Reduced antiviral seropositivity among patients with inflammatory bowel disease treated with immunosuppressive agents.

BACKGROUND: Although live-attenuated vaccines are contraindicated under immunosuppression, the immune status of patients with inflammatory bowel disease (IBD) has not been fully assessed prior to immunosuppressive therapy. AIMS: To investigate antiviral serostatus against viruses requiring live vaccines for prevention in IBD patients undergoing immunosuppressive therapy. METHODS: This multicenter study included IBD patients who were aged <40 years and were treated with thiopurine monotherapy, molecular-targeted monotherapy, or combination therapy. Gender- and age-matched healthy subjects (HS) living in the same areas were included as control group. Antibody titers against measles, rubella, mumps, and varicella were measured by enzyme-linked immunosorbent assays. RESULTS: A total of 437 IBD patients (163 ulcerative colitis [UC] and 274 Crohn's disease [CD]) and 225 HS were included in the final analysis. Compared with HS, IBD patients had lower seropositivity rates for measles (IBD vs. HS = 83.91% vs. 85.33%), rubella (77.55% vs. 84.89%), mumps (37.50% vs. 37.78%), and varicella (91.26% vs. 96.44%). Gender- and age-adjusted seropositivity rates were lower in UC patients than in both CD patients and HS for measles (UC, CD, and HS = 81.60%, 85.29%, and 85.33%), rubella (76.40%, 78.23%, and 84.89%), mumps (27.16%, 43.70%, and 37.78%), and varicella (90.80%, 91.54%, and 96.44%); the difference was significant for all viruses except measles. Divided by the degree of immunosuppression, there were no significant differences in seropositivity rates among IBD patients. CONCLUSIONS: IBD patients, especially those with UC, exhibit reduced seropositivity rates and may benefit from screening prior to the initiation of immunosuppressive therapy.

Factors Associated with Fibrosis during Colorectal Endoscopic Submucosal Dissection: Does Pretreatment Biopsy Potentially Elicit Submucosal Fibrosis and Affect Endoscopic Submucosal Dissection Outcomes?

BACKGROUND: Submucosal fibrosis observed during colorectal endoscopic submucosal dissection (ESD) is an important factor related to incomplete resection. Biopsy is generally accepted as having the potential to elicit submucosal fibrosis, but few reports have presented definitive proof. This study investigated the relation between submucosal fibrosis and colorectal ESD outcomes and assessed factors related to fibrosis, including pretreatment biopsy. METHODS: After reviewing 369 records of colorectal ESD performed between January 2011 and December 2016, we assessed the relation between fibrosis and ESD outcomes. Multiple logistic regression analysis revealed fibrosis risk factors. RESULTS: Severe fibrosis was related significantly to ESD outcomes such as the mean procedure time (p < 0.001), en bloc resection rate (p < 0.001), and R0 resection rate (p = 0.011). Multivariate analyses indicated residual lesions (ORs 175.4, p < 0.001), pretreatment biopsy (ORs 8.30, p = 0.002), nongranular-type laterally spreading tumors (LST-NG; ORs 5.86, p = 0.025), and invasive carcinoma (ORs 5.83, p = 0.03) as independent risk factors of severe fibrosis. In each macroscopic type, LST-NG was more strongly related to fibrosis induced by pretreatment than granular-type laterally spreading tumors with adjust ORs of 50.8 and 4.69. CONCLUSIONS: Pretreatment biopsy causes submucosal fibrosis resulting in prolonged procedure times and incomplete resection. These findings suggest important benefits of avoiding biopsy before ESD.

Long-term retention of adalimumab treatment and associated prognostic factors for 1189 patients with Crohn's disease.

