Faculty Profiles - SAWADA Tsunaki

Initial experience of tofacitinib for treating refractory moderate-to-severe ulcerative colitis

Factors related to delayed adverse events of endoscopic submucosal dissection in the duodenum.

Kawamura T, Hirose T, Kakushima N, Furukawa K, Furune S, Ishikawa E, Sawada T, Maeda K, Yamamura T, Ishikawa T, Ohno E, Nakamura M, Honda T, Ishigami M, Kawashima H, Fujishiro M

Digestive diseases (Basel, Switzerland) 2022.2

Nakamura Masanao, Yamamura Takeshi, Maeda Keiko, Sawada Tsunaki, Mizutani Yasuyuki, Ishikawa Eri, Ishikawa Takuya, Kakushima Naomi, Furukawa Kazuhiro, Ohno Eizaburo, Kawashima Hiroki, Honda Takashi, Ishigami Masatoshi, Fujishiro Mitsuhiro

NAGOYA JOURNAL OF MEDICAL SCIENCE Vol. 84 ( 1 ) page： 169 - 179 2022.2

Language：Japanese Publisher：Nagoya Journal of Medical Science

Ulcerative colitis (UC) is an incurable, chronic inflammatory disease of the large bowel whose etiology and pathogenesis have not yet been comprehensively explained. Tofacitinib is a small molecule Janus kinase inhibitor that was introduced for treating refractory UC. We aimed to examine the efficacy and safety of tofacitinib for the treatment of 18 patients with UC. Continuous treatment rates were 50, 38, and 33% at 8, 24, and 52 weeks, respectively. Overall, 83.3% of these patients showed tumor necrosis factor (TNF) antibody failure status. When the effective status was defined as a Lichtiger index (LI) that decreased by 3 points or more or was less than 4 points and remission status was defined as an LI less than 4 points, the effective and remission rates (%) at 2, 8, and 16 weeks were 55.5 (10/18) and 22.2 (4/18), 38.8 (7/18) and 33.3 (6/18), and 38.8 (7/18) and 38.8 (7/18), respectively. Background characteristics of 2-week responders and non-responders were compared. C-reactive protein level in responders was significantly lower than that in non-responders, and the hemoglobin level in responders was significantly higher than that in non-responders. This study provides preliminary results of the effectiveness of tofacitinib even for TNF antibody and tacrolimus failure patients.

DOI： 10.18999/nagjms.84.1.169

Endoscopic direct clipping versus indirect clipping for colonic diverticular bleeding: A large multicenter cohort study

Kishino, T; Nagata, N; Kobayashi, K; Yamauchi, A; Yamada, A; Omori, J; Ikeya, T; Aoyama, T; Tominaga, N; Sato, Y; Ishii, N; Sawada, T; Murata, M; Takao, A; Mizukami, K; Kinjo, K; Fujimori, S; Uotani, T; Fujita, M; Sato, H; Suzuki, S; Narasaka, T; Hayasaka, J; Funabiki, T; Kinjo, Y; Mizuki, A; Kiyotoki, S; Mikami, T; Gushima, R; Fujii, H; Fuyuno, Y; Gunji, N; Toya, Y; Narimatsu, K; Manabe, N; Nagaike, K; Kinjo, T; Sumida, Y; Funakoshi, S; Kawagishi, K; Matsuhashi, T; Komaki, Y; Miki, K; Watanabe, K; Kaise, M

UNITED EUROPEAN GASTROENTEROLOGY JOURNAL Vol. 10 ( 1 ) page： 93 - 103 2022.2

Language：English Publisher：United European Gastroenterology Journal

Background: Direct and indirect clipping treatments are used worldwide to treat colonic diverticular bleeding (CDB), but their effectiveness has not been examined in multicenter studies with more than 100 cases. Objective: We sought to determine the short- and long-term effectiveness of direct versus indirect clipping for CDB in a nationwide cohort. Methods: We studied 1041 patients with CDB who underwent direct clipping (n = 360) or indirect clipping (n = 681) at 49 hospitals across Japan (CODE BLUE-J Study). Results: Multivariate analysis adjusted for age, sex, and important confounding factors revealed that, compared with indirect clipping, direct clipping was independently associated with reduced risk of early rebleeding (<30 days; adjusted odds ratio [AOR] 0.592, p = 0.002), late rebleeding (<1 year; AOR 0.707, p = 0.018), and blood transfusion requirement (AOR 0.741, p = 0.047). No significant difference in initial hemostasis rates was observed between the two groups. Propensity-score matching to balance baseline characteristics also showed significant reductions in the early and late rebleeding rates with direct clipping. In subgroup analysis, direct clipping was associated with significantly lower rates of early and late rebleeding and blood transfusion need in cases of stigmata of recent hemorrhage with non-active bleeding on colonoscopy, right-sided diverticula, and early colonoscopy, but not with active bleeding on colonoscopy, left-sided diverticula, or elective colonoscopy. Conclusions: Our large nationwide study highlights the use of direct clipping for CDB treatment whenever possible. Differences in bleeding pattern and colonic location can also be considered when deciding which clipping options to use.

