Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
UEDA KEIJIRO Last modified date:2024.06.03

Assistant Professor / ​Department of Medicine and Bioregulatory Science / Department of Hepatology and Pancreatology / Kyushu University Hospital

1. 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..
2. 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..
3. Keijiro Ueda, Masayuki Hijioka, Lingaku Lee, Hisato Igarashi, Yusuke Niina, Takashi Osoegawa, Kazuhiko Nakamura, Shunsuke Takahashi, Shinichi Aishima, Takao Ohtsuka, Ryoichi Takayanagi, Tetsuhide Ito, A synchronous pancreatic neuroendocrine tumor and duodenal gastrointestinal stromal tumor., Internal medicine (Tokyo, Japan), 53, 21, 2483-8, 2014.11, We recently encountered the case of a patient with a synchronous duodenal gastrointestinal stromal tumor (GIST) and pancreatic neuroendocrine tumor (PNET). This is the first report of this specific combination of multiple primary tumors, although three cases involving both PNET and gastric GIST have previously been reported. Since the duodenal GIST developed close to the pancreatic uncus in this case, we considered the possibility of multiple PNETs in the differential diagnosis. However, a histopathological examination using endoscopic ultrasonography-guided fine-needle aspiration confirmed the diagnosis of multiple primary lesions, involving PNET and duodenal GIST..
4. Kohei Yasunaga, Tetsuhide Ito, Masami Miki, Keijiro Ueda, Takashi Fujiyama, Yuichi Tachibana, Nao Fujimori, Ken Kawabe, Yoshihiro Ogawa, Using CRISPR/Cas9 to Knock out Amylase in Acinar Cells Decreases Pancreatitis-Induced Autophagy., BioMed research international, 10.1155/2018/8719397, 2018, 8719397-8719397, 2018.05, 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..
5. Tetsuhide Ito, Lingaku Lee, Masayuki Hijioka, Ken Kawabe, Masaki Kato, Kazuhiko Nakamura, Keijiro Ueda, Takao Ohtsuka, Hisato Igarashi, The up-to-date review of epidemiological pancreatic neuroendocrine tumors in Japan., Journal of hepato-biliary-pancreatic sciences, 10.1002/jhbp.225, 22, 8, 574-7, 2015.08, Pancreatic neuroendocrine tumors (PNETs) were considered an extremely rare disease. However, in recent years, the number of patients with PNET has increased rapidly. According to an epidemiological survey conducted in Japan, the number of treated patients with PNETs in 2010 was approximately 1.2-times that in 2005, and the number of new incidences of non-functional PNETs in 2010 was approximately 1.7-times that in 2005. Among functional PNETs, insulinoma was most prevalent, followed by gastrinoma. To diagnose PNETs, correct histological diagnosis is most important. According to the World Health Organization 2010 classification criteria, neuroendocrine tumors (NETs) are categorized into well-differentiated NETs and poorly differentiated neuroendocrine carcinomas (NECs). NECs accounted for 7.6% of all NETs, and functional and non-functional PNETs accounted for 2.1% and 10.1%, respectively. Patients with distant metastasis accounted for 19.9%, and those with multiple endocrine neoplasia type 1 accounted for 4.3%. When treating PNETs, it is necessary to correctly evaluate the functionality and progression of tumors, the presence or absence of metastasis, and the degrees of differentiation and malignant potential of tumors. A new registration system from the Japan Neuroendocrine Tumor Society will start to be used in 2015, which will help further dissemination of Japanese epidemiological information to the world..
