Extraction of terminal ileal lipomas to cecum can facilitate endoscopic resection: A case series with video.

Large ileal lipomas over 2 cm can cause symptoms, that may require a resection. Due to the narrow lumen and thin walls of the ileum, endoscopic treatments can have a high risk of adverse events and require technical expertise, thus surgical resection is currently the mainstay of treatment. To overcome the technical challenges, we developed a novel method to endoscopically resect terminal ileal lipomas. The technique involves extracting the lesion into the cecum, which creates sufficient space to maneuver, and a better field of view. The lipoma is resected with endoscopic mucosal resection or endoscopic submucosal dissection. The appearance of the lipoma protruding out of the ileocecal valve resembles that of a tongue sticking out of the mouth, thus we named this the "tongue out technique". To assess the technical feasibility of this method, we retrospectively analyzed seven cases of terminal ileal lipoma that were endoscopically resected using the "tongue out technique" at NTT Medical Center Tokyo between January 2017 and October 2023. Technical success was 100% and en bloc resection was achieved in all cases. The median size was 31 (14-55) mm. Three cases were resected with endoscopic mucosal resection while endoscopic submucosal dissection was performed on the other four cases. There was one case of delayed post-endoscopic mucosal resection bleeding, which was caused by clip dislodgement. There were no perforations. No recurrence of the lipoma or associated symptoms have been observed. This new technique can allow more ileal lipomas to be treated with minimally invasive and organ-preserving endoscopic procedures.

Comparison of cold snare polypectomy for sessile serrated lesions ≥10 mm between experienced and trainee endoscopists: A propensity score matching cohort study.

Objectives: Previous studies of cold snare polypectomy (CSP) for sessile serrated lesions (SSLs) ≥10 mm were performed by experienced endoscopists, and therefore their skills might have significantly influenced results. In this study, we compared the efficacy and safety of CSP for SSLs ≥10 mm between experienced and trainee endoscopists. Methods: In a 1:1 propensity score matched retrospective cohort study, we compared the complete resection rate, en-bloc resection rate, adverse event rate, and procedure time between experienced and trainee groups. Thirteen endoscopists performed CSP, and we defined the experienced group as endoscopists with board certification from the Japan Gastroenterological Endoscopy Society. Results: We examined 616 lesions with SSLs ≥10 mm resected by CSP between February 2018 and May 2022. We excluded 61 lesions from the analysis because they had simultaneously undergone hot snare polypectomy (n = 57) or had been taken over by experienced endoscopists from trainees in the CSP procedure (n = 4). Finally, we identified 217 propensity score-matched pairs (n = 434). Between experienced and trainee groups, the results were complete resection rate (100 vs. 100%; p = 1.00), en-bloc resection rate (73.2 vs. 75.6%; p = 0.24), adverse event rate (3.2 vs. 2.8%; p = 0.77), or procedure time (6.2 vs. 5.9 min; p = 0.64). Conclusions: We have demonstrated the safety and efficacy of CSP for SSLs ≥10 mm performed by experienced and trainee endoscopists.

Endoscopic management of gastric ectopic pancreas with repeated ulcerations and bleeding: A case report.

A 25-year-old man was referred to our center for investigation of a gastric submucosal tumor and an ulcer that had developed on its oral side. Endoscopic ultrasonography findings suggested the presence of an ectopic pancreas, and treatment with an oral proton pump inhibitor was planned for the ulcer. Over the subsequent 3 years, the patient endured recurring epigastric pain and episodes of passing black stools. Emergency endoscopy revealed that the morphology of the gastric submucosal tumor had transformed into a pedunculated polyp-like morphology with a bleeding ulcer at the apex of the lesion. Endoscopic hemostasis using hemostatic forceps was performed. However, the patient continued to pass black stools. In light of the persistent symptoms and unique morphology of the lesion, endoscopic resection was attempted as a curative approach. The lesion was excised by hot snare polypectomy. Post-treatment, the patient exhibited no signs of recurrence, marking a successful resolution. Three months later, a gastroduodenal endoscopy showed that the excised site had undergone scar formation without recurrence of the lesion. This case holds significant clinical value as it demonstrates the efficacy of a minimally invasive treatment strategy in managing repeated bleeding ulcerations of an ectopic pancreas, ultimately achieving a complete cure.

Efficacy and safety of cap-assisted endoscopic mucosal resection for superficial duodenal epithelial neoplasia ≤ 10 mm.