DOI： 10.1002/ueg2.12197

Isotope effect of rovibrational distribution of hydrogen molecules desorbed from amorphous carbon

Nakamura Hiroaki, Saito Seiki, Sawada Takumi, Sawada Keiji, Kawamura Gakushi, Kobayashi Masahiro, Hasuo Masahiro

JAPANESE JOURNAL OF APPLIED PHYSICS Vol. 61 ( SA ) 2022.1

Language：Japanese Publisher：Japanese Journal of Applied Physics

When the hydrogen isotope atom is injected into the amorphous carbon with the incident energies E in of 20, 50, and 80 eV, we obtain the following physical quantities of hydrogen isotope atoms/molecules emitted from the amorphous carbon using molecular dynamics and heat conduction hybrid simulation. The physical quantities are the time evolution of the emission rate, the depth distribution of the original location of the hydrogen emitted from the target, the polar angular dependence, and the translational, rotational, and vibrational energy distributions. In addition, the approximate analysis yields the emission distributions at the vibrational (v) and rotational (J) levels. Using these distributions, we evaluate the rotational temperature T rot for v = 0 and small J states. From the above, it is found that molecules with higher rotational levels J tend to be emitted as E in increases or as the mass of hydrogen isotope increases. Moreover, the isotope effect appears in the mass dependence of T rot.

DOI： 10.35848/1347-4065/ac2435

Evaluation of ulcerative colitis activity using transabdominal ultrasound shear wave elastography

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

QUANTITATIVE IMAGING IN MEDICINE AND SURGERY Vol. 12 ( 1 ) page： 618 - 626 2022.1

Language：English Publisher：Quantitative Imaging in Medicine and Surgery

Background: Transabdominal ultrasound (US) has been reported to be effective in the evaluation of ulcerative colitis (UC). US can measure shear wave elastography (SWE) and shear wave dispersion (SWD), which may be correlated with inflammation and necrosis. We aimed to investigate the relationship between UC activity and SWE and SWD. Methods: Patients with UC who underwent US within 2 days before or after a colonoscopy between April 2019 and March 2020 were included. SWE and SWD were measured in the sigmoid colon; the correlations of SWE and SWD with the Lichtiger index and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) were investigated. We also compared SWE and SWD between patients with mucosal healing and those in the active phase according to the UCEIS. Results: Twenty-six UC patients were enrolled. The median Lichtiger index, UCEIS, SWE values, and SWD values were 8 [interquartile range (IQR), 5.3–10.8], 4 (IQR, 3.3–5), 1.69 (IQR, 1.49–2.16) m/s, and 11.9 (IQR, 10.9–13.3) (m/s)/kHz, respectively. The Lichtiger index and UCEIS were negatively correlated with the SWE values (rs=−0.404 and rs=−0.506) but not with the SWD values (rs=0.004 and rs=0.002). The SWE values differed significantly between the mucosal healing and active phase groups [2.40 (IQR, 2.18–3.38) vs. 1.62 (IQR, 1.44–1.95) m/s, P=0.007], whereas the SWD values did not [13.1 (IQR, 7.05–21.6) vs. 11.9 (IQR, 11.1–13.2) (m/s)/kHz, P=0.918]. Conclusions: SWE may be useful for the evaluation of UC activity and could be a noninvasive method of assessing disease severity.

