Is a small-caliber or large-caliber endoscope more suitable for colonic self-expandable metallic stent placement? A randomized controlled study

Objectives: The colonic self-expandable metallic stent (C-SEMS) with a 9-French (Fr) delivery system allows for a small-caliber endoscope (SCE) to be used to treat malignant colonic obstruction. Despite the lack of evidence, the SCE has become popular because it is considered easier to insert than the large-caliber endoscope (LCE). We aimed to determine whether the SCE is more suitable than the LCE for C-SEMS placement. Methods: Between July 2018 and November 2019, 50 consecutive patients who were scheduled to undergo C-SEMS for colon obstruction were recruited in this study. Patients were randomized to the SCE or LCE group. The SCE and LCE were used with 9-Fr and 10-Fr delivery systems, respectively. The primary outcome was the total procedure time. Secondary outcomes were the technical success rate, complication rate, clinical success rate, insertion time, guidewire-passage time, stent-deployment time, and colonic obstruction-scoring-system score. Results: Forty-five patients (SCE group, n = 22; LCE group, n = 23) were analyzed. The procedure time in the LCE group (median, 20.5 min) was significantly ( p = 0.024) shorter than that in the SCE group (median, 25.1 min). The insertion time in the LCE group (median, 2.0 min) was significantly ( p = 0.0049) shorter than that in the SCE group (median, 6.0 min). A sub-analysis of the procedure difficulties showed that the insertion time in the LCE group (median, 5.0 min) was significantly shorter than that in the SCE group (median, 8.5 min). Conclusion: Both LCE and SCE can be used for C-SEMS; however, LCE is more suitable than SCE as it achieved a faster and equally efficacious C-SEMS placement as that of SCE. Clinical trial registration number: University Hospital Medical Information Network Clinical Trials Registry (UMIN 32748)

The relationship between Helicobacter pylori infection and reflux esophagitis and the long-term effects of eradication of Helicobacter pylori on reflux esophagitis

Introduction: Whether the incidence of reflux esophagitis (RE) increases after the eradication of Helicobacter pylori ( H. pylori) is controversial. Few reports have evaluated the presence or absence of RE after a long period of time, taking into account the degree of atrophy and/or administration of acid secretion inhibitors. We investigated the relationship between H. pylori and RE taking into account these factors. Methods: This was a retrospective cohort study with approval by the Ethics Committee. Patients who succeeded in H. pylori eradication treatment, and in whom there were images of the gastroesophageal junction on endoscopic examinations within 1 year before eradication treatment and more than 3 years after eradication were included. The degrees of RE and atrophy were retrospectively determined from the endoscopic images. The prevalence of RE before and after eradication and the incidence of newly developed RE after eradication between patients with or without atrophy improvement were compared using Fisher’s exact test. Results: A total of 185 cases (male:female = 104:81; mean age, 63.5 years; mean observation period, 6.4 years) were examined. The prevalence of RE before and after eradication was 1.6% (3/185) and 7.0% (13/185), respectively ( P = 0.019). RE was present in 8 (7.5%) of 106 cases with closed-type atrophy and in 5 (6.3%) of 79 cases with open-type atrophy after eradication ( P = 0.75). Atrophy improved after eradication in 56 cases, of whom 4 (7.1%) had new onset of RE; the degree of atrophy did not improve in 126 cases, of whom 7 (5.4%) had new onset of RE ( P = 0.74). There was no difference between the percentage of cases who took acid secretion inhibitors before and after eradication ( P = 0.14). Conclusion: The prevalence of RE increased a long time after eradication, even in patients who were taking an acid secretion inhibitor. The prevalence of RE was not related to the degree of atrophy or change in atrophy.

