矢野 智則

We herein report a kidney transplant recipient with recurrent bleeding due to multiple ileal ulcerations associated with mycophenolate mofetil (MMF). Symptoms persisted despite surgical resection and embolization. Double-balloon enteroscopy revealed multiple ulcerations, and a biopsy helped exclude other causes. The discontinuation of MMF led to rapid symptom resolution and healing of the ulceration. Intestinal complications after renal transplantation vary, and MMF-induced enteritis, although rare, should be considered. This case highlights the diagnostic value of enteroscopy in identifying drug-induced small intestinal injuries and underscores the importance of including MMF in the differential diagnosis of post-transplant gastrointestinal bleeding.

BACKGROUND: Peutz-Jeghers syndrome (PJS), a rare genetic disorder characterized by hamartomatous gastrointestinal polyps, poses increased risks of various cancers. Despite the importance of early intervention, the optimal timing for jejunal-ileal polypectomy remains unclear owing to the limited number of comparative studies. METHODS: Herein, we conducted a nationwide survey in Japan and analyzed data from 184 patients with PJS identified through a two-stage sampling process. The initial screening of 2912 medical institutions yielded 1748 facilities, of which 1077 responded to the survey. Time-dependent Cox proportional hazards models and logistic regression analyses were used to examine the association between the timing of jejunal-ileal polypectomy and the risk of surgery for intussusception. RESULTS: Among 184 patients (47.0% women; mean age, 33.5 years), intussusception was the most common complication (67.7%). In the Cox proportional hazards analysis excluding surgeries within 1 year of diagnosis, early jejunal-ileal polypectomy was associated with a reduced risk of surgery for intussusception (adjusted hazard ratio, 0.17; 95% confidence interval [CI] 0.04-0.74, p = 0.018). Logistic regression analysis showed higher odds of surgery in the late treatment group compared with the early treatment group (adjusted odds ratio, 4.26; 95% CI 1.38-13.16, p = 0.012). CONCLUSIONS: Early jejunal-ileal polypectomy may reduce the risk of intussusception in patients with PJS. However, the need for frequent endoscopic procedures must be balanced considering patient burden. These findings support the importance of early intervention and highlight the need for optimized surveillance strategies that consider clinical effectiveness and patients' quality of life.

Introduction: Gel-immersion endoscopy (GIE) is a technique used to maintain a clear view during gastric endoscopic submucosal dissection (ESD). We aimed to identify cases most likely to benefit from GIE for ESD bleeding by reviewing our clinical experience and determining the associated factors. Methods: We retrospectively analyzed 470 lesions in 380 patients who underwent gastric ESD between October 2020 and March 2023. The patients were divided into conventional method (CM, n=433) and GIE groups (n=37). We compared the clinical and pathological characteristics between the groups. Univariate and multivariate logistic regression analyses were used to identify factors associated with GIE use. Among the GIE group, hemostasis times under gas, water, and gel conditions were compared using the Kruskal–Wallis test. Results: Multivariate analysis revealed that dialysis (odds ratio [OR]: 15.3), concurrent antiplatelet and anticoagulant use (OR: 9.5), and tumor location in the middle third (OR: 3.5), upper third (OR: 5.7), or remnant stomach (OR: 9.3) were independently associated with GIE use. No significant differences in overall hemostasis time were observed between gas, water, or gel. Of the nine bleeding events exceeding 300 s under gas immersion, seven achieved successful hemostasis by switching to GIE, with a median of 32 s to locate the source and 140 s to complete hemostasis. Conclusion: Dialysis, combined antithrombotic use, and certain tumor locations were key factors influencing GIE for ESD bleeding. Although the overall hemostasis times did not differ, GIE may be particularly beneficial in high-risk scenarios.

