| 1. |
Masatoshi Murakami, Nao Fujimori, Yu Takamatsu, Tetsuhide Ito, Kazuhide Matsumoto, Shotaro Kakehashi, Akihisa Ohno, Katsuhito Teramatsu, Keijiro Ueda, Kousei Ishigami, Yoshihiro Ogawa, Efficacy and safety of streptozocin-based chemotherapy for gastroenteropancreatic neuroendocrine tumors in Japanese clinical practice., Japanese journal of clinical oncology, 10.1093/jjco/hyae026, 2024.02, BACKGROUND: Streptozocin has been used to treat neuroendocrine tumors in Europe and the USA; however, its actual status in Japan has not been fully clarified owing to the rarity of this disease and the relatively recent approval of streptozocin in Japan. METHODS: We retrospectively analyzed 53 patients with gastroenteropancreatic neuroendocrine tumors who were treated with streptozocin-based chemotherapy at two Japanese hospitals between January 2004 and June 2023. RESULTS: The overall response and disease control rates were 27.7 and 74.5%, respectively, and the median progression-free survival and overall survival were 7.1 and 20.3 months, respectively. Performance status ≥1 showed a significant negative correlation with progression-free survival, and performance status ≥1 and liver tumor burden ≥25% showed a significant negative correlation with overall survival. No significant differences were observed in the treatment response between pancreatic and gastrointestinal neuroendocrine tumors. No treatment-related serious adverse events were observed; however, 87.7% of patients expressed a decrease in the estimated glomerular filtration rate, which negatively correlated with the duration of streptozocin treatment (r = 0.43, P = 0.0020). In the streptozocin re-administration group (n = 5), no differences were found in efficacy between the initial and second streptozocin treatments. CONCLUSIONS: Although streptozocin is a safe, streptozocin-induced renal dysfunction is a dilemma in streptozocin responders. Streptozocin may benefit patients with gastroenteropancreatic neuroendocrine tumors, especially those with a good performance status; however, in some cases, planned streptozocin withdrawal or switching to other drugs should be considered.. |
| 2. |
Tetsuya Takikawa, Kazuhiro Kikuta, Takanori Sano, Tsukasa Ikeura, Nao Fujimori, Takeji Umemura, Itaru Naitoh, Hiroshi Nakase, Hiroyuki Isayama, Atsushi Kanno, Ken Kamata, Yuzo Kodama, Dai Inoue, Akio Ido, Toshiharu Ueki, Hiroshi Seno, Hiroaki Yasuda, Eisuke Iwasaki, Takayoshi Nishino, Kensuke Kubota, Toshihiko Arizumi, Atsushi Tanaka, Kazushige Uchida, Ryotaro Matsumoto, Shin Hamada, Seiji Nakamura, Kazuichi Okazaki, Yoshifumi Takeyama, Atsushi Masamune, Maintenance steroid therapy is associated with decreased risk of malignancy and better prognosis of patients with autoimmune pancreatitis: A multicenter cohort study in Japan., Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.], 10.1016/j.pan.2024.01.008, 2024.01, BACKGROUND/OBJECTIVES: The association between autoimmune pancreatitis (AIP) and pancreatic cancer (PC) remains controversial. This study aimed to clarify the long-term prognosis and risk of malignancies in AIP patients in Japan. METHODS: We conducted a multicenter retrospective cohort study on 1364 patients with type 1 AIP from 20 institutions in Japan. We calculated the standardized incidence ratio (SIR) for malignancies compared to that in the general population. We analyzed factors associated with overall survival, pancreatic exocrine insufficiency, diabetes mellitus, and osteoporosis. RESULTS: The SIR for all malignancies was increased (1.21 [95 % confidence interval: 1.05-1.41]) in patients with AIP. Among all malignancies, the SIR was highest for PC (3.22 [1.99-5.13]) and increased within 2 years and after 5 years of AIP diagnosis. Steroid use for ≥6 months and ≥50 months increased the risk of subsequent development of diabetes mellitus and osteoporosis, respectively. Age ≥65 years at AIP diagnosis (hazard ratio [HR] = 3.73) and the development of malignancies (HR = 2.63), including PC (HR = 7.81), were associated with a poor prognosis, whereas maintenance steroid therapy was associated with a better prognosis (HR = 0.35) in the multivariate analysis. Maintenance steroid therapy was associated with a better prognosis even after propensity score matching for age and sex. CONCLUSIONS: Patients with AIP are at increased risk of developing malignancy, especially PC. PC is a critical prognostic factor for patients with AIP. Although maintenance steroid therapy negatively impacts diabetes mellitus and osteoporosis, it is associated with decreased cancer risk and improved overall survival.. |
| 3. |
Masatoshi Murakami, Keisuke Hirahata, Nao Fujimori, Takeo Yamamoto, Yoshinao Oda, Shingo Kozono, Keijiro Ueda, Testuhide Ito, Masafumi Nakamura, Yoshihiro Ogawa, Two cases of pancreatic neuroendocrine tumors with ectopic ACTH syndrome during their disease course., Clinical journal of gastroenterology, 10.1007/s12328-023-01908-5, 2024.01, Pancreatic neuroendocrine tumors (PanNETs) are rare malignant tumors that occur in the pancreas. They are divided into functioning and non-functioning tumors based on the presence or absence of their specific hormonal hyper-expression symptoms. Adrenocorticotropic hormone (ACTH)-producing PanNETs are rare, functional tumors, and their clinical characteristics and outcomes have not been well reported.Here, we report the cases of two patients with PanNETs who presented with ectopic ACTH syndrome (EAS) during the course of their disease. Case 1 involved a non-functioning PanNET at the time of surgery. During treatment for recurrent liver metastases, the patient presented with EAS and tumor-associated hypercalcemia, probably due to ACTH and parathyroid hormone-related peptide (PTHrP) production from the liver tumor. Case 2 was a gastrinoma, and similar to Case 1, this patient presented with EAS during the treatment of recurrent liver metastases.It is not uncommon for patients with PanNETs to have multiple hormones and develop secondary hormone secretion during their disease course, although tumor phenotypes differ between primary and metastatic sites. In patients with functioning PanNETs, symptom control with anti-hormonal therapy is essential, in addition to anti-tumor therapy, especially for EAS, which is an endocrine emergency disease that requires prompt diagnosis and treatment.. |
| 4. |
Yosuke Minoda, Nao Fujimori, Mitsuru Esaki, Shuzaburo Nagatomo, Yasuhiro Komori, Keijiro Ueda, Eikichi Ihara, Rare complications related to lumen-apposing metal stent placement, successfully treated by endoscopic hand-suturing device., Endoscopy, 10.1055/a-2072-5740, 55, S 01, E692-E693, 2023.12. |
| 5. |
Akihisa Ohno, Nao Fujimori, Kohei Nakata, Double traction technique for endoscopic ultrasound-guided drainage of small postoperative pancreatic fistula., Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society, 10.1111/den.14642, 2023.08. |
| 6. |
Masatoshi Murakami, Nao Fujimori, Kohei Nakata, Masafumi Nakamura, Shinichi Hashimoto, Hiroshi Kurahara, Kazuyoshi Nishihara, Toshiya Abe, Shunpei Hashigo, Naotaka Kugiyama, Eisuke Ozawa, Kazuhisa Okamoto, Yusuke Ishida, Keiichi Okano, Ryo Takaki, Yutaka Shimamatsu, Tetsuhide Ito, Masami Miki, Noriko Oza, Daisuke Yamaguchi, Hirofumi Yamamoto, Hironobu Takedomi, Ken Kawabe, Tetsuro Akashi, Koichi Miyahara, Jiro Ohuchida, Yasuhiro Ogura, Yohei Nakashima, Toshiharu Ueki, Kousei Ishigami, Hironobu Umakoshi, Keijiro Ueda, Takamasa Oono, Yoshihiro Ogawa, Machine learning-based model for prediction and feature analysis of recurrence in pancreatic neuroendocrine tumors G1/G2., Journal of gastroenterology, 10.1007/s00535-023-01987-8, 58, 6, 586-597, 2023.06, BACKGROUND: Pancreatic neuroendocrine neoplasms (PanNENs) are a heterogeneous group of tumors. Although the prognosis of resected PanNENs is generally considered to be good, a relatively high recurrence rate has been reported. Given the scarcity of large-scale reports about PanNEN recurrence due to their rarity, we aimed to identify the predictors for recurrence in patients with resected PanNENs to improve prognosis. METHODS: We established a multicenter database of 573 patients with PanNENs, who underwent resection between January 1987 and July 2020 at 22 Japanese centers, mainly in the Kyushu region. We evaluated the clinical characteristics of 371 patients with localized non-functioning pancreatic neuroendocrine tumors (G1/G2). We also constructed a machine learning-based prediction model to analyze the important features to determine recurrence. RESULTS: Fifty-two patients experienced recurrence (14.0%) during the follow-up period, with the median time of recurrence being 33.7 months. The random survival forest (RSF) model showed better predictive performance than the Cox proportional hazards regression model in terms of the Harrell's C-index (0.841 vs. 0.820). The Ki-67 index, residual tumor, WHO grade, tumor size, and lymph node metastasis were the top five predictors in the RSF model; tumor size above 20 mm was the watershed with increased recurrence probability, whereas the 5-year disease-free survival rate decreased linearly as the Ki-67 index increased. CONCLUSIONS: Our study revealed the characteristics of resected PanNENs in real-world clinical practice. Machine learning techniques can be powerful analytical tools that provide new insights into the relationship between the Ki-67 index or tumor size and recurrence.. |
| 7. |
Nobumasa Mizuno, Tatsuya Ioka, Gakuto Ogawa, Satoaki Nakamura, Nobuyoshi Hiraoka, Yoshinori Ito, Hiroshi Katayama, Ryoji Takada, Satoshi Kobayashi, Masafumi Ikeda, Haruo Miwa, Naohiro Okano, Hidekazu Kuramochi, Mitsugu Sekimoto, Takuji Okusaka, Masato Ozaka, Akiko Todaka, Kunihito Gotoh, Kazutoshi Tobimatsu, Hironori Yamaguchi, Toshio Nakagohri, Shinya Kajiura, Kentaro Sudo, Keiya Okamura, Satoshi Shimizu, Hirofumi Shirakawa, Naoya Kato, Keiji Sano, Tomohisa Iwai, Nao Fujimori, Makoto Ueno, Hiroshi Ishii, Junji Furuse, Effect of systemic inflammatory response on induction chemotherapy followed by chemoradiotherapy for locally advanced pancreatic cancer: an exploratory subgroup analysis on systemic inflammatory response in JCOG1106, Japanese Journal of Clinical Oncology, 10.1093/jjco/hyad044, 53, 8, 704-713, 2023.05, Abstract
Objective
JCOG1106, a randomized phase II trial conducted to compare chemoradiotherapy (S-1 concurrent radiotherapy) with (Arm B) or without (Arm A) induction chemotherapy using gemcitabine in patients with locally advanced pancreatic cancer, showed a more favorable long-term survival in Arm A. This study was aimed at exploring whether some subgroups classified by the systemic inflammatory response might derive greater benefit from either treatment.