6. Tetsuhide Ito, Hiroshi Ishiguro, Hirotaka Ohara, Terumi Kamisawa, Junichi Sakagami, Naohiro Sata, Yoshifumi Takeyama, Morihisa Hirota, Hiroyuki Miyakawa, Hisato Igarashi, Lingaku Lee, Takashi Fujiyama, Masayuki Hijioka, Keijiro Ueda, Yuichi Tachibana, Yoshio Sogame, Hiroaki Yasuda, Ryusuke Kato, Keisho Kataoka, Keiko Shiratori, Masanori Sugiyama, Kazuichi Okazaki, Shigeyuki Kawa, Yusuke Tando, Yoshikazu Kinoshita, Mamoru Watanabe, Tooru Shimosegawa, Evidence-based clinical practice guidelines for chronic pancreatitis 2015., Journal of gastroenterology, 10.1007/s00535-015-1149-x, 51, 2, 85-92, 2016.02, Chronic pancreatitis is considered to be an irreversible progressive chronic inflammatory disease. The etiology and pathology of chronic pancreatitis are complex; therefore, it is important to correctly understand the stage and pathology and provide appropriate treatment accordingly. The newly revised Clinical Practice Guidelines of Chronic Pancreatitis 2015 consist of four chapters, i.e., diagnosis, staging, treatment, and prognosis, and includes a total of 65 clinical questions. These guidelines have aimed at providing certain directions and clinically practical contents for the management of chronic pancreatitis, preferentially adopting clinically useful articles. These revised guidelines also refer to early chronic pancreatitis based on the Criteria for the Diagnosis of Chronic Pancreatitis 2009. They include such items as health insurance coverage of high-titer lipase preparations and extracorporeal shock wave lithotripsy, new antidiabetic drugs, and the definition of and treatment approach to pancreatic pseudocyst. The accuracy of these guidelines has been improved by examining and adopting new evidence obtained after the publication of the first edition..
7. Masami Miki, Tetsuhide Ito, Masayuki Hijioka, Lingaku Lee, Kohei Yasunaga, Keijiro Ueda, Takashi Fujiyama, Yuichi Tachibana, Ken Kawabe, Robert T Jensen, Yoshihiro Ogawa, Utility of chromogranin B compared with chromogranin A as a biomarker in Japanese patients with pancreatic neuroendocrine tumors., Japanese journal of clinical oncology, 10.1093/jjco/hyx032, 47, 6, 520-528, 2017.06, OBJECTIVE: Currently, serum chromogranin A is a well-established biomarker for pancreatic neuroendocrine tumors; however, other pancreatic diseases, oral use of a proton pump inhibitor and renal impairment can affect chromogranin A. Meanwhile, chromogranin B, belonging to the same granin family as chromogranin A, is not fully examined in these conditions. The present study aimed to evaluate the utility of chromogranin B as a pancreatic neuroendocrine tumor biomarker. METHODS: Serum chromogranin B levels were determined by radioimmunoassay and serum chromogranin A levels by enzyme-linked immunosorbent assay in pancreatic neuroendocrine tumor (n = 91) and other pancreatic conditions, and in healthy people (n = 104), to assess the relationships with clinical features. RESULTS: The diagnostic ability of chromogranin B was as good as chromogranin A. The area under the curve was 0.79 for chromogranin B (sensitivity/specificity: 72%/77%), and 0.78 for chromogranin A (sensitivity/specificity: 79%/64%). Chromogranin B was not affected by proton pump inhibitor use and age, which affected chromogranin A. The number of cases without liver metastases was larger in pancreatic neuroendocrine tumor patients with positive chromogranin B and negative chromogranin A. Though chromogranin A significantly elevated cases with proton pump inhibitor treatment and had positive correlation with age, chromogranin B did not have the tendencies. However, both chromogranin B and chromogranin A elevated in the case with renal impairment. In addition, the logistic regression analysis showed that chromogranin B was superior to chromogranin A in differentiation of pancreatic neuroendocrine tumor from other pancreatic diseases. CONCLUSIONS: Compared with chromogranin A, chromogranin B may be more useful during proton pump inhibitor treatment and can detect tumors without liver metastases. In addition, chromogranin B may be an excellent biomarker when differentiation of pancreatic neuroendocrine tumor from other pancreatic diseases is required..