OBJECTIVES: Endoscopic balloon dilation (EBD) is an effective treatment for intestinal strictures in Crohn's disease (CD). However, restenosis often occurs and requires repeat EBD or surgery. Previous studies have seldom examined restenosis with respect to stricture diameter, leaving the factors contributing to post-EBD restenosis unclear. Our retrospective study indicated that complete mucosal healing significantly reduces restenosis after EBD in CD-related small intestinal strictures. This prospective study aimed to validate these findings by accurately measuring stricture diameters in patients with CD. METHODS: We conducted a single-center prospective study of patients with CD and small intestinal strictures. The patients underwent an EBD session between June 2022 and December 2023. Stricture diameters were measured using a calibrated small-caliber-tip transparent hood. Multivariate analysis was performed to identify factors influencing stricture progression. RESULTS: This study included 41 patients (33 men). The number of strictures detected between sessions increased from 159 to 170. The average diameter of all strictures and the narrowest stricture per patient showed slight increases. However, 73% of patients experienced stricture progression. The presence of ulcers between sessions was identified as a significant risk factor for stricture progression (odds ratio 7.59, p = 0.031). Patients achieving complete mucosal healing demonstrated a significant increase in the narrowest stricture diameter (+1.5 mm, p = 0.00089). CONCLUSIONS: Complete mucosal healing is crucial for preventing stricture progression after EBD in patients with CD-related small intestinal strictures.

Gastric endoscopic mucosal resection is challenging due to the slippery mucosa, abundant blood vessels, and the presence of mucus. We developed gel immersion endoscopy to secure the visual field, even in a blood-filled gastrointestinal lumen in 2016. Clear gel with appropriate viscosity, instead of water, can prevent rapid mixture with blood and facilitate identification of the culprit vessel. We further optimized the gel for endoscopic treatment, and the resultant product, Viscoclear (Otsuka Pharmaceutical Factory) was first released in Japan in 2020. The viscosity of this gel has been optimized to maximize endoscopic visibility without compromising the ease of its irrigation. The aim of this study is to clarify the effectiveness of gel immersion endoscopic mucosal resection for small-sized early gastric neoplasms. Seven lesions in seven patients were treated by gel immersion endoscopic mucosal resection. The size of all lesions was under 10 mm. The median procedure time was 4.5 min. Intraoperative bleeding occurred in four of seven lesions immediately after snare resection and was easily controlled by endoscopic hemostatic forceps during the gel immersion endoscopy. The R0 resection rate was 100%. In conclusion, gel immersion endoscopic mucosal resection may be a straightforward, rapid, and safe technique for resecting superficial gastric neoplasms <10 mm in diameter.

Gastric mucosal changes associated with long-term potassium-competitive acid blocker and proton pump inhibitor (PPI) therapy may raise concern. In contrast to that for PPIs, the evidence concerning the safety of long-term potassium-competitive acid blocker use is scant. Vonoprazan (VPZ) is a representative potassium-competitive acid blocker released in Japan in 2015. In order to shed some comparative light regarding the outcomes of gastric mucosal lesions associated with a long-term acid blockade, we have reviewed six representative gastric mucosal lesions: fundic gland polyps, gastric hyperplastic polyps, multiple white and flat elevated lesions, cobblestone-like gastric mucosal changes, gastric black spots, and stardust gastric mucosal changes. For these mucosal lesions, we have evaluated the association with the type of acid blockade, patient gender, Helicobacter pylori infection status, the degree of gastric atrophy, and serum gastrin levels. There is no concrete evidence to support a significant relationship between VPZ/PPI use and the development of neuroendocrine tumors. Current data also shows that the risk of gastric mucosal changes is similar for long-term VPZ and PPI use. Serum hypergastrinemia is not correlated with the development of some gastric mucosal lesions. Therefore, serum gastrin level is unhelpful for risk estimation and for decision-making relating to the cessation of these drugs in routine clinical practice. Given the confounding potential neoplastic risk relating to H. pylori infection, this should be eradicated before VPZ/PPI therapy is commenced. The evidence to date does not support the cessation of clinically appropriate VPZ/PPI therapy solely because of the presence of these associated gastric mucosal lesions.

BACKGROUND/AIMS: Underwater endoscopic mucosal resection (UEMR) is the standard resection method for superficial non-ampullary duodenal tumors (SNADETs). We developed a novel UEMR technique that creates an anchor by protruding the distal fold with a saline injection (UEMR-A). The aim of this study was to clarify the usefulness of UEMR-A compared to conventional UEMR (UEMR-C). METHODS: This retrospective observational study included patients who underwent UEMR for SNADETs. RESULTS: A total of 141 patients were included and divided into UEMR-A (n=54) and UEMR-C (n=87) groups. Lesion resection was performed significantly more frequently by an expert endoscopist in the UEMR-C group compared to the UEMR-A group (p<0.001). The procedure time for UEMR-A was significantly shorter than that for UEMR-C (p=0.018), despite the additional time required for submucosal injection. The R0 resection rate was significantly higher in the UEMR-A group than in the UEMR-C group (p=0.004). The horizontal margins were significantly clearer in the UEMR-A group than in the UEMR-C group (p=0.018). Multivariate analysis revealed that the use of UEMR-A was the only significant positive factor for R0 resection. CONCLUSIONS: The UEMR-A technique for SNADETs appears to improve R0 resection rates and reduce procedure times compared to the UEMR-C technique.