Methods
All subjects eligible for JCOG1106 were included in this analysis (n = 51/49 in Arm A/B). This exploratory subgroup analysis was performed by Cox regression analysis to investigate the impact of the systemic inflammatory response, as assessed based on the serum C-reactive protein, serum albumin (albumin), Glasgow Prognostic Score and derived neutrophil–lymphocyte ratio, at the baseline on overall survival. P values
Results
Glasgow prognostic score showed significant treatment interactions for overall survival. Hazard ratios of Arm B to Arm A were 1.35 (95% confidence interval, 0.82–2.23) in the Glasgow Prognostic Score 0 (C-reactive protein ≤10 mg/L and albumin ≥35 g/L) (n = 44/34 in Arm A/B) and 0.59 (95% confidence interval, 0.24–1.50) in the Glasgow Prognostic Score 1/2 (C-reactive protein >10 mg/L and/or albumin
Conclusions
Survival benefits of induction chemotherapy in chemoradiotherapy for locally advanced pancreatic cancer were observed in patients with elevated Glasgow Prognostic Score, high C-reactive protein and low albumin. These results suggest that systemic inflammatory response might be considered to apply induction chemotherapy preceding chemoradiotherapy.. |
| 8. |
Nobuhiro Fujita, Yasuhiro Ushijima, Masahiro Itoyama, Daisuke Okamoto, Keisuke Ishimatsu, Noriaki Wada, Seiichiro Takao, Ryo Murayama, Nao Fujimori, Kohei Nakata, Masafumi Nakamura, Takeo Yamamoto, Yoshinao Oda, Kousei Ishigami, Extracellular volume fraction determined by dual-layer spectral detector CT: Possible role in predicting the efficacy of preoperative neoadjuvant chemotherapy in pancreatic ductal adenocarcinoma., European journal of radiology, 10.1016/j.ejrad.2023.110756, 162, 110756-110756, 2023.05, PURPOSE: To clarify the relationship between extracellular volume (ECV) measured by dual-energy CT (DECT) and efficacy of preoperative neoadjuvant chemotherapy (NAC) in patients with pancreatic ductal adenocarcinoma (PDAC), as compared with single-energy CT (SECT). METHODS: We enrolled 67 patients with PDAC who underwent dynamic contrast-enhanced CT with a dual-energy CT system prior to NAC. Attenuation values were measured on unenhanced and the equilibrium-phase 120-kVp equivalent CT images for PDAC and the aorta. ΔHU-tumor, ΔHU-tumor/ΔHU-aorta, and SECT-ECV were calculated. Iodine densities of the tumor and aorta were measured in the equilibrium phase, and DECT-ECV of the tumor was calculated. Response to NAC was evaluated and the correlation between imaging parameters and response to NAC was statistically assessed. RESULTS: Tumor DECT-ECVs were significantly lower in the response group (n = 7) than in the non-response group (n = 60), with most significant difference (p = 0.0104). DECT-ECV showed highest diagnostic value with an Az value of 0.798. When using the optimal cut off value of DECT-ECV ( |
| 9. |
Takahiro Ueda, Akihisa Ohno, Nao Fujimori, Usefulness of a peroral cholangioscope with a colonoscope to retrieve an internal pancreatic stent migrated into the bile duct after pancreaticoduodenectomy, Digestive Endoscopy, 10.1111/den.14535, 35, 4, e65-e66, 2023.03. |
| 10. |
Naoki Ikenaga, Kohei Nakata, Masataka Hayashi, So Nakamura, Toshiya Abe, Noboru Ideno, Masatoshi Murakami, Nao Fujimori, Nobuhiro Fujita, Takuro Isoda, Shingo Baba, Kousei Ishigami, Yoshinao Oda, Masafumi Nakamura, Clinical Implications of FDG-PET in Pancreatic Ductal Adenocarcinoma Patients Treated with Neoadjuvant Therapy., Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract, 10.1007/s11605-023-05591-2, 27, 2, 337-346, 2023.02, PURPOSE: To evaluate the clinical significance of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with pancreatic ductal adenocarcinoma who underwent neoadjuvant therapy. METHODS: Among 285 consecutive patients who underwent pancreatic resection for pancreatic ductal adenocarcinoma between 2015 and 2021, 86 who underwent preoperative 18F-fluorodeoxyglucose positron emission tomography/computed tomography after completion of neoadjuvant treatment were reviewed. Among preoperative factors, including post-treatment maximum standardized uptake value, predictors of early recurrence and poor prognosis were identified using multivariate analysis for decision making in surgery. RESULTS: Nineteen (22%) patients with pancreatic ductal adenocarcinoma demonstrated high maximum standardized uptake (≥ 4.5). High post-treatment maximum standardized uptake (≥ 4.5) predicted early recurrence within 6 months after surgery and correlated with shorter recurrence-free survival. Elevated post-treatment CA19-9 level (> 37 U/ml) and maximum standardized uptake ≥ 4.5 were independent prognostic factors. Post-treatment, a high maximum standardized uptake value indicated a poorer prognosis than a low maximum standardized uptake value in both patients with elevated CA19-9 and normal CA19-9 levels. The median overall survival in patients with elevated post-treatment CA19-9 and high maximum standardized uptake was only 17 months; 67% experienced early recurrence. Dynamic changes in maximum standardized uptake during neoadjuvant therapy were correlated with pathological response to neoadjuvant therapy, but not with radiological response or change in CA19-9 level. CONCLUSIONS: Post-treatment assessment using maximum standardized uptake value is useful for stratifying patients with pancreatic ductal adenocarcinoma who will benefit from surgery. Instead of subsequent curative resection, additional neoadjuvant therapy should be considered in patients with a persistently high maximum standardized uptake value.. |
| 11. |
Naoki Ikenaga, Kohei Nakata, Toshiya Abe, Noboru Ideno, Nao Fujimori, Takamasa Oono, Nobuhiro Fujita, Kousei Ishigami, Masafumi Nakamura, Risks and benefits of pancreaticoduodenectomy in patients aged 80 years and over., Langenbeck's archives of surgery, 10.1007/s00423-023-02843-2, 408, 1, 108-108, 2023.02, PURPOSE: The frequency of pancreaticoduodenectomy is increasing in oldest old patients owing to population aging. We aimed to clarify the clinical significance of pancreaticoduodenectomy in patients aged ≥ 80 years with multiple underlying diseases. METHODS: A total of 649 consecutive patients who underwent pancreaticoduodenectomy from April 2010 to March 2021 in our institute were divided into two groups according to their age: ≥ 80 years (51) and ≤ 79 years (598). We compared mortality and morbidity between the groups. The age-related prognosis was analyzed in 302 patients who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma treatment. RESULTS: There were no significant differences in morbidity (Clavien-Dindo classification grade III or higher; P = 0.1300), mortality (P = 0.0786), or postoperative hospital stay (P = 0.5763) between the groups. Patients aged ≥ 80 years, who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma, had shorter overall survival than those aged ≤ 79 years (median survival time, 16.7 months vs. 32.7 months; P = 0.0206). However, the overall survival of patients aged ≥ 80 years who received perioperative chemotherapy was comparable to that of patients aged ≤ 79 years (P = 0.9795). In the multivariate analysis, the absence of perioperative chemotherapy was identified as an independent prognostic factor, while age ≥ 80 years was not. Perioperative chemotherapy was the sole independent prognostic factor in patients aged ≥ 80 years who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. CONCLUSIONS: Pancreaticoduodenectomy is safe for patients aged ≥ 80 years. The survival benefits of pancreaticoduodenectomy for patients with pancreatic ductal adenocarcinoma aged ≥ 80 years might be limited to those who can receive perioperative chemotherapy.. |
| 12. |
Masato Ozaka, Kohei Nakachi, Satoshi Kobayashi, Akihiro Ohba, Hiroshi Imaoka, Takeshi Terashima, Hiroshi Ishii, Junki Mizusawa, Hiroshi Katayama, Tomoko Kataoka, Takuji Okusaka, Masafumi Ikeda, Naoki Sasahira, Haruo Miwa, Eishiro Mizukoshi, Naohiro Okano, Nobumasa Mizuno, Tomohisa Yamamoto, Yoshito Komatsu, Akiko Todaka, Ken Kamata, Masayuki Furukawa, Nao Fujimori, Akio Katanuma, Yukiko Takayama, Hidetaka Tsumura, Haruhiko Fukuda, Makoto Ueno, Junji Furuse, A randomised phase II study of modified FOLFIRINOX versus gemcitabine plus nab-paclitaxel for locally advanced pancreatic cancer (JCOG1407)., European journal of cancer (Oxford, England : 1990), 10.1016/j.ejca.2022.12.014, 181, 135-144, 2022.12, AIM: We compared the efficacy of modified 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX) with that of gemcitabine plus nab-paclitaxel (GnP) for locally advanced pancreatic cancer (LAPC). METHODS: Patients with untreated LAPC were randomly assigned (1:1) to receive mFOLFIRINOX or GnP. One-year overall survival (OS) was the primary endpoint. The major secondary end-points included progression-free survival (PFS), response rate (RR), carbohydrate antigen 19-9 (CA19-9) response, and adverse events. The sample size was 124 patients to select a more effective regimen with a minimum probability of 0.85 and to examine the null hypothesis of the 1-year OS |
| 13. |
Kosuke Minaga, Masayuki Kitano, Yoshito Uenoyama, Keiichi Hatamaru, Hideyuki Shiomi, Kenji Ikezawa, Tsukasa Miyagahara, Hajime Imai, Nao Fujimori, Hisakazu Matsumoto, Yuzo Shimokawa, Atsuhiro Masuda, Mamoru Takenaka, Masatoshi Kudo, Yasutaka Chiba, Feasibility and efficacy of endoscopic reintervention after covered metal stent placement for EUS-guided hepaticogastrostomy: A multicenter experience., Endoscopic ultrasound, 10.4103/EUS-D-22-00029, 2022.12, BACKGROUND AND OBJECTIVES: Although the use of a long metal stent is favored for EUS-guided hepaticogastrostomy (EUS-HGS) for the relief of malignant biliary obstruction (MBO), endoscopic reintervention (E-RI) at the time of recurrent biliary obstruction (RBO) is challenging due to a long intragastric portion. This study evaluated the feasibility and safety of E-RI after a long partially covered metal stent (L-PCMS) placement during EUS-HGS. MATERIALS AND METHODS: We performed a multicenter retrospective study between January 2015 and December 2019 examining patients with MBO who underwent E-RI for RBO through the EUS-HGS route after the L-PCMS placement. Technical and clinical success rates, details of E-RI, adverse events (AEs), stent patency, and survival time were evaluated. RESULTS: Thirty-three patients at eight referral centers in Japan who underwent E-RI through the EUS-HGS route were enrolled. The location of MBO was distal in 54.5%. The median intragastric length of the L-PCMS was 5 cm. As the first E-RI attempt, E-RI via the distal end of the existing L-PCMS was successful in 60.6%. The overall technical and clinical success rates of E-RI were 100% and 81.8%, respectively. Liver abscess was noted in one patient. A proximal biliary stricture was associated with the clinical ineffectiveness of E-RI in multivariable analysis (odds ratio, 12.5, P = 0.04). The median survival and stent patency duration after E-RI were 140 and 394 days, respectively. CONCLUSIONS: Our study findings suggest that E-RI for RBO after EUS-HGS with a L-PCMS is technically feasible and clinically effective, without any severe AEs, especially for patients with distal MBO.. |
| 14. |
Tsukasa Miyagahara, Nao Fujimori, Keijiro Ueda, Yu Takamatsu, Kazuhide Matsumoto, Katsuhito Teramatsu, Takehiro Takaoka, Yuta Suehiro, Yuzo Shimokawa, Kaoru Omori, Yusuke Niina, Yuichi Tachibana, Tetsuro Akashi, Takamasa Oono, Yoshihiro Ogawa, Incidence and appropriate management of drug-induced interstitial lung disease in Japanese patients with unresectable pancreatic cancer: A multicenter retrospective study., Asia-Pacific journal of clinical oncology, 10.1111/ajco.13903, 19, 4, 533-541, 2022.12, AIM: Drug-induced interstitial lung disease (DI-ILD) is a serious adverse event during chemotherapy. This study aimed to obtain real-world data of the incidence, clinical characteristics, predictive factors, and prognosis of patients with pancreatic cancer who developed DI-ILD. METHODS: In patients with locally advanced or metastatic pancreatic cancer who underwent standard chemotherapy at our hospital and its participating facilities between April 2014 and March 2019, the clinical features, occurrence rate and clinical course of DI-ILD, and prognosis were retrospectively evaluated. RESULTS: Altogether, 390 patients were finally enrolled. DI-ILD occurred in 24 cases (6.2%). The median period from diagnosis of pancreatic cancer to the onset of DI-ILD was 2.2 months (.6-13.3 months). The rate of DI-ILD onset according to each regimen was 5.8% of gemcitabine (GEM) plus albumin-bound paclitaxel therapy (18/308), 3.8% of GEM (4/106), and 2.3% of FOLFIRINOX (2/88). The incidence of DI-ILD in GEM-based regimens was significantly higher than that in non-GEM-based regimens (p |
| 15. |
Yosuke Minoda, Mitsuru Esaki, Eikichi Ihara, Shuzaburo Nagatomo, Kei Nishioka, Nao Fujimori, Haruei Ogino, Xiaopeng Bai, Yoshimasa Tanaka, Takatoshi Chinen, Qingjiang Hu, Mitsuhiko Ota, Shinya Umekita, Hidetaka Yamamoto, Yoshihiro Ogawa, Auxiliary diagnosis of subepithelial lesions by impedance measurement during endoscopic ultrasound guided fine-needle biopsy., Gastrointestinal endoscopy, 10.1016/j.gie.2022.11.022, 97, 5, 977-984, 2022.11, INTRODUCTION: Endoscopic ultrasound guided fine-needle aspiration/biopsy (EUS-FNA/B) is the gold standard for diagnosing subepithelial lesions (SELs); however, its diagnostic ability for SELs |
| 16. |