DOI： 10.21037/qims-21-403

Comparison of Endoscopic Ultrasonography and Conventional Endoscopy for Prediction of Tumor Depth in Superficial Nonampullary Duodenal Epithelial Tumors

Matsuda, N; Hirose, T; Kakushima, N; Furukawa, K; Furune, S; Ishikawa, E; Sawada, T; Maeda, K; Yamamura, T; Ishikawa, T; Ohno, E; Nakamura, M; Honda, T; Ishigami, M; Kawashima, H; Fujishiro, M

DIGESTION Vol. 103 ( 4 ) page： 319 - 328 2022

Language：English Publisher：Digestion

Background: The utility of endoscopic ultrasonography (EUS) in predicting tumor depth among superficial nonampullary duodenal epithelial tumors (SNADETs) is unclear. The aim was to compare EUS with conventional endoscopy (CE) for the evaluation of tumor invasion of SNADETs. Methods: A retrospective analysis was performed on consecutive 174 lesions/169 patients with duodenal dysplasia or adenocarcinoma with invasion up to submucosa who underwent both CE and EUS before endoscopic (n = 133) or surgical (n = 41) treatment. Endoscopic staging by CE was performed based on the characteristic endoscopic criteria of submucosal invasion (irregular surface, submucosal tumor [SMT]-like marginal elevation, and fusion of converging folds). The diagnostic performance of each test was compared with the final histology. Results: The sensitivity and accuracy of estimating the depth were higher for CE compared to that of EUS (99.4% vs. 89.4%, p < 0.01 and 97.7% vs. 87.9%, p < 0.01, respectively). Univariate analysis of endoscopic factors revealed that tumor diameter, red color, SMT-like appearance, and hypoechogenicity were factors related to advanced histology. Multivariate analysis revealed that the presence of SMT-like appearance based on CE was an independent factor to predict submucosal invasion (p = 0.025). Gross morphology of the combined type was associated to incorrect diagnosis of EUS (p = 0.007). Among 3 cases in which EUS overestimated the tumor depth, carcinoma extension in submucosal Brunner's gland or nontumorous submucosal cystic dilation was observed. Conclusion: EUS may not be necessary, and CE may be sufficient for determining the optimal therapeutic strategy for SNADETs.

DOI： 10.1159/000524841

小腸Dieulafoy病変（矢野-山本分類Type 2a）の診断と治療についての臨床的検討

中村正直, 山村健史, 前田啓子, 澤田つな騎, 石川恵里, 川嶋啓揮

日本小腸学会学術集会プログラム・抄録集 Vol. 6 ( 0 ) page： 65 - 65 2022

Language：Japanese Publisher：日本小腸学会

【背景】小腸Dieulafoy病変は、内視鏡観察時に自然止血されている可能性があるため確定診断と治療が遅れる傾向を有する。一方では、Dieulafoy病変の臨床的特徴を把握しておくことによって診断のタイミングや治療戦略を事前に検討できるかもしれない。本研究の目的は、当院で経験された同病変の臨床的特徴を後方視的に調査し、その最適な診断と治療につき検討することであった。【対象・方法】対象は当院において2003年6月から2022年7月の間に小腸出血が疑われダブルバルーン内視鏡（以下DBE）を施行し、Dieulafoy病変と診断、内視鏡治療を受けた36例であった。本研究におけるDieulafoy病変の定義は、粘膜面の変化は露出血管部のみとし、付着する血栓を認める場合と露出血管からの噴出性かそれに準じる活動性出血を認める場合とした。臨床的背景、治療方法などを検討した。【結果】男性/女性は19/17例、平均年齢は71±10歳であった。33例でなんらかの基礎疾患を有していた。抗血栓薬の使用を19例で認め、ワーファリン10例、バイアスピリン7例（重複あり）の順で多かった。累計の出血エピソードは中央値で2回（1-18回）であった。最低血中ヘモグロビン値は5.9±1.7g/dl、赤血球輸血は2例以外の全例で行われていた。症状発現からDBEまでは中央値18日（2-63日）であった。DBE時の所見について、病変部位は深部十二指腸、上部空腸、中部空腸、下部空腸、中部回腸、下部回腸で各々3、18、8、2、2,6例で認められた（重複あり）。治療はクリッピング34例、APC凝固2例であった。偶発症は再出血10例（27.7％）、急性膵炎1例であった。【結語】小腸Dieulafoy病変は診断に苦慮し、治療までに時間と輸血処置などを多く要していた。本病変が疑われた際には早めの内視鏡検査が検討される。

DOI： 10.32264/shocho.6.0_65

CiNii Research

Immunoproliferative Small Intestinal Disease Diagnosed by Double-balloon Endoscopy with Biopsy Sampling

