Digestion最新文献

Introduction: Gap junctions can transmit signals between cells, including miRNAs, leading to the amplification of adjacent cell damage. No previous study has addressed gap junctions and miRNAs in sepsis because the internal mechanism of sepsis-induced intestinal injury is complex. Therefore, we studied the relationship between connexin43 (Cx43) and miR-181b and provided a research direction for further study of sepsis.

Methods: A mouse caecal ligation and puncture method was used to construct a mouse sepsis model. Firstly, damage to intestinal tissues at different time points was analysed. The levels of Cx43, miR-181b, Sirt1, and FOXO3a in intestinal tissues and the transcription and translation of the apoptosis-related genes Bim and puma, which are downstream of FOXO3a were analysed. Secondly, the effect of Cx43 levels on miR-181b and Sirt1/FOXO3a signalling pathway activity was explored by using the Cx43 inhibitor heptanol. Finally, luciferase assays were used to determine miR-181b binding to the predicted target sequence.

Results: The results show that during sepsis, intestinal injury becomes increasingly worse with time, and the expression of Cx43 and miR-181b increase. In addition, we found that heptanol could significantly reduce intestinal injury. This finding indicates that inhibiting Cx43 regulates the transfer of miR-181b between adjacent cells, thereby reducing the activity of the Sirt1/FOXO3a signalling pathway and reducing the degree of intestinal injury during sepsis.

Conclusions: In sepsis, the enhancement of Cx43 gap junctions leads to an increase in miR-181b intercellular transfer, affects the downstream SIRT1/FOXO3a signalling pathway and causes cell and tissue damage.

Background: The specific etiopathogenesis of inflammatory bowel disease (IBD) is still unknown. Although the conventional anti-inflammatory or immunomodulatory drugs relatively nonspecific to pathogenesis have been quite useful in many cases, elucidating the pathogenesis has gradually facilitated developments of disease-specific therapies for refractory cases in the last 2 decades.

Summary: With a greater understanding of the multiple overactive signaling pathways of the gut mucosal immune response and enhanced leukocyte trafficking, several biological agents or small molecule drugs following the first novel biologic, anti-tumor necrosis factor α (anti-TNFα), have been developed against several modes of action including adhesion molecules, sphingosine-1-phospate receptors, cytokines (IL-12/23, TL1A, and IL-36), Janus kinase (JAK), and phosphodiesterase. Although preceding biological agents have dramatically changed the IBD treatment strategy, many patients still require alternative therapies due to failure or side effects. Newer treatments are now expected to be provided for better efficacy with an improved adverse event profile. In addition, translational studies have highlighted the new therapeutic concepts' potential, including modulation of host-microbiome interactions, stem therapy for perianal fistula, regulation of fibrosis, regulation of the gut-brain axis, and control of previously less targeted immune cells (B cells and innate lymphoid cells). This paper comprehensively reviewed not only the latest already or shortly available therapies but also emerging promising treatments that will be hopefully established in the future for IBD.

Key messages: Many kinds of new treatments are available, and promising treatments with new perspectives are expected to emerge for refractory IBD in the future.

Introduction: Liver surgery leads to a high degree of heterogeneity in the prognosis of hepatocellular carcinoma (HCC) patients. However, most previous studies focused on the postoperative therapeutic effects of other treatments, with relatively few studies on the impacts on liver function. This study investigated the impact of transarterial chemoembolization (TACE) and hepatic artery infusion chemotherapy (HAIC) on liver function after HCC resection from various angles.

Methods: 138 HCC patients were enrolled, including 27 patients who received TACE and 80 patients who received HAIC. Besides routine treatment such as liver protection and antiviral therapy, 31 patients received no other treatment. The different groups were compared with various biological parameters with four types of scoring methods.