BACKGROUND AND AIM: There are few studies on the long-term efficacy of adalimumab treatment for patients with Crohn's disease. We have conducted a large, multicenter, retrospective cohort study to evaluate the long-term retention rate and prognostic factors associated with the discontinuation of adalimumab treatment in patients with Crohn's disease. METHODS: Data were collected from all patients with Crohn's disease who had received at least one induction dose of 160 mg of adalimumab between October 2010 and December 2013 at 41 institutions. The cumulative retention rates of adalimumab treatment following the first administration were estimated using the Kaplan-Meier method. Prognostic factors related to the cumulative retention rates were evaluated by log-rank tests and multivariate Cox regression analysis. RESULTS: A total of 1189 patients were included in the study. The 1-, 2-, 3-, and 4-year cumulative retention rates of adalimumab were 81%, 72%, 65%, and 62%, respectively. The multivariate Cox regression analysis confirmed female sex, previous infliximab use, perianal disease, concomitant treatment with prednisolone at baseline, higher C-reactive protein levels, and lower albumin levels as significant independent predictors of poor retention rate of adalimumab treatment. Significantly, more female patients than male patients discontinued adalimumab because of adverse events, especially skin reactions, infections, and arthralgia. CONCLUSIONS: Our data demonstrated a good retention rate of adalimumab in patients with Crohn's disease over a 4-year period. Female sex, perianal disease, concomitant treatment with prednisolone at baseline, previous infliximab use, higher C-reactive protein levels, and lower albumin levels were associated with poor retention of adalimumab treatment.

Long-term course of inflammatory bowel disease after the Great East Japan Earthquake.

BACKGROUND AND AIM: This study analyzed inflammatory bowel disease activity for 2 years after the Great East Japan Earthquake. METHODS: We compared the relapse rates of patients with ulcerative colitis or Crohn's disease 1 and 2 years after the earthquake with rates immediately after the earthquake. To evaluate continuous disease courses, we also performed multivariate time-to-event analyses from the time of the earthquake to the onset of additional treatments. RESULTS: Of 903 patients with ulcerative colitis or Crohn's disease in our previous study, we could evaluate 2-year courses in 677 patients (394 ulcerative colitis and 283 Crohn's disease). Compared with the relapse rates of ulcerative colitis and Crohn's disease immediately after the earthquake (15.8% and 7.0%, respectively), those in the corresponding periods in 2012 (2.5% and 1.1%, respectively) and 2013 (2.3% and 2.5%, respectively) significantly decreased. There were 226 patients who required additional treatments after the earthquake. Multivariate time-to-event analyses revealed that only patients who had experienced the death of family members or friends were likely to need additional treatments (hazard ratio = 1.77, 95% confidence interval = 1.25-2.47). No other factors had a significant influence. CONCLUSIONS: The relapse rates 1 and 2 years after the earthquake significantly decreased. The factors that influenced long-term relapse were different from those that influenced short-term relapse.

Clinical and genetic risk factors for decreased bone mineral density in Japanese patients with inflammatory bowel disease.

BACKGROUND AND AIM: Patients with inflammatory bowel disease (IBD) are at a high risk of low bone mineral density (BMD). Reportedly, clinical and genetic factors cause low BMD in Caucasians; however, studies in non-Caucasian populations remain scarce. METHODS: Clinical risk factors for low BMD were investigated in 266 Japanese patients with IBD, and a genome-wide association analysis (GWAS) was performed using linear regression with associated clinical factors as covariates. Genotyping was performed using a population-optimized genotyping array (Japonica array® ). After quality control, the genotype data of 4 384 682 single-nucleotide polymorphisms (SNPs) from 254 patients with IBD were used for GWAS. RESULTS: Body mass index, age, and disease duration were independently associated with the BMD of the femoral neck (P = 1.41E - 13, 1.04E - 5, and 1.58E - 3, respectively), and body mass index and sex were associated with the BMD of the lumbar spine (P = 6.90E - 10 and 6.84E - 3, respectively). In GWAS, 118 and 42 candidate SNPs of the femoral neck and lumbar spine, respectively, were identified. Among 118, 111 candidate SNPs of the femoral neck were located within the SLC22A23 gene, which is a known IBD susceptibility gene (minimum P = 1.42E - 07). Among 42, 18 candidate SNPs of the lumbar spine were located within the MECOM gene, which is associated with osteopenia (minimum P = 5.86E - 07). Interestingly, none of the known loci showed a significant association with BMD. CONCLUSIONS: Although clinical risk factors for low BMD in IBD were similar to those in the general population, genetic risk factors were rather different.

