Faculty Profiles - SAWADA Tsunaki

Papers - SAWADA Tsunaki

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Endoscopic Ultrasound Elastography as a Novel Diagnostic Method for the Assessment of Hardness and Depth of Invasion in Colorectal Neoplasms

Esaki, M; Yamamura, T; Nakamura, M; Maeda, K; Sawada, T; Mizutani, Y; Ishikawa, E; Suzuki, H; Kuno, T; Yamada, K; Hasegawa, I; Ishikawa, T; Kakushima, N; Furukawa, K; Ohno, E; Kawashima, H; Hirooka, Y; Fujishiro, M

DIGESTION Vol. 102 ( 5 ) page： 701 - 713 2021.9

Language：English Publisher：Digestion

Introduction: We aimed to compare the efficacy of endoscopic ultrasound elastography (EUS-EG) with that of magnifying chromoendoscopy (MCE) and endoscopic ultrasonography (EUS) for the diagnosis of the depth of invasion in colorectal neoplasms. This is an important clinical issue as the depth of invasion is associated with the risk of metastasis. Methods: Consecutive patients with suspected superficial colorectal neoplasms, evaluated by MCE, EUS, and EUS-EG, for whom endoscopic submucosal dissection was considered, were enrolled in 2018 (derivation study) and in 2019-2020 (validation study). The primary clinical endpoint was the diagnostic yield differentiating intramucosal and shallow submucosal neoplasms from deep submucosal (dSM) and advanced colorectal cancers. In addition, inter- and intra-observer agreements of the elastic score of colorectal neoplasm (ES-CRN) were evaluated by 2 expert and 2 non-expert endoscopists. Results: Thirty-one (33 lesions) and 50 (55 lesions) patients were enrolled in the derivation and validation studies, respectively. Sensitivity, specificity, positive, and negative predictive values, and accuracy of assessment of the depth of submucosal or deeper invasion in the derivation and validation groups were as follows: EUS-EG, 100/88.2/86.7/100/93.3% and 77.8/86.1/73.7/88.6/83.3%; MCE, 66.7/94.4/90.9/77.3/81.8% and 84.2/91.4/84.2/91.4/88.9%; and EUS, 93.3/77.8/77.8/93.3/84.8% and 89.5/65.7/58.6/92.0/74.1%, respectively. For the 2 expert endoscopists, interobserver agreement for the ES-CRN (first and second assessments) in the derivation group was 0.84 and 0.78, respectively; these values were 0.73 and 0.49, respectively, for the 2 non-expert endoscopists. Discussion/Conclusion: All 3 modalities presented similar diagnostic yield. Inter- and intra-observer agreements of the ES-CRN were substantial, even for non-expert endoscopists. Therefore, EUS-EG may be a useful modality in determining the depth of invasion in colorectal neoplasms.

DOI： 10.1159/000511589

Detection of Colorectal Neoplasms Using Linked Color Imaging: A Prospective, Randomized, Tandem Colonoscon Trial

Hasegawa, I; Yamamura, T; Suzuki, H; Maeda, K; Sawada, T; Mizutani, Y; Ishikawa, E; Ishikawa, T; Kakushima, N; Furukawa, K; Ohno, E; Kawashima, H; Nakamura, M; Fujishiro, M

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 19 ( 8 ) page： 1708 - + 2021.8

Language：English Publisher：Clinical Gastroenterology and Hepatology

Background and aims: A higher adenoma detection rate (ADR) has been shown to be related to a lower incidence and mortality of colorectal cancer. We analyzed the efficacy of linked color imaging (LCI) by assessing the detection, miss, and visibility of various featured adenomas as compared with white light imaging (WLI). Methods: This was a prospective, randomized, tandem trial. The participants were randomly assigned to 2 groups: first observation by LCI, then second observation by WLI (LCI group); or both observations by WLI (WLI group). Suspected neoplastic lesions were resected after magnifying image-enhanced endoscopy. The primary outcome was to compare the ADR during the first observation. Secondary outcomes included evaluation of adenoma miss rate (AMR) and visibility score. Results: A total of 780 patients were randomized, 700 of whom were included in the final analysis. The ADR was 69.6% and 63.2% in the LCI and WLI groups, respectively, with no significant difference. However, LCI improved the average ADR in low-detectors compared with high-detectors (76.0% vs 55.1%; P < .001). Total AMR was 20.6% in the LCI group, which was significantly lower than that in the WLI group (31.1%) (P < .001). AMR in the LCI group was significantly lower, especially for diminutive adenomas (23.4% vs 35.1%; P < .001) and nonpolypoid lesions (25.6% vs 37.9%; P < .001) compared with the WLI group. Conclusion: Although both methods provided a similar ADR, LCI had a lower AMR than WLI. LCI could benefit endoscopists with lower ADR, an observation that warrants additional study. (UMIN Clinical Trials Registry, Number: UMIN000026359).