Katsuhito Teramatsu, Takamasa Oono, Koki Oyama, Nao Fujimori, Masatoshi Murakami, Sho Yasumori, Akihisa Ohno, Kazuhide Matsumoto, Ayumu Takeno, Kohei Nakata, Masafumi Nakamura, Yoshihiro Ogawa, Circulating CD8+CD122+ T cells as a prognostic indicator of pancreatic cancer., BMC cancer, 10.1186/s12885-022-10207-0, 22, 1, 1134-1134, 2022.11, PURPOSE: The distribution of tissue infiltrating lymphocytes has been shown to affect the prognosis of patients with pancreatic cancer in some previous studies. However, the role of peripheral lymphocytes in pancreatic cancer remains debated. The purpose of this study was to analyze the peripheral subtypes of T lymphocytes, and establish their association with the prognosis of patients with pancreatic cancer. METHODS: Blood and tissue samples were collected from patients with metastatic pancreatic cancer (n = 54), resectable pancreatic cancer (n = 12), and benign pancreatic cysts (n = 52) between April 2019 and January 2022 and analyzed. RESULTS: Patients with metastatic pancreatic cancer had a larger proportion of both tumor-suppressive and tumor-promoting cells than those with benign pancreatic cysts. In addition, the proportion of peripheral CD4+ T cells positively correlated with the survival of patients with metastatic pancreatic cancer, and the proportion of peripheral CD8+CD122+ T cells was associated with early mortality ( |
| 17. |
Kensuke Shibata, Chihiro Motozono, Masamichi Nagae, Takashi Shimizu, Eri Ishikawa, Daisuke Motooka, Daisuke Okuzaki, Yoshihiro Izumi, Masatomo Takahashi, Nao Fujimori, James B Wing, Takahide Hayano, Yoshiyuki Asai, Takeshi Bamba, Yoshihiro Ogawa, Makoto Furutani-Seiki, Mutsunori Shirai, Sho Yamasaki, Symbiotic bacteria-dependent expansion of MR1-reactive T cells causes autoimmunity in the absence of Bcl11b., Nature communications, 10.1038/s41467-022-34802-8, 13, 1, 6948-6948, 2022.11, MHC class I-related protein 1 (MR1) is a metabolite-presenting molecule that restricts MR1-reactive T cells including mucosal-associated invariant T (MAIT) cells. In contrast to MAIT cells, the function of other MR1-restricted T cell subsets is largely unknown. Here, we report that mice in which a T cell-specific transcription factor, B-cell lymphoma/leukemia 11B (Bcl11b), was ablated in immature thymocytes (Bcl11b∆iThy mice) develop chronic inflammation. Bcl11b∆iThy mice lack conventional T cells and MAIT cells, whereas CD4+IL-18R+ αβ T cells expressing skewed Traj33 (Jα33)+ T cell receptors (TCR) accumulate in the periphery, which are necessary and sufficient for the pathogenesis. The disorders observed in Bcl11b∆iThy mice are ameliorated by MR1-deficiency, transfer of conventional T cells, or germ-free conditions. We further show the crystal structure of the TCR expressed by Traj33+ T cells expanded in Bcl11b∆iThy mice. Overall, we establish that MR1-reactive T cells have pathogenic potential.. |
| 18. |
Kosuke Minaga, Masayuki Kitano, Yoshito Uenoyama, Keiichi Hatamaru, Hideyuki Shiomi, Kenji Ikezawa, Tsukasa Miyagahara, Hajime Imai, Nao Fujimori, Hisakazu Matsumoto, Yuzo Shimokawa, Atsuhiro Masuda, Mamoru Takenaka, Masatoshi Kudo, Yasutaka Chiba, Feasibility and efficacy of endoscopic reintervention after covered metal stent placement for EUS-guided hepaticogastrostomy: A multicenter experience., Endoscopic ultrasound, 10.4103/EUS-D-22-00029, 11, 6, 478-486, 2022.11, BACKGROUND AND OBJECTIVES: Although the use of a long metal stent is favored for EUS-guided hepaticogastrostomy (EUS-HGS) for the relief of malignant biliary obstruction (MBO), endoscopic reintervention (E-RI) at the time of recurrent biliary obstruction (RBO) is challenging due to a long intragastric portion. This study evaluated the feasibility and safety of E-RI after a long partially covered metal stent (L-PCMS) placement during EUS-HGS. MATERIALS AND METHODS: We performed a multicenter retrospective study between January 2015 and December 2019 examining patients with MBO who underwent E-RI for RBO through the EUS-HGS route after the L-PCMS placement. Technical and clinical success rates, details of E-RI, adverse events (AEs), stent patency, and survival time were evaluated. RESULTS: Thirty-three patients at eight referral centers in Japan who underwent E-RI through the EUS-HGS route were enrolled. The location of MBO was distal in 54.5%. The median intragastric length of the L-PCMS was 5 cm. As the first E-RI attempt, E-RI via the distal end of the existing L-PCMS was successful in 60.6%. The overall technical and clinical success rates of E-RI were 100% and 81.8%, respectively. Liver abscess was noted in one patient. A proximal biliary stricture was associated with the clinical ineffectiveness of E-RI in multivariable analysis (odds ratio, 12.5, P = 0.04). The median survival and stent patency duration after E-RI were 140 and 394 days, respectively. CONCLUSIONS: Our study findings suggest that E-RI for RBO after EUS-HGS with a L-PCMS is technically feasible and clinically effective, without any severe AEs, especially for patients with distal MBO.. |
| 19. |
Akihisa Ohno, Nao Fujimori, Toshiya Abe, Masafumi Nakamura, Yoshihiro Ogawa, Bile peritonitis after placement of a metallic stent in endoscopic ultrasound-guided hepaticogastrostomy: A pitfall and the rescue technique., Endoscopy, 10.1055/a-1937-9781, 55, S 01, E94-E95, 2022.10. |
| 20. |
Yosuke Minoda, Eikichi Ihara, Nao Fujimori, Shuzaburo Nagatomo, Mitsuru Esaki, Yoshitaka Hata, Xiaopeng Bai, Yoshimasa Tanaka, Haruei Ogino, Takatoshi Chinen, Qingjiang Hu, Eiji Oki, Hidetaka Yamamoto, Yoshihiro Ogawa, Efficacy of ultrasound endoscopy with artificial intelligence for the differential diagnosis of non-gastric gastrointestinal stromal tumors., Scientific reports, 10.1038/s41598-022-20863-8, 12, 1, 16640-16640, 2022.10, Gastrointestinal stromal tumors (GISTs) are common subepithelial lesions (SELs) and require treatment considering their malignant potential. We recently developed an endoscopic ultrasound-based artificial intelligence (EUS-AI) system to differentiate GISTs from non-GISTs in gastric SELs, which were used to train the system. We assessed whether the EUS-AI system designed for diagnosing gastric GISTs could be applied to non-gastric GISTs. Between January 2015 and January 2021, 52 patients with non-gastric SELs (esophagus, n = 15; duodenum, n = 26; colon, n = 11) were enrolled. The ability of EUS-AI to differentiate GISTs from non-GISTs in non-gastric SELs was examined. The accuracy, sensitivity, and specificity of EUS-AI for discriminating GISTs from non-GISTs in non-gastric SELs were 94.4%, 100%, and 86.1%, respectively, with an area under the curve of 0.98 based on the cutoff value set using the Youden index. In the subanalysis, the accuracy, sensitivity, and specificity of EUS-AI were highest in the esophagus (100%, 100%, 100%; duodenum, 96.2%, 100%, 0%; colon, 90.9%, 100%, 0%); the cutoff values were determined using the Youden index or the value determined using stomach cases. The diagnostic accuracy of EUS-AI increased as lesion size increased, regardless of lesion location. EUS-AI based on gastric SELs had good diagnostic ability for non-gastric GISTs.. |
| 21. |
Kyoko Shimizu, Tetsuhide Ito, Atsushi Irisawa, Takao Ohtsuka, Hirotaka Ohara, Atsushi Kanno, Mitsuhiro Kida, Junichi Sakagami, Naohiro Sata, Yoshifumi Takeyama, Junko Tahara, Morihisa Hirota, Nao Fujimori, Atsushi Masamune, Satoshi Mochida, Nobuyuki Enomoto, Tooru Shimosegawa, Kazuhiko Koike, Evidence-based clinical practice guidelines for chronic pancreatitis 2021., Journal of gastroenterology, 10.1007/s00535-022-01911-6, 57, 10, 709-724, 2022.10, BACKGROUND: Chronic pancreatitis (CP) is defined according to the recently proposed mechanistic definition as a pathological fibro-inflammatory syndrome of the pancreas in individuals with genetic, environmental, and/or other risk factors who develop persistent pathological responses to parenchymal injury or stress. METHODS: The clinical practice guidelines for CP in Japan were revised in 2021 based on the 2019 Japanese clinical diagnostic criteria for CP, which incorporate the concept of a pathogenic fibro-inflammatory syndrome in the pancreas. In this third edition, clinical questions are reclassified into clinical questions, background questions, and future research questions. RESULTS: Based on analysis of newly accumulated evidence, the strength of evidence and recommendations for each clinical question is described in terms of treatment selection, lifestyle guidance, pain control, treatment of exocrine and endocrine insufficiency, and treatment of complications. A flowchart outlining indications, treatment selection, and policies for cases in which treatment is ineffective is provided. For pain control, pharmacological treatment and the indications and timing for endoscopic and surgical treatment have been updated in the revised edition. CONCLUSIONS: These updated guidelines provide clinicians with useful information to assist in the diagnosis and treatment of CP.. |
| 22. |
Akihisa Ohno, Nao Fujimori, Toyoma Kaku, Masayuki Hijioka, Ken Kawabe, Naohiko Harada, Makoto Nakamuta, Takamasa Oono, Yoshihiro Ogawa, The feasibility of percutaneous transhepatic gallbladder aspiration for acute cholecystitis after self-expandable metallic stent placement for malignant biliary obstruction: a 10-year retrospective analysis in a single center., Clinical endoscopy, 10.5946/ce.2021.244, 55, 6, 784-792, 2022.10, Background/Aims: Patients with acute cholecystitis (AC) after metallic stent (MS) placement for malignant biliary obstruction (MBO) have a high surgical risk. We performed percutaneous transhepatic gallbladder aspiration (PTGBA) as the first treatment for AC. We aimed to identify the risk factors for AC after MS placement and the poor response factors of PTGBA. Methods: We enrolled 401 patients who underwent MS placement for MBO between April 2011 and March 2020. The incidence of AC was 10.7%. Of these 43 patients, 37 underwent PTGBA as the first treatment. The patients' responses to PTGBA were divided into good and poor response groups. Results: There were 20 patients in good response group and 17 patients in poor response group. Risk factors for cholecystitis after MS placement included cystic duct obstruction (p |
| 23. |
Kensuke Kubota, Takaya Oguchi, Nao Fujimori, Kenta Yamada, Itaru Naitoh, Yoshinobu Okabe, Eisuke Iwasaki, Atsushi Masamune, Tsukasa Ikeura, Terumi Kamisawa, Dai Inoue, Teru Kumagi, Takeshi Ogura, Yuzo Kodama, Akio Katanuma, Kenji Hirano, Kazuo Inui, Hiroyuki Isayama, Junichi Sakagami, Takayoshi Nishino, Atsushi Kanno, Yusuke Kurita, Kazuichi Okazaki, Seiji Nakamura, Steroid therapy has an acceptable role as the initial treatment in autoimmune pancreatitis patients with pancreatic cyst formation: based on a Japanese nationwide study., Journal of hepato-biliary-pancreatic sciences, 10.1002/jhbp.1227, 30, 5, 664-677, 2022.08, BACKGROUND: We attempted to determine the indications and limitations of steroid therapy as the 1st line therapy in patients with autoimmune pancreatitis (AIP) with cyst formation (ACF). METHODS: This Japanese multicenter survey was conducted to examine the merits/demerits of steroid treatment as the initial therapy for ACF. RESULT: Data of a total of 115 patients with ACF were analyzed. Complete remission was achieved in 86% (86/100) of patients who had received steroid treatment, but only 33.3% (5/15) of patients who had not received steroids. Relapse after the remission (n=86) occurred in 7.6% (6/86) of patients who had received steroid therapy, but 40% (2/5) of patients who had not received steroid therapy. Multivariate analysis identified adoption of the wait&watch approach without steroid treatment (odds ratio=0.126, p |
| 24. |
Masami Miki, Nao Fujimori, Keijiro Ueda, Lingaku Lee, Masatoshi Murakami, Yu Takamatsu, Yuzo Shimokawa, Yusuke Niina, Takamasa Oono, Terumasa Hisano, Masayuki Furukawa, Yoshihiro Ogawa, Treatment Effect and Safety of Nanoliposomal Irinotecan with Fluorouracil and Folinic Acid after Gemcitabine-Based Therapy in Patients with Advanced Pancreatic Cancer: A Multicenter, Prospective Observational Study., Journal of clinical medicine, 10.3390/jcm11175084, 11, 17, 2022.08, Although the combination of nanoliposomal irinotecan plus fluorouracil/folinic acid (nal-IRI/FF) exhibited survival benefits in gemcitabine-refractory patients with advanced pancreatic cancer (APC) in the phase III NAPOLI-1 trial, there is limited data on the efficacy and safety of this regimen in real-world settings in Japan. This multicenter, prospective observational study enrolled patients with APC who received nal-IRI/FF after a gemcitabine-based regimen from July 2020 to June 2021. We collected and analyzed clinical data and conducted survival and multivariate analyses. Thirty-one (78%) of the 40 patients had metastases. Nal-IRI/FF was the second-line therapy in 36 patients (90%). The median duration was 3.2 months. The disease control rate was 57%. The median progression-free survival and overall survival (OS) were 4.5 months (95% confidence interval [CI]: 2.8-5.5) and 7.4 months (95% CI: 5.1-10.6), respectively. Common ≥grade 3 toxicities included neutropenia (28%) and fatigue (23%). Fatigue led to treatment discontinuation in 6 out of 10 patients. Multivariate analysis showed that a neutrophil-to-lymphocyte ratio > 4 was a significant risk factor for a short OS (hazard ratio (HR) = 3.08, 95% CI: 1.21-7.85, p = 0.02). In conclusion, nal-IRI/FF is an appropriate treatment option for APC following gemcitabine-containing regimens.. |
| 25. |