Short-term tolerability and effectiveness of methotrexate monotherapy in adult patients with Crohn’s disease: a retrospective study

Introduction: Immunomodulators remain fundamental for the medical treatment of Crohn’s disease (CD). Methotrexate (MTX) is widely used as a second-line immunomodulator; however, there is a lack of recent data on MTX monotherapy among the Asian population with CD. Therefore, in this study, we aimed to investigate the tolerability and clinical outcomes of MTX in Korean patients with CD. Methods: A retrospective chart review was performed for CD patients treated with MTX monotherapy or in combination with 5-aminosalicylic acid (5-ASA), at the Asan Medical Center, Seoul, South Korea. The tolerability of MTX monotherapy within 6 months was assessed and the clinical effectiveness of MTX was evaluated based on the Crohn’s disease activity index (CDAI). Results: In total, 85 patients were included, of which 29 (34.1%) discontinued MTX due to intolerability during the follow-up. Adverse events (AEs) were reported in 41 (48.2%) patients. The most common AE was gastrointestinal disorders (17/41) and only one patient experienced a serious AE, a systemic infection that required hospitalization. Among the 56 patients who tolerated MTX within 6 months, 44 (65.9%) showed a clinical response. Moreover, no factor was significantly associated with intolerability. The administration method was the only factor significantly associated with a response to MTX ( p = 0.041). The adjusted odds ratio of parenteral injection compared to oral administration was 5.68 (95% confidence interval (CI), 1.07–30.08). Conclusion: In this study, one-third of patients were intolerant to MTX; nonetheless, the response rate was as high as 65.9% among tolerant patients. In addition, no significant factors affected intolerability. In terms of the clinical response, parenteral injection could be better than oral administration.

Systematic review with meta-analysis: effectiveness of hyperbaric oxygenation therapy for ulcerative colitis

Background and aims: Hyperbaric oxygenation therapy has been used in the treatment of ulcerative colitis in the past few years. However, its efficacy still remains unclear. The aim of the study was to investigate the efficacy of hyperbaric oxygen combination therapy in patients with ulcerative colitis. Methods: We conducted a comprehensive study search up to September 2020, from the online databases Embase, PubMed, Cochrane Library, China National Knowledge Infrastructure, WanFang and VIP. Results: Thirteen studies comprising 780 patients were included. We found that compared with conventional therapy, hyperbaric oxygen combination therapy was superior in reaching clinical remission [risk ratio (RR)=1.62; 95% confidence interval (CI) 1.42 to 1.84; p < 0.001] and clinical response (RR=1.29; 95% CI 1.21 to 1.38; p < 0.001), with lower disease activity scores [standard mean difference (SMD)= −1.19; 95%CI −1.74 to −0.65; p < 0.001]. An obvious reduction of serum levels of tumor necrosis factor-α (SMD= −1.96; 95%CI −2.50 to −1.41; p < 0.001) and interleukin (IL)-6 (SMD= −2.49; 95% CI −2.84 to −2.15; p < 0.001), and elevation of IL-10 level (SMD=2.40; 95% CI 0.68 to 4.12; p = 0.006) were also observed. Conclusion: Hyperbaric oxygen combination therapy was effective in patients with ulcerative colitis, and has potential as a complementary method for its treatment.

Update on the role of pembrolizumab in patients with unresectable or metastatic colorectal cancer

Colorectal cancer (CRC) is the third most common cancer type in both men and women in the USA. Most patients with CRC are diagnosed as local or regional disease. However, the survival rate for those diagnosed with metastatic disease remains disappointing, despite multiple treatment options. Cancer therapies for patients with unresectable or metastatic CRC are increasingly being driven by particular biomarkers. The development of various immune checkpoint inhibitors has revolutionized cancer therapy over the last decade by harnessing the immune system in the treatment of cancer, and the role of immunotherapy continues to expand and evolve. Pembrolizumab is an anti-programmed cell death protein 1 immune checkpoint inhibitor and has become an essential part of the standard of care in the treatment regimens for multiple cancer types. This paper reviews the increasing evidence supporting and defining the role of pembrolizumab in the treatment of patients with unresectable or metastatic CRC.