DOI： 10.1016/j.cgh.2021.04.004

A forward-viewing radial-array echoendoscope is useful for diagnosing the depth of colorectal neoplasia invasion

Kuno, T; Yamamura, T; Nakamura, M; Maeda, K; Sawada, T; Mizutani, Y; Esaki, M; Ishikawa, T; Furukawa, K; Ohno, E; Kawashima, H; Fujishiro, M

SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES Vol. 35 ( 8 ) page： 4389 - 4398 2021.8

Language：English Publisher：Surgical Endoscopy

Background: It is important to accurately diagnose the depth of colorectal neoplasia invasion. We aimed to evaluate the usefulness of a new forward-viewing radial-array echoendoscope (FRE), relative to the pit pattern method. Methods: In this prospective study, the invasion depth of suspected early-stage carcinoma was diagnosed using the pit pattern and FRE methods. The diagnoses were classified as T1a (submucosal invasion distance < 1,000 μm) or shallower and T1b (≥ 1,000 μm) or deeper. Pathological diagnoses were used to compare the diagnostic capabilities of the two methods. Results: The final analyses included 110 lesions. The FRE was successfully inserted to the lesion in all cases. There were no significant differences between the two methods regarding the correct prediction rate (79.1% vs. 75.5%, P = 0.57), accuracy (81.3% vs. 79.0%, P = 0.68), specificity (81.3% vs. 70.8%, P = 0.135), positive predictive value (65.0% vs. 60.4%, P = 0.649), negative predictive value (91.0% vs. 98.1%, P = 0.108), or frequency of unevaluable cases (2.7% vs. 4.5%, P = 0.471). The correct prediction rate was calculated by adding the number of unevaluable cases to the denominator of accuracy. Relative to the pit pattern method, the FRE method offered significantly higher sensitivity for predicting T1b or deeper invasion (81.3% vs. 97.0%, P = 0.048). The pit pattern method had significantly poorer accuracy for large lesions (> 36 mm) than for smaller lesions (≤ 36 mm). In contrast, the accuracy of the FRE method did not differ significantly with lesion size. When using the FRE method, no cases were unevaluable because of attenuation. The FRE method provided correct diagnoses in 2 of 3 cases that were unevaluable using the pit pattern method. Conclusions: The pit pattern and FRE methods offered similar diagnostic performance for invasion depth. Furthermore, the FRE method may be used to correctly diagnose cases that are unevaluable using the pit pattern method.

DOI： 10.1007/s00464-020-07936-3

Feasibility of patency capsule and colon capsule endoscopy in patients with suspected gastrointestinal stenosis: a prospective study.

Otsuka H, Nakamura M, Yamamura T, Maeda K, Sawada T, Mizutani Y, Ishikawa E, Ishikawa T, Kakushima N, Furukawa K, Ohno E, Kawashima H, Honda T, Ishigami M, Fujishiro M

Nagoya journal of medical science Vol. 83 ( 3 ) page： 419 - 430 2021.8

Language：English Publisher：Nagoya Journal of Medical Science

Patency capsule (PC) can evaluate the patency of gastrointestinal (GI) tract. We hypothesized preceding patient selection using PC would improve the successful rate of colon capsule endoscopy (CCE). Therefore, a prospective single-arm study using PC followed by CCE was conducted with a control group of CCE alone. Patients with suspected or known GI stenosis scheduled for CCE were enrolled. CCE was performed only when the PC was excreted out of the body within 33 hours of ingestion. Primary endpoint was the rate of observation of the entire GI tract within the duration of examination. The secondary endpoints were complications and CCE findings. Twenty-three patients (17 men) were enrolled. The mean age was 50.5±19.8 years. Suspected stenotic sites were 8, 5, and 10 in the small, large, and small and large bowel, respectively. Sixteen, 12, and 10 patients had abdominal pain, active inflammatory bowel disease, and history of surgery for suspected stenosis, respectively. Patency of GI tract was confirmed in 96% (22/23) of the patients by administered PC. Of the 22 patients who underwent CCE, the entire GI tract was observed in 86% (19/22). No complications were observed. The median transit times in the small bowel and colon were 99 (21–682) and 160 (5–328) minutes, respectively. CCE findings revealed ulcers, erosions, and diverticula in 5, 9, and 4 patients, respectively. In conclusion, CCE with PC might be a safer and useful modality to observe the large colon for patients with suspected GI stenosis.

DOI： 10.18999/nagjms.83.3.419

Difference of efficacy for small bowel lesion in Crohn

Sawada, T; Nakamura, M; Yamamura, T; Maeda, K; Ishikawa, E; Fujishiro, M

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY Vol. 36 page： 116 - 116 2021.8

Fecal incontinence and oral regurgitation during duodenal endoscopic submucosal dissection using the water pressure method

Takada Yoshihisa, Hirose Takashi, Nishida Kazuki, Kakushima Naomi, Furukawa Kazuhiro, Furune Satoshi, Ishikawa Eri, Sawada Tsunaki, Maeda Keiko, Yamamura Takeshi, Ishikawa Takuya, Ohno Eizaburo, Nakamura Masanao, Honda Takashi, Ishigami Masatoshi, Kawashima Hiroki, Fujishiro Mitsuhiro