Meza Miguel Ricardo Rodriguez, Nakamura Masanao, Yamamura Takeshi, Maeda Keiko, Sawada Tsunaki, Ishikawa Eri, Kakushima Naomi, Furukawa Kazuhiro, Ohno Eizaburo, Honda Takashi, Kawashima Hiroki, Ishigami Masatoshi

INTERNAL MEDICINE Vol. 61 ( 17 ) page： 2593 - 2599 2022

Immunoproliferative Small Intestinal Disease Diagnosed by Double-balloon Endoscopy with Biopsy Sampling

Meza Miguel Ricardo Rodríguez, Nakamura Masanao, Yamamura Takeshi, Maeda Keiko, Sawada Tsunaki, Ishikawa Eri, Kakushima Naomi, Furukawa Kazuhiro, Ohno Eizaburo, Honda Takashi, Kawashima Hiroki, Ishigami Masatoshi

Internal Medicine Vol. advpub ( 0 ) 2022

Language：English Publisher：The Japanese Society of Internal Medicine

We herein report an 80-year-old man diagnosed with immunoproliferative small intestine disease (IPSID) via small bowel endoscopy with a biopsy. He developed persistent diarrhea and subsequently presented with hypoproteinemia and moderate anemia. Transanal double-balloon endoscopy showed prominent villous edema in the middle and lower ileum, while a histological examination showed high lymphocyte/plasma cell infiltration in the mucosal layer. Furthermore, an immunostaining analysis showed that CD3 and CD20 were partially positive, while CD138 was diffusely positive. Immunoglobulin A positivity was also observed. He was diagnosed with IPSID and received a nutritional agent and minocycline. After three months, the patients' symptoms improved.

DOI： 10.2169/internalmedicine.8847-21

Immunoproliferative Small Intestinal Disease Diagnosed by Double-balloon Endoscopy with Biopsy Sampling

CiNii Research

Meza M.R.R., Nakamura M., Yamamura T., Maeda K., Sawada T., Ishikawa E., Kakushima N., Furukawa K., Ohno E., Honda T., Kawashima H., Ishigami M.

Internal Medicine Vol. 61 ( 17 ) page： 2593 - 2599 2022

Publisher：Internal Medicine

We herein report an 80-year-old man diagnosed with immunoproliferative small intestine disease (IPSID) via small bowel endoscopy with a biopsy. He developed persistent diarrhea and subsequently presented with hypoproteinemia and moderate anemia. Transanal double-balloon endoscopy showed prominent villous edema in the middle and lower ileum, while a histological examination showed high lymphocyte/plasma cell infiltration in the mucosal layer. Furthermore, an immunostaining analysis showed that Cluster of differentiation (CD)3 and CD20 were partially positive, while CD138 was diffusely positive. Immunoglobulin A positivity was also observed. He was diagnosed with IPSID and received a nutritional agent and minocycline. After three months, the patients’ symptoms improved.

DOI： 10.2169/internalmedicine.8847-21

Treatment strategies for reducing early and late recurrence of colonic diverticular bleeding based on stigmata of recent hemorrhage: a large multicenter study.

Gobinet MS, Nagata N, Kobayashi K, Yamauchi A, Yamada A, Omori J, Ikeya T, Aoyama T, Tominaga N, Sato Y, Kishino T, Ishii N, Sawada T, Murata M, Takao A, Mizukami K, Kinjo K, Fujimori S, Uotani T, Fujita M, Sato H, Suzuki S, Narasaka T, Hayasaka J, Funabiki T, Kinjo Y, Mizuki A, Kiyotoki S, Mikami T, Gushima R, Fujii H, Fuyuno Y, Gunji N, Toya Y, Narimatsu K, Manabe N, Nagaike K, Kinjo T, Sumida Y, Funakoshi S, Kawagishi K, Matsuhashi T, Komaki Y, Miki K, Watanabe K, Uemura N, Itawa E, Sugimoto M, Fukuzawa M, Kawai T, Kaise M, Itoi T