Tacrolimus Dose Optimization Strategy for Refractory Ulcerative Colitis Based on the Cytochrome P450 3A5 Polymorphism Prediction Using Trough Concentration after 24 Hours.

BACKGROUND: In the tacrolimus treatment for refractory ulcerative colitis (UC), dose adjustment is necessary because the required doses to keep appropriate drug concentrations are significantly different among individuals. Cytochrome P450 (CYP) 3A5 polymorphism affects tacrolimus blood concentrations. However, it is difficult to obtain genetic information in real clinical practice. In the present study, we investigated possible factors that may predict CYP3A5 polymorphism and proposed a dose optimization strategy based on the obtained predicting factors. SUMMARY: We retrospectively analyzed 41 patients who underwent remission induction therapy with tacrolimus for UC in our hospital. First, we performed a correlation analysis of CYP3A5 polymorphism and pharmacokinetics. In the CYP3A5 non-expressers, the dose of tacrolimus (mg/kg) was lower and dose-adjusted trough levels (ng/mL per mg/kg) were higher compared with those in expressers. Next, we investigated factors that could predict CYP3A5 polymorphism. Trough concentration 24 h following tacrolimus administration was extracted as a significant factor. When the trough cutoff value at 24 h was set to 2.6 ng/mL, sensitivity and specificity for estimation of CYP3A5 polymorphism were 63 and 96% respectively. Therefore, when the trough concentration 24 h after administration is ≤2.6 ng/mL, the patient can be estimated as a CYP3A5 expresser and an increase in dose should be proposed. Key Message: The trough concentration 24 h after the first tacrolimus administration appears to be a useful predictor of -CYP3A5 polymorphism. Performing dose optimization strategy based on the prediction of CYP3A5 polymorphism can lead to earlier and safer remission induction.

Residual Lesions on Capsule Endoscopy Is Associated with Postoperative Clinical Recurrence in Patients with Crohn's Disease.

BACKGROUND: In order to optimize postoperative therapy in patients with Crohn's disease (CD), it is important to detect endoscopic recurrence preceding clinical recurrence. However, we have little knowledge about how high the rate of residual lesions is and whether these lesions have an influence on postoperative course or not. AIMS: To assess residual lesions in small bowel immediately after surgery. METHODS: Capsule endoscopy (CE) was performed immediately after surgery (< 3 months), and endoscopic activity was assessed using the Lewis score (LS) composed of the highest tertile score (in first, second, and third tertile) and the stenosis score (in whole small intestine). The relationship between these residual lesions and postoperative clinical recurrence was prospectively evaluated. RESULTS: After assessing patency using a patency capsule, CE was performed in 25 patients. The mean LS was 751.3, and 84.0% (21/25) had endoscopic activity. These lesions were detected by preoperative examinations in 0% and by a serosal side view during surgery in 16.0%. Regarding the cumulative clinical recurrence rate according to endoscopic severity (normal, mild, and moderate-to-severe) immediately after surgery, no significant difference was found. However, comparing groups divided according to the highest tertile score, the cumulative clinical recurrence rate was significantly higher in the group with the highest third tertile score. Furthermore, patients with ulcers in the third tertile had a significantly higher recurrence rate. CONCLUSIONS: Many cases with CD had endoscopic activity immediately after "curative" surgery. These residual lesions, especially in the distal small intestine, were associated with postoperative clinical recurrence.

Postoperative therapy with infliximab for Crohn's disease: a 2-year prospective randomized multicenter study in Japan.

PURPOSE: The prevention of postoperative recurrence is a critical issue in surgery for Crohn's disease. Prospective randomized trials in Western countries have shown that the postoperative use of anti-tumor necrosis factor α-antibodies was effective in reducing the recurrence rate. We investigated the efficacy of infliximab (IFX) for the prevention of postoperative Crohn's disease recurrence. METHODS: We performed a prospective randomized multicenter study. Patients who underwent intestinal resection were assigned to groups treated with or without IFX. Immediately after surgery, patients in the IFX group received IFX at 5 mg/kg at 0, 2, and 6 weeks, followed by every 8 weeks for 2 years. The primary study outcome was the proportion of patients with endoscopic and/or clinical recurrence at 2 years after surgery. RESULTS: Thirty-eight eligible patients participated in this study: 19 in the IFX group and 19 in the non-IFX group. The disease recurrence rate in the IFX group was 52.6% (10/19), which was significantly lower than that in the non-IFX group (94.7% [18/19]). CONCLUSION: The postoperative use of IFX is effective in preventing Crohn's disease recurrence for 2 years.