Yosuke Minoda, Eikichi Ihara, Soichi Itaba, Yorinobu Sumida, Kazuhiro Haraguchi, Akira Aso, Takahiro Mizutani, Takashi Osoegawa, Mitsuru Esaki, Shuzaburo Nagatomo, Kei Nishioka, Kazumasa Muta, Xiaopeng Bai, Haruei Ogino, Nao Fujimori, Daisuke Tsurumaru, Kenoki Ohuchida, Hu Qingjiang, Eiji Oki, Hidetaka Yamamoto, Yoshihiro Ogawa, Negligible procedure-related dissemination risk of mucosal incision-assisted biopsy for gastrointestinal stromal tumors versus endoscopic ultrasound-guided fine-needle aspiration/biopsy., Surgical endoscopy, 10.1007/s00464-022-09419-z, 37, 1, 101-108, 2022.07, BACKGROUND: Mucosal incision-assisted biopsy (MIAB) is a valuable alternative to endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNAB) for sampling gastric subepithelial lesions (SELs). This study aimed to evaluate the potential risk of dissemination and impact on postoperative prognosis associated with MIAB, which has not yet been investigated. METHODS: Study 1: A prospective observational study was conducted to examine the presence or absence and growth rate of tumor cells in gastric juice before and after the procedure in patients with SELs who underwent MIAB (n = 25) or EUS-FNAB (n = 22) between September 2018 and August 2021. Study 2: A retrospective study was conducted to examine the impact of MIAB on postoperative prognosis in 107 patients with gastrointestinal stromal tumors diagnosed using MIAB (n = 39) or EUS-FNAB (n = 68) who underwent surgery between January 2001 and July 2020. RESULTS: In study 1, although no tumor cells were observed in gastric juice in MIAB before the procedure, they were observed in 64% of patients after obtaining samples (P |
| 26. |
Akihisa Ohno, Nao Fujimori, Toyoma Kaku, Yu Takamatsu, Kazuhide Matsumoto, Masatoshi Murakami, Katsuhito Teramatsu, Ayumu Takeno, Masayuki Hijioka, Ken Kawabe, Naohiko Harada, Makoto Nakamuta, Akira Aso, Takamasa Oono, Yoshihiro Ogawa, Feasibility and Efficacy of Endoscopic Ultrasound-Guided Hepaticogastrostomy Without Dilation: A Propensity Score Matching Analysis., Digestive diseases and sciences, 10.1007/s10620-022-07555-z, 67, 12, 5676-5684, 2022.06, BACKGROUND: Recently, endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) procedures have been gradually established; nonetheless, some adverse events (AEs) have been reported. Dilation procedures using a non-cautery or cautery device increase the incidence of AEs in EUS-HGS. AIMS: We evaluated EUS-HGS procedures without dilation and the factors associated with dilation. METHODS: We enrolled 79 patients who underwent EUS-HGS between July 2015 and March 2021 at two centers, 72 of whom had technical success (72/79, 91%). During the EUS-HGS procedures, we defined patients without dilation procedures as the dilation (-) group. We divided the patients into two groups: the dilation (+) (35 patients) and dilation (-) (37 patients) groups. We performed a propensity score matching analysis to adjust for confounding bias between the two groups. Multivariable logistic regression analysis was conducted to identify factors associated with dilation. RESULTS: There was no difference in clinical success rate between the dilation (+) and dilation (-) groups (91% vs. 95%, P = 0.545). The AE rate (P = 0.013) and long procedure time (P = 0.017) were significantly higher in the dilation (+) group than in the dilation (-) group before and after propensity score matching. Factors associated with dilation were plastic stent placement (odds ratio [OR], 6.96; 95% confidence interval [CI], 1.68-28.7; P = 0.007) and puncture angle of ≤ 90° (OR, 44.6; 95% CI, 5.1-390; P |
| 27. |
Yu Takamatsu, Nao Fujimori, Tsukasa Miyagahara, Yuta Suehiro, Toyoma Kaku, Ken Kawabe, Akihisa Ohno, Kazuhide Matsumoto, Masatoshi Murakami, Katsuhito Teramatsu, Ayumu Takeno, Takamasa Oono, Yoshihiro Ogawa, The Glasgow Prognostic Score and stricture site can predict prognosis after endoscopic duodenal stent placement for malignant gastric outlet obstruction., Scientific reports, 10.1038/s41598-022-13209-x, 12, 1, 9746-9746, 2022.06, Endoscopic duodenal stent (DS) placement for malignant gastric outlet obstruction (GOO) is rapidly increasing in clinical practice; however, the most suitable patient candidates for DS placement have not been determined. One hundred and thirty-five patients with GOO who underwent DS placement in three Japanese referral centers between January 2010 and October 2019 were retrospectively evaluated. Overall survival (OS) after DS placement, technical/clinical success rates, adverse events, and predictive factors affecting OS after DS placement were also analyzed. The median OS after DS placement of all patients was 81 (7-901) days. Technical and clinical success rates were 99.3% and 83.7%, respectively. The GOO Scoring System score significantly increased before and after DS placement (0.9 vs. 2.7, P |
| 28. |
Masatoshi Murakami, Nao Fujimori, Kazuhide Matsumoto, Akihisa Ohno, Katsuhito Teramatsu, Yu Takamatsu, Ayumu Takeno, Keijiro Ueda, Takamasa Oono, Tetsuhide Ito, Yoshihiro Ogawa, A clinical analysis on functioning pancreatic neuroendocrine tumors (focusing on VIPomas): a single-center experience., Endocrine journal, 10.1507/endocrj.EJ22-0111, 69, 10, 1201-1209, 2022.05, VIPomas are generally rare functioning pancreatic neuroendocrine tumors (PanNETs) that cause watery diarrhea, hypokalemia, and achlorhydria. Due to their extreme rarity, the clinicopathological features and outcomes of VIPomas have not been well reported. This study aimed to determine the diagnostic and therapeutic characteristics and prognosis of VIPomas and to compare them with other PanNETs at a Japanese reference hospital. Medical records of 293 patients with PanNETs were collected. Patient and tumor characteristics and outcomes were retrospectively reviewed. This cohort had only 1.4% (four patients) of patients with VIPomas, and three of these patients changed from non-functioning (NF-) PanNETs during their disease course. Recurrences of hormonal symptoms were observed in all patients despite the initial controls, and all of them died from their disease, more specifically mainly from hormonal symptoms. Compared to the other PanNETs, VIPomas were all located at the pancreatic tail, were larger, and had a higher Ki-67 index and more metastasis. The median survival time was significantly shorter for patients with VIPoma than for those with NF-PanNET (5.9 vs. 26.7 years, p |
| 29. |
Kazuhide Matsumoto, Nao Fujimori, Yoshitaka Hata, Yosuke Minoda, Masatoshi Murakami, Katsuhito Teramatsu, Yu Takamatsu, Ayumu Takeno, Takamasa Oono, Eikichi Ihara, Kohei Nakata, Masafumi Nakamura, Takeo Yamamoto, Yutaka Koga, Yoshinao Oda, Tetsuhide Ito, Yoshihiro Ogawa, Ampullary Neuroendocrine Neoplasm: Clinicopathological Characteristics and Novel Endoscopic Entity., Digestive diseases (Basel, Switzerland), 10.1159/000525013, 41, 2, 316-324, 2022.05, BACKGROUND: Neuroendocrine neoplasms of the ampulla of Vater (ampullary NEN) have features of both gastrointestinal and pancreato-biliary (PB) NEN. However, the limited number of studies examining ampullary NEN makes it difficult to clarify their unique characteristics. This study aimed to elucidate the clinical characteristics of ampullary NEN. METHODS: We enrolled 162 patients with PB-NEN diagnosed at Kyushu University Hospital between 2011 and 2020. Clinical features, pathological diagnoses, treatments, and prognoses were retrospectively analyzed. We also compared ampullary NEN with pancreatic NEN (PanNEN). RESULTS: We analyzed 10 ampullary NEN cases and 149 PanNEN cases. The ampullary NEN cases consisted of four cases of NET G1 (neuroendocrine tumor Grade 1), one NET G2 (Grade 2), and five NECs (neuroendocrine carcinoma). The incidences of NEC and cholangitis were significantly higher in ampullary NEN than in PanNEN. All ampullary NETs had a submucosal tumor-like appearance, as identified by endoscopic ultrasound-guided fine needle aspiration. We treated small NET G1 ( |
| 30. |
Masayuki Kitano, Makoto Yoshida, Reiko Ashida, Emiri Kita, Akio Katanuma, Takao Itoi, Rintaro Mikata, Kenichiro Nishikawa, Hiroyuki Matsubayashi, Yukiko Takayama, Hironari Kato, Mamoru Takenaka, Toru Ueki, Yohei Kawashima, Yousuke Nakai, Shinichi Hashimoto, Minoru Shigekawa, Hiroko Nebiki, Hidetaka Tsumura, Yosinobu Okabe, Shomei Ryozawa, Yoshiyuki Harada, Akira Mitoro, Tamito Sasaki, Hiroaki Yasuda, Natsuki Miura, Tetsuya Ikemoto, Eisuke Ozawa, Kazuhiko Shioji, Atsushi Yamaguchi, Toru Okuzono, Ichiro Moriyama, Hiroyuki Hisai, Koichi Fujita, Takuma Goto, Nakao Shirahata, Yoshinori Iwata, Yoshihiro Okabe, Kazuo Hara, Yusuke Hashimoto, Masaki Kuwatani, Hiroyuki Isayama, Nao Fujimori, Atsushi Masamune, Keiichi Hatamaru, Toshio Shimokawa, Kazuichi Okazaki, Yoshifumi Takeyama, Hiroki Yamaue, Needle tract seeding after endoscopic ultrasound-guided tissue acquisition of pancreatic tumors: A nationwide survey in Japan., Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society, 10.1111/den.14346, 2022.05, OBJECTIVES: Endoscopic ultrasound-guided tissue acquisition (EUS-TA) plays a crucial role in the diagnosis of pancreatic tumors. The present study aimed to investigate the current status of needle tract seeding (NTS) after EUS-TA of pancreatic tumors based on a nationwide survey in Japan. METHODS: Patients who underwent surgical resection of primary pancreatic tumors after EUS-TA performed between April 2010 and March 2018 were surveyed. The incidence rates of NTS were determined, and compared in patients with pancreatic ductal adenocarcinomas (PDACs) and other tumors, and in patients who underwent transgastric and transduodenal EUS-TA of PDACs. The detailed features and prognosis of patients with NTS were also assessed. RESULTS: A total of 12,109 patients underwent surgical resection of primary pancreatic tumors after EUS-TA. The overall incidence rate of NTS was 0.330%, and the NTS rate was significantly higher in patients with PDAC than in those with other tumors (0.409% vs. 0.071%, P=0.004). NTS was observed in 0.857% of patients who underwent transgastric EUS-TA, but in none of those who underwent transduodenal EUS-TA. Of the patients with NTS of PDACs, the median time from EUS-TA to occurrence of NTS and median patient survival were 19.3 and 44.7 months, respectively, with 97.4% of NTS located in the gastric wall and 65.8% of NTS resected. The patient survival was significantly longer in patients who underwent NTS resection than in those without NTS resection (P=0.037). CONCLUSIONS: NTS appeared only after transgastric not after transduodenal EUS-TA. Careful follow-up provides an opportunity to remove localized NTS lesions by gastrectomy.. |
| 31. |
Nao Fujimori, Yosuke Minoda, Yoshihiro Ogawa, What is the best modality for diagnosing pancreatic cancer?, Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society, 10.1111/den.14283, 34, 4, 744-746, 2022.05. |
| 32. |
Takeshi Ogura, Hirotoshi Ishiwatari, Nao Fujimori, Eisuke Iwasaki, Kazuma Ishikawa, Tatsunori Satoh, Junichi Kaneko, Junya Sato, Takamasa Oono, Kazuhide Matsumoto, Seiichiro Fukuhara, Atsuto Kayashima, Akitoshi Hakoda, Kazuhide Higuchi, Propensity score matching analysis for adverse events of EUS-guided biliary drainage in advanced elderly patients (PEACE study)., Therapeutic advances in gastroenterology, 10.1177/17562848221092612, 15, 17562848221092612-17562848221092612, 2022.05, Background: Several studies have suggested that elderly patients, as well as younger patients, can be safely treated using endoscopic retrograde cholangiopancreatography (ERCP). However, endoscopic ultrasound-guided biliary drainage (EUS-BD) has not been clinically evaluated for very elderly patients. The present multicenter, retrospective study aimed to determine the safety of EUS-BD for advanced elderly patients. Method: Patients who underwent EUS-BD during this period were retrospectively enrolled, and they were divided into two groups based on age: group A (age |
| 33. |
Masatoshi Murakami, Nao Fujimori, Akihisa Ohno, Kazuhide Matsumoto, Katsuhito Teramatsu, Yu Takamatsu, Ayumu Takeno, Takamasa Oono, Toshiya Abe, Noboru Ideno, Naoki Ikenaga, Kohei Nakata, Masafumi Nakamura, Kousei Ishigami, Yoshihiro Ogawa, Predictive factors of operability after neoadjuvant chemotherapy in resectable or borderline resectable pancreatic cancer: a single-center retrospective study., Discover. Oncology, 10.1007/s12672-021-00462-1, 13, 1, 2-2, 2022.01, BACKGROUND/AIMS: Recently neoadjuvant chemotherapy (NAC) for pancreatic cancer has been shown to be superior to upfront surgery, but it remains a matter of debate for resectable cases. In clinical practice, some resectable cases may become unresectable after NAC. This study aimed to reveal the outcomes after NAC and to clarify the characteristics of unresected cases. METHODS: The medical records of 142 patients who underwent NAC between 2016 and 2020 were retrospectively reviewed. Patient characteristics, effectiveness of NAC, and outcomes were compared between the surgical group and non-surgical group (NSG). Furthermore, the risk of recurrence limited to in the patients who received NAC with gemcitabine plus nab-paclitaxel, which were mostly administered in this cohort, following R0/R1 resection was assessed. RESULTS: The overall and R0 resection rates after NAC were 89.1% and 79.7%, respectively. The neutrophil to lymphocyte ratio (NLR) > 2.78 (p = 0.0120) and anatomical borderline resectable pancreatic cancer (p = 0.0044) revealed a statistically significantly correlation with the NSG. On the other hand, NAC week IIA (P = 0.0003) were significantly associated with recurrence. The tumor response rate was approximately 26.1%, and three patients with ≥ 30% reduction of primary tumor lost excision opportunities because of metastasis, interstitial pneumonia, and vascular invasion. CONCLUSIONS: This study shows incomplete tumor shrinkage benefits, but pre-NAC NLR is a predictive factor for predicting operability after NAC. The NLR can be easily calculated by normal blood test, and can be considered as a suitable marker of operability.. |