Background and study aims Endoscopic treatment strategies for small superficial duodenal epithelial neoplasia (SDET) have not been established, and the R0 resection rates of all previously reported endoscopic techniques are somewhat low. Furthermore, no reports of cap-assisted endoscopic mucosal resection (EMRC), which is reportedly associated with a relatively high R0 resection rate, have been evaluated in sufficient numbers of patients. Therefore, we assessed the efficacy and safety of EMRC for SDETs ≤ 10 mm in a retrospective cohort study. Patients and methods We examined a prospectively maintained database and identified 248 consecutive patients (248 lesions) who had undergone endoscopic resection for SDETs ≤ 10 mm between January 2017 and June 2022. Our treatment strategy was consistent, with EMRC indicated for all SDETs ≤ 10 mm without non-lifting signs. The primary endpoint was the R0 resection rate. Results Overall, 20 lesions had non-lifting signs and were selected for endoscopic submucosal dissection, while the remaining 228 lesions were treated with EMRC. As a result of EMRC, the median tumor size was 5 mm, and the mean procedure time was 5 minutes. Most of the lesions (89.2%) were located in the descending part. The R0 resection rate was 97.4% (222/228 cases), and the en bloc resection rate was 99.6%. Only seven patients(3.1%) experienced adverse events (6 patients, delayed bleeding; 1 patient, acute pancreatitis), which were successfully managed without surgical intervention. Furthermore, no recurrences were observed. Conclusions We have demonstrated that EMRC is an effective and safe treatment for SDETs ≤ 10 mm that do not have non-lifting signs.

Ruptured mycotic coronary artery aneurysm hybrid treatment with covered stent and surgical debridement.

We present a case of a ruptured mycotic coronary aneurysm effectively treated with covered stents and phased surgery. The covered stent, however, became occluded two years later. Because of the low invasiveness, a covered stent treatment may be advantageous over conventional surgery but trade off long-term vascular patency. Learning objective: To recognize the presence of a ruptured infectious coronary aneurysm after a primary coronary stenting for ST-elevation myocardial infarction.To discuss the treatment strategies for a ruptured infectious coronary aneurysm with a covered stent.

Efficacy and Safety of Radium-223 for Castration-resistant Prostate Cancer With Bone Metastasis Before and After Docetaxel.

BACKGROUND/AIM: Radium-223 (Ra-223) therapy provides a survival benefit for castration-resistant prostate cancer (CRPC) patients with bone metastasis. The optimal timing of using Ra-223 has not been determined. We evaluated the efficacy and safety of Ra-223 before and after docetaxel (DOC) therapy. PATIENTS AND METHODS: We retrospectively reviewed 36 CRPC patients with bone metastasis who were treated with Ra-223 in our institution and satellite hospitals. Ra-223 was used before DOC (pre-DOC group) in 17 patients (47%) and after DOC (post-DOC group) in 19 patients (53%). The treatment completion rate of 6 cycles, progression-free survival (PFS), cause-specific survival (CSS) and occurrence rate of adverse events were compared between the groups. RESULTS: The median follow-up duration was 45 months. In the pre-DOC compared with the post-DOC group, treatment completion rate was significantly higher (94% vs. 52%, p<0.01), PFS was significantly longer (median: 8 vs. 5 months, p=0.024) and CSS was significantly longer (median: 32 vs. 15 months, p=0.028). The difference in CSS was significant in multivariate analysis. In the pre-DOC compared with the post-DOC group, the occurrence rate of grade ≥3 adverse events tended to be lower (6% vs. 36%, p=0.322), and the CSS tended to be longer (median: not reached vs. 45 months, p=0.208). CONCLUSION: Ra-223 could be used more safely and more effectively for CRPC patients with bone metastasis before than after DOC therapy.

[A Cohort Study on the Prognosis of Patients with Urothelial Carcinoma Using the Miyazaki Urological Cancer Database (MUCD)].

