Therapeutic Advances in Gastroenterology最新文献

Background: Microscopic colitis (MC) causes chronic diarrhea. It has two histologic subtypes: lymphocytic colitis (LC) and collagenous colitis (CC). Little is known about the natural progression of disease with time and with treatment.

Objectives: We aimed to assess histological changes over time.

Design: We designed a retrospective study including adults diagnosed with MC from January 1992 to January 2020 at Mayo Clinic.

Methods: Pathology reports were reviewed until 31 October 2020. Histological assessments at least 8 weeks apart were considered as adequate follow-up. Histological change from one subtype to the other and resolution were tracked with univariate and multivariable Cox proportional hazards models.

Results: Overall, 416 patients with a median age at diagnosis of 63.9 years with >1 histopathological assessment were identified. Histology at initial diagnosis was CC in 218 (52.4%) patients and LC in 198 (47.6%). No medications were associated with a histological change. However, histological resolution was more likely with the use of aspirin [hazard ratio (HR): 2.10, 95% confidence interval (CI): 1.34-3.31, p = 0.001) and proton-pump inhibitors (PPIs; HR: 2.01, 95% CI: 1.34-3.02, p = 0.001). Histological resolution was more likely with budesonide treatment (HR: 1.86, 95% CI: 1.16-3.00, p = 0.010) and less likely with mesalamine (HR: 0.40, 95% CI: 0.19-0.83, p = 0.014), compared to medications such as prednisone, loperamide, and bismuth. Patients with CC were less likely to change their histology compared to patients with LC (HR: 0.24, 95% CI: 0.14-0.42, p < 0.001). There was no difference in histological resolution between the two subtypes (HR: 0.70, 95% CI: 0.47-1.05, p = 0.084).

Conclusion: Patients with LC have a higher chance of changing their histology as compared to CC. However, histological resolution was associated with the use of PPIs and aspirin, and treatment with budesonide.

Alcohol-associated liver disease (ALD) is a complex disease with rapidly increasing prevalence. Although there are promising therapeutic targets on the horizon, none of the newer targets is currently close to an Food and Drug Administration approval. Strategies are needed to overcome challenges in study designs and conducting clinical trials and provide impetus to the field of drug development in the landscape of ALD and alcoholic hepatitis. Management of ALD is complex and should include therapies to achieve and maintain alcohol abstinence, preferably delivered by a multidisciplinary team. Although associated with clear mortality benefit in select patients, the use of early liver transplantation still requires refinement to create uniformity in selection protocols across transplant centers. There is also a need for reliable noninvasive biomarkers for prognostication. Last but not the least, strategies are urgently needed to implement integrated multidisciplinary care models for treating the dual pathology of alcohol use disorder and of liver disease for improving the long-term outcomes of patients with ALD.

The SARS-CoV2 pandemic has had a profound and lasting impact on healthcare delivery. Gastrointestinal endoscopy services were limited during the early phases of the pandemic, which has resulted in ongoing procedural backlog. Procedural delays have had continuing effects including delayed colorectal cancer (CRC) diagnoses and exacerbation of existing disparities in the CRC-screening and treatment pathways. In this review, we outline these effects as well as the variety of strategies that have been proposed to eliminate this backlog, including increased endoscopy hours, re-triaging of referrals, and alternative CRC-screening strategies.

With the exception of South Africa, inflammatory bowel disease (IBD) has long been considered uncommon in sub-Saharan Africa (SSA) with a dearth of peer-reviewed publications from the subcontinent. This most likely reflects underreporting as some cases may be missed due to the high burden of infectious diseases which may closely mimic IBD. In addition, many countries in SSA have limited endoscopic capacity, inadequate access to diagnostic imaging and a notable scarcity of histopathologists, radiologists and gastroenterologists. Beyond these obstacles, which significantly impact patient care, there are many other challenges in SSA, particularly the unavailability of key IBD therapies. In this review, we discuss barriers in diagnosing and managing IBD in SSA, as well as some of the initiatives currently in place to address these short comings.

Background/aims: Anti-tumor necrosis factor (anti-TNF) drugs have been the mainstay therapy for moderate to severe inflammatory bowel disease (IBD) over the past 25 years. Nevertheless, these drugs are associated with serious opportunistic infections like tuberculosis (TB). Brazil is ranked among the 30 countries with the highest incidence of TB in the world. This study aimed at identifying risk factors for the development of active TB and describing clinical characteristics and outcomes in IBD patients followed at a tertiary referral center in Brazil.