| 34. |
Akihisa Ohno, Nao Fujimori, Keisuke Hirahata, Takahiro Ueda, Yu Takamatsu, Takamasa Oono, The novel basket catheter for retrieval of a migrated biliary inside stent., Endoscopy, 10.1055/a-1711-4161, 2021.12. |
| 35. |
Tetsuhide Ito, Toshihiko Masui, Izumi Komoto, Ryuichiro Doi, Robert Y Osamura, Akihiro Sakurai, Masafumi Ikeda, Koji Takano, Hisato Igarashi, Akira Shimatsu, Kazuhiko Nakamura, Yuji Nakamoto, Susumu Hijioka, Koji Morita, Yuichi Ishikawa, Nobuyuki Ohike, Atsuko Kasajima, Ryoji Kushima, Motohiro Kojima, Hironobu Sasano, Satoshi Hirano, Nobumasa Mizuno, Taku Aoki, Takeshi Aoki, Takao Ohtsuka, Tomoyuki Okumura, Yasutoshi Kimura, Atsushi Kudo, Tsuyoshi Konishi, Ippei Matsumoto, Noritoshi Kobayashi, Nao Fujimori, Yoshitaka Honma, Chigusa Morizane, Shinya Uchino, Kiyomi Horiuchi, Masanori Yamasaki, Jun Matsubayashi, Yuichi Sato, Masau Sekiguchi, Shinichi Abe, Takuji Okusaka, Mitsuhiro Kida, Wataru Kimura, Masao Tanaka, Yoshiyuki Majima, Robert T Jensen, Koichi Hirata, Masayuki Imamura, Shinji Uemoto, JNETS clinical practice guidelines for gastroenteropancreatic neuroendocrine neoplasms: diagnosis, treatment, and follow-up: a synopsis., Journal of gastroenterology, 10.1007/s00535-021-01827-7, 56, 11, 1033-1044, 2021.11, Neuroendocrine neoplasms (NENs) are rare neoplasms that occur in various organs and present with diverse clinical manifestations. Pathological classification is important in the diagnosis of NENs. Treatment strategies must be selected according to the status of differentiation and malignancy by accurately determining whether the neoplasm is functioning or nonfunctioning, degree of disease progression, and presence of metastasis. The newly revised Clinical Practice Guidelines for Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NENs) comprises 5 chapters-diagnosis, pathology, surgical treatment, medical and multidisciplinary treatment, and multiple endocrine neoplasia type 1 (MEN1)/von Hippel-Lindau (VHL) disease-and includes 51 clinical questions and 19 columns. These guidelines aim to provide direction and practical clinical content for the management of GEP-NEN preferentially based on clinically useful reports. These revised guidelines also refer to the new concept of "neuroendocrine tumor" (NET) grade 3, which is based on the 2017 and 2019 WHO criteria; this includes health insurance coverage of somatostatin receptor scintigraphy for NEN, everolimus for lung and gastrointestinal NET, and lanreotide for GEP-NET. The guidelines also newly refer to the diagnosis, treatment, and surveillance of NEN associated with VHL disease and MEN1. The accuracy of these guidelines has been improved by examining and adopting new evidence obtained after the first edition was published.. |
| 36. |
Akihisa Ohno, Toyoma Kaku, Nao Fujimori, Balloon guidewire technique during EUS-guided hepaticogastrostomy., Endoscopic ultrasound, 10.4103/EUS-D-21-00067, 2021.11. |
| 37. |
Tetsuhide Ito, Nao Fujimori, Yoshitaka Honma, Atsushi Kudo, Susumu Hijioka, Shinji Katsushima, Yasutoshi Kimura, Akira Fukutomi, Seiichi Hisamatsu, Akihiro Nakajima, Akira Shimatsu, Long-term safety and efficacy of lanreotide autogel in Japanese patients with neuroendocrine tumors: Final results of a phase II open-label extension study., Asia-Pacific journal of clinical oncology, 10.1111/ajco.13371, 17, 5, e153-e161, 2021.10, AIM: The aim of this study was to describe the long-term safety and efficacy of lanreotide in Japanese patients with neuroendocrine tumors. METHODS: The final analyses of a 48-week open-label phase II study (n = 32) and its extension study (n = 17) were conducted. Patients received 4-weekly subcutaneous injections of lanreotide autogel 120 mg. Safety was evaluated by adverse events. Efficacy endpoints included tumor response by RECIST and change in tumor size. Post hoc analyses including tumor growth rate were performed. RESULTS: The median (range) of lanreotide exposure in the safety analysis set (n = 17) and efficacy analysis set (n = 28) were 151.4 (52-181) and 52.7 (12-181) weeks, respectively. Sixteen patients developed adverse drug reaction; of these, upper abdominal pain and urticaria were not reported before 48 weeks. No patient discontinued lanreotide or died from an adverse event. Two serious events of bile duct stones in one patient were drug-related. Partial response was observed in 2 patients (7.1%; at 60 and 108 weeks), stable disease in 20 (71.4%) and progressive disease in 6 (21.4%). The mean of the greatest change from baseline in the sum of diameters of target lesions was -5.5%. The mean (standard deviation) tumor growth rate before treatment and from baseline to last observation was 25.3% (35.7%)/month and 6.4% (9.6%)/month, respectively. CONCLUSION: Lanreotide treatment had an acceptable safety profile and was effective over long-term treatment in Japanese patients with neuroendocrine tumors. No unexpected serious adverse events developed during prolonged use of lanreotide.. |
| 38. |
Yosuke Minoda, Shuzaburo Nagatomo, Nao Fujimori, Kei Nishioka, Shotaro Kakehashi, Katsuhito Teramatsu, Yu Takamatsu, Haruei Ogino, Eikichi Ihara, Usefulness of a gel immersion-assisted EUS-guided fine-needle aspiration/biopsy for ampullary lesions (with videos)., Endoscopic ultrasound, 10.4103/EUS-D-21-00043, 2021.09. |
| 39. |
Nao Fujimori, Kazuhide Matsumoto, Masatoshi Murakami, Yuta Suehiro, Takamasa Oono, Endoscopic tamponade using a fully covered self-expandable metallic stent for massive biliary bleeding from a pseudoaneurysm rupture during metallic stent removal., VideoGIE : an official video journal of the American Society for Gastrointestinal Endoscopy, 10.1016/j.vgie.2020.08.009, 6, 1, 24-26, 2021.01. |
| 40. |
Masatoshi Murakami, Nao Fujimori, Yuta Suehiro, Tomonobu Hioki, Kazuhide Matsumoto, Takamasa Oono, Yoshihiro Ogawa, Successful endoscopic removal of a fully covered self-expandable metallic stent that fractured above a benign distal bile duct stricture., Endoscopy, 10.1055/a-1167-7861, 53, 1, E11-E12, 2021.01. |
| 41. |
Nao Fujimori, Takashi Osoegawa, Akira Aso, Soichi Itaba, Yosuke Minoda, Masatoshi Murakami, Kazuhide Matsumoto, Katsuhito Teramatsu, Yu Takamatsu, Takehiro Takaoka, Takamasa Oono, Eikichi Ihara, Tomoharu Yoshizumi, Takao Ohtsuka, Masafumi Nakamura, Yoshihiro Ogawa, Efficacy of Early Endoscopic Ultrasound-Guided Transluminal Drainage for Postoperative Pancreatic Fistula, Canadian Journal of Gastroenterology and Hepatology, 10.1155/2021/6691705, 2021, 1-8, 2021.01, Background. Endoscopic ultrasound-guided transluminal drainage (EUS-TD) is generally performed 4 weeks after disease onset for evacuating pancreatic fluid collections. However, the optimal timing for conducting the procedure in those diagnosed with postoperative pancreatic fistula (POPF) has not been established. We aimed to elucidate the efficacy and safety of early EUS-TD procedures for treating POPF. Methods. We retrospectively reviewed patients diagnosed with POPF who underwent EUS-TD in the Kyushu University Hospital between 2008 and 2019. Clinical features were comparatively analyzed between the two patient groups who underwent either early (≤15 days postoperatively) or late (>15 days postoperatively) EUS-TD. Factors prolonging hospital stay were also analyzed using Cox proportional hazard models. Results. Thirty patients (median age, 64.5 years) were enrolled. The most common initial operation was distal pancreatectomy with splenectomy (60.0%). Median size of POPF was 69.5 (range, 38–145) mm, and median time interval between surgery and EUS-TD was 17.5 (range, 3–232) days. Totally, 47% patients underwent early EUS-TD. Rates of technical success, clinical success, and complications were 100%, 97%, and 6.9%, respectively. No recurrence of POPF occurred during a median follow-up period of 14 months. Clinical characteristics and outcomes were comparable between the early and late drainage patient groups, except for the rates of infection and nonencapsulation of POPF, which were significantly higher in the early drainage group. Performing simultaneous internal and external drainage (hazard ratio (HR): 0.31; 95% confidence interval (CI): 0.11–0.93,
) and conducting ≥2 treatment sessions (HR: 0.26; 95% CI: 0.08–0.84,
) were significantly associated with prolonged hospitalization after EUS-TD. Conclusions. EUS-TD is a safe and effective method for managing POPF, regardless of when it is performed in the postoperative period. Once infected POPF occurs, clinicians should not hesitate to perform EUS-TD even within 15 days of the initial operation.. |
| 42. |
Masatoshi Murakami, Nao Fujimori, Yoshihiro Nagao, Tomoharu Yoshizumi, Kazuhide Matsumoto, Sho Yasumori, Katsuhito Teramatsu, Yu Takamatsu, Takamasa Oono, Yoshihiro Ogawa, Colonic varices: a rare complication of pancreatic cancer., Clinical journal of gastroenterology, 10.1007/s12328-020-01225-1, 13, 6, 1355-1359, 2020.12, A 55-year-old man was diagnosed with pancreatic cancer of the uncus and received chemotherapy (modified FOLFIRINOX). Ten months later, he was admitted to our hospital with massive lower gastrointestinal bleeding. Contrast-enhanced CT showed ascending colon varices caused by the occlusion of the superior mesenteric vein (SMV) due to pancreatic cancer invasion. Colonoscopy revealed tortuous varices with red spots in the ascending colon. The patient received blood transfusions and was discharged; however, he was hospitalized for recurrent massive lower gastrointestinal bleeding 3 months later. During this readmission, we performed the transileocolic vein obliteration method due to SMV stenosis and the absence of an obvious shunt. He experienced an uneventful post-operative recovery, and contrast-enhanced CT after 2 months revealed no recurrence of colonic varices. Ectopic varices are portosystemic venous collaterals resulting from portal hypertension occurring in any locations other than the esophagogastric region. Colonic varices have rarely been reported before. Patients with pancreatic cancer may present with gastrointestinal bleeding caused by tumor bleeding or esophagogastric varices; however, ectopic varices such as colon varices, a rare complication of pancreatic cancer, should be considered in patients with obscure gastrointestinal bleeding.. |
| 43. |
Akihisa Ohno, Nao Fujimori, Masami Miki, Takamasa Oono, Hisato Igarashi, Ryota Matsuda, Yutaka Koga, Yoshinao Oda, Takao Ohtsuka, Masafumi Nakamura, Tetsuhide Ito, Yoshihiro Ogawa, Collision of a pancreatic ductal adenocarcinoma and a pancreatic neuroendocrine tumor associated with multiple endocrine neoplasm type 1., Clinical journal of gastroenterology, 10.1007/s12328-020-01234-0, 14, 1, 358-363, 2020.09, A 54-year-old man with pancreatic head tumor had undergone pancreaticoduodenectomy and was diagnosed with pancreatic neuroendocrine tumor (P-NET) associated with sporadic multiple endocrine neoplasm type 1. Five years after the resection, P-NET recurred and liver metastases were observed. He was treated with a somatostatin analog. Eleven years after the resection, computed tomography revealed a new pancreatic hypodense and hypovascular mass adjacent to the P-NET that was diagnosed as pancreatic adenocarcinoma via endoscopic ultrasound-guided fine-needle aspiration. He underwent a total remnant pancreatectomy. Pathological examination showed that the lesion was constituted by a pancreatic ductal adenocarcinoma (PDAC) and a neuroendocrine tumor. Additionally, the invasive ductal carcinoma collided with the neuroendocrine tumor. Both PDAC and P-NET cells were observed in the collision area. We could observe the onset of PDAC during the treatment of P-NET. Moreover, we are the first to report the case of a collision of pancreatic endocrine and exocrine tumors diagnosed preoperatively.. |
| 44. |
Kosuke Minaga, Mamoru Takenaka, Takeshi Ogura, Takashi Tamura, Taira Kuroda, Toyoma Kaku, Yoshito Uenoyama, Chishio Noguchi, Hidefumi Nishikiori, Hajime Imai, Ryota Sagami, Nao Fujimori, Kazuhide Higuchi, Masatoshi Kudo, Yasutaka Chiba, Masayuki Kitano, Endoscopic ultrasound-guided biliary drainage for malignant biliary obstruction with surgically altered anatomy: a multicenter prospective registration study., Therapeutic advances in gastroenterology, 10.1177/1756284820930964, 13, 1756284820930964-1756284820930964, 2020.07, Background: Endoscopic treatment for malignant biliary obstruction (MBO) in patients bearing surgically altered anatomy (SAA) is not well-established. Although endoscopic ultrasound-guided biliary drainage (EUS-BD) has emerged as a new treatment option for MBO, limited data are available regarding the efficacy and safety of EUS-BD in patients with SAA. We conducted a multicenter prospective registration study to evaluate the efficacy and safety of EUS-BD in this population. Methods: This study involved 10 referral centers in Japan. Patients with SAA who were scheduled to receive EUS-BD for unresectable MBO between May 2016 and September 2018 were prospectively registered. The primary endpoint was technical success and the secondary outcomes were clinical success, procedure time, procedure-related adverse events (AEs), stent patency, and overall survival. Results: In total, 40 patients were prospectively enrolled. The surgical reconstruction methods were gastrectomy with Roux-en-Y reconstruction (47.5%), gastrectomy with Billroth-II reconstruction (15%), pancreaticoduodenectomy (27.5%), and hepaticojejunostomy with Roux-en-Y reconstruction (10%). EUS-BD was performed for primary biliary drainage in 31 patients and for rescue biliary drainage in nine patients. Transmural stenting alone (60%), antegrade stenting alone (5%), and a combination of the two techniques (35%) were selected for patients treated with EUS-BD. Technical and clinical success rates were 100% (95% confidence interval, 91.2-100.0%) and 95% (95% confidence interval, 83.1-99.4%), respectively. Mean procedure time was 36.5 min. Early AEs were noted in six patients (15%): three self-limited bile leak, one bile peritonitis, and two pneumoperitonea. Late AEs occurred in six patients (15%): one jejunal ulcer and five stent occlusions. Stent patency rate after 3 months of survival was 95.7% (22/23). Median overall survival was 96 days. Conclusion: EUS-BD for MBO in patients with SAA appears to be effective and safe not only as a rescue drainage technique after failed endoscopic retrograde cholangiography but also as a primary drainage technique. Clinical Trial Registration: UMIN000022101.. |