DIGESTIVE ENDOSCOPY Vol. 34 ( 3 ) page： 526 - 534 2021.7

Language：Japanese Publisher：Digestive Endoscopy

Objectives: Endoscopic submucosal dissection (ESD) in the duodenum is challenging. The water pressure method (WP-ESD) has been developed with a decreased rate of perforation. However, details of perioperative adverse events of WP-ESD are unknown. The purpose of this study was to clarify the frequency and related factors of fecal incontinence and oral regurgitation during WP-ESD. Methods: A chart-based retrospective analysis was performed on 43 patients who underwent duodenal WP-ESD. The saline volume given into the body was calculated in all cases. All adverse events during WP-ESD until 6 weeks were extracted, and factors related to intraoperative fecal incontinence or oral regurgitation were analyzed. The frequency of fecal incontinence and oral regurgitation was also compared to those of 83 conventional ESD cases. Results: In WP-ESD, intraoperative fecal incontinence occurred in 12 (28%), oral regurgitation in six (14%), and aspiration pneumonia in one patient. For fecal incontinence, the infusion speed (saline volume divided by resection time) around 17 mL/min was a significant factor in multivariable analysis. For oral regurgitation, only tumor size was a significant factor in univariate analysis (P = 0.027). Significant difference was observed in the frequency of fecal incontinence between WP-ESD and conventional ESD (28% vs. 0%, P < 0.001), but no difference was observed in oral regurgitation or aspiration pneumonia. Conclusions: Intraoperative fecal incontinence is a unique adverse event of WP-ESD related to the infusion speed. WP-ESD did not pose a risk for oral regurgitation, but we should be aware of the risk in large tumor cases.

DOI： 10.1111/den.14070

Lewis score on capsule endoscopy can predict the prognosis in patients with small bowel lesions of Crohn's disease

Nishikawa, T; Nakamura, M; Yamamura, T; Maeda, K; Sawada, T; Mizutani, Y; Ishikawa, E; Ishikawa, T; Kakushima, N; Furukawa, K; Ohno, E; Honda, T; Kawashima, H; Ishigami, M; Fujishiro, M

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY Vol. 36 ( 7 ) page： 1851 - 1858 2021.7

Language：English Publisher：Journal of Gastroenterology and Hepatology (Australia)

Background and Aim: Endoscopic evaluation of disease activity, including mucosal healing, is poorly established in Crohn's disease. We previously reported that patients with a Lewis score (LS) on capsule endoscopy < 270 had a lower risk of exacerbation without additional treatment. This study investigated prognostic predictors in patients undergoing capsule endoscopy and determined the optimal LS cut-off value. Methods: In a retrospective single-center study, 102 patients with Crohn's disease who underwent capsule endoscopy were reviewed. We reviewed the clinical course and the patients' characteristics, Crohn's Disease Activity Index, laboratory findings, LS, and Prognostic Nutritional Index (PNI) for factors potentially associated with Crohn's disease-related emergency hospitalization. Subsequently, we prospectively enrolled 66 patients with Crohn's disease and analyzed clinical outcomes according to these factors. Results: In the retrospective study, LS ≥ 270 and PNI < 45 were identified as independent predictors of Crohn's disease-related emergency hospitalization with hazard ratios of 9.48 and 3.01, respectively. Even in patients with LS ≥ 270, cumulative hospitalization rates decreased after intervention based on capsule endoscopy findings. The prospective study confirmed that patients with LS ≥ 270 or PNI < 45 had a significantly higher risk of Crohn's disease-related emergency hospitalization and that additional treatment reduced the risk of relapse. Conclusions: LS and PNI are the best available prognostic predictors in patients with Crohn's disease without gastrointestinal stenosis and can guide decisions on treatment escalation. Patients with LS ≥ 270 and PNI < 45 were at increased risk for exacerbation, and additional treatments should be considered for this group.

DOI： 10.1111/jgh.15366

Subjective Symptoms in Patients with Eosinophilic Esophagitis Are Related to Esophageal Wall Thickness and Esophageal Body Pressure

Muroi, K; Kakushima, N; Furukawa, K; Ishikawa, E; Sawada, T; Ishikawa, T; Maeda, K; Yamamura, T; Ohno, E; Nakamura, M; Kawashima, H; Funasaka, K; Miyahara, R; Fujishiro, M

DIGESTIVE DISEASES AND SCIENCES Vol. 66 ( 7 ) page： 2291 - 2300 2021.7

Language：English Publisher：Digestive Diseases and Sciences

Background: Endoscopic ultrasonography (EUS) and high-resolution manometry (HRM) can be used in the evaluation of eosinophilic esophagitis (EoE) for frequent symptoms such as dysphagia. However, the role of these examinations is not clear. Aims: The aim of this study was to objectively evaluate the subjective symptoms of EoE patients with EUS and HRM. Methods: Patients who had endoscopic findings indicative of EoE and matched the number of eosinophil infiltrates used as diagnostic criteria were recruited between September 2018 and August 2019. Evaluable subjects underwent EUS and HRM and completed the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire. The esophageal wall thickness (evaluated with EUS) and HRM parameters between patients with and without symptoms were retrospectively compared. Symptomatic patients were re-examined using EUS and HRM 6 months after treatment. Results: A total of 35 patients (29 males, median age of 49 years) were divided into symptomatic (20 patients) and asymptomatic groups (15 patients). The esophageal wall was thicker, and the distal contractile integral (DCI) values were higher in the symptomatic group (P < 0.001). In addition, DCI values were positively correlated with esophageal wall thickness. After treatment, the GSRS scores showed an improving trend for each item. Esophageal wall thickness and DCI values were significantly decreased (Ps < 0.001). Conclusions: Esophageal wall thickening and increased esophageal body pressure may be involved in subjective symptoms. In addition, treatment may reduce esophageal thickness and pressure along with improvement of subjective symptoms.