The appearance of 'web-like mucus' in the stomach is a novel phenomenon associated with vonoprazan (VPZ) usage, characterized by a descriptive mucus pattern resembling a spider web or net. The present study aimed to determine its prevalence and related factors. In this retrospective observational study, the medical records and endoscopic reports of 547 patients who underwent an esophagogastroduodenoscopy were reviewed. The overall prevalence of web-like mucus was 6% (33/547), with 97% (32/33) of these patients being VPZ users. Specifically, 19% (32/167) of VPZ users exhibited this web-like mucus pattern, which was significantly more prevalent in the VPZ group than in the control (no acid blocker intake), proton pump inhibitor, and histamine-2 receptor antagonist groups. Multivariate analysis identified that VPZ use was positively associated with web-like mucus, while open-type gastric atrophy and multiple white and flat elevated lesions were negatively associated. A retrospective analysis of endoscopic findings before initiating VPZ therapy showed that none of the 32 VPZ users with web-like mucus had exhibited the pattern previously. Furthermore, the Cochran-Armitage trend test indicated no significant association between the duration of VPZ therapy and the prevalence of web-like mucus. In conclusion, web-like mucus in the stomach is strongly associated with VPZ use but is not associated with the duration of VPZ therapy.

INTRODUCTION: Follicular lymphoma is an indolent B-cell lymphoma that can involve the gastrointestinal tract, most commonly the small intestine. Although rituximab-based therapy is effective, transformation to diffuse large B-cell lymphoma (DLBCL) can occur and becomes difficult to diagnose after CD20 loss. CASE PRESENTATION: We report the case of a 64-year-old woman initially diagnosed with primary small intestinal follicular lymphoma who subsequently developed transformation to DLBCL 2 years after rituximab therapy. Double-balloon enteroscopy revealed progression of mucosal lesions, raising suspicion of histologic transformation. However, endoscopic biopsy was inconclusive because of the loss of CD20 expression, likely resulting from prior rituximab therapy. Surgical resection was performed to relieve intestinal obstruction and to establish a definitive diagnosis. Histopathological examination confirmed transformation to CD20-negative DLBCL. CONCLUSION: This case highlights the diagnostic limitation of endoscopic biopsy following rituximab therapy. Therefore, clinicians should be cautious in relying solely on endoscopic findings and remain open to surgical intervention to achieve a timely and accurate diagnosis.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is a minimally invasive and effective treatment for rectal tumors but maintaining a clear surgical field during the procedure is challenging, especially for novice operators. This study aimed to investigate whether continuous drainage using a Foley catheter could enhance efficiency and safety of rectal ESD performed by novice endoscopists under expert supervision. PATIENTS AND METHODS: This retrospective study involved 26 patients who underwent rectal ESD between March 2023 and October 2024. Patients were divided into two groups: those who received continuous drainage with Foley catheter placement (n = 12) and those who did not (n = 14). Key outcomes evaluated were dissection speed, total procedure time, R0 resection rates (complete tumor resection with clear margins), and occurrence of any adverse events (AEs) during or after the procedure. All procedures were performed by novice endoscopists under expert guidance. RESULTS: The results showed that dissection speed was significantly higher in the Foley catheter group, with a median of 18.6 mm²/min compared with 10.5 mm²/min in the non-catheter group ( P = 0.027). Although total procedure time and sodium hyaluronate usage were lower in the catheter group, these differences were not statistically significant. Importantly, no AEs were reported in either group. CONCLUSIONS: Foley catheter placement notably improved efficiency of rectal ESD performed by novice endoscopists, particularly by increasing dissection speed. This technique may contribute to safer and more effective ESD. However, larger studies are needed to confirm these findings and further assess their benefits.

