%) of patients, and the pooled rate for alanine aminotransferase levels outside reference ranges was 14.6% (95% CI, 12.8%-16.6%) of patients. Fecal tests that were positive for SARS-CoV-2 were reported in 8 studies, and viral RNA shedding was detected in feces in 40.5% (95% CI, 27.4%-55.1%) of patients. There was high level of heterogeneity (I-2 = 94%), but no statistically significant publication bias noted. Conclusions and Relevance These findings suggest that that 12% of patients with COVID-19 will manifest GI symptoms; however, SAR-CoV-2 shedding was observed in 40.5% of patients with confirmed SARS-CoV-2 infection. This highlights the need to better understand what measures are needed to prevent further spread of this highly contagious pathogen.Question What are the incidence rates of gastrointestinal symptoms among patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection? Findings This systematic review and meta-analysis of 23 published and 6 preprint studies found that approximately 12% of patients with SARS-CoV-2 infection reported gastrointestinal symptoms, including diarrhea, nausea, and vomiting. Liver enzyme levels outside reference ranges were observed in 15% to 20% of patients, and SARS-CoV-2 RNA shedding in stool was detected in up to 41% of patients. Meaning These findings suggest that patients with SARS-CoV-2 infection can present with gastrointestinal symptoms with possible fecal-oral route of transmission due to the presence of viral RNA in stool.This systematic review and meta-analysis examines the prevalence of reported gastrointestinal symptoms in patients with coronavirus disease 2019 and of viral RNA shedding detected in these patients' stool

Prevalence of Gastrointestinal Symptoms and Fecal Viral Shedding in Patients With Coronavirus Disease 2019: A Systematic Review and Meta-analysis.

Importance: Coronavirus disease 2019 (COVID-19) is a global pandemic and can involve the gastrointestinal (GI) tract, including symptoms like diarrhea and shedding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in feces. Objective: To provide a pooled estimate of GI symptoms, liver enzyme levels outside reference ranges, and fecal tests positive for SARS-CoV-2 among patients with COVID-19. Data Sources: An electronic literature search was performed for published (using MEDLINE/PubMed and Embase) and preprint (using bioRxiv and medRxiv) studies of interest conducted from November 1, 2019, to March 30, 2020. Search terms included COVID-19, SARS-Cov-2, and/or novel coronavirus. Study Selection: Eligible studies were those including patients with SARS-CoV-2 infection who reported GI symptoms. Data Extraction and Synthesis: Data on patients with GI symptoms (ie, diarrhea, nausea, or vomiting), liver enzyme level changes, and fecal shedding of virus were extracted. Quality of studies was examined using methodological index for nonrandomized studies. Pooled estimates (%) were reported with 95% CIs with level of heterogeneity (I2). Main Outcomes and Measures: Study and patient characteristics with pooled detection rates for diarrhea, nausea or vomiting, liver enzyme levels outside reference ranges, and SARS-CoV-2 positivity in feces tests were analyzed. Results: Of 1484 records reviewed, 23 published and 6 preprint studies were included in the analysis, with a total of 4805 patients (mean [SD] age, 52.2 [14.8] years; 1598 [33.2%] women) with COVID-19. The pooled rates were 7.4% (95% CI, 4.3%-12.2%) of patients reporting diarrhea and 4.6% (95% CI, 2.6%-8.0%) of patients reporting nausea or vomiting. The pooled rate for aspartate aminotransferase levels outside reference ranges was 20% (95% CI, 15.3%-25.6%) of patients, and the pooled rate for alanine aminotransferase levels outside reference ranges was 14.6% (95% CI, 12.8%-16.6%) of patients. Fecal tests that were positive for SARS-CoV-2 were reported in 8 studies, and viral RNA shedding was detected in feces in 40.5% (95% CI, 27.4%-55.1%) of patients. There was high level of heterogeneity (I2 = 94%), but no statistically significant publication bias noted. Conclusions and Relevance: These findings suggest that that 12% of patients with COVID-19 will manifest GI symptoms; however, SAR-CoV-2 shedding was observed in 40.5% of patients with confirmed SARS-CoV-2 infection. This highlights the need to better understand what measures are needed to prevent further spread of this highly contagious pathogen