8. Keijiro Ueda, Tetsuhide Ito, Ken Kawabe, Lingaku Lee, Takashi Fujiyama, Yuichi Tachibana, Masami Miki, Kohei Yasunaga, Takehiro Takaoka, Akihiro Nishie, Yoshiki Asayama, Robert T Jensen, Yoshihiro Ogawa, Should the Selective Arterial Secretagogue Injection Test for Insulinoma Localization Be Evaluated at 60 or 120 Seconds?, Internal medicine (Tokyo, Japan), 10.2169/internalmedicine.9107-17, 56, 22, 2985-2991, 2017.11, Objective The selective arterial secretagogue injection (SASI) test is considered indispensable for the accurate localization of insulinoma. However, the optimum timing of the post-injection evaluation is controversial, as some studies recommend 60 seconds [SASI (60 seconds)] while others support 120 seconds [SASI (120 seconds)]. The aim of this study was to determine the optimum timing for the SASI test evaluation for insulinoma localization. Methods Thirteen patients with surgically proven insulinoma were studied retrospectively. For the SASI test, immunoreactive insulin (IRI) was determined at baseline and at 30, 60, 90, and 120 seconds after calcium gluconate injection. A two-fold or greater increase in IRI over the baseline value was considered positive. The localization abilities of SASI (60 seconds) and SASI (120 seconds) were then compared. Results In 13 patients, a secretagogue was injected into 40 arteries supplying the pancreas. In the SASI (60 seconds) and SASI (120 seconds), the respective findings were as follows: positive predictive value, 72.2% and 68.2%; false positive rate, 25.0% and 35.0%; and rate of positivity in the head and body/tail, 38.5% and 46.2%. When the artery with the largest change was taken as the dominant artery, the localization detection sensitivity was 76.9% for SASI (60 seconds) and 92.3% for SASI (120 seconds). The sensitivity of morphological imaging techniques for localization ranged from 61.5-91.7%. Conclusion Compared with SASI (60 seconds) or morphological imaging, the insulinoma localization ability of SASI (120 seconds) was superior. Given these findings, we believe that the IRI level should be measured at 120 seconds in the SASI test..
9. Takashi Fujiyama, Tetsuhide Ito, Keijiro Ueda, Yuichi Tachibana, Kohei Yasunaga, Masami Miki, Takehiro Takaoka, Lingaku Lee, Ken Kawabe, Yoshihiro Ogawa, Serum levels of Wisteria floribunda agglutinin-positive Mac-2 binding protein reflect the severity of chronic pancreatitis., Journal of digestive diseases, 10.1111/1751-2980.12475, 18, 5, 302-308, 2017.05, OBJECTIVES: To evaluate the utility of serum Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA + -M2BP) level as a marker for chronic pancreatitis (CP). METHODS: We measured the serum WFA+ -M2BP level of 74 patients with CP who had undergone endoscopic retrograde cholangiopancreatography and 30 normal controls (NC) using a glycan sugar chain-based immunoassay and investigated the relationship between serum WFA+ -M2BP levels and the Cambridge classification of CP. RESULTS: Serum WFA+ -M2BP level was significantly higher in patients with CP than in NC (0.64 ± 0.28 vs 0.34 ± 0.25, P 
10. Lingaku Lee, Tetsuhide Ito, Hisato Igarashi, Keijiro Ueda, Takashi Fujiyama, Ken Kawabe, Yoshihiro Ogawa, Impact of everolimus on Japanese patients with advanced pancreatic neuroendocrine neoplasms., Journal of hepato-biliary-pancreatic sciences, 10.1002/jhbp.418, 24, 2, 95-102, 2017.02, BACKGROUND: Although everolimus has become a key therapeutic agent in patients with advanced pancreatic neuroendocrine neoplasms (PNEN), its efficacy and safety in clinical practice remains unclear. METHODS: Forty-seven patients with advanced PNEN treated with everolimus were reviewed retrospectively. To evaluate the safety of everolimus as a long-term treatment, the patients were divided into two groups according to treatment duration: group A, ≤1 year (n = 21); group B, >1 year (n = 26). RESULTS: Among 42 patients with pancreatic neuroendocrine tumors (PNET), the median progression-free survival, overall survival, and objective response rate were 27.5 months, 60.8 months, and 19.0%, respectively. Two patients with pancreatic neuroendocrine carcinomas (PNEC) with lower Ki-67 index and well-differentiated tumors showed favorable responses. More patients in group A discontinued everolimus owing to adverse drug reactions (ADRs) than in group B. The median relative dose intensity was significantly lower in group B than group A (P = 0.045), whereas the drug interruption rate was significantly higher in group B than group A (P 
11. 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..