BACKGROUND AND AIM: Peutz-Jeghers syndrome (PJS) and juvenile polyposis syndrome (JPS) are autosomal dominant diseases associated with high cancer risk. In Japan, knowledge about the prevalence and incidence of PJS and JPS is lacking despite being crucial for providing appropriate medical support. We aimed to determine the prevalence and incidence of these diseases. METHODS: In 2022, a nationwide questionnaire survey was conducted to determine the number of patients with PJS or JPS by sex and the number of newly confirmed cases from 2019 to 2021. The target facilities included gastroenterology, pediatrics, and pediatric surgery departments, which were stratified into seven classes on the basis of the total number of beds. We randomly selected target facilities using different extraction rates in each class, resulting in 1748/2912 facilities (extraction rate: 60%) as the final sample. We calculated the estimated number of patients using the response and extraction rates. RESULTS: A total of 1077 facilities responded to the survey. The estimated numbers of patients with PJS and JPS were 701 (95% confidence interval [CI]: 581-820) and 188 (95% CI: 147-230), respectively. The 3-year period prevalences of PJS and JPS were 0.6/100000 and 0.15/100000, whereas the incidences in 2021 were 0.07/100000 and 0.02/100000, respectively. Male patients constituted 53.5% and 59.6% in the PJS and JPS groups, respectively. CONCLUSIONS: We determined the prevalence and incidence of PJS and JPS in Japan for the first time. Further research is needed to obtain more detailed information, including the clinical differences and outcomes in Japan.

Ulcerative colitis (UC), a subtype of inflammatory bowel disease, occasionally manifests with extraintestinal manifestations. We present a 51-year-old male with refractory UC and immune thrombocytopenia (ITP) resistant to conventional treatments. The introduction of biologics, ustekinumab or adalimumab, resulted in clinical remission of colitis and improvements in platelet count. This case underscores the efficacy of biologics in managing refractory UC associated with ITP, emphasizing their potential to control intestinal inflammation and address concurrent thrombocytopenia, potentially avoiding surgical intervention.

BACKGROUND: Gastroesophageal reflux disease (GERD) symptoms frequently recur after cessation of acid blockers. The presence of a hiatal hernia may worsen GERD symptoms and increase the risk of esophageal malignancy. The aim of this study is to clarify the timing and predictors for recurrence of GERD symptoms after cessation of vonoprazan (VPZ) therapy. METHODS: A retrospective observational study involved 86 patients who underwent cessation of VPZ therapy for symptomatic GERD. Collated data from medical record review included the endoscopic findings and Izumo scale score. RESULTS: The mean duration of continuous VPZ therapy before cessation was 7.9 months. GERD symptoms requiring the resumption of VPZ therapy recurred in 66 of 86 patients (77%). Kaplan-Meier analysis showed that overall recurrence-free rates at 6 months, one and two years after VPZ cessation were 44%, 32% and 23%, respectively. Alcohol use, the presence of a hiatal hernia and long-term therapy for more than six months were identified as significant positive predictors for symptomatic recurrence. Notably, hiatal hernia had the highest hazard ratio in both univariate and multivariate analyses. The recurrence-free rate in patients with a hiatal hernia was much lower at 6 months than in patients without a hiatal hernia (15% and 51%, respectively p = 0.002). After the symptomatic recurrence, GERD symptoms improved significantly after one-month VPZ therapy. CONCLUSION: The rate of symptomatic recurrence after VPZ cessation in patients with GERD is considerable. Cessation of acid suppression therapy should be cautious in patients with both a hiatal hernia and GERD.

症例は62歳女性で、右腰部の悪性黒色腫に対し皮膚悪性腫瘍切除と分層植皮、右鼠径リンパ節センチネル生検を施行し、pStage IIID(pT4bN3cM0)と診断した。術後放射線治療とニボルマブによる補助療法を1年間施行したが、鉄欠乏性貧血と間欠的な腹痛、便潜血検査陽性を認めた。術後2年3ヵ月時の腹部単純CTで近位空腸内腔に軟部組織陰影、および近位空腸の拡張と一部腸重積、近傍の腸間膜リンパ節腫大を認めた。経口ダブルバルーン内視鏡検査では十二指腸水平部および上部空腸に黒色の上皮を伴う隆起性病変を認め、易出血性であり、病理検査で悪性黒色腫の空腸転移と診断した。腸重積は自然に解除され、ニボルマブとイピリムマブを2コース施行したが、近位空腸内腔の軟部組織陰影の増大や肝転移を認め、全身状態不良のためBest Supportive Careの方針とした。