Risk factors associated with postoperative recurrence and repeat surgery in Japanese patients with Crohn's disease.

PURPOSE: To avoid frequent surgery in patients with Crohn's disease, it is important to identify the risk factors for postoperative recurrence or repeat surgery. However, there have so far been few studies on this topic from Asian countries. In addition, the recent development of anti-tumor necrosis factor (TNF) therapy may have changed the risk factors. We aimed to identify the factors associated with postoperative recurrence and repeat surgery. METHODS: The postoperative courses of 168 patients were reviewed. We analyzed the cumulative postoperative recurrence and repeat surgery rates and identified the factors affecting these rates. RESULTS: Postoperative recurrence was observed in 70 patients, and the 1-, 3-, and 5-year cumulative recurrence rates were 17.1, 40.1, and 54.9%, respectively. The recurrence rate was significantly higher in patients with anal lesions and lower in patients newly treated with anti-TNF agents following surgery. In a multivariate analysis, the new introduction of anti-TNF agents was identified as an independent suppressor (hazard ratio 0.50, 95% confidence interval 0.28-0.88). Twenty-four patients underwent repeat surgery, and the 1-, 3-, and 5-year cumulative repeat surgery rates were 4.6, 11.2, and 18.7%, respectively. The surgery rate was significantly higher in patients with penetrating-type disease. In a multivariate analysis, penetrating-type disease (6.98, 2.37-23.35), anal lesions (4.40, 1.14-30.53), and first-time surgery (5.28, 1.17-17.93) were identified as independent risk factors. CONCLUSIONS: Anti-TNF agents have the potential to prevent postoperative recurrence. The new introduction, dose escalation, or switching of anti-TNF agents is recommended in patients with some risk factors.

ATP-binding cassette subfamily B member 1 1236C/T polymorphism significantly affects the therapeutic outcome of tacrolimus in patients with refractory ulcerative colitis.

BACKGROUND AND AIM: Tacrolimus is now considered to be one of the main therapeutic options for refractory ulcerative colitis. Both cytochrome P-450 3A5 (CYP3A5) and ATP-binding cassette subfamily B member 1 (ABCB1) associated with tacrolimus metabolism are known to have several genetic polymorphisms. However, it remains controversial whether these polymorphisms affect the therapeutic efficacy for ulcerative colitis. We aimed to investigate the influence of both CYP3A5 and ABCB1 polymorphisms on the efficacy of tacrolimus in ulcerative colitis treatment under the tight dose-adjusting strategy. METHODS: Sixty-one Japanese patients with ulcerative colitis treated with tacrolimus were enrolled retrospectively. Tacrolimus treatment was performed using the tight dose-adjusting strategy. Genotyping for CYP3A5*3, ABCB1 1236C>T, 2677G>A,T, and 3435C>T were performed, and the clinical outcomes at 12 weeks after the initiation of tacrolimus were compared among the genotypes. RESULTS: There was no association between the CYP3A5 genotypes and therapeutic efficacy. In contrast, a significant association was observed with the ABCB1 1236C > T polymorphism and therapeutic efficacy. The ABCB1 1236CC+CT groups (n = 41) had a significantly higher response rate (73% vs 35%; P = 0.004) and remission rate (61% vs 20%; P = 0.002) than the TT group (n = 20). The multivariate logistic regression analysis also revealed that ABCB1 1236C>T was identified as an independent factor associated with remission. CONCLUSIONS: ABCB1 1236C>T polymorphism significantly affects the therapeutic efficacy of tarcolimus at 12 weeks under the tight dose-adjusting treatment for ulcerative colitis.