12. Yusuke Watanabe, Sho Endo, Kazuyoshi Nishihara, Keijiro Ueda, Mari Mine, Sadafumi Tamiya, Toru Nakano, Masao Tanaka, The validity of the surgical indication for intraductal papillary mucinous neoplasm of the pancreas advocated by the 2017 revised International Association of Pancreatology consensus guidelines., Surgery today, 10.1007/s00595-018-1691-2, 48, 11, 1011-1019, 2018.11, PURPOSE: This study was performed to evaluate the surgical indication for intraductal papillary mucinous neoplasm (IPMN) advocated by the 2017 revised International Association of Pancreatology consensus guidelines (IAPCG2017). METHODS: The medical records of 63 patients who underwent pancreatectomy for IPMN were retrospectively reviewed. RESULTS: Thirteen patients had main-duct IPMN, 25 had mixed IPMN, and 25 had branch-duct IPMN with frequencies of high-grade dysplasia or invasive carcinoma of 62, 24, and 28%, respectively. The sensitivity and specificity of high-risk stigmata for high-grade dysplasia or invasive carcinoma advocated by the IAPCG2017 were 90 and 67%, respectively. Of 17 patients with invasive carcinoma, all patients had high-risk stigmata, and 16 had an enhanced mural nodule (MN) of ≥ 5 mm. The sensitivity and specificity of a ≥ 5-mm enhanced MN for predicting invasive carcinoma were 94% and 87%, respectively. CONCLUSIONS: Introducing a size threshold for enhanced MNs into the assessment of high-risk stigmata increases the specificity without jeopardizing the sensitivity. The surgical indication for any type of IPMN may be determined using only a ≥ 5-mm enhanced MN. When the type of IPMN is classified strictly, about half of IPMNs are mixed type, and most are benign. The surgical indication for mixed IPMN should be reconsidered..
13. Hitoshi Shibuya, Susumu Hijioka, Yasunari Sakamoto, Tetsuhide Ito, Keijiro Ueda, Izumi Komoto, Noritoshi Kobayashi, Atsushi Kudo, Hiroaki Yasuda, Hayato Miyake, Junichi Arita, Sho Kiritani, Masafumi Ikeda, Hiroshi Imaoka, Makoto Ueno, Satoshi Kobayashi, Mitsuhiro Furuta, Yoshikuni Nagashio, Gou Murohisa, Taku Aoki, Shigemi Matsumoto, Masayo Motoya, Nobuaki Azemoto, Jun Itakura, Shigeru Horiguchi, Tatsuji Yogi, Tetsuro Kawagoe, Youichi Miyaoka, Fumito Imamura, Michio Senju, Hitoshi Arioka, Kazuo Hara, Masayuki Imamura, Takuji Okusaka, Multi-center clinical evaluation of streptozocin-based chemotherapy for advanced pancreatic neuroendocrine tumors in Japan: focus on weekly regimens and monotherapy., Cancer chemotherapy and pharmacology, 10.1007/s00280-018-3656-y, 82, 4, 661-668, 2018.10, PURPOSE: Streptozocin (STZ) is a key agent for treating advanced pancreatic neuroendocrine tumors (pNET). Most STZ regimens for pNET are daily and also include 5-fluorouracil (5FU), whereas STZ monotherapy and weekly regimens have also been applied in daily practice in Japan. The present study aimed to evaluate responses to weekly regimens and to STZ monotherapy, and to identify a predictive marker of a response to STZ. METHODS: Clinical data regarding STZ-based chemotherapy for pNET were collected between 2015 and 2017 at 25 facilities. We analyzed the effects, safety, progression-free survival (PFS), and factors that correlate with responses to STZ. RESULTS: The overall objective response rate (ORR) of 110 patients who underwent STZ-based chemotherapy (monotherapy, 81.8%; weekly regimen 46.4%) was 21.8%, and PFS was 9.8 months. The ORR of weekly vs. daily regimens was 21.6 vs. 22.0% (P = 1.000), and that of monotherapy vs. combination therapy was 21.1 vs. 25.0% (P = 0.766). A Ki67 proliferation index (Ki67) of > 5% was a predictive marker of a response to STZ (P = 0.017), whereas regimen type, mono- or combination therapy, treatment line and liver tumor burden were not associated with responses. The frequencies of Grade ≥ 3 nausea and hematological adverse events were significantly lower for monotherapy than combination therapy (P = 0.032). CONCLUSIONS: The effects of weekly STZ monotherapy on pNET are comparable to those previously reported and the toxicity profile was acceptable. Ki67 > 5% was the sole predictive marker of an objective response..
