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World Journal of Gastroenterology Aug 2019Crohn's disease (CD) can affect the entire gastrointestinal tract. Proximal small bowel (SB) lesions are associated with a significant risk of stricturing disease and...
BACKGROUND
Crohn's disease (CD) can affect the entire gastrointestinal tract. Proximal small bowel (SB) lesions are associated with a significant risk of stricturing disease and multiple abdominal surgeries. The assessment of SB in patients with CD is therefore necessary because it may have a significant impact on prognosis with potential therapeutic implications. Because of the weak correlation that exists between symptoms and endoscopic disease activity, the "treat-to-target" paradigm has been developed, and the associated treatment goal is to achieve and maintain deep remission, encompassing both clinical and endoscopic remission. Small bowel capsule endoscopy (SBCE) allows to visualize the mucosal surface of the entire SB. At that time, there is no recommendation regarding the use of SBCE during follow-up.
AIM
To investigate the impact of SBCE in a treat-to-target strategy in patients with CD.
METHODS
An electronic literature search was conducted in PubMed and Cochrane library using the following search terms: "capsule endoscopy", in combination with "Crohn's disease" and "treat-to-target" or synonyms. Two authors independently reviewed titles and abstracts identified by the search strategy after duplicates were removed. Following the initial screening of abstracts, all articles containing information about SBCE in the context of treat-to-target strategy in patients with CD were included. Full-text articles were retrieved, reference lists were screened manually to identify additional studies.
RESULTS
Forty-seven articles were included in this review. Two indexes are currently used to quantify disease activity using SBCE, and there is good correlation between them. SBCE was shown to be useful for disease reclassification in patients who are suspected of having or who are diagnosed with CD, with a significant incremental diagnostic yield compared to other diagnostic modalities. Nine studies also demonstrated that the mucosal healing can be evaluated by SBCE to monitor the effect of medical treatment in patients with CD. This review also demonstrated that SBCE can detect post-operative recurrence to a similar extent as ileocolonoscopy, and proximal SB lesions that are beyond the reach of the colonoscope in over half of the patients.
CONCLUSION
SBCE could be incorporated in the treat-to-target algorithm for patients with CD. Randomized controlled trials are required to confirm its usefulness and reliability in this indication.
Topics: Capsule Endoscopy; Clinical Protocols; Constriction, Pathologic; Crohn Disease; Humans; Ileum; Intestinal Mucosa; Jejunum; Prognosis; Recurrence; Reproducibility of Results; Treatment Outcome
PubMed: 31496630
DOI: 10.3748/wjg.v25.i31.4534 -
Drug Metabolism and Disposition: the... Aug 2019The aim of this study was to derive region-specific transporter expression data suitable for in vitro-to-in vivo extrapolation (IVIVE) within a physiologically based... (Meta-Analysis)
Meta-Analysis
The aim of this study was to derive region-specific transporter expression data suitable for in vitro-to-in vivo extrapolation (IVIVE) within a physiologically based pharmacokinetic (PBPK) modeling framework. A meta-analysis was performed whereby literary sources reporting region-specific transporter expression obtained via absolute and relative quantification approaches were considered in healthy adult Caucasian individuals. Furthermore, intestinal total membrane protein yield was calculated to enable mechanistic IVIVE via absolute transporter abundances. Where required, authors were contacted for additional information. A refined database was constructed where samples were excluded based on quantification in, non-Caucasian subjects, disease tissue, subjects <18 years old, duplicated samples, non-total membrane matrix, pooled matrices, or cDNA. Demographic data were collected where available. The weighted and geometric mean, coefficient of variation, and between-study homogeneity was calculated in each of eight gut segments (duodenum, two jejunum, four ileum, and colon) for 16 transporters. Expression data were normalized to that in the proximal jejunum. From a total of 47 articles, the final database consisted of 2238 measurements for 16 transporters. The solute carrier peptide transporter 1 (PepT1) showed the highest jejunal abundance, while multidrug resistance-associated protein (MRP) 2 was the highest abundance ATP-binding cassette transporter. Transporters displaying significant region-specific expression included the ileal bile acid transporter, which showed 18-fold greater terminal ileum expression compared with the proximal jejunum, while MRP3, organic cation transporter type 1 (OCTN1), and OCT1 showed >2-fold higher expression in other regions compared with the proximal jejunum. This is the first systematic analysis incorporating absolute quantification methodology to determine region-specific intestinal transporter expression. It is expected to be beneficial for mechanistic transporter IVIVE in healthy adult Caucasians. SIGNIFICANCE STATEMENT: Given the burgeoning reports of absolute transporter abundances in the human intestine, the incorporation of such information into mechanistic IVIVE-PBPK models could offer a distinct advantage in facilitating the robust assessment of the impact of gut transporters on drug disposition. The systematic and formal assessment via a literature meta-analysis described herein, enables assignment of the regional-specific expression, absolute transporter abundances, interindividual variability, and other associated scaling factors to healthy Caucasian populations within PBPK models. The resulting values are available to incorporate into PBPK models, and offer a verifiable account describing intestinal transporter expression within PBPK models for persons wishing to utilize them. Furthermore, these data facilitate the development of appropriate IVIVE scaling strategies using absolute transporter abundances.