The interplay of Clostridioides difficile infection and inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic disease of the intestinal tract that commonly presents with diarrhea. Clostridioides difficile infection (CDI) is one of the most common complications associated with IBD that lead to flare-ups of underlying IBD. The pathophysiology of CDI includes perturbations of the gut microbiota, which makes IBD a risk factor due to the gut microbial alterations that occur in IBD, predisposing patients CDI even in the absence of antibiotics. Superimposed CDI not only worsens IBD symptoms but also leads to adverse outcomes, including treatment failure and an increased risk of hospitalization, surgery, and mortality. Due to the overlapping symptoms and concerns with false-positive molecular tests for CDI, diagnosing CDI in patients with IBD remains a clinical challenge. It is crucial to have a high index of suspicion for CDI in patients who seem to be experiencing an exacerbation of IBD symptoms. Vancomycin and fidaxomicin are the first-line treatments for the management of CDI in IBD. Microbiota restoration therapies effectively prevent recurrent CDI in IBD patients. Immunosuppression for IBD in IBD patients with CDI should be managed individually, based on a thorough clinical assessment and after weighing the pros and cons of escalation of therapy. This review summarizes the epidemiology, pathophysiology, the diagnosis of CDI in IBD, and outlines the principles of management of both CDI and IBD in IBD patients with CDI.

Does inflammatory bowel disease have different characteristics according to stage of adolescence?

Background: There is a lack of data about demographic and treatment characteristics of adolescent patients with inflammatory bowel disease (IBD). The aim of this retrospective, epidemiological study was to evaluate characteristics and therapeutic features of Hungarian adolescents with IBD. Methods: We analysed the social security databases of the National Health Insurance Fund. Adolescent patients with IBD for whom data from 2009 to 2016 were observable in the database were enrolled. Patients aged 14 to 17 years and 18 to 21 years were defined as middle and late adolescent patients. Results: The incidences of IBD were 20.12 per 100,000 middle adolescent patients and 29.72 per 100,000 late adolescent patients. Admission to gastroenterology department was higher in both groups compared with admissions to surgery department. Mesalazine was used by a high proportion of Crohn’s disease and ulcerative colitis patients. Rates of corticosteroid use were similar in both groups, with a tendency to decrease over time. The need for biologic agents was higher in the middle adolescent patients. The proportion of patients in the middle adolescent group who received anti-TNF therapy showed an increasing tendency. Conclusion: Our data suggest differences in the treatment strategies of gastroenterologists for these age groups. The greater need of anti-TNF therapy among the middle adolescent group indicates that adolescent patients before the transition to adult care may have a more severe disease phenotype. We expect that a strategy of early, effective treatment will significantly ameliorate the subsequent disease course, which is manifested in adult care.

Alternative chemoradiotherapy in anal carcinoma patients with mutations in thymidylate synthase and dihydropyrimidine dehydrogenase genes

Background: 5-fluorouracil (5-FU) and mitomycin-C (MMC) with radiotherapy (RT) remain an established treatment for patients with anal cancer (AC). Genetic mutations in two major metabolizing enzymes for 5-FU; dihydropyrimidine dehydrogenase ( DPYD and thymidylate synthetase ( TYMS), have been associated with clinical response and toxicity. However, their place in the treatment of AC remains undetermined. Methods: We retrospectively reviewed 21 patients with AC, including T2-4, N0-1, M0 or T1-4, N2-3, and M0 treated between 2012 and 2018. All patients were treated with 5-FU 1,000 mg/m2/day via continuous intravenous (IV) infusion 1–4 and 29–32, MMC 10 mg/m2 IV bolus days 1 and 29 plus RT. Patients who developed ⩾3 grade toxicities were tested for the DPYD and TYMS genes. Treatment was either modified with reduced doses or changed to MMC 10 mg/m2 day 1 and 29 with cisplatin 25 mg/m2/week plus RT. Toxicities and responses were collected. Results: Six out of 21 patients who developed ⩾3 grade toxicities including pancytopenia, neutropenia, thrombocytopenia, mucositis, nausea, rash, and nephritis were found to have genetic mutations: TYMS 2RG/3RC ( n = 2), 3RG/3RC ( n = 1), 2R/2R ( n = 2), T YMS 3′UTR del/Ins ( n = 2), and DPYD c.2864A > T heterozygous ( n = 1). Two patients received 5-FU at a 50% reduced dose on days 29–32; one patient refused to receive 5-FU (continued with MMC and RT); one patient received only radiation therapy due to persistent pancytopenia despite the use of growth factors; two patients received an alternative regimen consisting of MMC 10 mg/m2 on day 29 with cisplatin (CDDP) 25 mg/m2/week plus RT; and two patients received cisplatin/MMC with RT from the beginning as they were prospectively detected to have TYMS abnormalities prior to dosing the chemotherapy. These patients tolerated treatment very well with only grade 2 toxicities. All the patients (4/4) on cisplatin/MMC achieved clinical complete response (cCR), while four patients (4/15) on 5-FU/MMC reached cCR at the first assessment. Radiological response showed complete response at the end of 24 weeks assessment. Conclusions: Molecular testing for DPYD and TYMS genes can allow us to identify patients who are most likely to respond or face severe toxicity to 5-FU in a potentially curable cancer. Combining radiation with CDDP with MMC in patients with AC is feasible. A prospective study based on pharmacogenetic testing comparing MMC/cisplatin with MMC/5-FU is indicated in patients with AC.