DOI： 10.1007/s10620-020-06527-5

Comparison of High-Resolution Manometry in Patients Complaining of Dysphagia among Patients with or without Diabetes Mellitus

Muroi, K; Miyahara, R; Funasaka, K; Furukawa, K; Sawada, T; Maeda, K; Yamamura, T; Ishikawa, T; Ohno, E; Nakamura, M; Kawashima, H; Onoue, T; Arima, H; Hirooka, Y; Fujishiro, M

DIGESTION Vol. 102 ( 4 ) page： 554 - 562 2021.6

Language：English Publisher：Digestion

Introduction: Dysphagia is a common symptom that occurs in patients with diabetes mellitus (DM). There have been few prospective observational studies on esophageal motility disorders in DM using high-resolution manometry (HRM). This study aimed to clarify the characteristics of esophageal motility disorders using HRM in patients with dysphagia and compare them between DM and non-DM patients. Methods: Patients with dysphagia were prospectively recruited between October 2018 and July 2019. Patients (n = 89) underwent esophagogastroduodenoscopy and HRM and completed the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire. Manometry parameters and motility disorder classifications were compared between DM and non-DM patients. We also investigated the differences in clinical backgrounds and questionnaire scores among DM patients with normal and abnormal manometry results. Results: A higher prevalence of esophageal motility disorder was observed in DM patients (60%, 21/35) compared to non-DM patients (29.6%, 16/54) (p = 0.001). The prevalence of minor disorders such as ineffective esophageal motor disorder and fragmented peristalsis was significantly higher (45 vs. 11%), and the distal contractile integral, integrated relaxation pressure, and contractile front velocity values were lower in the DM group. Among DM patients, those with abnormal esophageal motility had a significantly higher prevalence of neuropathy, retinopathy, and nephropathy, as well as higher reflux or constipation scores on the GSRS, than those with normal results. Conclusions: Among patients with dysphagia, the frequency of minor esophageal motility disorders was higher in DM patients than in non-DM patients. Abnormal esophageal motility related to poor esophageal clearance was associated with higher prevalence of diabetic complications.

DOI： 10.1159/000510081

Long-Term Prognostic Predictors of Esophageal Squamous Cell Carcinoma Potentially Indicated for Endoscopic Submucosal Dissection

Suzuki, T; Furukawa, K; Funasaka, K; Ishikawa, E; Sawada, T; Maeda, K; Yamamura, T; Ishikawa, T; Ohno, E; Nakamura, M; Kawashima, H; Miyahara, R; Fujishiro, M

DIGESTION Vol. 102 ( 4 ) page： 563 - 571 2021.6

Language：English Publisher：Digestion

Introduction: Patients with esophageal squamous cell carcinoma (ESCC) have various comorbidities. Thus, it is necessary to determine the appropriateness of performing treatment based on the patient's general condition. Aim: This study aimed to clarify the prognostic predictors of ESCC indicated for endoscopic submucosal dissection (ESD). Methods: This retrospective study enrolled 241 patients with superficial ESCC endoscopically diagnosed as ESD-indicated lesions at the Nagoya University Hospital between January 2007 and December 2017. We evaluated the 3- and 5-year overall survival (OS) rates and prognostic predictors, such as the Prognostic Nutritional Index (PNI), Charlson Comorbidity Index (CCI), Psoas Muscle Index, and Controlling Nutritional Status score. Furthermore, we created a score-based classification using the prognostic predictors identified by multivariate analysis, and the 3- and 5-year OS rates were compared among the calculated scores. Results: In the multivariate analysis, PNI < 45 (hazard ratio [HR]: 2.39; 95% confidence interval [CI]: 1.28-4.46; p = 0.006) and CCI ≥ 3 (HR: 4.42; 95% CI: 2.40-8.12; p < 0.001) were significantly associated with the OS. Based on the HR, 0 and 1 were assigned to PNI and 0, 2, and 4 were assigned to CCI, and the score classification of 0-5 points was created. The 3- and 5-year OS rates in patients with a score 3 were significantly higher than in those with scores 4 and 5. As a result of scoring, the prognosis was stratified; the 3- and 5-year OS rates in patients with scores 4 and 5, that is, CCI ≥ 6, were clearly low, at approximately 10%. Conclusions: CCI and PNI can be prognostic predictors of patients with superficial ESCC indicated for ESD. Observation without ESD might be an acceptable strategy among patients with CCI ≥ 6.