Gastrointestinal endoscopy 2021.12

Language：English Publisher：Gastrointestinal Endoscopy

Background and Aims: Treatment strategies for colonic diverticular bleeding (CDB) based on stigmata of recent hemorrhage (SRH) remain unstandardized, and no large studies have evaluated their effectiveness. We sought to identify the best strategy among combinations of SRH identification and endoscopic treatment strategies. Methods: We retrospectively analyzed 5823 CDB patients who underwent colonoscopy at 49 hospitals throughout Japan (CODE-BLUE J-Study). Three strategies were compared: find SRH (definitive CDB) and treat endoscopically, find SRH (definitive CDB) and treat conservatively, and without finding SRH (presumptive CDB) treat conservatively. In conducting pairwise comparisons of outcomes in these groups, we used propensity score–matching analysis to balance baseline characteristics between the groups being compared. Results: Both early and late recurrent bleeding rates were significantly lower in patients with definitive CDB treated endoscopically than in those with presumptive CDB treated conservatively (<30 days, 19.6% vs 26.0% [P < .001]; <365 days, 33.7% vs 41.6% [P < .001], respectively). In patients with definitive CDB, the early recurrent bleeding rate was significantly lower in those treated endoscopically than in those treated conservatively (17.4% vs 26.7% [P = .038] for a single test of hypothesis; however, correction for multiple testing of data removed this significance). The late recurrent bleeding rate was also lower, but not significantly, in those treated endoscopically (32.0% vs 36.1%, P = .426). Definitive CDB treated endoscopically showed significantly lower early and late recurrent bleeding rates than when treated conservatively in cases of SRH with active bleeding, nonactive bleeding, and in the right-sided colon but not left-sided colon. Conclusions: Treating definitive CDB endoscopically was most effective in reducing recurrent bleeding over the short and long term, compared with not treating definitive CDB or presumptive CDB. Physicians should endeavor to find and treat SRH for suspected CDB.

DOI： 10.1016/j.gie.2021.12.023

特集小腸内視鏡が変えた疾患マネージメント小腸疾患に対するアプローチ

中村正直, 大宮直木, 山村健史, 前田啓子, 澤田つな騎, 石川恵里

消化器内視鏡 Vol. 33 ( 12 ) page： 1792 - 1798 2021.12

Real-world local recurrence rate after cold polypectomy in colorectal polyps less than 10 mm using propensity score matching

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

WORLD JOURNAL OF GASTROENTEROLOGY Vol. 27 ( 47 ) page： 8182 - 8193 2021.12

Language：English Publisher：World Journal of Gastroenterology

BACKGROUND Cold polypectomy (CP) is a simple and safe procedure for polyps less than 10 mm in size; however, there is concern about local recurrence following CP because of unidentified margins of excised specimens and the lack of tumor suppression effect by coagulation. Some clinical trials have evaluated local persistent recurrence; their results suggest that a higher rate of local recurrence has not been documented so far. There were few reports that observed the course over long periods of time after CP in clinical practice. AIM To evaluate the presence of local recurrence following CP and hot polypectomy (HP) using propensity score matching. METHODS We analyzed 275 patients who underwent polypectomy for non-pedunculated colorectal polyps less than 10 mm (959 Lesions) between October 2016 and 2017 and underwent follow-up endoscopy subsequently. We divided them into the CP group (706 Lesions), wherein CP was performed, and the HP group (253 Lesions), wherein HP was performed. Using propensity score matching, we extracted 215 Lesions in each group and evaluated the local recurrence and content of CP in the real clinic and adverse events using medical records. RESULTS After propensity score matching, there were no significant differences in the patients’ and their endoscopic background (age, use of antithrombotics, indications, size, morphology, location of polyps, and polypectomy device) between the groups. The mean duration between colorectal polypectomy and the next follow-up colonoscopy was 17.5 ± 7.1 (range, 6-39) mo in the CP group and 15.7 ± 6.0 (range, 6-35) mo in the HP group, which was significantly longer in the CP group (P = 0.005). The local recurrence rate was 0.93% in the CP group and 0.93% in the HP group, without a significant difference (P = 0.688). Additionally, no differences were observed in the macroscopic en bloc resection rate, histopathological complete resection rate, and pathological results between the groups. Adverse events did not occur in either group. CONCLUSION Local recurrence after CP was equivalent to that following HP in clinical practice. CP is useful and safe in the treatment of non-pedunculated polyps of less than 10 mm.

DOI： 10.3748/wjg.v27.i47.8182

Effectiveness and adverse events of endoscopic clipping versus band ligation for colonic diverticular hemorrhage: a large-scale multicenter cohort study.