Topics: Adult; Humans; Intestinal Absorption; Intestinal Mucosa; Jejunum; Membrane Transport Proteins; Models, Biological; Multidrug Resistance-Associated Protein 2; Proteomics; White People
PubMed: 31076413
DOI: 10.1124/dmd.119.086959 -
Digestive Surgery 2020Bile duct injury (BDI) is a devastating complication following cholecystectomy. After initial management of BDI, patients stay at risk for late complications including...
BACKGROUND
Bile duct injury (BDI) is a devastating complication following cholecystectomy. After initial management of BDI, patients stay at risk for late complications including anastomotic strictures, recurrent cholangitis, and secondary biliary cirrhosis.
METHODS
We provide a comprehensive overview of current literature on the long-term outcome of BDI. Considering the availability of only limited data regarding treatment of anastomotic strictures in literature, we also retrospectively analyzed patients with anastomotic strictures following a hepaticojejunostomy (HJ) from a prospectively maintained database of 836 BDI patients.
RESULTS
Although clinical outcomes of endoscopic, radiologic, and surgical treatment of BDI are good with success rates of around 90%, quality of life (QoL) may be impaired even after "clinically successful" treatment. Following surgical treatment, the incidence of anastomotic strictures varies from 5 to 69%, with most studies reporting incidences around 10-20%. The median time to stricture formation varies between 11 and 30 months. Long-term BDI-related mortality varies between 1.8 and 4.6%. Of 91 patients treated in our center for anastomotic strictures after HJ, 81 (89%) were treated by percutaneous balloon dilatation, with a long-term success rate of 77%. Twenty-four patients primarily or secondarily underwent surgical revision, with recurrent strictures occurring in 21%.
CONCLUSIONS
The long-term impact of BDI is considerable, both in terms of clinical outcomes and QoL. Treatment should be performed in tertiary expert centers to optimize outcomes. Patients require a long-term follow-up to detect anastomotic strictures. Strictures should initially be managed by percutaneous dilatation, with surgical revision as a next step in treatment.
Topics: Anastomosis, Roux-en-Y; Bile Ducts; Cholangitis; Cholecystectomy; Constriction, Pathologic; Dilatation; Humans; Iatrogenic Disease; Jejunum; Liver Cirrhosis, Biliary; Prognosis; Quality of Life; Recurrence; Reoperation; Retrospective Studies
PubMed: 30654363
DOI: 10.1159/000496432 -
Paediatrics and International Child... Nov 2019Systemic lupus erythematosus (SLE) is a multisystem, autoimmune inflammatory disease which can affect any organ, including the gastrointestinal tract. Lupus enteritis is...
Systemic lupus erythematosus (SLE) is a multisystem, autoimmune inflammatory disease which can affect any organ, including the gastrointestinal tract. Lupus enteritis is one of the manifestations of gastrointestinal involvement in SLE patients. However, it is exceedingly rare that lupus enteritis is the sole initial presentation of SLE. A 12-year-old Thai girl who had had recurrent abdominal pain for 2 months with no other signs of SLE on initial presentation is described. A single-balloon enteroscopy demonstrated segmental erythema of the proximal and mid-jejunum. Histopathology demonstrated active enteritis and submucosal vasculitis. On the basis of evidence of intestinal vasculitis, autoimmune profiles were performed; the results supported the possibility of SLE. She subsequently developed leucopenia, lymphopenia and an oral ulcer, leading to a robust diagnosis of SLE. Her clinical condition improved dramatically with prednisolone. Even though lupus enteritis is rare, it can be the initial presentation of SLE. In young adolescent girls with recurrent abdominal pain, the possibility of lupus enteritis should be borne in mind.
Topics: Adolescent; Anti-Inflammatory Agents; Balloon Enteroscopy; Child; Enteritis; Female; Histocytochemistry; Humans; Jejunum; Lupus Erythematosus, Systemic; Male; Prednisolone; Treatment Outcome
PubMed: 30191770
DOI: 10.1080/20469047.2018.1504430