| 45. |
Fujimori N, Miki M, Lee L, Matsumoto K, Takamatsu Y, Takaoka T, Teramatsu K, Suehiro Y, Murakami M, Igarashi H, Oono T, Ohtsuka T, Nakamura M, Koga Y, Oda Y, Ito T, Ogawa Y, Natural history and clinical outcomes of pancreatic neuroendocrine neoplasms based on the WHO 2017 classification; a single-center experience of 30 years., Pancreatology, 10.1016/j.pan.2020.04.003, 20, 4, 709-715, 2020.06. |
| 46. |
Atsushi Masamune, Kazuhiro Kikuta, Shin Hamada, Ichiro Tsuji, Yoshifumi Takeyama, Tooru Shimosegawa, Kazuichi Okazaki, Ryotaro Matsumoto, Kiyoshi Kume, Shin Miura, Tetsuya Takikawa, Seiji Hongo, Yu Tanaka, Toshitaka Sakai, Masayuki Ueno, Jun Unno, Masao Toki, Mamoru Nishimura, Katsuya Kitamura, Kasen Kobashigawa, Kiyoshi Ashida, Kuniyuki Takahashi, Takashi Watanabe, Yuichirou Sato, Akihiko Satoh, Naoki Yoshida, Kei Tanaka, Hiromu Kondo, Noriaki Suzuki, Hiroko Sato, Akira Mitoro, Kazuhiro Minami, Eisuke Iwasaki, Kosuke Okuwaki, Tsuyoshi Mukai, Yasushi Kudo, Shunjiro Azuma, Yasuhito Takeda, Morimichi Setsuda, Kohei Tsuchida, Atsushi Irisawa, Daisuke Motoya, Nakao Shirahata, Keisuke Iwata, Noriko Oza, Yasunori Kawaguchi, Atsumi Hoshino, Atsuyuki Hirano, Ichiro Sakakihara, Nao Fujimori, Clinical practice of acute pancreatitis in Japan An analysis of nationwide epidemiological survey in 2016, Pancreatology, 10.1016/j.pan.2020.04.013, 20, 4, 629-636, 2020.06, Background: To provide updates on clinical practice of acute pancreatitis (AP) in Japan, we conducted a nationwide epidemiological survey. Methods: This study consisted of a two-staged survey; the number of AP patients was estimated by the first-stage survey and their clinical features were examined by the second-stage survey. We surveyed AP patients who had visited hospitals in 2016. Results: The estimated number of AP patients in 2016 was 78,450, with an overall incidence of 61.8 per 100,000 persons. We obtained detailed clinical information of 2994 AP patients, including 706 (23.6%) severe cases classified according to the Japanese severity criteria. The male-to-female sex ratio was 2.0, and the mean age at onset was 59.9 years in males and 66.5 years in females. Alcohol was the most common etiology (42.8%) in males and gallstones in females (37.7%). The AP-associated mortality was 6.1% in severe AP cases, which was decreased by 40% compared to the 2011 survey. Antibiotics were administered to most cases, with carbapenem being frequently used. Enteral nutrition was given in 31.8% of severe cases, but majority cases received after 48 h. Among the 107 patients who received intervention for walled-off necrosis, five patients received surgery-first approach, 66 received endoscopic ultrasound-guided transluminal drainage, and 19 underwent step-up approach. Conclusions: We clarified the current status of AP in Japan including the significant reduction of mortality in severe cases, shift to endoscopic approaches for walled-off necrosis, and poor compliance of the recommendations in the guidelines including management of enteral nutrition and antibiotic administration.. |
| 47. |
Nao Fujimori, Masami Miki, Lingaku Lee, Kazuhide Matsumoto, Yu Takamatsu, Takehiro Takaoka, Katsuhito Teramatsu, Yuta Suehiro, Masatoshi Murakami, Hisato Igarashi, Takamasa Oono, Takao Ohtsuka, Masafumi Nakamura, Yutaka Koga, Yoshinao Oda, Tetsuhide Ito, Yoshihiro Ogawa, Natural history and clinical outcomes of pancreatic neuroendocrine neoplasms based on the WHO 2017 classification; a single-center experience of 30 years, Pancreatology, 10.1016/j.pan.2020.04.003, 20, 4, 709-715, 2020.06, Background/Objectives: This single-center study aimed to evaluate treatment outcomes and long-term prognosis of patients with pancreatic neuroendocrine neoplasms (PanNENs) based on the World Health Organization (WHO) 2017 classification. Methods: We enrolled 245 patients with PanNENs treated at Kyushu University Hospital between January 1987 and March 2018. PanNENs were categorized according to the WHO 2017 classification or further subdivisions of Ki-67 index. Clinicopathological features, median survival time (MST), and prognostic factors were retrospectively analyzed. Results: The number of PanNENs, especially non-functioning PanNENs, has increased over the last decade. The mean MST of all patients was 202 months; which was longest in patients with NET G1 (n = 145, MST = 261 months) relative to NET G2 (n = 72, 132 months), NET G3 (n = 3, 34 months) and NEC G3 (n = 17, 9 months). Prognosis in patients with surgery as the first-line treatment was significantly better than in those with drug therapy. However, 26% of patients who underwent curative resection developed recurrence after a median time of 28.7 months. In unresectable PanNENs (n = 97), the MST and 5-year survival rate were 78 months and 55.8%, respectively. Poor differentiation, Ki-67 index of >10% and presence of liver metastasis were significant unfavorable predictors. Response to first-line therapy (stable disease/partial response) and three or more treatment regimens were significant favorable predictors for unresectable PanNENs according to multivariate analyses (p |
| 48. |
nobuhiro fujita, Akihiro Nishie, Yoshiki Asayama, Kousei Ishigami, Nao Fujimori, Tetsuhide Ito, Hiroshi Honda, Intravoxel incoherent motion magnetic resonance imaging for assessment of chronic pancreatitis with special focus on its early stage, Acta Radiologica, 10.1177/0284185119872687, 61, 5, 579-585, 2020.05, Background: It is clinically necessary to validate a new non-invasive and reliable imaging method to detect early chronic pancreatitis. Intravoxel incoherent motion magnetic resonance imaging (MRI) is useful for quantitative assessment in abdominal solid organs. Purpose: To investigate the usefulness of intravoxel incoherent motion MRI parameters in the diagnosis of chronic pancreatitis. Material and Methods: Sixty patients with early chronic pancreatitis (n = 44) and chronic pancreatitis (n = 16) were assessed with intravoxel incoherent motion imaging. For comparison, a control group of 71 individuals without chronic pancreatitis was also enrolled. The perfusion fraction (f), pseudo-diffusion coefficient (D*), true diffusion coefficient (D), and apparent diffusion coefficient of pancreatic parenchyma were calculated. These measurements were compared between the three groups. The diagnostic accuracy of imaging parameters was assessed. Results: The f values of the early chronic pancreatitis group and the chronic pancreatitis group were significantly lower than those of the control group (P |
| 49. |
Yosuke Minoda, Keishi Komori, Nao Fujimori, Endoscopy-guided suction method for residual food in the stomach caused by the obstruction of a duodenal stent., Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society, 10.1111/den.13637, 32, 4, e69-e70, 2020.05. |
| 50. |
Atsushi Masamune, Kazuhiro Kikuta, Shin Hamada, Ichiro Tsuji, Yoshifumi Takeyama, Tooru Shimosegawa, Kazuichi Okazaki, Atsushi Kanno, Takanori Sano, Kazushige Uchida, Tsukasa Ikeura, Nao Fujimori, Yousuke Nakai, Terumi Kamisawa, Kensuke Kubota, Masayo Motoya, Kyoko Shimizu, Tomoyuki Ushijima, Mitsuharu Fukasawa, Itaru Naitoh, Masayuki Ueno, Kosuke Okuwaki, Norimitsu Uza, Masanori Asada, Tsuyoshi Mukai, Yasushi Kudo, Kota Uetsuki, Akira Mitoro, Hiroyuki Watanabe, Shuji Terai, Kazunao Hayashi, Yoshiki Imamura, Shin Haba, Kazuo Hara, Toshio Fujisawa, Eisuke Iwasaki, Fumihiro Okumura, Yuki Kawaji, Masayuki Kitano, Takayoshi Nishino, Masatsugu Nagahama, Atsuyuki Hirano, Yukio Aruga, Satoshi Yamamoto, Kazuo Inui, Yoshimasa Kubota, Kuniyuki Takahashi, Junichi Sakagami, Takashi Kobayashi, Takashi Miraki, Nationwide epidemiological survey of autoimmune pancreatitis in Japan in 2016, Journal of gastroenterology, 10.1007/s00535-019-01658-7, 55, 4, 462-470, 2020.04, Background: To further clarify the clinico-epidemiological features of autoimmune pancreatitis (AIP) in Japan, we conducted the fourth nationwide epidemiological survey. Methods: This study consisted of two stage surveys; the number of AIP patients was estimated by the first survey and their clinical features were assessed by the second survey. We surveyed the AIP patients who had visited hospitals in 2016. Results: The estimated number of AIP patients in 2016 was 13,436, with an overall prevalence rate of 10.1 per 100,000 persons. The estimated number of newly diagnosed patients was 3984, with an annual incidence rate of 3.1 per 100,000 persons. Compared to the 2011 survey, both numbers more than doubled. We obtained detailed clinical information of 1474 AIP patients. The male-to-female sex ratio was 2.94, the mean age was 68.1, and mean age at diagnosis was 64.8. At diagnosis, 63% patients were symptomatic and nearly half of them presented jaundice. Pancreatic cysts were found in 9% of the patients and calcifications in 6%. Histopathological examination was performed in 64%, mainly by endoscopic ultrasonography-guided fine needle aspiration. Extra-pancreatic lesions were detected in 60% of the patients. Eighty-four % patients received the initial steroid therapy, and 85% received maintenance steroid therapy. Kaplan–Meier analysis revealed that the relapsed survival was 14% at 3 years, 25% at 5 years, 40% at 10 years, and 50% at 15 years. Mortality was favorable, but pancreatic cancer accounted for death in one quarter of fatal cases. Conclusion: We clarified the current status of AIP in Japan.. |
| 51. |
Kazuki Takeishi, Tomoharu Yoshizumi, Toru Ikegami, Shinji Itoh, Noboru Harada, Nao Fujimori, Takamasa Ohno, Masaki Mori, Transgastric Endoscopic Lumen-Apposing Metal Stents for Intra-abdominal Fluid Collections After Living Donor Liver Transplantation., Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 10.1002/lt.25707, 26, 4, 598-601, 2020.04. |
| 52. |
Nao Fujimori, Yosuke Minoda, Masatoshi Murakami, Yuta Suehiro, Takamasa Oono, Eikichi Ihara, Yoshihiro Ogawa, Endoscopic removal of a lumen-apposing metal stent that migrated into the walled-off necrosis during the first drainage procedure, Endoscopy, 10.1055/a-0992-8900, 52, 2, E51-E52, 2020.02. |
| 53. |
Yosuke Minoda, Nao Fujimori, Eikichi Ihara, Forward-viewing endoscopic ultrasound-guided fine-needle biopsy using the clip-with-thread method for small gastric subepithelial lesions., Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society, 10.1111/den.13476, 31, 6, e103-e104, 2019.11. |
| 54. |
Miki M, Oono T, Fujimori N, Takaoka T, Kawabe K, Miyasaka Y, Ohtsuka T, Saito D, Nakamura M, Ohkawa Y, Oda Y, Suyama M, Ito T, Ogawa Y, CLEC3A, MMP7, and LCN2 as Novel Markers for Predicting Recurrence in Resected G1 and G2 Pancreatic Neuroendocrine Tumors, Cancer Medicine, 2019.05. |
| 55. |
Yoshihiro Miyasaka, Takao Ohtsuka, Ryuichiro Kimura, Ryota Matsuda, Yasuhisa Mori, Kohei Nakata, Daisuke Kakihara, Nao Fujimori, Takamasa Ohno, Yoshinao Oda, Masafumi Nakamura, Neoadjuvant Chemotherapy with Gemcitabine Plus Nab-Paclitaxel for Borderline Resectable Pancreatic Cancer Potentially Improves Survival and Facilitates Surgery., Annals of surgical oncology, 10.1245/s10434-019-07309-8, 26, 5, 1528-1534, 2019.05, BACKGROUND: Accumulation of evidence suggests that neoadjuvant chemotherapy improves the outcomes of borderline resectable pancreatic cancer (BRPC). Gemcitabine plus nab-paclitaxel (GnP) has been widely accepted as systemic chemotherapy for unresectable pancreatic cancer and reportedly results in remarkable tumor shrinkage. This study was performed to evaluate the safety and efficacy of neoadjuvant chemotherapy using neoadjuvant GnP for BRPC. METHODS: The medical records of 57 patients who underwent treatment of BRPC from 2010 to 2017 were retrospectively reviewed. The patient characteristics and short- and intermediate-term outcomes were compared between the GnP and upfront surgery (UFS) groups. RESULTS: The GnP group comprised 31 patients and the UFS group comprised 26 patients. The patient characteristics were comparable with the exception of a higher prevalence of arterial involvement in the GnP group. Twenty-seven of the 31 patients (87%) in the GnP group and all 26 patients in the UFS group underwent resection. The GnP group showed a significantly shorter operation time (429 vs. 509.5 min, p = 0.0068), less blood loss (760 vs. 1324 ml, p = 0.0115), and a higher R0 resection rate (100% vs. 77%, p = 0.0100) than the UFS group. Postoperative complications and hospital stay were comparable between the two groups, and no treatment-related mortality occurred in either group. Both the disease-free survival and overall survival times were significantly longer in the GnP group (p = 0.0018 and p = 0.0024, respectively). CONCLUSIONS: Neoadjuvant GnP is a safe and effective treatment strategy for BRPC. It potentially improves patients' prognosis and facilitates surgical procedures.. |