DOI： 10.1159/000510091

An evaluation of resectability among endoscopic treatment methods for rectal neuroendocrine tumors <10 mm

Toriyama, K; Yamamura, T; Nakamura, M; Maeda, K; Sawada, T; Mizutani, Y; Ishikawa, E; Furukawa, K; Ishikawa, T; Ohno, E; Kawashima, H; Fujishiro, M

ARAB JOURNAL OF GASTROENTEROLOGY Vol. 22 ( 2 ) page： 104 - 110 2021.6

Language：English Publisher：Arab Journal of Gastroenterology

Background and Study Aims: With respect to rectal neuroendocrine tumor (NET) resection, it remains unclear which of the following methods is the most effective: conventional endoscopic mucosal resection (cEMR), EMR using a fitted cap (EMR-C), EMR with a ligation band device (EMR-L), or endoscopic submucosal dissection (ESD). Thus, in this study, we aim to retrospectively evaluate the most effective endoscopic resection for rectal NETs < 10 mm. Patients and methods: In total, 61 consecutive patients with primary rectal NETs < 10 mm in diameter were included in this study; they were then divided into three groups: those with cEMR; those with modified EMR (mEMR) involving EMR-C and EMR-L; and those with ESD. The primary endpoint was to evaluate the difference in the complete en bloc resection rate. The secondary endpoint was to investigate differences in procedure time and complications. Results: Among the three groups, a significant difference was found in procedure time (cEMR vs ESD, P < .01; mEMR vs ESD, P < .01), en bloc resection rate (cEMR vs mEMR, P = .015), tumor size (mEMR vs ESD, P < .01), percentage of tumor diameter ≥ 5 mm (mEMR vs ESD, P < .01), and complete en bloc resection rate (cEMR vs mEMR, P = .014). Meanwhile, no significant difference was noted in terms of complication rate among the three groups. Conclusion: The mEMR was the most suitable resection method for rectal NETs < 10 mm with respect to the risks and benefits from procedure-related factors, such as complete en bloc resection rate, procedure time, and complication rate.

DOI： 10.1016/j.ajg.2021.05.007

New modality for the quantitative evaluation of tissue elasticity using a forward-viewing radial-array echoendoscope for colorectal neoplasms

Esaki, M; Yamamura, T; Nakamura, M; Maeda, K; Sawada, T; Mizutani, Y; Ishikawa, E; Furukawa, K; Kawashima, H; Hirooka, Y; Fujishiro, M

INTERNATIONAL JOURNAL OF COLORECTAL DISEASE Vol. 36 ( 5 ) page： 919 - 927 2021.5

Language：English Publisher：International Journal of Colorectal Disease

Purpose: Sound speed correction (SSC) is a non-invasive modality that quantifies the hardness of neoplasms. The aim of our study was to evaluate the usefulness of SSC for the diagnostic accuracy of colorectal neoplasms and to differentiate the depth of invasion. Methods: Forty colorectal neoplasms, contributed by 40 patients, were included in the analysis. The primary outcome was the diagnostic ability of SSC for the depth of invasion of colorectal neoplasms, with the secondary endpoint being the clinical efficacy of SSC to distinguish between a neoplasm and normal mucosa. Results: The median sound speeds for colorectal neoplasms and normal mucosa were 1580 m/s and 1515 m/s, respectively (p < 0.001), with a median sound speed of 1583 m/s for lesions with a depth shallower than that of the muscularis propria and 1610 m/s for depths deeper than that of the muscularis propria (p = 0.002). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 80.0%, 100%, 100%, 83.3%, 90.0%, and 100%, respectively, for the diagnosis of neoplasms (using a cut-off sound speed of 1557 m/s) and 100%, 77.8%, 33.3%, 100%, 80.0%, respectively, for the diagnosis of the depth of invasion (using a cut-off of 1590 m/s). Conclusion: We identified absolute sound speeds for colorectal neoplasms and the depth of invasion of neoplasms which yielded a good diagnostic performance. SSC provides an objective evaluation of colorectal neoplasms and the depth of invasion of neoplasms and, thus, might be a useful modality in practice. Trial registration : UMIN000038235, Date of registration; October 8, 2019

DOI： 10.1007/s00384-020-03790-w

Clinical Features of Ischemic Enteritis Diagnosed by Double-Balloon Endoscopy

Nakamura, M; Yamamura, T; Maeda, K; Sawada, T; Mizutani, Y; Ishikawa, E; Kakushima, N; Furukawa, K; Ishikawa, T; Ohno, E; Honda, T; Kawashima, H; Ishigami, M; Fujishiro, M

CANADIAN JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY Vol. 2021 page： 8875564 2021.4

