Background and Aim Autoimmune pancreatitis (AIP) and inflammatory bowel disease (IBD) are categorized into immune‐mediated inflammatory disorders (IMIDs). While AIP is a pancreato‐biliary IMID with an increased incidence and prevalence among patients with IBD, its features are still unclear. This systematic review and meta‐analysis aims to assess the prevalence and clinical characteristics of AIP‐IBD patients. Methods Electronic databases were searched to identify observational studies assessing AIP and IBD. The primary outcome was the prevalence of IBD among AIP patients, and vice versa. Secondary outcomes included clinical findings and outcomes of each IMID in AIP‐IBD patients. The pooled rate of each outcome was determined using a random effects model. Results For primary outcomes, 40 observational studies with 4031 AIP patients were included and the pooled prevalence of IBD was 10.5% (95% CI 7.2–15.0%). Meanwhile, five studies with 10,551 IBD patients were included and the pooled prevalence of AIP was 0.6% (95% CI 0.2–1.9%). For secondary outcomes, 53 observational studies with 469 AIP‐IBD patients were assessed. The rates of type 2 AIP and ulcerative colitis were 79.2% (95% CI 69.1–86.6%) and 74.8% (95% CI 68.2–80.4%), respectively. We also demonstrated AIP‐IBD patients were at a significant increased risk of AIP recurrence and colectomy compared with patients with either AIP or IBD (RR = 1.9, 95% CI 1.1–3.1 and P = 0.014 and RR = 3.7, 95% CI 1.9–6.9, P < 0.001, respectively). Conclusions Our meta‐analysis reported the prevalence of AIP‐IBD patients and demonstrated patients with both IMIDs had a high risk of poor outcomes.

Background/Aim: Bevacizumab-based chemotherapy is the standard treatment for metastatic colorectal cancer (mCRC) but has several specific adverse events. The cumulative bevacizumab dose (CBD) increases with longterm treatment as it is often used beyond the first disease progression, based on existing evidence. However, the association between CBD and the frequency and severity of adverse events in mCRC patients who received bevacizumab for long-term treatment remains unclear. Patients and Methods: Among the mCRC patients who received bevacizumab-based chemotherapy between March 2007 and December 2017 at the University of Tsukuba Hospital, those who continued treatment for more than 2 years were eligible for the study. The onset and worsening of proteinuria, hypertension, bleeding, and thromboembolic events were assessed to determine their relationship with CBD. Results: Of the 109 patients who received bevacizumab-based chemotherapy, 24 were included in the study. Grade 3 proteinuria was observed in 21 (88%) and 9 (38%) patients. The severity of proteinuria markedly increased after administering >100 mg/kg of CBD and progressed to grade 3 at concentrations exceeding 200 mg/kg. Thromboembolic events were observed in three (13%) patients, and two of them developed acute myocardial infarction after receiving a CBD of >300 mg/kg. Grade 2 or higher hypertension and grade 1 bleeding were observed in 9 (38%) patients and in 6 (25%) patients, respectively, regardless of the CBD. Conclusion: Proteinuria and thromboembolic events occurred and worsened in mCRC patients when the bevacizumab dose exceeded the threshold dose.Colorectal cancer is the third leading cause of cancer-related deaths worldwide and the second leading cause of cancerrelated deaths in Japan (1). For metastatic colorectal cancer (mCRC), bevacizumab, an angiogenesis inhibitor, is used as the standard treatment in fluoropyrimidine combination with oxaliplatin or irinotecan-based doublet chemotherapy, which is generally administered at 2.5 mg/kg/week (2). The median progression-free survival time with first-line chemotherapy, including bevacizumab, is 8-15 months (2-4). In addition, the significance of continuing bevacizumab treatment even after disease progression has been proven in a previous randomized phase III trial; bevacizumab is frequently used as a second-line treatment after failure of bevacizumab-based first-line therapies (5-7). Although the long-term administration of bevacizumab has shown a survival benefit, the increased incidence and severity of bevacizumab-related adverse events (AEs) remain a concern.Bevacizumab-related AEs included proteinuria, hypertension, arterial or venous thrombosis, bleeding, gastrointestinal perforation, and delayed wound healing (2). Several studies have investigated the association between bevacizumab treatment duration and bevacizumab-related AEs. The severity of proteinuria and cardiovascular events increases with longterm use of bevacizumab (8). A similar relationship has been shown between the risk of protein...

Patients with inflammatory bowel disease (IBD) are more likely to have concurrent immune-mediated inflammatory diseases (IMIDs) than those without IBD. IMIDs have been observed to alter the phenotype and outcomes of IBD in recent studies. Several studies have found that IBD patients with concurrent IMIDs may have more extensive or severe disease phenotypes, and are considered to be at increased risk of requiring biologics and IBD-related surgeries, suggesting that having multiple IMIDs is a poor prognostic factor for IBD. Furthermore, IBD patients with primary sclerosing cholangitis and Takayasu arteritis are reported to have unique endoscopic phenotypes, suggesting concurrent IMIDs can influence IBD phenotype with specific intestinal inflammatory distributions. In this review, we discuss the pathogenesis, disease phenotypes, and clinical outcomes in IBD patients with concomitant IMIDs.

No abstract

Dihydropyrimidine dehydrogenase (DPD) deficiency induces severe adverse events in patients receiving fluoropyrimidines. We encountered a 64-year-old DPD-deficient man with a severe capecitabine-related gastrointestinal disorder. He received capecitabine-containing chemotherapy after rectal cancer resection. During the first course of chemotherapy, he developed severe diarrhea, a fever, and hematochezia. Endoscopy revealed mucosal shedding with bleeding throughout the gastrointestinal tract. DPD deficiency was suspected because he developed many severe adverse events of capecitabine early and was finally confirmed based on the finding of a low DPD activity level in peripheral blood mononuclear cells. After one month of intensive care, hemostasis and mucosal healing were noted, although his gastrointestinal function did not improve, and he had persistent nutritional management issues.