Probiotics use is associated with improved clinical outcomes among hospitalized patients with COVID-19

Background and aims: Currently, there are no definitive therapies for coronavirus disease 2019 (COVID-19). Gut microbial dysbiosis has been proved to be associated with COVID-19 severity and probiotics is an adjunctive therapy for COIVD-19. However, the potential benefit of probiotics in COVID-19 has not been studied. We aimed to assess the relationship of probiotics use with clinical outcomes in patients with COVID-19. Methods: We conducted a propensity-score matched retrospective cohort study of adult patients with COVID-19. Eligible patients received either probiotics plus standard care (probiotics group) or standard care alone (non-probiotics group). The primary outcome was the clinical improvement rate, which was compared among propensity-score matched groups and in the unmatched cohort. Secondary outcomes included the duration of viral shedding, fever, and hospital stay. Results: Among the propensity-score matched groups, probiotics use was related to clinical improvement rates (log-rank p = 0.028). This relationship was driven primarily by a shorter (days) time to clinical improvement [difference, −3 (−4 to −1), p = 0.022], reduction in duration of fever [−1.0 (−2.0 to 0.0), p = 0.025], viral shedding [−3 (−6 to −1), p < 0.001], and hospital stay [−3 (−5 to −1), p = 0.009]. Using the Cox model with time-varying exposure, use of probiotics remained independently related to better clinical improvement rate in the unmatched cohort. Conclusion: Our study suggested that probiotics use was related to improved clinical outcomes in patients with COVID-19. Further studies are required to validate the effect of probiotics in combating the COVID-19 pandemic.

Burden of major gastrointestinal bleeding among oral anticoagulant-treated non-valvular atrial fibrillation patients

Background: Gastrointestinal (GI) bleeding is the most common type of major bleeding associated with oral anticoagulant (OAC) treatment. Patients with major bleeding are at an increased risk of a stroke if an OAC is not reinitiated. Methods: Non-valvular atrial fibrillation (NVAF) patients initiating OACs were identified from the Centers for Medicare and Medicaid Services ( CMS) Medicare data and four US commercial claims databases. Patients who had a major GI bleeding event (hospitalization with primary diagnosis of GI bleeding) while on an OAC were selected. A control cohort of patients without a major GI bleed during OAC treatment was matched to major GI bleeding patients using propensity scores. Stroke/systemic embolism (SE), major bleeding, and mortality (in the CMS population) were examined using Cox proportional hazards models with robust sandwich estimates. Results: A total of 15,888 patients with major GI bleeding and 833,052 patients without major GI bleeding were included in the study. Within 90 days of the major GI bleed, 58% of patients discontinued the initial OAC treatment. Patients with a major GI bleed had a higher risk of stroke/SE [hazard ratio (HR): 1.57, 95% confidence interval (CI): 1.42–1.74], major bleeding (HR: 2.79, 95% CI: 2.64–2.95), and all-cause mortality (HR: 1.29, 95% CI: 1.23–1.36) than patients without a major GI bleed. Conclusion: Patients with a major GI bleed on OAC had a high rate of OAC discontinuation and significantly higher risk of stroke/SE, major bleeding, and mortality after hospital discharge than those without. Effective management strategies are needed for patients with risk factors for major GI bleeding.