特集 Cold polypectomyの課題 4.症例からみえた課題(1)小腸ポリープに対するcold polypectomy

山村健史, 中村正直, 前田啓子, 澤田つな騎, 石川恵里, 角嶋直美, 古川和宏, 川嶋啓揮

臨床消化器内科 Vol. 37 ( 1 ) page： 93 - 96 2021.12

Kobayashi K, Nagata N, Furumoto Y, Yamauchi A, Yamada A, Omori J, Ikeya T, Aoyama T, Tominaga N, Sato Y, Kishino T, Ishii N, Sawada T, Murata M, Takao A, Mizukami K, Kinjo K, Fujimori S, Uotani T, Fujita M, Sato H, Suzuki S, Narasaka T, Hayasaka J, Kaise M, CODE BLUE-J study collaborators., Funabiki T, Kinjo Y, Mizuki A, Kiyotoki S, Mikami T, Gushima R, Fujii H, Fuyuno Y, Gunji N, Toya Y, Narimatsu K, Manabe N, Nagaike K, Kinjo T, Sumida Y, Funakoshi S, Kawagishi K, Matsuhashi T, Komaki Y, Miki K, Watanabe K, Kitano N, Kato S, Sakai S, Oshina E, Mochida T, Okura Y, Matsuoka M, Nozaka T, Sato A, Yauchi M, Matsumoto T, Asano T

Endoscopy 2021.11

Language：English Publisher：Endoscopy

Background Prior studies have shown the effectiveness of both endoscopic band ligation (EBL) and clipping for colonic diverticular hemorrhage (CDH) but have been small and conducted at single centers. Therefore, we investigated which was the more effective and safe treatment in a multicenter long-term cohort study. Methods We reviewed data for 1679 patients with CDH who were treated with EBL (n=638) or clipping (n=1041) between January 2010 and December 2019at 49 hospitals across Japan (CODE BLUE-J study). Logistic regression analysis was used to compare outcomes between the two treatments. Results In multivariate analysis, EBL was independently associated with reduced risk of early rebleeding (adjusted odds ratio [OR] 0.46; P <0.001) and late rebleeding (adjusted OR 0.62; P <0.001) compared with clipping. These significantly lower rebleeding rates with EBL were evident regardless of active bleeding or early colonoscopy. No significant differences were found between the treatments in the rates of initial hemostasis or mortality. Compared with clipping, EBL independently reduced the risk of needing interventional radiology (adjusted OR 0.37; P =0.006) and prolonged length of hospital stay (adjusted OR 0.35; P <0.001), but not need for surgery. Diverticulitis developed in one patient (0.16%) following EBL and two patients (0.19%) following clipping. Perforation occurred in two patients (0.31%) following EBL and none following clipping. Conclusions Analysis of our large endoscopy dataset suggests that EBL is an effective and safe endoscopic therapy for CDH, offering the advantages of lower early and late rebleeding rates, reduced need for interventional radiology, and shorter length of hospital stay.

DOI： 10.1055/a-1705-0921

Clinical characteristics of gastrointestinal immune-related adverse events of immune checkpoint inhibitors and their association with survival Reviewed

Yamada, K; Sawada, T; Nakamura, M; Yamamura, T; Maeda, K; Ishikawa, E; Iida, T; Mizutani, Y; Kakushima, N; Ishikawa, T; Furukawa, K; Ohno, E; Honda, T; Kawashima, H; Ishigami, M; Furune, S; Hase, T; Yokota, K; Maeda, O; Hashimoto, N; Akiyama, M; Ando, Y; Fujishiro, M