Results: In the short term after TACE, the mean (±SD) alanine transaminase and aspartate transaminase values increased by 79.22 ± 117.43 U/L and 66.33 ± 94.54 U/L, respectively (p < 0.01). The mean (±SD) total bilirubin (TBIL) values increased by 4.02 ± 6.08 μmol/L (p < 0.01). The mean (±SD) albumin (ALB) values decreased by 3.54 ± 2.93 g/L (p < 0.001). The mean (±SD) albumin bilirubin (ALBI) scores increased by 0.39 ± 0.22 (p < 0.001). In the short term after HAIC, the mean (±SD) TBIL values increased by 2.11 ± 5.57 μmol/L (p < 0.01). The mean (±SD) ALB values decreased by 2.52 ± 3.26 g/L (p < 0.001), and the mean (±SD) ALBI scores increased by 0.21 ± 0.42 (p < 0.001). In both treatment groups, the long-term liver function was not significantly different from that before treatment and also from that of the untreated group (p > 0.05).

Conclusion: TACE after HCC resection has a significant impact on short-term liver function, whereas HAIC has a relatively small impact, but neither has a major impact on long-term liver function.

Introduction: Length of stay (LOS) in hospital affects cost, patient quality of life, and hospital management; however, existing gastrointestinal bleeding models applicable at hospital admission have not focused on LOS. We aimed to construct a predictive model for LOS in acute lower gastrointestinal bleeding (ALGIB).

Methods: We retrospectively analyzed the records of 8,547 patients emergently hospitalized for ALGIB at 49 hospitals (the CODE BLUE-J Study). A predictive model for prolonged hospital stay was developed using the baseline characteristics of 7,107 patients and externally validated in 1,440 patients. Furthermore, a multivariate analysis assessed the impact of additional variables during hospitalization on LOS.

Results: Focusing on baseline characteristics, a predictive model for prolonged hospital stay was developed, the LONG-HOSP score, which consisted of low body mass index, laboratory data, old age, nondrinker status, nonsteroidal anti-inflammatory drug use, facility with ≥800 beds, heart rate, oral antithrombotic agent use, symptoms, systolic blood pressure, performance status, and past medical history. The score showed relatively high performance in predicting prolonged hospital stay and high hospitalization costs (area under the curve: 0.70 and 0.73 for derivation, respectively, and 0.66 and 0.71 for external validation, respectively). Next, we focused on in-hospital management. Diagnosis of colitis or colorectal cancer, rebleeding, and the need for blood transfusion, interventional radiology, and surgery prolonged LOS, regardless of the LONG-HOSP score. By contrast, early colonoscopy and endoscopic treatment shortened LOS.

Conclusions: At hospital admission for ALGIB, our novel predictive model stratified patients by their risk of prolonged hospital stay. During hospitalization, early colonoscopy and endoscopic treatment shortened LOS.

Introduction: Computer-aided diagnostic systems are emerging in the field of gastrointestinal endoscopy. In this study, we assessed the clinical performance of the computer-aided detection (CADe) of colonic adenomas using a new endoscopic artificial intelligence system.

Methods: This was a single-center prospective randomized study including 415 participants allocated into the CADe group (n = 207) and control group (n = 208). All endoscopic examinations were performed by experienced endoscopists. The performance of the CADe was assessed based on the adenoma detection rate (ADR). Additionally, we compared the adenoma miss rate for the rectosigmoid colon (AMRrs) between the groups.

Results: The basic demographic and procedural characteristics of the CADe and control groups were as follows: mean age, 54.9 and 55.9 years; male sex, 73.9% and 69.7% of participants; and mean withdrawal time, 411.8 and 399.0 s, respectively. The ADR was 59.4% in the CADe group and 47.6% in the control group (p = 0.018). The AMRrs was 11.9% in the CADe group and 26.0% in the control group (p = 0.037).

Conclusion: The colonoscopy with the CADe system yielded an 11.8% higher ADR than that performed by experienced endoscopists alone. Moreover, there was no need to extend the examination time or request the assistance of additional medical staff to achieve this improved effectiveness. We believe that the novel CADe system can lead to considerable advances in colorectal cancer diagnosis.

Background: Peutz-Jeghers syndrome (PJS) is a rare disease characterized by the presence of hamartomatous polyposis throughout the gastrointestinal tract, except for the esophagus, along with characteristic mucocutaneous pigmentation. It is caused by germline pathogenic variants of the STK11 gene, which exhibit an autosomal dominant mode of inheritance. Some patients with PJS develop gastrointestinal lesions in childhood and require continuous medical care until adulthood and sometimes have serious complications that significantly reduce their quality of life. Hamartomatous polyps in the small bowel may cause bleeding, intestinal obstruction, and intussusception. Novel diagnostic and therapeutic endoscopic procedures such as small-bowel capsule endoscopy and balloon-assisted enteroscopy have been developed in recent years.