Miyazaki Urological Cancer Database (MUCD) is a web-based database containing background, treatment, and prognosis of patients with prostate, renal, and urothelial cancers diagnosed in Miyazaki. We entered information on patients diagnosed with urothelial carcinoma from 2014 to 2018 at 4 of the 17 facilities that diagnose urothelial carcinoma in Miyazaki Prefecture. We analyzed the overall survival for bladder cancer and upper urinary tract cancer, and examined its correlation with the presence of symptoms, urine cytology, and clinical TNM classification. There were 487 patients with urothelial carcinoma, comprising 372 (76%) with bladder cancer and 115 (24%) with upper tract urinary cancer. In the bladder cancer group, 301 (81%) patients had symptomatic disease and 119 (32%) had positive urine cytology. The stage according to the TNM classification was Ta-1N0, T2-4N0, N1-2M0 and M1 in 248 (67%), 94 (26%), 19 (5%) and 11 (3%) patients, respectively. In the upper urinary tract cancers group, 89 (76%) had symptomatic disease and 41 (36%) had positive urine cytology. The stage according to the TNM classification was Ta-1N0, T2-4N0, N1-2M0 and M1 in 45 (39%), 37 (32%), 11 (10%) and 22 (19%) patients, respectively. The 3-year survival rates for bladder and upper urinary tract cancer were 83.4% and 67.8%, respectively. TNM classification (≤T1 vs ≥T2≥) was significantly associated with overall survival (bladder cancer : HR＝7.07, 95% CI＝3.13-16.0, p＜0.0001 ; upper tract urinary cancer : HR＝6.33, 95% CI＝2.13-18.8, p＝0.0009). The prognosis of patients with urothelial carcinoma diagnosed in multiple institutions could be evaluated using MUCD. The clinical T stage was significantly associated with overall survival in patients with bladder cancer and patients with upper urinary tract cancer.

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.

Gastric adenocarcinoma with enteroblastic differentiation followed endoscopically: A case report.

A 70-year-old man underwent endoscopy, which revealed a slightly depressed and elevated gastric cancer with suspected submucosal invasion of the mid gastric body. Biopsy specimens revealed differentiated tubular adenocarcinoma. We also detected lung and esophageal cancer and prioritized treatment of these lesions, and the patient underwent three endoscopies to monitor changes in gastric cancer. The tumor size and color remained unchanged; however, the marginal ridge was prominent, and the depressed area was deeper on subsequent evaluation. Total gastrectomy was performed 9 months after the first endoscopy. Histopathological examination of the resected specimens showed muscularis propria invasion, well-differentiated tubular adenocarcinoma involving the superficial mucosa, and tumor cells showing clear cytoplasm and a columnar or three-dimensional structure, between the deep mucosa and submucosa. The cells were immunopositive for Sal-like protein 4 and glypican 3; therefore, the patient was diagnosed with gastric adenocarcinoma with enteroblastic differentiation (GAED). This rare gastric cancer variant constituted approximately 70% of the entire lesion, and we observed significant lymphovascular invasion and lymph node metastasis. GAED is a rare histopathological subtype of gastric cancer described in recent years. Few cases of this tumor are reported to date; therefore, our study significantly contributes to the literature.

An Integrated Genomic and Transcriptomic Analysis Reveals Candidates of Susceptibility Genes for Crohn's Disease in Japanese Populations.

Expression quantitative trait locus (eQTL) analyses have enabled us to predict the function of disease susceptibility SNPs. However, eQTL for the effector memory T cells (TEM) located in the lamina propria mononuclear cells (LPMCs), which play an important role in Crohn's disease (CD), are not yet available. Thus, we conducted RNA sequencing and eQTL analyses of TEM cells located in the LPMCs from IBD patients (n = 20). Genome-wide association study (GWAS) was performed using genotyping data of 713 Japanese CD patients and 2,063 controls. We compared the results of GWAS and eQTL of TEM, and also performed a transcriptome-wide association study using eQTL from Genotype Tissue Expression project. By eQTL analyses of TEM, correlations of possible candidates were confirmed in 22,632 pairs and 2,463 genes. Among these candidates, 19 SNPs which showed significant correlation with tenascin-XA (TNXA) expression were significantly associated with CD in GWAS. By TWAS, TNFSF15 (FDR = 1.35e-13) in whole blood, ERV3-1 (FDR = 2.18e-2) in lymphocytes, and ZNF713 (FDR = 3.04e-2) in the sigmoid colon was significantly associated with CD. By conducting integration analyses using GWAS and eQTL data, we confirmed multiple gene transcripts are involved in the development of CD.

Pancreatic Neuroendocrine Neoplasm Invading the Entire Main Pancreatic Duct Diagnosed by a Preoperative Endoscopic Biopsy.

A 78-year-old man was referred to our hospital for a detailed examination of a pancreatic tumor that filled the main pancreatic duct (MPD). The histological diagnosis of the endoscopic biopsy specimen was neuroendocrine tumor (NET) G3. The patient subsequently underwent total pancreatectomy. The histological diagnosis of the surgical specimen was also NET G3. This is the first report of a NET that occupied the MPD and was diagnosed by a preoperative endoscopic biopsy through the papilla of Vater. This case is a good example of a histopathological diagnostic method for pancreatic tumors invading the entire MPD.