Methods: We conducted a retrospective, case-control study between January 2010 and December 2021. Active TB cases in IBD patients were randomly matched 1:3 to controls (IBD patients with no previous history of active TB) according to gender, age, and type of IBD.

Design: This was a retrospective, case-control study.

Results: A total of 38 (2.2%) cases of TB were identified from 1760 patients under regular follow-up at our outpatient clinics. Of the 152 patients included in the analysis (cases and controls), 96 (63.2%) were male, and 124 (81.6%) had Crohn's disease. Median age at TB diagnosis was 39.5 [interquartile range (IQR) 30.8-56.3]. Half of the active TB cases were disseminated (50%). Overall, 36 patients with TB (94.7%) were being treated with immunosuppressive medications. Of those, 31 (86.1%) were under anti-TNF drugs. Diagnosis of TB occurred at a median of 32 months after the first dose of anti-TNF (IQR 7-84). In multivariate analysis, IBD diagnosis older than 17 years and anti-TNF therapy were significantly associated with the development of TB (p < 0.05). After the TB treatment, 20 (52.7%) patients received anti-TNF therapy, and only one developed 'de novo' TB 10 years after the first infection.

Conclusions: TB remains a significant health problem in IBD patients from endemic regions, especially those treated with anti-TNFs. In addition, age at IBD diagnosis (>17 years old) was also a risk factor for active TB. Most cases occur after long-term therapy, suggesting a new infection. The reintroduction of anti-TNFs agents after the anti-TB treatment seems safe. These data highlight the importance of TB screening and monitoring in IBD patients living in endemic areas.

Pancreatic fluid collection often occurs as a local complication of acute pancreatitis, and drainage is indicated in symptomatic patients. The drainage may be surgical, percutaneous, or endoscopic ultrasound (EUS) guided. In symptomatic collections older than 4 weeks and localized in the upper abdomen, EUS-guided drainage is the first choice of treatment. Lumen-apposing metal stents are useful in cases of walled-off necrosis, facilitating access to the cavity; however, they do not reduce the number of necrosectomy sessions required. In most pancreatic pseudocysts requiring drainage, plastic stents remain the first choice of treatment. This review aimed to summarize the principles and techniques of step-up therapy of pancreatic fluid collections, including preprocedural and postprocedural assessment and practical approaches of drainage and necrosectomy, making available evidence more accessible to endoscopists aiming to train for this procedure. Successful and safe EUS drainage connotes early recognition and treatment of complications and the presence of a multidisciplinary team for optimal patient management. However, the best time for necrosectomy, modality of drainage method (lumen-apposing metal stents or plastic stents), and duration of antibiotherapy are still under evaluation.

Esophageal cancer (EC) is the seventh most common malignancy worldwide. Although systemic chemotherapy is the standard treatment for advanced EC, the available cytotoxic agents have limited efficacy. Pembrolizumab, a humanized monoclonal immunoglobulin G4 antibody that inhibits programmed cell death protein 1, has recently been developed for the treatment of patients with advanced EC. In the KEYNOTE-181 trial, pembrolizumab achieved a clinical meaningful overall survival benefit over chemotherapy alone when used as second-line treatment in patients with esophageal squamous cell carcinoma (ESCC) who had a combined positive score ⩾10 for expression of programmed death ligand 1. Furthermore, KEYNOTE-590 showed that pembrolizumab + chemotherapy was more effective than chemotherapy alone as first-line chemotherapy for patients with advanced EC. Accordingly, immune checkpoint inhibitor (ICI) chemotherapy has become the standard first-line treatment for advanced EC. The use of ICIs in primary therapy has helped to improve the prognosis, especially for ESCC. Moreover, in CheckMate 577, patients who received postoperative nivolumab therapy had a reduced risk of recurrence, and the ability of preoperative ICI chemotherapy to reduce the incidence of recurrence is now under investigation. This review outlines the evidence for use of pembrolizumab as a first-line treatment for advanced unresectable or metastatic EC, summarizes the ongoing research on ICI combination chemotherapy, and discusses the associated issues.