Feasibility of colorectal endoscopic submucosal dissection (ESD) carried out by endoscopists with no or little experience in gastric ESD.

BACKGROUND AND AIM: Colorectal endoscopic submucosal dissection (ESD) is recommended to be carried out only by endoscopists with sufficient experience in gastric ESD. However, early gastric carcinoma is less common in Western countries than in Japan, and endoscopic maneuverability differs between the stomach and colorectum. We assessed the feasibility of colorectal ESD carried out by endoscopists with no or little experience in gastric ESD. METHODS: We analyzed en bloc resection, R0 resection and perforation rates in 180 consecutive colorectal ESD carried out by three endoscopists who had no or <5 cases of experience in gastric ESD. We also identified factors associated with R0 resection failure. RESULTS: Overall en bloc and R0 resection rates were 93.3% (168/180) and 82.2% (148/180), respectively. All 11 cases with perforation were treated endoscopically. Dividing 180 cases into three learning phases (early, middle, or late phases), the en bloc and R0 resection rates increased from 88.3% and 75.0% in the early phase to 98.3% and 88.3% in the late phase, respectively. Perforation rate also improved from 10.0% to 3.3%. Factors associated with R0 resection failure were location at junctions (odds ratio: 6.8, 95% CI: 1.9-27.5), preoperative factors reflecting fibrosis (5.8, 1.9-19.0), and late phase (0.2, 0.1-0.7). CONCLUSION: Endoscopists without experience in gastric ESD carried out colorectal ESD safely. In the early and middle phases (≤40 cases), they should treat mainly rectal lesions but may also resect lesions in the colon avoiding flexures. Lesions located at junctions and those with preoperative factors reflecting fibrosis should be resected after completing 40 procedures.

Usefulness of a peripherally inserted central catheter for total parenteral nutrition in patients with inflammatory bowel disease.

BACKGROUNDS AND AIMS: Peripherally inserted central catheters (PICC) have been widely used as a blood access route for total parenteral nutrition (TPN) in recent years. However, there have been few reports that evaluated the usefulness of PICC for patients with inflammatory bowel disease (IBD). In this study, we compared the clinical courses in patients with IBD who received TPN during their hospitalization by conventional central venous catheters (CVC) and PICC. PATIENTS AND METHODS: A total of 137 IBD patients were enrolled. The CVC group and the PICC group included 56 and 81 patients, respectively. The clinical courses in both groups were compared retrospectively. RESULTS: As a complication of the puncture, pneumothorax occurred in two patients (3.6%) in the CVC group, but in none (0%) in the PICC group. The PICC group had significantly higher rates of achieving the scheduled TPN without removing the catheter, lower rates of catheter-related blood stream infection (CRBSI) and longer periods without CRBSI than the CVC group. CONCLUSION: PICC might be more useful than CVC in terms of safety and the ability to deliver scheduled TPN for IBD patients.

Genetics of inflammatory bowel disease in Japanese.

Several genetic studies have identified >200 susceptibility loci for inflammatory bowel disease (IBD), mostly shared between ulcerative colitis (UC) and Crohn's disease (CD). By analyzing the genetic background associated with disease sub-phenotypes, colonic Crohn's disease located intermediate between Crohn's disease with ileal involvement and UC. However, these loci were analyzed mainly in Caucasian IBD, less is known about IBD genetics in other population including Japanese. Recently, a SNP array designed specifically for the Japanese population were developed. To clarify Japanese-specific genetic background of IBD, a genome-wide association study of Japanese IBD with this kind of population specific array is needed to be performed.

Colorectal endoscopic submucosal dissection (ESD) performed by experienced endoscopists with limited experience in gastric ESD.