[A Case of Neuroendcrine Carcinoma of the Prostate Diagnosed by Prostate Re-Biopsy during Hormonal Treatment and Effectively Treated by Multidisciplinary Therapy].

A 73-year-old Japanese man visited the urology clinic with the chief complaint of gross hematuria in June 2015. His prostate specific antigen (PSA) level was 146.7 ng/ml and he was diagnosed with prostate adenocarcinoma with a Gleason Score of 5+4. With bone metastasis in the right femur (cT3aN0M1), he was treated by orchiectomy and bicalutamide. He had gross hematuria in October 2017 and a prostate tumor was detected by computed tomography (CT) and magnetic resonance imaging without increasing PSA levels. Prostate re-biopsy showed prostate neuroendocrine carcinoma and local radiation therapy (74 Gy) was performed. Follow-up CT revealed a left adrenal tumor with a positive positron emission tomographic scan in October 2018. Under the diagnosis of metastatic neuroendocrine carcinoma, chemotherapy using cisplatinum and etoposide was performed. The tumor shrunk after five courses of treatment, followed by regrowth in April 2019. Radiation therapy (50 Gy) was added to the left adrenal tumor and it shrunk again. However, a left retroperitoneal tumor was detected in July 2019 and it was resected under laparoscopic surgery and diagnosed as metastatic neuroendocrine carcinoma. Since then, no recurrence has been observed.

A Genome-wide Association Study Identifying RAP1A as a Novel Susceptibility Gene for Crohn's Disease in Japanese Individuals.

BACKGROUND AND AIMS: Genome-wide association studies [GWASs] of European populations have identified numerous susceptibility loci for Crohn's disease [CD]. Susceptibility genes differ by ethnicity, however, so GWASs specific for Asian populations are required. This study aimed to clarify the Japanese-specific genetic background for CD by a GWAS using the Japonica array [JPA] and subsequent imputation with the 1KJPN reference panel. METHODS: Two independent Japanese case/control sets (Tohoku region [379 CD patients, 1621 controls] and Kyushu region [334 CD patients, 462 controls]) were included. GWASs were performed separately for each population, followed by a meta-analysis. Two additional replication sets [254 + 516 CD patients and 287 + 565 controls] were analysed for top hit single nucleotide polymorphisms [SNPs] from novel genomic regions. RESULTS: Genotype data of 4 335 144 SNPs from 713 Japanese CD patients and 2083 controls were analysed. SNPs located in TNFSF15 (rs78898421, Pmeta = 2.59 × 10-26, odds ratio [OR] = 2.10), HLA-DQB1 [rs184950714, pmeta = 3.56 × 10-19, OR = 2.05], ZNF365, and 4p14 loci were significantly associated with CD in Japanese individuals. Replication analyses were performed for four novel candidate loci [p <1 × 10-6], and rs488200 located upstream of RAP1A was significantly associated with CD [pcombined = 4.36 × 10-8, OR = 1.31]. Transcriptome analysis of CD4+ effector memory T cells from lamina propria mononuclear cells of CD patients revealed a significant association of rs488200 with RAP1A expression. CONCLUSIONS: RAP1A is a novel susceptibility locus for CD in the Japanese population.

Long-term prognosis of Japanese patients with biologic-naïve Crohn's disease treated with anti-tumor necrosis factor-α antibodies.

BACKGROUND/AIMS: Few reports have described the long-term treatment outcomes of the anti-tumor necrosis factor-α antibody for Japanese Crohn's disease (CD) patients. The aim of this study was to evaluate them and clarify the clinical factors that affect the long-term prognosis of the anti-tumor necrosis factor-α treatments. METHODS: This was a retrospective, observational, single-center cohort study. Japanese CD patients treated with either infliximab or adalimumab as a first-line therapy were analyzed. The cumulative retention rates of the biologics, relapse-free survival, and surgery-free survival were analyzed using Kaplan-Meier methods. The clinical factors associated with the long-term outcomes were estimated by both the log-rank test and Cox proportional hazard model. RESULTS: The cumulative retention rate was significantly higher in the group with a concomitant elemental diet of ≥900 kcal/day, baseline C-reactive protein (CRP) levels <2.6 mg/dL, and baseline serum albumin levels ≥3.5 g/dL, respectively. The baseline serum albumin levels were also associated with both relapse-free and surgery-free survival. The lack of concomitant use of an elemental diet ≥900 kcal/day was identified as the only independent risk factor for the withdrawal of the biologics. CONCLUSIONS: Baseline CRP levels and serum albumin levels could affect the long-term outcomes in CD patients. Concomitant elemental diet of ≥900 kcal/day could have a positive influence on clinical treatment course.