Language：English Publisher：Canadian Journal of Gastroenterology and Hepatology

Introduction. Ischemic enteritis (IE) is a relatively rare small bowel disease that is diagnosed via double-balloon endoscopy (DBE), although the lack of established diagnostic criteria can make it difficult to confirm the diagnosis. This study aimed to describe the clinical characteristics, endoscopic imaging features, and treatments for IE at our center. Patients and Methods. We retrospectively searched the DBE database (1,521 patients) at Nagoya University Hospital for patients with IE and collected data regarding endoscopic findings, clinical background, and histological findings. The cases were categorized according to whether they involved transient or stenotic IE. Results. The DBE database included 24 patients (14 men) with IE. Transient IE was identified in 9 patients, and stenotic IE was identified in 15. Half of the patients had a history of cerebrovascular and cardiovascular disease. A granular structure at the ulcer base was the most frequently observed DBE finding at the stenotic site. Enterography using the contrast medium revealed that transient IE had a similar stenotic lesion length, relative to stenotic IE, although stenotic IE had a significantly higher stenosis ratio (81% vs. 63%, P=0.033). Small bowel enteroclysis revealed the "lead pipe"sign (11 patients), thumbprinting (3 patients), and the serrated lumen sign (1 patient). Only 1 patient with stenotic IE experienced recurrence after conservative treatment. Conclusion. During DBE, IE was characterized by cannular stenosis with extended and variable ulceration types, which spread over the edge of the stenosis, and a granular appearance at the ulcer base. These findings may help guide the diagnosis of IE.

DOI： 10.1155/2021/8875564

Filtrated Adipose Tissue-Derived Mesenchymal Stem Cell Lysate Ameliorates Experimental Acute Colitis in Mice

Nishikawa, T; Maeda, K; Nakamura, M; Yamamura, T; Sawada, T; Mizutani, Y; Ito, T; Ishikawa, T; Furukawa, K; Ohno, E; Miyahara, R; Kawashima, H; Honda, T; Ishigami, M; Yamamoto, T; Matsumoto, S; Hotta, Y; Fujishiro, M

DIGESTIVE DISEASES AND SCIENCES Vol. 66 ( 4 ) page： 1034 - 1044 2021.4

Language：English Publisher：Digestive Diseases and Sciences

Background: Inflammatory bowel disease (IBD) is a chronic, persistent, and intractable enteritis; however, an effective treatment strategy is yet to be established. Mesenchymal stem cells (MSCs) and their paracrine factors exhibit anti-inflammatory actions and have been proposed as a new therapeutic candidate for IBD treatment, although the efficacy of MSC lysate on enteritis is unclear. Aims: Here, we examined the efficacy and appropriate regimen of filtrated murine adipose-derived mesenchymal stem cell lysate (FADSTL) in an acute colitis mouse model as a novel cell-free MSC therapy. Methods: To confirm the clinical effects of FADSTL, survival rate, body weight, and disease activity index (DAI) were investigated in the DSS-induced colitis mouse model. Further, differences in efficacy with dosing frequency were assessed to optimize the proper regimen. Colon length, histological findings, gene expression of inflammatory mediators and tight junction proteins in colon tissues, and anti-apoptotic effects were also compared in 3-day continuous FADSTL administration and PBS groups. Results: Three-day continuous FADSTL administration significantly improved weight loss and DAI score compared to those in the PBS-treated group, whereas the effect was not observed with single administration. Additionally, colon shortening and histological inflammation were suppressed in the FADSTL-treated group. Further, this treatment decreased gene expression of inflammatory mediators, maintained expression of tight junction proteins in the colon, and showed anti-apoptotic effects. Conclusions: FADSTL effects were dependent on its administration frequency, suggesting the requirement of continuous FADSTL administration. FADSTL improved colitis by maintaining the intestinal barrier function through its anti-inflammatory and anti-apoptotic actions.

DOI： 10.1007/s10620-020-06359-3

Diagnostic yield of colon capsule endoscopy for Crohn's disease lesions in the whole gastrointestinal tract Reviewed

Yamada, K; Nakamura, M; Yamamura, T; Maeda, K; Sawada, T; Mizutani, Y; Ishikawa, E; Ishikawa, T; Kakushima, N; Furukawa, K; Ohno, E; Kawashima, H; Honda, T; Ishigami, M; Fujishiro, M

BMC GASTROENTEROLOGY Vol. 21 ( 1 ) page： 75 2021.2

Language：English Publisher：BMC Gastroenterology

Background: Crohn’s disease (CD) can involve the upper gastrointestinal (GI) tract as well as the small and large bowel. PillCam colon capsule endoscopy (PCCE-2) enables observation of the whole GI tract, but its diagnostic yield for CD lesions in the whole GI tract remains unknown. Aim: To elucidate the diagnostic yield of PCCE-2 in patients with CD. Methods: Patients with CD who underwent PCCE-2 and double-balloon endoscopy (DBE) using oral and anal approaches were evaluated for CD lesions in the whole GI tract. We divided the small bowel into three segments (jejunum, ileum, and terminal ileum), and the large bowel into four segments (right colon, transverse colon, left colon, rectum). Detection of ulcer scars, erosion, ulcers, bamboo joint-like appearance, and notch-like appearance was assessed in each segment. The diagnostic yield of PCCE-2 was analyzed based on the DBE results as the gold standard. Results: Of the total 124 segments, the sensitivities of PCCE-2 for ulcer scars, erosion, and ulcers were 83.3%, 93.8%, and 88.5%, respectively, and the specificities were 76.0%, 78.3%, and 81.6%, respectively. For the 60 small bowel segments, the sensitivities were 84.2%, 95.5%, and 90.0%, respectively, and the specificities were 63.4%, 86.8%, and 87.5%, respectively. For the 64 large bowel segments, the sensitivities were 80.0%, 90.0%, and 83.3%, respectively, and the specificities were 84.7%, 72.2%, and 77.6%, respectively. Conclusion: PCCE-2 provides a high diagnostic yield for lesions in the whole GI tract of patients with CD. Thus, we recommend its use as a pan-enteric tool in clinical settings.