| 56. |
Miki M, Fujimori N, Oono T, Kawabe K, Ohno A, Matsumoto K, Teramatsu K, Tachibana Y, Ogawa Y, Relapse patterns and predictors of IgG4-related diseases involved with autoimmune pancreatitis: A single-center retrospective study of 115 patients, Journal of Digestive Diseases, 2019.01. |
| 57. |
Yoshihiro Miyasaka, Takao Ohtsuka, Ryuichiro Kimura, Ryota Matsuda, Yasuhisa Mori, Kohei Nakata, Daisuke Kakihara, Nao Fujimori, Takamasa Ohno, Yoshinao Oda, Masafumi Nakamura, Neoadjuvant Chemotherapy with Gemcitabine Plus Nab-Paclitaxel for Borderline Resectable Pancreatic Cancer Potentially Improves Survival and Facilitates Surgery, Annals of Surgical Oncology, 10.1245/s10434-019-07309-8, 2019.01, Background: Accumulation of evidence suggests that neoadjuvant chemotherapy improves the outcomes of borderline resectable pancreatic cancer (BRPC). Gemcitabine plus nab-paclitaxel (GnP) has been widely accepted as systemic chemotherapy for unresectable pancreatic cancer and reportedly results in remarkable tumor shrinkage. This study was performed to evaluate the safety and efficacy of neoadjuvant chemotherapy using neoadjuvant GnP for BRPC. Methods: The medical records of 57 patients who underwent treatment of BRPC from 2010 to 2017 were retrospectively reviewed. The patient characteristics and short- and intermediate-term outcomes were compared between the GnP and upfront surgery (UFS) groups. Results: The GnP group comprised 31 patients and the UFS group comprised 26 patients. The patient characteristics were comparable with the exception of a higher prevalence of arterial involvement in the GnP group. Twenty-seven of the 31 patients (87%) in the GnP group and all 26 patients in the UFS group underwent resection. The GnP group showed a significantly shorter operation time (429 vs. 509.5 min, p = 0.0068), less blood loss (760 vs. 1324 ml, p = 0.0115), and a higher R0 resection rate (100% vs. 77%, p = 0.0100) than the UFS group. Postoperative complications and hospital stay were comparable between the two groups, and no treatment-related mortality occurred in either group. Both the disease-free survival and overall survival times were significantly longer in the GnP group (p = 0.0018 and p = 0.0024, respectively). Conclusions: Neoadjuvant GnP is a safe and effective treatment strategy for BRPC. It potentially improves patients’ prognosis and facilitates surgical procedures.. |
| 58. |
Yasunaga K, Ito T, Miki M, Ueda K, Fujiyama T, Tachibana Y, Fujimori N, Kawabe K, Ogawa Y, Using CRISPR/Cas9 to Knock out Amylase in Acinar Cells, Biomed Res Int, 10.1155/2018/8719397, 2018, 8719397-8719397, 2018.04, Pancreatic cancer is a malignant neoplasm that originates from acinar cells. Acinar cells get reprogrammed to become duct cells, resulting in pancreatic cancer. Pancreatitis is an acinar cell inflammation, leading to "impaired autophagy flux". Pancreatitis promotes acinar-to-ductal transdifferentiation. Expression of amylase gets eliminated during the progression of pancreatic cancer. Amylase is considered as an acinar cell marker; however, its function in cells is not known. Thus, we investigated whether amylase affects the acinar cell autophagy and whether it plays any role in development of pancreatitis. Here, we knocked out ATG12 in a pancreatic cancer cells and acinar cells using CRISPR/Cas9. Autophagy inhibition led to an increase in the expression of duct cell markers and a simultaneous decrease in that of acinar cell markers. It also caused an increase in cell viability and changes in mitochondrial morphology. Next, we knocked out amylase in acinar cells. Amylase deficiency decreased autophagy induced by pancreatitis. Our results suggest that amylase controls pancreatitis-induced autophagy. We found that eliminating amylase expression contributes to pancreatic cancer etiology by decreasing autophagy. Furthermore, our results indicate that amylase plays a role in selective pancreatitis-induced autophagy of pancreatic enzyme vesicles.. |
| 59. |
Ohtsuka T, Gotoh Y, Nakashima Y, Okayama Y, Nakamura S, Morita M, Aly MYF, Velasquez VVDM, Mori Y, Sadakari Y, Nakata K, Miyasaka Y, Ishigami K, Fujimori N, Mochidome N, Oda Y, Shimizu S, Nakamura M, Role of SpyGlass-DStm in the preoperative assessment of pancreatic intraductal papillary mucinous neoplasm involving the main pancreatic duct, Pancreatology, 2018.04. |
| 60. |
Kazuhiro Toriyama, Susumu Hijioka, Izumi Komoto, Noritoshi, Kobayashi, Takuji Okusaka, Yonson Ku, Kentaro Sudo, Masayuki Furukawa, Yuichi Tachibana, Masanobu Takahashi, Hiroaki Yasuda, Shoji Nakamori, Yoshitaka Honma, Mitsuhiro Kida, Nao Fujimori, Tomomi Kashiwada, Toshihiko Masui, Hiroshi Ishii, Yoshiaki Tsuchiya, Shuji Isaji, Nobumasa Mizuno, Kazuo Hara, Motohiro Sakamine, Masayuki Imamura, Tatsuo Kagimura, Tetsuhide Ito, Study Protocol for Prospective Observational Study 1 on the Prognosis of Patients with Unresectable Advanced Gastrointestinal and Pancreatic Neuroendocrine Tumors (PROP-UP 1 Study) in Japan, J Clin Trials, 2018.04. |
| 61. |
Keijiro Ueda, Ken Kawabe, Lingaku Lee, Yuichi Tachibana, Nao Fujimori, Hisato Igarashi, Yoshinao Oda, Robert T Jensen, Ryoichi Takayanagi, Tetsuhide Ito, Diagnostic Performance of 48-Hour Fasting Test and Insulin Surrogates in Patients With Suspected Insulinoma., Pancreas, 10.1097/MPA.0000000000000772, 46, 4, 476-481, 2017.04, OBJECTIVES: This study aimed to evaluate the usefulness of the 48-hour fasting test and insulin surrogates followed by a glucagon stimulatory test (GST) for the diagnosis of insulinoma. METHODS: Thirty-five patients with suspected insulinoma who underwent 48-hour fasting test and GST were retrospectively included in our study: 15 patients with surgically proven insulinomas and 20 patients in whom insulinoma was clinically ruled out. We determined the duration of the fasting test, plasma glucose levels, serum levels of immunoreactive insulin and C-peptide, and insulin surrogates (serum levels of β-hydroxybutyrate, free fatty acid, and response of plasma glucose to intravenous glucagon [ΔPG]) at the end of the fast. RESULTS: The sensitivity and specificity of the 48-hour fasting test were 100.0% and 80.0%, respectively, for the diagnosis of insulinoma. When the 48-hour fasting test and immunoreactive insulin, C-peptide, or insulin surrogates were combined, the combination with GST showed the best results. The sensitivity, specificity, and accuracy rate were 93.3%, 95.0%, and 94.3%, respectively, with 1 false-negative case and 1 false-positive case occurring. CONCLUSIONS: A more accurate and less invasive diagnosis of insulinoma was possible by combining the 48-hour fasting test with the GST, compared with the existing method.. |
| 62. |
切除不能進行・再発胆道癌に対するゲムシタビン+シスプラチン併用療法の多施設前向き観察研究
切除不能進行・再発胆道癌に対する標準化学療法は、英国のABC-02試験と日本のBT22試験の良好な結果から、ゲムシタビン+シスプラチン(GC療法)とされるが、BT22試験のGC群は42例にすぎず、さらに症例を重ねて有効性と安全性を検討する必要があると考えられた。そこで、福岡・北九州地区においてGC療法の安全性・有効性を多施設前向き観察研究にて確認した。登録症例は再発例2例を含む37例。年齢の中央値は67.5(43～84)歳、肝内胆管癌12例、肝外胆管癌13例、胆嚢癌12例であった。生存期間中央値(median survival time:MST)は14.9ヵ月、1年生存率は54.5%であり、無増悪生存期間(progression free survival:PFS)の中央値は7.7ヵ月であった。治療関連死亡は認めず、Grade3以上の有害事象は白血球減少13例(35.1%)、好中球減少12例(32.4%)など血液毒性が主であった。MST、1年生存率、PFS、有害事象発生状況などはBT22試験と同様であり、本多施設前向き観察研究により、切除不能進行・再発胆道癌に対するGC療法の有効性と安全性が確認された。(著者抄録). |
| 63. |
Motoyuki Kohjima, Tsuyoshi Yoshimoto, Munechika Enjoji, Nobuyoshi Fukushima, Kunitaka Fukuizumi, Tsukasa Nakamura, Miho Kurokawa, Nao Fujimori, Yusuke Sasaki, Yasushi Shimonaka, Yusuke Murata, Susumu Koyama, Ken Kawabe, Kazuhiro Haraguchi, Yorinobu Sumida, Naohiko Harada, Masaki Kato, Kazuhiro Kotoh, Makoto Nakamuta, Hepcidin/ferroportin expression levels involve efficacy of pegylated-interferon plus ribavirin in hepatitis C virus-infected liver., World journal of gastroenterology, 10.3748/wjg.v21.i11.3291, 21, 11, 3291-9, 2015.03, AIM: To investigate the relationship between the iron-metabolism-related gene expression profiles and efficacy of antiviral therapy in chronic hepatitis C patients. METHODS: The hepatic expression profile of iron-metabolism-related genes was analyzed and its association with virological response to pegylated-interferon plus ribavirin combination therapy was evaluated. A hundred patients with chronic hepatitis C (genotype1b, n = 50; genotype 2, n = 50) were enrolled and retrospectively analyzed. Liver biopsy samples were subjected to quantitative polymerase chain reaction for iron-metabolism-related genes and protein expression (Western blotting analysis) for ferroportin. As a control, normal liver tissue was obtained from 18 living donors of liver transplantation. Serum hepcidin level was measured by sensitive liquid chromatography/electrospray ionization tandem mass spectrometry. RESULTS: Iron overload is associated with liver damage by increasing oxidative stress and hepatitis C virus (HCV) is reported to induce iron accumulation in hepatocytes in vivo. Conversely, iron administration suppresses HCV replication in vitro. Therefore, the association between HCV infection and iron metabolism remains unclear. Compared with controls, patients had significantly higher gene expression for transferrin, iron-regulatory proteins 1 and 2, divalent metal transporter 1, and ferroportin, but similar for transferrin receptors 1 and 2, and hepcidin. When the expression profiles were compared between sustained virological response (SVR) and non-SVR patients, the former showed significantly lower transcription and protein expression of hepcidin and ferroportin. Expression of hepcidin-regulating genes, BMPR1, BMPR2, and hemojuvelin, was significantly increased, whereas BMP2 was decreased in HCV-infected liver. BMPR2 and hemojuvelin expression was significantly lower in the SVR than non-SVR group. HCV infection affects the expression of iron-metabolism-related genes, leading to iron accumulation in hepatocytes. CONCLUSION: Decreased expression of hepcidin and ferroportin in SVR patients indicates the importance of hepatocytic iron retention for viral response during pegylated-interferon plus ribavirin treatment.. |
| 64. |
Masayuki Hijioka, Tetsuhide Ito, Hisato Igarashi, Nao Fujimori, Lingaku Lee, Taichi Nakamura, Robert T Jensen, Ryoichi Takayanagi, Serum chromogranin A is a useful marker for Japanese patients with pancreatic neuroendocrine tumors., Cancer science, 10.1111/cas.12533, 105, 11, 1464-71, 2014.11, Although chromogranin A (CGA) is a useful marker for pancreatic neuroendocrine tumors (pNET) in the West, its usefulness in Japanese populations is unclear. To assess this, we evaluated the serum CGA levels in 189 patients with various pancreatic diseases, including proven pNET (n = 69), pancreatic cancer (PC) (n = 50), chronic pancreatitis (CP) (n = 50) and autoimmune pancreatitis (AIP) (n = 20), and 112 normal controls (controls) using an ELISA kit. The mean CGA level of patients with pNET was significantly higher than any of the other groups (407.8 ± 984.6 ng/mL [pNET] vs 91.8 ± 101.8 ng/mL [PC], 93.6 ± 57.5 ng/mL [CP], 69.9 ± 52.4 ng/mL [AIP] and 62.5 ± 48.3 ng/mL [controls]). Limiting the analysis to patients not using proton pump inhibitors (PPI), the CGA level of patients with PC or CP was not significantly different compared with the controls. Discriminant analysis revealed that the best cut-off value of CGA to distinguish patients with pNET from the controls was 78.7 ng/mL, with a sensitivity and specificity of 53.6% and 78.6%, respectively. In patients with pNET, significant factors associating with elevated CGA levels were tumor classification, tumor size, and the presence of liver metastases in univariate analysis as well as PPI use and the presence of liver metastases in multivariate analysis. We show that CGA is a useful marker for diagnosing pNET in Japanese populations and for distinguishing patients with pNET from patients with other pancreatic diseases. The increased use of CGA in Japan will likely be a helpful tool in managing these patients, as found in the West.. |
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Nao Fujimori, Hisato Igarashi, Akira Asou, Ken Kawabe, Lingaku Lee, Takamasa Oono, Taichi Nakamura, Yusuke Niina, Masayuki Hijioka, Masahiko Uchida, Kazuhiro Kotoh, Kazuhiko Nakamura, Tetsuhide Ito, Ryoichi Takayanagi, Endoscopic approach through the minor papilla for the management of pancreatic diseases., World journal of gastrointestinal endoscopy, 10.4253/wjge.v5.i3.81, 5, 3, 81-8, 2013.03, AIM: To clarify the efficacy and safety of an endoscopic approach through the minor papilla for the management of pancreatic diseases. METHODS: This study included 44 endoscopic retrograde cholangiopancreatography (ERCP) procedures performed in 34 patients using a minor papilla approach between April 2007 and March 2012. We retrospectively evaluated the clinical profiles of the patients, the endoscopic interventions, short-term outcomes, and complications. RESULTS: Of 44 ERCPs, 26 were diagnostic ERCP, and 18 were therapeutic ERCP. The most common cause of difficult access to the main pancreatic duct through the major papilla was pancreas divisum followed by distortion of Wirsung's duct. The overall success rate of minor papilla cannulation was 80% (35/44), which was significantly improved by wire-guided cannulation (P = 0.04). Endoscopic minor papillotomy (EMP) was performed in 17 of 34 patients (50%) using a needle-knife (13/17) or a pull-type papillotome (4/17). EMP with pancreatic stent placement, which was the main therapeutic option for patients with chronic pancreatitis, recurrent acute pancreatitis, and pancreatic pseudocyst, resulted in short-term clinical improvement in 83% of patients. Mild post-ERCP pancreatitis occurred as an early complication in 2 cases (4.5%). CONCLUSION: The endoscopic minor papilla approach is technically feasible, safe, and effective when the procedure is performed in a high-volume referral center by experienced endoscopists.. |