WORLD JOURNAL OF GASTROENTEROLOGY Vol. 27 ( 41 ) page： 7190 - 7206 2021.11

Language：English Publisher：World Journal of Gastroenterology

BACKGROUND Despite the popularity of immune checkpoint inhibitors (ICIs) in the treatment of advanced cancer, patients often develop gastrointestinal (GI) and non-GI immune- related adverse events (irAEs). The clinical characteristics and survival outcomes of GI-irAEs have not been fully elucidated in previous reports. This necessitates the evaluation of the impact of GI-irAEs on patients receiving ICI treatment. AIM To evaluate the clinical characteristics of GI-irAEs and their impact on survival in patients treated with ICIs. METHODS In this single-center, retrospective, observational study, we reviewed the records of 661 patients who received ICIs for various cancers at Nagoya University Hospital from September 2014 to August 2020. We analyzed the clinical characteristics of patients who received ICI treatment. We also evaluated the correlation between GI-irAE development and prognosis in non-small cell lung cancer (LC) and malignant melanoma (MM). Kaplan-Meier analysis was used to compare the median overall survival (OS). Multivariate Cox proportional hazards models were used to identify prognostic factors. A P value < 0.05 was considered statistically significant. RESULTS GI-irAEs occurred in 34 of 605 patients (5.6%) treated with an anti-programmed cell death-1/programmed death-ligand 1 (anti-PD-1/PD-L1) antibody alone and in nine of 56 patients (16.1%) treated with an anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibody alone or a combination of anti-PD-1 and anti-CTLA-4 antibodies. The cumulative incidence and median daily diarrhea frequency were significantly higher in patients receiving anti-CTLA-4 antibodies (P < 0.05). In 130 patients with MM, OS was significantly prolonged in the group that continued ICI treatment despite the development of GI-irAEs compared to the group that did not experience GI-irAEs (P = 0.035). In contrast, in 209 patients with non-small cell LC, there was no significant difference in OS between the groups. The multivariate analyses showed that a performance status of 2-3 (hazard ratio: 2.406; 95% confidence interval: 1.125-5.147; P = 0.024) was an independent predictive factor for OS in patients with MM. CONCLUSION Patients receiving anti-CTLA-4 antibodies develop GI-irAEs more frequently and with higher severity than those receiving anti-PD-1/PD-L1 antibodies. Continuing ICI treatment in patients with MM with GI-irAEs have better OS.

DOI： 10.3748/wjg.v27.i41.7190

Endocytoscopy Is Useful for the Diagnosis of Superficial Nonampullary Duodenal Epithelial Tumors

Hirose, T; Kakushima, N; Furukawa, K; Furune, S; Ishikawa, E; Sawada, T; Maeda, K; Yamamura, T; Ishikawa, T; Ohno, E; Nakamura, M; Nishida, K; Yokoi, T; Kawashima, H; Fujishiro, M

DIGESTION Vol. 102 ( 6 ) page： 895 - 902 2021.11

Language：English Publisher：Digestion

Introduction: Endoscopic criteria for the diagnosis of superficial nonampullary duodenal epithelial tumors (SNADETs) are lacking. The aim of this study was to explore the usefulness of endocytoscopy (ECS) in the duodenum. Methods: A total of 77 ECS images stained by methylene blue and 58 images with double staining of methylene blue and crystal violet were obtained from 20 patients. Images were classified into 3 grades based on nuclear and villi atypia: EC A, B, and C. Diagnostic performance of ECS classification to predict histology and interobserver agreement was evaluated. The performance was compared between staining methods and ×520 or ×936 zoom. Results: With methylene blue staining, high rates of accuracy, sensitivity, specificity, and positive predictive value (PPV) over 90% were achieved for tumor and nontumor diagnosis as assessed by EC A versus EC B. High rates of accuracy, sensitivity, PPV, and negative predictive value over 90% were achieved for the differentiation between the diagnosis of the Vienna category 3 and 4/5 as assessed by EC B versus C. The accuracy rate of interpreting ECS images with ×936 zoom among 10 endoscopists was 82%, and the interobserver agreement rate was 0.803 (Kendall's coefficient of concordance). In the ×936 zoom group, methylene blue staining was significantly associated with higher accuracy rate (odds ratio 1.76 [1.06-2.92], p value 0.0297). No benefit was observed by double staining. Conclusions: ECS diagnosis with methylene blue provides a high accuracy rate and good interobserver agreement to predict histology of SNADETs.

DOI： 10.1159/000516512

Identifying Bleeding Etiologies by Endoscopy Affected Outcomes in 10,342 Cases With Hematochezia: CODE BLUE-J Study

Nagata, N; Kobayashi, K; Yamauchi, A; Yamada, A; Omori, J; Ikeya, T; Aoyama, T; Tominaga, N; Sato, Y; Kishino, T; Ishii, N; Sawada, T; Murata, M; Takao, A; Mizukami, K; Kinjo, K; Fujimori, S; Uotani, T; Fujita, M; Sato, H; Suzuki, S; Narasaka, T; Hayasaka, J; Funabiki, T; Kinjo, Y; Mizuki, A; Kiyotoki, S; Mikami, T; Gushima, R; Fujii, H; Fuyuno, Y; Gunji, N; Toya, Y; Narimatsu, K; Manabe, N; Nagaike, K; Kinjo, T; Sumida, Y; Funakoshi, S; Kawagishi, K; Matsuhashi, T; Komaki, Y; Miki, K; Watanabe, K; Fukuzawa, M; Itoi, T; Uemura, N; Kawai, T; Kaise, M