Summary: Under these circumstances, there is growing concern about the management of PJS in Japan, and there are no practice guidelines available. To address this situation, the guideline committee was organized by the Research Group on Rare and Intractable Diseases granted by the Ministry of Health, Labour and Welfare with specialists from multiple academic societies. The present clinical guidelines explain the principles in the diagnosis and management of PJS together with four clinical questions and corresponding recommendations based on a careful review of the evidence and involved incorporating the concept of the Grading of Recommendations Assessment, Development and Evaluation system.

Key messages: Herein, we present the English version of the clinical practice guidelines of PJS to promote seamless implementation of accurate diagnosis and appropriate management of pediatric, adolescent, and adult patients with PJS.

Background: Colon capsule endoscopy (CCE) is useful as an alternative examination for patients in whom colonoscopy is difficult. The Japanese Association for Capsule Endoscopy has published a recommended regimen for CCE using castor oil, which is becoming a standard examination method for CCE in Japan. However, castor oil has an unpleasant flavor. Therefore, patient acceptance is not good.

Objectives: The aims were to develop a castor oil-filled capsule and evaluate its feasibility and patient acceptance in a retrospective, comparative study.

Method: A dissolution study of pig-derived gelatin capsules filled with castor oil was performed using artificial gastric juice. The CCE excretion rates within battery lifetime, CCE examination times, endoscopic colonic cleansing levels, and patient acceptability between CCE boosters with a castor oil-filled capsule and without castor oil were retrospectively compared using medical information, clinical data, and endoscopic findings at Takada Chuo Hospital from September 2016 to August 2019.

Results: The castor oil-filled capsules were completely disintegrated at approximately 1-3 min in artificial gastric juice. Bowel preparation with oil-filled capsules and without castor oil was performed in 27 and 24 patients, respectively. CCE excretion rates within battery life were 100% and 91.7% (p = 0.217), small bowel transit times were 115 min and 143 min (p = 0.046), colon transit times were 168 min and 148 min (p = 0.733), and adequate colonic cleansing rates were 85.2% and 86.3% (p = 1.000) in patients using bowel preparation with and without oil-filled capsules, respectively. Regarding acceptance, the taste was not problematic in 85.2%, and tolerability for the next CCE was 96.3%.

Conclusions: CCE using a castor oil-filled capsule method achieved high examination performance and sufficient patient tolerability.

Background: Biologics and immunomodulators are key drugs in the long-term treatment of inflammatory bowel diseases, while they may negatively impact patients' quality of life due to concerns of adverse events, need for frequent hospital visits, and medical expenses. The basic concept of drug withdrawal should be based on the risk of relapse and the efficacy of re-treatment. Considering a number of patients may relapse even if treatment is continued, the disadvantage of discontinuation should be recognized not by all relapse after discontinuation, but by the increase in relapse.

Summary: Discontinuation of immunomodulator monotherapy is associated with an increased risk of relapse. However, prolonged remission might be an indication of withdrawal, concerning the long-term adverse effect including lymphoma and nonmelanoma skin cancers. When considering discontinuation from combination therapy of anti-tumor necrosis factor (TNF) agents with immunomodulators, therapeutic drug monitoring may be useful to understand the pharmacokinetic effect. However, recent randomized controlled trials, as well as large-scale observational studies, demonstrated that discontinuation of anti-TNF agents, but not of immunomodulators, resulted in a significantly higher risk of relapse even in deep remission. Therefore, discontinuation of anti-TNF agents should be considered with caution and close monitoring combined with fecal calprotectin may be necessary. On the other hand, evidence of not only short-term relapse rate but of the true long-term influence on the patient's quality of life should be clarified by a multidimensional approach.

Key messages: Discontinuation of treatment should be implemented based on shared decision-making with careful interpretation of evidence and the condition.