矢野 智則

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.

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.

＜文献概要＞●Crohn病は再燃・寛解を繰り返すことで,消化管に狭窄を形成して難治化していくことが多い.腸管切除や狭窄形成術を行うことで狭窄の解除はできるが,術後も再燃する.手術回避に内視鏡的バルーン拡張術(endoscopic balloon dilation;EBD)は有用である.特に有症状の狭窄や,口側腸管の拡張を伴う狭窄に関してはEBDのよい適応である.寛解状態での施行が望ましく,術前に血液検査や画像検査で病勢・範囲を把握する.内視鏡時に炎症が残存していた場合には治療強化を行うことで,再狭窄の予防が期待できる.実際の内視鏡治療にはいくつかのコツがあり,実際の症例も提示しながら当施設でのEBDについて解説する.

＜文献概要＞●胃の血管走行の解剖学的な特徴を把握する。●大量出血をさせないために粘膜下層の血管を常に認識し,盲目的な剥離をしない。●止血鉗子による出血点のピンポイントな把持・焼灼を基本とする。●特に水没する領域で出血点が同定できないときはgel immersion法に切り替えて出血点を同定する。

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.

Balloon-assisted enteroscopy allows endoscopic treatments in the deeper segments of the small bowel. Endoscopic balloon dilation has become a popular minimally invasive alternative for the treatment of Crohn's disease-associated small intestinal strictures. As a supplement to the Clinical Practice Guidelines for Enteroscopy, the Japan Gastroenterological Endoscopy Society's Working Committee has developed the present "Guidelines for endoscopic balloon dilation in treating Crohn's disease-associated small intestinal strictures," based on new scientific techniques and evidence. The guidelines cover standard procedures for the insertion route of the balloon endoscope, bowel preparation, indications, procedure-related complications, efficacy, target diameter and duration, management of multiple strictures, and the current state of combined and alternative treatments. Unresolved future research questions are also listed in this guideline.

Balloon-assisted enteroscopy allows endoscopic treatments in the deeper segments of the small bowel. Endoscopic balloon dilation has become a popular minimally invasive alternative for the treatment of Crohn's disease-associated small intestinal strictures. As a supplement to the Clinical Practice Guidelines for Enteroscopy, the Japan Gastroenterological Endoscopy Society's Working Committee has developed the present "Guidelines for endoscopic balloon dilation in treating Crohn's disease-associated small intestinal strictures," based on new scientific techniques and evidence. The guidelines cover standard procedures for the insertion route of the balloon endoscope, bowel preparation, indications, procedure-related complications, efficacy, target diameter and duration, management of multiple strictures, and the current state of combined and alternative treatments. Unresolved future research questions are also listed in this guideline.

BACKGROUND: Long-term acid suppression during vonoprazan therapy causes hypergastrinemia which may induce gastric mucosal changes such as fundic gland and hyperplastic polyps. The aim of this study is to clarify the long-term changes in serum gastrin levels and risk factors for hypergastrinemia. METHODS: From July 2016 to April 2020, 48 patients receiving vonoprazan 10 mg once daily for more than one year were reviewed. Serum gastrin level was evaluated by radioimmunoassay in a fasting condition (reference range 37-172 pg/ml). RESULTS: The baseline median gastrin level was 100 (range, 54-415) pg/ml. The gastrin level over 4 years was 700-1200 pg/ml, which plateaued at 1.5 years. Multivariate analysis revealed factors associated with gastrin levels 12 months after starting vonoprazan and identified severe gastric atrophy as a significant positive risk factor (p = .046). The gastrin level over 4 years in patients with severe gastric atrophy and no atrophy was approximately 900-1500 and 500-1000 pg/ml, respectively. Female gender was also identified as a positive factor, although it was not statistically significant (p = .087). The gastrin level over 4 years in females was approximately 900-1300 pg/ml, greater than in males (500-900 pg/ml). CONCLUSION: A continued increase in gastrin levels was not found during long-term vonoprazan therapy. Severe gastric atrophy is a significant risk factor for hypergastrinemia.

肝移植後胆道合併症は依然として発症率が高く、予後に影響する重要な合併症である。胆道合併症は胆管狭窄、胆汁瘻に大別されるが、肝内結石はまれであり、とくに小児肝移植後肝内結石の診断・治療は確立されていない。小児肝移植症例の胆道再建は胆管空腸吻合がほとんどであるため、胆道合併症に対する治療は経皮経肝的胆道ドレナージ(PTBD)下カテーテル治療か外科的治療に限られていた。近年、ダブルバルーン小腸内視鏡(DBE)の改良とデバイスの進歩により、小児肝移植後胆道合併症においてもDBE下カテーテル治療が可能になってきている。低侵襲治療であるDBE下治療により、小児肝移植後肝内結石に対しても早期発見治療が可能となり、今後長期予後の向上が期待できる。(著者抄録)