DOI： 10.1186/s12876-021-01657-0

Ustekinumab is effective against small bowel lesions in Crohn's disease: two case reports

Murate, K; Nakamura, M; Yamamura, T; Maeda, K; Sawada, T; Mizutani, Y; Ishikawa, E; Kakushima, N; Furukawa, K; Ohno, E; Honda, T; Kawashima, H; Ishigami, M; Fujishiro, M

CLINICAL JOURNAL OF GASTROENTEROLOGY Vol. 14 ( 1 ) page： 129 - 135 2021.2

Language：English Publisher：Clinical Journal of Gastroenterology

We encountered two patients with Crohn’s disease (CD) for whom induction of ustekinumab was effective for the management of small intestinal lesions with stenosis. The first symptomatic CD case was a 40-year-old female with longitudinal ulcers in the small bowel found at double-balloon endoscopy. She was in a biologic-naïve condition. Her symptoms improved immediately after ustekinumab induction. We confirmed the condition of intestinal mucosa by double-balloon endoscopy. Deep ulcers remained open at 24 weeks and were scarred at 72 weeks. The second case was a 50-year-old male who failed to respond to treatment with anti-TNFα agents. The lumen was narrow caused by circumferential ulcer, and an endoscope could not pass the site before induction. The circumferential ulcer had been healed by ustekinumab induction, and an endoscope passed through at 72 weeks. These two cases support the therapeutic efficacy of ustekinumab in alleviating small bowel lesions in CD patients.

DOI： 10.1007/s12328-020-01242-0

Gastrointestinal tract metastasis of lung cancer: The PD-L1 expression and correlated clinicopathological variables

Ishikawa, E; Nakaguro, M; Nakamura, M; Yamamura, T; Sawada, T; Mizutani, Y; Maeda, K; Furukawa, K; Shimoyama, Y; Kawashima, H; Fujishiro, M

PATHOLOGY INTERNATIONAL Vol. 71 ( 1 ) page： 33 - 41 2021.1

Language：English Publisher：Pathology International

The gastrointestinal tract is a rare site for metastatic lung cancer. Programmed cell death-ligand 1 (PD-L1) expression in lung cancer is a biomarker for the response to anti-PD-1/PD-L1 therapy. We investigated clinicopathological features and PD-L1 expression in 25 gastrointestinal metastatic tumors from the lung and primary adenocarcinoma of the small bowel. The small bowel was the most common site (16/25; 64%) of gastrointestinal tract lung cancer metastasis. A total of 19 (76%) of the gastrointestinal metastasis showed PD-L1 expression in ≥5% of tumor cells, with 14 (56%) showing high expression levels (≥50%). In contrast, 21 (84%) expressed PD-L1 in ≥5% immune cells, including 4 (16%) showing a high expression levels (≥50%). The PD-L1 expression on tumor cells and immune cells in primary lung cancer and corresponding gastrointestinal metastasis was concordant in 13 (68%) and 11 (58%) of the 19 paired cases, respectively. Small-bowel metastasis of lung cancer was characterized by a higher incidence of perforation (31% vs. 0%), ulcerated mass (83% vs. 60%), and neoplastic PD-L1 expression (75% vs. 0%) compared to primary small-bowel adenocarcinoma. Gastrointestinal metastasis from lung cancer might be a potential target for immune checkpoint inhibitor therapy, given its high expression of PD-L1.

DOI： 10.1111/pin.13048

The microbiome can predict mucosal healing in small intestine in patients with Crohn's disease

Hattori, S; Nakamura, M; Yamamura, T; Maeda, K; Sawada, T; Mizutani, Y; Yamamoto, K; Ishikawa, T; Furukawa, K; Ohno, E; Honda, T; Kawashima, H; Ishigami, M; Hirooka, Y; Fujishiro, M

JOURNAL OF GASTROENTEROLOGY Vol. 55 ( 12 ) page： 1138 - 1149 2020.12

Language：English Publisher：Journal of Gastroenterology

Background: Mucosal healing is the main treatment goal for Crohn’s disease. In this situation, some patients have difficulty with endoscopic evaluation of the entire small intestine. Crohn’s disease is closely associated with the gut microbiota, but the relationship between the microbiome and disease activity in the small intestine remains unclear. We examined the association between the microbiome and endoscopic findings in the small intestine and determined whether the microbiome can predict mucosal healing. Methods: The patients with Crohn’s disease who were scheduled for capsule or balloon-assisted endoscopy were included in this prospective study. Patients whose entire small intestine was evaluated were divided into two groups based on ulcerative findings. The microbiomes in the fecal samples were analyzed using 16S rRNA sequencing. Results: The 38 enrolled patients were divided into the ulcer group (24) and mucosal healing group (14). The ulcer group exhibited lower α diversity. Six genera, namely Faecalibacterium (P = 0.008), Lachnospira (P = 0.009), Paraprevotella (P = 0.01), Dialister (P = 0.012), Streptococcus (P = 0.025), and Clostridium (P = 0.028) were enriched in the mucosal healing group. A predictive score for mucosal healing was defined using these six genera. The area under the curve was 0.795 and the sensitivity and specificity for predicting mucosal healing were 0.643 and 0.917, respectively. Conclusions: Fecal microbiome is corelated with disease activity in the entire small intestine in Crohn’s disease patients. The predictive score proposed by microbiota characteristics was a potential biomarker for mucosal healing in the small intestine.