Behcet's disease (BD) is a chronic and recurrent systemic vasculitis involving large, medium and small blood vessels as well as arteries and veins. BD with predominant gastrointestinal manifestations is diagnosed as intestinal BD, which is associated with severe complications such as massive gastrointestinal hemorrhage, perforation, and obstruction. Recently, treat-to-target (T2T) strategies have been successfully used in many chronic diseases and been suggested in the management of BD, while there are no related reviews about the global treatment strategy including treatment principles and targets for intestinal BD in detail. Herein, we review the treatment principles from the aspects of departments of Rheumatology and Gastroenterology. In addition, treatment targets of intestinal BD are reviewed from three aspects such as evaluable markers, effective markers and potency-ratio markers. Some definitions and conceptions from inflammatory bowel disease (IBD) bring us reference and enlightenments.

Background: Readmission shortly after discharge is indicative of an increased disease severity for patients with ulcerative colitis (UC) and ineffectiveness to medical therapy, which may contribute to a dismal prognosis.

Objectives: This study aimed to explore prognostic variables with a nomogram to predict unplanned UC-related readmission within 1 year after discharge.

Design: A retrospective cohort study.

Methods: Electronic medical records of all UC patients treated at our center between 1 January 2014 and 31 June 2021 were reviewed. A comprehensive analysis of various characteristics, such as demographics, comorbidities, medical history, follow-up appointments, admission endoscopy, histopathologic features, etc., was used to determine the primary end point, which was unplanned UC-related calendar year readmission.

Results: We found that the unplanned UC-related readmission rate within 1 year was 20.8%. In multivariable cox analysis, the predictors of the Elixhauser comorbidity index [Hazard ratio (HR): 3.50, 95% confidence interval (CI): 1.93-6.37], regular follow-up (HR: 0.29, 95% CI: 0.16-0.53), any history of corticosteroid use (HR: 3.38, 95% CI: 1.83-6.27), seral level of C-reactive protein (HR: 1.01, 95% CI: 1.00-1.02), and the UC endoscopic index of severity (HR: 1.29, 95% CI: 1.05-1.57) independently predicted calendar year readmission after discharge. The established nomogram had a consistently high accuracy in predicting calendar year readmission in the training cohort, with a concordance index of 0.784, 0.825, and 0.837 at 13, 26, and 52 weeks, respectively, which was validated in both the internal and external validation cohorts. Therefore, UC patients were divided into clinically low-, high-, and extremely high-risk groups for readmission, based on the calculated score of 272.5 and 378.

Conclusion: The established nomogram showed good discrimination and calibration powers in predicting calendar year readmission in high-risk UC patients, who may need intensive treatment and regular outpatient visits.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has complicated the management of inflammatory bowel diseases (IBD).

Objectives: This study aimed to assess the efficacy of different anti-SARS-CoV-2 vaccines under different treatments in IBD patients and identify predictive factors associated with lower serological response, including anti-tumor necrosis factor (anti-TNF) drug levels.

Design: A prospective, double-center study of IBD patients was conducted following messenger ribonucleotide acid (mRNA) and non-mRNA anti-SARS-CoV-2 vaccination.

Methods: Healthy control (HC) patients were enrolled to reduce bias. Baseline and control samples were obtained 14 days after the second dose to assess the impact of conventional and biological treatments. Clinical and biochemical activity, serological response level, and anti-TNF drug levels were measured.

Results: This study included 199 IBD (mean age, 40.9 ± 12.72 years) and 77 HC participants (mean age, 50.3 ± 12.36 years). Most patients (76.9%) and all HCs received mRNA vaccines. Half of the IBD patients were on biological treatment (anti-TNF 68.7%). Biological and thiopurine combined immunomodulation and biological treatment were associated with lower serological response (p < 0.001), and mRNA vaccination promoted better antibody levels (p < 0.001). Higher adalimumab levels caused lower serological response (p = 0.006). W8 persistence of anti-SARS-CoV-2 level was equal in IBD and HC groups. Vaccination did not aggravate clinical disease activity (p = 0.65).

Conclusion: Anti-SARS-CoV-2 vaccination is considerably efficacious in IBD patients, with mRNA vaccines promoting better antibody levels. The negative impact of combined biological treatment, especially with high adalimumab drug levels, on serological response to vaccination should be considered. Although midterm durability of vaccination is encouraging, more data are needed to expand the existing understanding on this issue.