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.

Effective and less invasive diagnostic strategy for gastrointestinal GVHD.

BACKGROUND AND STUDY AIMS: Rectosigmoidoscopy with biopsy has been regarded to be a useful procedure to diagnose gastrointestinal graft-versus-host disease (GVHD). However, little is known about the specific colonoscopic features of gastrointestinal GVHD. In this study, we focused on the 4 unique colonoscopic findings - orange peel appearance, spotty redness, small mucosal sloughing, and diffuse mucosal defect - which are possible specific findings of gastrointestinal GVHD. We aimed to estimate the usefulness of these four unique colonoscopic findings in the rectosigmoid portion to diagnose gastrointestinal GVHD. PATIENTS AND METHODS: Seventy patients who were histologically diagnosed with gastrointestinal GVHD at our institute were retrospectively enrolled. Colonoscopic findings were reviewed, focusing on the four characteristic findings. The percentage of the positive cases for the characteristic findings was calculated. The final scoping portion and the number of cases showing any of the four characteristic findings in the rectosigmoid portion were also evaluated. The relationships between biopsy sites and the histological findings were also evaluated. RESULTS: Orange peel appearance was observed in 66 cases (94.3 %). Spotty redness was observed in 45 cases (64.3 %). Small mucosal sloughing was observed in 49 cases (70.0 %). Diffuse mucosal defect was observed in six cases (8.6 %). The number of cases that were concurrently positive for one, two, and three findings were 16 (20.8 %), 20 (26.0 %), and 34 (48.6 %), respectively. Fifty-eight cases (82.9 %) were investigated up to the rectosigmoid portion, and 12 (17.1 %) were investigated beyond the sigmoid colon. All of the cases showed at least 1 of the 4 characteristics in the rectosigmoid portion. The percentage of crypt apoptosis in the biopsy specimen from orange peel appearance, spotty redness, small mucosal sloughing, and diffuse mucosal defect were 87.5 %, 83.3 %, 87.2 %, and 88.9 %, respectively. CONCLUSION: Orange peel appearance, spotty redness, small mucosal sloughing, and diffuse mucosal defect are the characteristic colonoscopic findings useful for diagnosis of gastrointestinal GVHD. These findings are frequently observed in the rectosigmoid portion. The histological detection rates for crypt cell apoptosis from these findings are high. Identifying the four characteristic findings on rectosigmoidoscopy and taking biopsies from these areas could be essential for the diagnostic strategy for gastrointestinal GVHD.

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.

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.

Increased expression of IL12B mRNA transcribed from the risk haplotype for Crohn's disease is a risk factor for disease relapse in Japanese patients.

BACKGROUND: IL12B is a promising candidate for a susceptibility gene in Crohn's disease (CD). The aim of this study was to perform a candidate gene analysis of IL12B in Japanese CD patients, investigate whether the genotype is associated with disease phenotypes, and determine how the risk allele affects susceptibility to CD. METHODS: Three hundred seventy-five patients with CD, 265 patients with ulcerative colitis, and 463 healthy controls were examined. Ten single-nucleotide polymorphisms (SNPs) around IL12B were genotyped. Case-control and subphenotype (including disease course) analyses were performed. The allelic expression ratio of IL12B messenger RNA (mRNA) was examined by a SNaPshot analysis in lipopolysaccharide-stimulated monocytes. RESULTS: Four SNPs located upstream of the IL12B gene were significantly associated with CD. A conditional analysis revealed that these associations included two independent signals tagged by IL12B_1 and IL12B_3 (P = 9.42 × 10-6 and  1.49 × 10-4 respectively). IL12B_3 was also associated with earlier relapse in CD (P = 0.0144). The allelic expression ratios of IL12B mRNA transcribed from the risk haplotype to the protective haplotype tagged by IL12B_3 in lipopolysaccharide-stimulated monocytes from ten healthy controls heterozygous for IL12B_3 were significantly higher than that of the respective genomic DNA (P = 0.00923). No SNP was associated with ulcerative colitis. CONCLUSIONS: We confirmed the association of SNPs located upstream of IL12B with CD in Japanese patients. The demonstrated allelic expression imbalance supports the idea that the IL12B risk haplotype confers susceptibility not only to CD onset but to also relapse through increased IL12B mRNA expression.