DOI： 10.1007/s00535-020-01728-1

Accuracy of carbon dioxide insufflation for endoscopic retrograde cholangiopancreatography using double-balloon endoscopy

Niwa, Y; Nakamura, M; Kawashima, H; Yamamura, T; Maeda, K; Sawada, T; Mizutani, Y; Ishikawa, E; Ishikawa, T; Kakushima, N; Furukawa, K; Ohno, E; Honda, T; Ishigami, M; Fujishiro, M

WORLD JOURNAL OF GASTROENTEROLOGY Vol. 26 ( 42 ) page： 6669 - 6678 2020.11

Language：English Publisher：World Journal of Gastroenterology

BACKGROUND Retrograde cholangiopancreatography using double-balloon endoscopic retrograde cholangiography (DBERC) is a valuable technique to treat biliary stone and jejunobiliary anastomotic stenosis in patients with altered gastrointestinal anatomy. The accurate selection of the route at the anastomosis branch is one of the most important factors in reaching the target in a timely manner. AIM To determine the accuracy of carbon dioxide insufflation enterography (CDE) at the branch for selecting the correct route during DBERC. METHODS We enrolled 52 consecutive patients scheduled for DBERC at our institution from June 2015 to November 2017. Route selection via two methods (visual observation and CDE) was performed in each patient. We determined the correct rate of route selection using CDE. RESULTS Thirty-three patients had a jejunojejunal anastomosis and 19 patients had a gastrojejunal anastomosis. The therapeutic target region was reached in 50 patients. The mean procedure times from the teeth to the target (total insertion time), from the teeth to the branch, and from the branch to the target, and the mean total examination time were 15.2, 5.0, 8.2, and 60.3 min, respectively. The rate of correct route selection using visual observation and CDE were 36/52 (69.2%) and 48/52 (92.3%), respectively (P = 0.002). The rate of correct route selection using CDE in patients with a jejunojejunal anastomosis was 29/33 (87.8%), and the rate in patients with a gastrojejunal anastomosis was 19/19 (100%). CONCLUSION CDE is helpful in selecting the route at the branch in the anastomosis for more timely access to the target in patients with altered gastrointestinal anatomy undergoing DBERC.

DOI： 10.3748/wjg.v26.i42.6669

Endoscopic Activity and Serum TNF-α Level at Baseline Are Associated With Clinical Response to Ustekinumab in Crohn's Disease Patients

Murate, K; Maeda, K; Nakamura, M; Sugiyama, D; Wada, H; Yamamura, T; Sawada, T; Mizutani, Y; Ishikawa, T; Furukawa, K; Ohno, E; Honda, T; Kawashima, H; Miyahara, R; Ishigami, M; Nishikawa, H; Fujishiro, M

INFLAMMATORY BOWEL DISEASES Vol. 26 ( 11 ) page： 1669 - 1681 2020.11

Language：English Publisher：Inflammatory Bowel Diseases

Background and Aims: The therapeutic efficacy and safety of ustekinumab for Crohn's disease (CD) have been reported from randomized controlled trials and real-world data. However, there are few studies describing the identification of patients most suitable for ustekinumab therapy. The aim of this study was to prospectively evaluate the patients receiving ustekinumab and identify predictors of the treatment efficacy. Methods: Patients with moderate to severe active CD scheduled to receive ustekinumab were enrolled. The responders and nonresponders were compared at weeks 0, 8, 24, and 48 by evaluating patient demographics, simple endoscopic scores (SES-CD), ustekinumab and cytokine concentrations, and cellular fractions. Results: The clinical response and clinical remission rates in the 22 enrolled patients were 59.1% and 31. 8% at week 8, 68.2% and 45.5% at week 24, and 54.4% and 40.9% at week 48, respectively. There were no significant differences in patients' demographic and disease characteristics at baseline between responders and nonresponders. A combination of low SES-CD and high serum TNF-α concentration at baseline showed a good correlation with the clinical response. Serum TNF-α concentration was decreased because of the therapy. The ratio of CD4+TNF-α cells at baseline was significantly higher in responders than in nonresponders; however, the ratios of CD45+CD11b+TNF-α and CD45+CD11c+TNF-α cells were not different. The ratio of CD4+ TNF-α cells decreased with the treatment in the responders but not in the nonresponders. Conclusions: The combination of 2 factors, namely higher serum TNF-α concentration and lower SES-CD at baseline, may assist clinicians in selecting the appropriate therapy for patients with moderate to severe CD.

DOI： 10.1093/ibd/izaa086

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