PURPOSE: Since colorectal endoscopic submucosal dissection (ESD) requires higher-level skills than endoscopic mucosal resection (EMR), it is recommended to acquire sufficient experience in gastric ESD prior to attempting colorectal ESD. We evaluated the ability of experienced endoscopists with limited experience in gastric ESD to perform colorectal ESD. METHODS: We retrospectively reviewed 120 colorectal ESDs performed by two endoscopists who had expertise in colonoscopy and colorectal EMR but experience of fewer than five gastric ESDs. Main outcomes were the en bloc resection rate with tumor-free margins (R0 resection rate) and adverse events rate. Using only clinical characteristics prior to ESD, we also identified factors affecting outcomes. RESULTS: A total of 113 patients (94.2 %) received en bloc resection, and the R0 resection rate was 80.0 % (96/120). Perforation and postoperative hemorrhage occurred in eight (6.7 %) and two (1.7 %) patients, respectively. Dividing the 120 cases into three learning phases, R0 resection and perforation rates improved from 77.5 % (31/40) and 12.5 % (5/40) in phase 1 to 85.0 % (34/40) and 2.5 % (1/40) in phase 3, respectively. Multivariate analysis revealed that lesions at junctions (dentate line, sigmoid-descending junction, splenic flexure, hepatic flexure, ileocecal valve) and lesions with factors reflecting fibrosis in the submucosal layer (based on endoscopic findings before ESD) were significantly correlated with R0 resection failure, with adjusted odds ratios of 10.5 (95 % CI 2.1-67.6) and 10.4 (2.7-48.6), respectively. CONCLUSIONS: Colorectal ESD is feasible for experienced endoscopists with limited experience in gastric ESD. Novices should avoid lesions at junctions or those with factors reflecting fibrosis.

Modulation of endoplasmic reticulum (ER) stress-induced autophagy by C/EBP homologous protein (CHOP) and inositol-requiring enzyme 1α (IRE1α) in human colon cancer cells.

To explore the relationship between UPR and autophagy in intestinal epithelial cells, we investigated whether autophagy was induced by endoplasmic reticulum (ER) stress in colon cancer cell lines. We demonstrated that autophagy was induced by ER stress in HT29, SW480, and Caco-2 cells. In these cells, inositol-requiring enzyme1α (IRE1α) and C/EBP homologous protein (CHOP) were involved in the ER stress-autophagy pathway, and CHOP was a regulator of IRE1α protein expression. Our findings suggest that CHOP promotes IRE1α and autophagy especially in ER stress conditions. This study will provide important insights into the disclosure of the ER stress-autophagy pathway.

Endoscopic submucosal dissection for colorectal neoplasia during the clinical learning curve.

BACKGROUND: The efficacy of colorectal endoscopic submucosal dissection (ESD) has been reported mainly from Japanese referral centers. However, ESD is technically difficult and associated with a higher risk of adverse events than endoscopic mucosal resection, especially for novices performing colorectal ESD with little experience in gastric ESD. The current study evaluated the results of colorectal ESD during the clinical learning curve by retrospectively examining the results of colorectal ESD performed by four endoscopists who had experience with fewer than five cases of gastric ESD. METHODS: The study retrospectively investigated the first 20 cases managed by each endoscopist, for a total of 80 cases. The main outcome measurements were procedural time, en bloc resection rate with tumor-free margins (R0 resection rate), and adverse events rate. From among clinicopathologic characteristics, factors that affected main outcome measurements were identified. RESULTS: Of the 80 cases (56 colonic and 24 rectal lesions; 44 granular laterally spreading tumors (LSTs) and 23 nongranular LSTs, 5 depressed, and 8 protruding), 54 cases (67.5%) had resection using a standard tip-type knife, and 26 cases (32.5%) had resection using a small scissors-type knife. The mean tumor diameter was 34.9 ± 14.1 mm, and the mean procedural time was 108.8 ± 53.4 min. The resection in 75 cases (93.8%) was performed en bloc, and the R0 resection rate was 75% (60/80). Perforation occurred in six cases (7.5%) and postoperative hemorrhage in three cases (3.8%). Multivariate analyses showed that colonic lesions and larger lesions (≥40 mm) were significantly associated with prolonged procedural time (≥90 min). Use of the scissors-type knife was significantly associated with a higher R0 resection rate. Perforation occurred only in colonic lesions. CONCLUSIONS: For novices in colorectal ESD, beginning with rectal and smaller lesions may be advisable. Also, using scissors-type knives may increase the R0 resection rate.

Real-world NUDT15 genotyping and thiopurine treatment optimization in inflammatory bowel disease: a multicenter study.