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Masahiko Uchida, Tetsuhide Ito, Taichi Nakamura, Hisato Igarashi, Takamasa Oono, Nao Fujimori, Ken Kawabe, Koichi Suzuki, Robert T Jensen, Ryoichi Takayanagi, ERK pathway and sheddases play an essential role in ethanol-induced CX3CL1 release in pancreatic stellate cells., Laboratory investigation; a journal of technical methods and pathology, 10.1038/labinvest.2012.156, 93, 1, 41-53, 2013.01, The clinical course of chronic pancreatitis (CP) worsens with drinking, and pancreatic stellate cells (PSCs) have an important role in the pathogenesis of alcoholic CP. Chemokines recruit inflammatory cells, resulting in chronic pancreatic inflammation. Although serum levels of fractalkine (CX3CL1) are significantly elevated in patients with alcoholic CP, the mechanism of this elevation remains unclear. This study aims to determine the effects of cytokines, pathogen-associated molecular patterns (PAMPs), and ethanol and its metabolites on CX3CL1 secretion by PSCs. Male Wistar/Bonn Kobori (WBN/Kob) rats aged 15 to 20 weeks were used as rodent models of CP in vivo. PSCs were isolated from 6-week-old male Wistar rats. The effects of cytokines, PAMPs, and ethanol and its metabolites on chemokine production and activation of signaling pathways in PSCs in vitro were examined by real-time reverse transcription-polymerase chain reaction (RT-PCR), western blotting, and enzyme-linked immunosorbent assay. Expression of CX3CL1 and matrix metalloprotease (MMP)-2 was increased in the pancreas of WBN/Kob rats. The rat PSCs expressed CX3CL1, MMP-2, and a disintegrin and metalloprotease domain (ADAM) 17. Cytokines and PAMPs induced CX3CL1 release and activated extracellular signal-regulated kinase (ERK), MMP-9, and ADAM17. CX3CL1 release was suppressed by specific inhibitors of ERK, MMP, and ADAM, and ERK was associated with CX3CL1 transcription. Ethanol and phorbol myristate acetate synergistically increased CX3CL1 release. Real-time PCR and western blotting confirmed the synergistic activation of ERK and ADAM17. Ethanol synergistically increased CX3CL1 release via ERK and ADAM17 activation in PSCs. In conclusion, we demonstrated for the first time that ethanol synergistically increased CX3CL1 release from PSCs at least in part through activation of ERK mitogen-activated protein kinase and ADAM17. This might be one of the mechanisms of serum CX3CL1 elevation and disease progression in patients with alcoholic CP.. |
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Yusuke Niina, Nao Fujimori, Taichi Nakamura, Hisato Igarashi, Takamasa Oono, Kazuhiko Nakamura, Masaki Kato, Robert T. Jensen, Tetsuhide Ito, Ryoichi Takayanagi, The Current Strategy for Managing Pancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1, GUT AND LIVER, 10.5009/gnl.2012.6.3.287, 6, 3, 287-294, 2012.07, Multiple endocrine neoplasia type 1 (MEN1) is an inherited autosomal dominant disease presenting with pancreatic neuroendocrine tumors (pNETs), parathyroid tumors, or pituitary tumors. Using the PubMed database, we reviewed the literature on information regarding the proper diagnosis and treatment of MEN1-associated pNET. Many cases of MEN1-associated pNET are functioning pNETs. Gastrinomas and insulinomas tend to occur frequently in the duodenum and pancreas, respectively. In addition to diagnostic imaging, the selective arterial secretagogue injection test (SASI test) is useful for localizing functioning pNET. The standard treatment is surgical resection. However, in the case of a functioning pNET, the tumor should first be accurately located using the SASI test before an appropriate surgical method is selected. In cases of a MEN1-associated non-functioning pNET that exceeds 2 cm in diameter, the incidence of distant metastasis is significantly increased, and surgery is recommended. In cases of unresectable pNET, a somatostatin analog has been shown to demonstrate antitumor effects and is considered to be a promising treatment. In addition, molecular-targeted drugs have recently been found to be effective in phase III clinical trials. (Gut Liver 2012;6:287-294). |
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Epidemiology, symptoms and diagnosis. |
| 69. |
Taichi Nakamura, Tetsuhide Ito, Takamasa Oono, Hisato Igarashi, Nao Fujimori, Masahiko Uchida, Yusuke Niina, Mikihiko Yasuda, Koichi Suzuki, Ryoichi Takayanagi, Bacterial DNA promotes proliferation of rat pancreatic stellate cells thorough toll-like receptor 9: potential mechanisms for bacterially induced fibrosis., Pancreas, 10.1097/MPA.0b013e318224a501, 40, 6, 823-31, 2011.08, OBJECTIVES: We hoped to clarify the possible role of CpG DNA as a trigger factor for overt pancreatic inflammation of pancreatic stellate cells (PSCs). METHODS: Pancreatic stellate cells were isolated from the male Lewis rat. The expression of Toll-like receptor 9 (TLR9) messenger RNA and protein were evaluated by reverse transcription-polymerase chain reaction and immunofluorescent cytochemistry. Internalization of CpG DNA was analyzed by confocal laser scanning microscopy. Pancreatic stellate cells were incubated with CpG DNA, and then cell proliferation and migration were assessed. RESULTS: Constitutive expression of TLR9 occurs at the messenger RNA and protein levels. After several minutes of CpG DNA administration, CpG DNA was observed on the cell membrane surface and in the cytoplasm and found to be translocating into the perinucleus of PSCs. Pancreatic stellate cells migrated and proliferated in dose- and time-dependent manners in response to simulation by CpG DNA. Proliferation of PSCs was observed 3 hours after administration (earlier than platelet-derived growth factor-induced proliferation), suggesting that PSCs respond readily to provide innate immunity. Endosomal acidification inhibitors attenuated CpG DNA-induced signaling, leading to suppression of DNA synthesis by PSCs. CONCLUSIONS: Our findings demonstrate that bacterial DNA promotes migration and proliferation of PSCs and suggest that bacterial DNA can initiate and sustain pancreatic inflammation and fibrosis by means of TLR9.. |
| 70. |
Tetsuhide Ito, Makoto Otsuki, Hisato Igarashi, Yasuyuki Kihara, Ken Kawabe, Taichi Nakamura, Nao Fujimori, Takamasa Oono, Ryoichi Takayanagi, Tooru Shimosegawa, Epidemiological study of pancreatic diabetes in Japan in 2005: a nationwide study., Pancreas, 10.1097/MPA.0b013e3181ca3da4, 39, 6, 829-35, 2010.08, OBJECTIVES: There have been few epidemiological studies on pancreatic diabetes. In this study, we determined the incidence and pathology of pancreatic diabetes in Japan. METHODS: We examined the epidemiology of pancreatic diabetes in Japan in 2005 by using a nationwide stratified random-sampling method. Especially, we focused on newly developed diabetes in association with the occurrence of pancreatic disease (true pancreatic diabetes). RESULTS: A total of 19,500 individuals received treatment for true pancreatic diabetes, accounting for 0.8% of patients with diabetes. Prevalence was estimated to be 15.2 per 100,000 with an annual onset incidence of 1.1 per 100,000. With regard to the complications in true pancreatic diabetes, the incidence of retinopathy was lower than that in types 1 and 2 diabetes. Among true pancreatic diabetes with chronic pancreatitis, alcoholic pancreatitis was found in the largest sector. Furthermore, as many as 53.7% were continuous drinkers, and 66.7% received insulin therapy. The frequency of hypoglycemia was high in regular drinkers treated with insulin. Hypoglycemia was a major cause of death in patients who were on insulin and continuous drinkers. CONCLUSION: We clarified the epidemiology of pancreatic diabetes in Japan. Patients with chronic pancreatitis-associated pancreatic diabetes should receive lifestyle guidance focused on drinking cessation.. |
| 71. |
Fujimori Nao, Nakamura Taichi, Oono Takamasa, Igarashi Hisato, Takahata Shunichi, Nakamura Masafumi, Tanaka Masao, Hayashi Akifumi, Aishima Shinichi, Ishigami Kousei, Ogoshi Keiichiro, Ito Tetsuhide, Takayanagi Ryoichi, Adenocarcinoma Involving the Whole Pancreas with Multiple Pancreatic Masses, Internal Medicine, 10.2169/internalmedicine.49.3347, 49, 15, 1527-1532, 2010.08, A 77-year-old man was referred to our hospital for further investigation of pancreatic masses. Imaging studies revealed hypovascular masses in the pancreatic head and body. Total pancreatectomy was performed under the diagnosis of double primary pancreatic carcinomas. Macroscopic examination revealed 3 nodules: one each in the pancreatic head, body, and tail. Microscopically, all 3 lesions showed similar carcinoma cells, which communicated with each other via the intraductal component, indicating a single large tumor. Incidentally, we also identified an adenocarcinoma of the common bile duct (CBD). The final diagnosis was synchronous double cancer involving the whole pancreas and the CBD.
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| 72. |
Mikihiko Yasuda, Yusuke Niina, Masahiko Uchida, Nao Fujimori, Taichi Nakamura, Akamasa Oono, Hisato Igarashi, Kousei Ishigami, Yumi Yasukouchi, Kazuhiko Nakamura, Tetsuhide Ito, Ryoichi Takayanagi, A case of lipomatous pseudohypertrophy of the pancreas diagnosed by typical imaging, Journal of the Pancreas, 11, 4, 385-388, 2010.07, Context Lipomatous pseudohypertrophy of the pancreas is an extremely rare disease, and is characterized by the replacement of pancreatic acinar cells with adipose tissue, although the pancreatic duct and islets are preserved. Case report We report the case of a 64-year-old female who was undergoing treatment for Hashimoto's disease at a nearby clinic. For the previous two years, she had experienced an unpleasant feeling in the upper abdominal area after eating oily foods. For the previous six months, she had also suffered from lower-back pain, and presented at our hospital. Abdominal computed tomography and magnetic resonance imaging revealed marked fat replacement over the entire pancreas. Endoscopic retrograde cholangiopancreatography revealed no anatomical abnormality or narrowing of the main pancreatic duct
the main pancreatic duct was normal up to the pancreatic tail and the branchesof the pancreatic duct did not show any abnormalities. While the serum levels of the pancreatic enzymes were considerably low, according to the data of the pancreatic exocrine function test (N-benzoyl-tyrosyl-p-aminobenzoic acid test), endocrine function was maintained. On the basis of the abovementioned findings, we diagnosed lipomatous pseudohypertrophy of the pancreas. Conclusions Lipomatous pseudohypertrophy of the pancreas is a very rare disease characterized by the disappearance of pancreatic exocrine tissue due to adipose tissue replacement, although the pancreatic duct and islets remain intact. Even though it has been suggested that the diagnosis of lipomatous pseudohypertrophy of the pancreas should be based on histological findings, this case indicated the possibility that lipomatous pseudohypertrophy of the pancreas may be diagnosed solely by typical imaging findings and serological data.. |
| 73. |
Lipomatous pseudohypertrophy of the pancreas(LPP)の一症例. |
| 74. |
4. Treatment of Chronic Pancreatitis.. |
| 75. |
Junya Gibo, Tetsuhide Ito, Ken Kawabe, Terumasa Hisano, Masanobu Inoue, Nao Fujimori, Takamasa Oono, Yoshiyuki Arita, Hajime Nawata, Camostat mesilate attenuates pancreatic fibrosis via inhibition of monocytes and pancreatic stellate cells activity., Laboratory investigation; a journal of technical methods and pathology, 85, 1, 75-89, 2005.01, Camostat mesilate (CM), an oral protease inhibitor, has been used clinically for the treatment of chronic pancreatitis in Japan. However, the mechanism by which it operates has not been fully understood. Our aim was to evaluate the therapeutic efficacy of CM in the experimental pancreatic fibrosis model induced by dibutyltin dichloride (DBTC), and we also determined the effect of CM on isolated monocytes and panceatic stellate cells (PSCs). In vivo, chronic pancreatitis was induced in male Lewis rats by single administration of 7 mg/kg DBTC and a special diet containing 1 mg/g CM was fed to the DBTC+CM-treated group from day 7, while the DBTC-treated group rats were fed a standard diet. At days 0, 7, 14 and 28, the severity of pancreatitis and fibrosis was examined histologically and enzymologically in both groups. In vitro, monocytes were isolated from the spleen of a Lewis rat, and activated with lipopolysaccharide stimulation. Thereafter, the effect of CM on monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) production from monocytes was examined. Subsequently, cultured rat PSCs were exposed to CM and tested to see whether their proliferation, MCP-1 production and procollagen alpha1 messenger RNA expression was influenced by CM. In vivo, the oral administration of CM inhibited inflammation, cytokines expression and fibrosis in the pancreas. The in vitro study revealed that CM inhibited both MCP-1 and TNF-alpha production from monocytes, and proliferation and MCP-1 production from PSCs. However, procollagen alpha1 expression in PSCs was not influenced by CM. These results suggest that CM attenuated DBTC-induced rat pancreatic fibrosis via inhibition of monocytes and PSCs activity.. |