14. Yusuke Watanabe, Keijiro Ueda, So Nakamura, Sho Endo, Shingo Kozono, Kazuyoshi Nishihara, Toru Nakano, Endoscopic Transpapillary Pancreatic Duct Stent Placement for Symptomatic Peripancreatic Fluid Collection Caused by Clinically Relevant Postoperative Pancreatic Fistula After Distal Pancreatectomy., Surgical laparoscopy, endoscopy & percutaneous techniques, 10.1097/SLE.0000000000000694, 29, 4, 261-266, 2019.08, This study aimed to evaluate the safety and efficacy of endoscopic transpapillary pancreatic duct stent placement (ETPS) for symptomatic peripancreatic fluid collection caused by postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP). ETPS was also compared with percutaneous drainage (PTD). Retrospectively 38 patients were studied who developed clinically relevant POPF. Of 38 patients, 4 underwent PTD and 11 underwent ETPS. Technical and clinical success rates of ETPS (100% and 91%, respectively) were comparable with PTD (100% and 75%, respectively). The tip of a pancreatic stent was placed over the pancreatic stump in 4 patients and draining of pus through the pancreatic stent was observed. The hospital stay after DP and the interval from intervention to discharge were significantly shorter in the ETPS group than in the PTD group. ETPS is safe and successful for managing peripancreatic fluid collection caused by POPF after DP and should be considered as a therapeutic option..
15. 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..
16. 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, 2022.10, 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
17. Yuji Mizuno, Tetsuhide Ito, Keijiro Ueda, Ayaka Tashiro, Yumiko Kubota, Azusa Yamashita, Maiko Miura, Himiko Hayama, Masafumi Oya, Masazumi Tsuneyoshi, A case of erythema multiforme-like rash induced by everolimus in a patient with a pancreatic neuroendocrine tumor., Clinical journal of gastroenterology, 10.1007/s12328-022-01709-2, 15, 6, 1193-1197, 2022.12, A 66-year-old Japanese woman had been diagnosed with a neuroendocrine tumor of the pancreatic head (G2) 3 years previously and undergone pancreaticoduodenectomy. Nine months postoperatively, recurrence with multiple liver metastases developed and she was referred to our department. A regimen of 10 mg of everolimus for 2 weeks plus 1-week washout was instituted, and no adverse events were observed. Fourteen months after treatment initiation, she developed severe generalized erythema multiforme (EM). Skin biopsy revealed spongiosis in the epidermis and interface change and edema in the superficial dermis. Mast cells were observed from the dermis to the subcutaneous tissue, as well as perivascular eosinophilic infiltration, leading to EM being diagnosed. Oral everolimus was discontinued, and the EM was relieved by treatment including steroid therapy. Everolimus is an inhibitor of the mammalian target of rapamycin, and its indications include neuroendocrine tumors. Skin disorders are commonly seen in the early stages of everolimus treatment, but their severity is almost always mild and never severe. This is the first report on a patient who presented with severe generalized EM more than 1 year after everolimus treatment initiation. Patients on everolimus therapy should be monitored for skin disorders on a long-term basis..
18. 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.
19. 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..
20. 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, 2023.08, 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
21. Murakami M, Fujimori N, Matsumoto K, Ohno A, Teramatsu K, Takamatsu Y, Takeno A, Ueda K, Oono T, Ito T, Ogawa Y., A clinical analysis on functioning pancreatic neuroendocrine tumors (focusing on VIPomas):a single-center experience.

, Endocr J., 2023.05.
22. Miki M, Fujimori N, Ueda K, Lee L, Murakami M, Takamatsu Y, Shimokawa Y, Niina Y, Oono T, Hisano T, Furukawa M, Ogawa Y., 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.

, J Clin Med. , 2023.05.
23. Miyagahara T, Fujimori N, Ueda K, Takamatsu Y, Matsumoto K, Teramastu K, Takaoka T, Suehiro Y, Shimokawa Y, Omori K, Niina Y, Tachibana Y, Akashi T, Oono T, Ogawa Y., Incidence and appropriate management of drug-induced interstitial lung disease in Japanese patients with unresectable pancreatic cancer: A multicenter retrospective study., Asia Pac J Clin Oncol., 2022.11.
24. Watanabe Y, Ueda K, Nakamura S, Endo S, Kozono S, Nishihara K, Nakano T., Endoscopic Transpapillary Pancreatic Duct Stent Placement for Symptomatic Peripancreatic Fluid Collection Caused by Clinically Relevant Postoperative Pancreatic Fistula After Distal Pancreatectomy., Surg Laparosc Endosc Percutan Tech, 2019.08.