BACKGROUND: This study evaluated the effectiveness of NUDT15 codon 139 genotyping in optimizing thiopurine treatment for inflammatory bowel disease (IBD) in Japan, using real-world data, and aimed to establish genotype-based treatment strategies. METHODS: A retrospective analysis of 4628 IBD patients who underwent NUDT15 codon 139 genotyping was conducted. This study assessed the purpose of the genotyping test and subsequent prescriptions following the obtained results. Outcomes were compared between the Genotyping group (thiopurine with genotyping test) and Non-genotyping group (thiopurine without genotyping test). Risk factors for adverse events (AEs) were analyzed by genotype and prior genotyping status. RESULTS: Genotyping test for medical purposes showed no significant difference in thiopurine induction rates between Arg/Arg and Arg/Cys genotypes, but nine Arg/Cys patients opted out of thiopurine treatment. In the Genotyping group, Arg/Arg patients received higher initial doses than the Non-genotyping group, while Arg/Cys patients received lower ones (median 25 mg/day). Fewer AEs occurred in the Genotyping group because of their lower incidence in Arg/Cys cases. Starting with < 25 mg/day of AZA reduced AEs in Arg/Cys patients, while Arg/Arg patients had better retention rates when maintaining ≥ 75 mg AZA. Nausea and liver injury correlated with thiopurine formulation but not dosage. pH-dependent mesalamine reduced leukopenia risk in mesalamine users. CONCLUSIONS: NUDT15 codon 139 genotyping effectively reduces thiopurine-induced AEs and improves treatment retention rates in IBD patients after genotype-based dose adjustments. This study provides data-driven treatment strategies based on genotype and identifies risk factors for specific AEs, contributing to a refined thiopurine treatment approach.

FCGR3A-158 polymorphism influences the biological response to infliximab in Crohn's disease through affecting the ADCC activity.

An association between FCGR3A-158 V/F polymorphism and biological responses to infliximab has been reported in Crohn's disease (CD) in Western countries. However, little is known about the mechanism by which gene polymorphism affects the responses to infliximab. The aims of this study were to confirm the association in Japanese CD patients and to reveal the effect of gene polymorphism on biological responses to infliximab. Japanese CD patients were examined retrospectively at weeks 8 and 30. Clinical and biological responses were assessed by the Crohn's disease activity index and C-reactive protein levels, respectively. The infliximab-binding affinity of natural killer (NK) cells from FCGR3A-158 V/V, V/F and F/F donors was examined. Infliximab-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) activities were also determined using transmembrane TNF-α-expressing Jurkat T cells as target cells and peripheral blood mononuclear cells (PBMCs) from V/V, V/F and F/F donors as effector cells. Biological responses at week 8 were statistically higher in V/V patients, whereas no significant differences were observed in either clinical responses at weeks 8 and 30 or biological responses at week 30 among the three genotypes. NK cells and PBMCs from V/V patients also showed higher infliximab-binding affinity and infliximab-mediated ADCC activity, respectively. Our results suggest that FCGR3A-158 polymorphism is a predicting factor of biological responses to infliximab in the early phases. FCGR3A-158 polymorphism was also found to affect the infliximab-binding affinity of NK cells and infliximab-mediated ADCC activity in vitro, suggesting that an effect on ADCC activity influences biological responses to infliximab in CD patients.

[A case of Peutz-Jeghers syndrome with repeated small intestinal intussusception successfully treated by intraoperative endoscopic polypectomy].

Intestinal polyps are a distinctive feature of Peutz-Jeghers syndrome (PJS). These hamartomas can lead to significant complications such as intussusception or gastrointestinal bleeding which necessitate multiple laparotomies and bowel resections. In an operation for intestinal intussusception, it is preferable to simultaneously resect as many polyps as possible to prevent recurrence of complications caused by intestinal polyps. We report a case of a woman in her twenties with PJS, diagnosed as small intestinal intussusception caused by an intestinal polyp. We performed not only repair of the intussusception but also endoscopic polypectomy without resection of the small intestine. We successfully resected all polyps larger than 10mm from the duodenum to the ascending colon during the operation.