Background and study aims Small-bowel polyps in patients with Peutz-Jeghers syndrome (PJS) are sometimes difficult to reach using double-balloon enteroscopy (DBE). However, they can induce intussusception, especially when ≧15 mm. This study aimed to review the outcomes of patients with such polyps. Patients and methods All patients with PJS with small-bowel polyps that bidirectional DBE failed to reach and were ≧5 mm as shown by DBE enterography at our institution from May 2006 to April 2022 were retrospectively evaluated. The endpoint was the earliest occurrence of symptomatic intussusception induced by the polyp, endoscopic removal by repeat DBE or intraoperative endoscopy, or the last medical record describing the patient's condition. Results This study included 27 polyps in 13 patients. All patients had extraluminal adhesions. None developed symptomatic intussusception, eight patients underwent endoscopic removal at repeat DBE without surgery, two patients underwent removal with intraoperative endoscopy, two patients were observed without polyp removal, and one patient had a polyp removed at repeat DBE and three unreachable polyps remained. Repeat DBE without surgery was able to remove 14 polyps (52%). Polyps ≧15 mm included 11 lesions in eight patients and were observed for a median of 14 months without symptomatic intussusception. Conclusions The difficult-to-reach polyps may have a low risk of immediate symptomatic intussusception, possibly due to limited bowel mobility by extraluminal adhesions, and the likelihood of reaching them at repeat DBE was substantial. Hence, repeat DBE 1 year later may be proper in such patients with PJS.

During balloon enteroscopy-assisted endoscopic retrograde cholangiography, the minimal water exchange method facilitates reaching the site and prevents pneumobilia, hepatic portal venous gas, and air embolism. However, the water may mix with bile or blood, obscuring the visual field. Yokoyama and colleagues demonstrate how the gel immersion method helps overcome this problem.

BACKGROUND: Endoscopic balloon dilation (EBD) is an effective, minimally invasive treatment for Crohn's disease (CD) related intestinal strictures. However, restenosis frequently occurs and requires repetitive EBD or surgical resection. Since previous studies could not evaluate restenosis based on stricture diameter, factors affecting restenosis after EBD were unclear. This study aimed to identify these factors by precisely measuring the diameter of small intestinal strictures in patients with CD. METHODS: This single-center retrospective study enrolled patients with CD with de novo small intestinal strictures who underwent two double-balloon enteroscopy sessions (EBD and follow-up) between January 2016 and October 2021. Clinical and endoscopic data were obtained from electronic medical records. A calibrated small-caliber-tip transparent hood was used to precisely measure stricture diameters. Multivariate analysis was performed to identify factors associated with restenosis. RESULTS: Forty-eight patients (37 male) were analyzed. The total number of strictures detected decreased from 162 to 143. The mean diameter of all strictures and the narrowest stricture in each patient increased significantly from 8.6 to 9.8 mm and from 7.6 to 8.7 mm, respectively. Thirty-two (67%) patients developed endoscopic restenosis. Multivariate analysis showed that the presence of ulcers at the follow-up session was a risk factor for restenosis (odds ratio 9.4, p = 0.01). Patients with complete mucosal healing at both sessions (n = 21) showed significant improvement in the narrowest stricture (+1.7 mm, p = 0.001). CONCLUSIONS: Maintenance of complete mucosal healing is significantly associated with avoiding restenosis after EBD in CD-related small intestinal strictures.

BACKGROUND AND AIMS: Acid suppression improves dyspepsia symptoms but the efficacy of vonoprazan for functional dyspepsia remains unclear. The aim of this study is to evaluate the effectiveness of vonoprazan therapy for functional dyspepsia without heartburn. METHODS: Patients receiving vonoprazan 10 mg once daily or acotiamide 100 mg three times daily for more than one month were included and retrospectively reviewed. Functional dyspepsia was diagnosed based on the ROME IV criteria. Patients with heartburn were excluded. Eighty-five patients were divided into vonoprazan (n=48) and acotiamide (n=37) groups. RESULTS: There were no significant differences at baseline between the vonoprazan and acotiamide groups. The functional dyspepsia score significantly improved in both groups (p<0.001). The degree of score reduction (55% vs 59%, p=0.559) and the resolution rates (21% vs 30%, p=0.345) were similar. Epigastric pain and postprandial distress scores were significantly improved in both groups, and the degree of improvement of each score was similar. Constipation and diarrhea scores were significantly improved in both groups, and the degree of improvement similar. CONCLUSION: These preliminary results suggest that vonoprazan is effective for the treatment of functional dyspepsia without heartburn in the short-term, with results similar to acotiamide therapy.