AMERICAN JOURNAL OF GASTROENTEROLOGY Vol. 116 ( 11 ) page： 2222 - 2234 2021.11

Language：English Publisher：American Journal of Gastroenterology

INTRODUCTION:The bleeding source of hematochezia is unknown without performing colonoscopy. We sought to identify whether colonoscopy is a risk-stratifying tool to identify etiology and predict outcomes and whether presenting symptoms can differentiate the etiologies in patients with hematochezia.METHODS:This multicenter retrospective cohort study conducted at 49 hospitals across Japan analyzed 10,342 patients admitted for outpatient-onset acute hematochezia.RESULTS:Patients were mostly elderly population, and 29.5% had hemodynamic instability. Computed tomography was performed in 69.1% and colonoscopy in 87.7%. Diagnostic yield of colonoscopy reached 94.9%, most frequently diverticular bleeding. Thirty-day rebleeding rates were significantly higher with diverticulosis and small bowel bleeding than with other etiologies. In-hospital mortality was significantly higher with angioectasia, malignancy, rectal ulcer, and upper gastrointestinal bleeding. Colonoscopic treatment rates were significantly higher with diverticulosis, radiation colitis, angioectasia, rectal ulcer, and postendoscopy bleeding. More interventional radiology procedures were needed for diverticulosis and small bowel bleeding. Etiologies with favorable outcomes and low procedure rates were ischemic colitis and infectious colitis. Higher rates of painless hematochezia at presentation were significantly associated with multiple diseases, such as rectal ulcer, hemorrhoids, angioectasia, radiation colitis, and diverticulosis. The same was true in cases of hematochezia with diarrhea, fever, and hemodynamic instability.DISCUSSION:This nationwide data set of acute hematochezia highlights the importance of colonoscopy in accurately detecting bleeding etiologies that stratify patients at high or low risk of adverse outcomes and those who will likely require more procedures. Predicting different bleeding etiologies based on initial presentation would be challenging.

DOI： 10.14309/ajg.0000000000001413

Outcomes in high and low volume hospitals in patients with acute hematochezia in a cohort study

Ishii, N; Nagata, N; Kobayashi, K; Yamauchi, A; Yamada, A; Omori, J; Ikeya, T; Aoyama, T; Tominaga, N; Sato, Y; Kishino, T; Sawada, T; Murata, M; Takao, A; Mizukami, K; Kinjo, K; Fujimori, S; Uotani, T; Fujita, M; Sato, H; Suzuki, S; Narasaka, T; Hayasaka, J; Funabiki, T; Kinjo, Y; Mizuki, A; Kiyotoki, S; Mikami, T; Gushima, R; Fujii, H; Fuyuno, Y; Gunji, N; Toya, Y; Narimatsu, K; Manabe, N; Nagaike, K; Kinjo, T; Sumida, Y; Funakoshi, S; Kawagishi, K; Matsuhashi, T; Komaki, Y; Miki, K; Watanabe, K; Omata, F; Shiratori, Y; Imamura, N; Yano, T; Kaise, M

SCIENTIFIC REPORTS Vol. 11 ( 1 ) page： 20373 2021.10

Language：English Publisher：Scientific Reports

Outcomes of acute lower gastrointestinal bleeding have not been compared according to hospital capacity. We aimed to perform a propensity score-matched cohort study with path and mediation analyses for acute hematochezia patients. Hospitals were divided into high- versus low-volume hospitals for emergency medical services. Rebleeding and death within 30 days were compared. Computed tomography, early colonoscopy (colonoscopy performed within 24 h), and endoscopic therapies were included as mediators. A total of 2644 matched pairs were yielded. The rebleeding rate within 30 days was not significant between high- and low-volume hospitals (16% vs. 17%, P = 0.44). The mortality rate within 30 days was significantly higher in the high-volume cohort than in the low-volume cohort (1.7% vs. 0.8%, P = 0.003). Treatment at high-volume hospitals was not a significant factor for rebleeding (odds ratio [OR] = 0.91; 95% confidence interval [CI], 0.79–1.06; P = 0.23), but was significant for death within 30 days (OR = 2.03; 95% CI, 1.17–3.52; P = 0.012) on multivariate logistic regression after adjusting for patients’ characteristics. Mediation effects were not observed, except for rebleeding within 30 days in high-volume hospitals through early colonoscopy. However, the direct effect of high-volume hospitals on rebleeding was not significant. High-volume hospitals did not improve the outcomes of acute hematochezia patients.

DOI： 10.1038/s41598-021-99832-6