849 results on '"Mitsuhiro, Fujishiro"'
Search Results
2. Successful endoscopic removal of a retained guidewire in the intrahepatic bile duct using a novel tapered sheath dilator
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Rintaro Fukuda, MD, Naminatsu Takahara, MD, PhD, Yousuke Nakai, MD, PhD, Tatsuya Sato, MD, PhD, Ryunosuke Hakuta, MD, PhD, Tomotaka Saito, MD, PhD, Tsuyoshi Hamada, MD, MPH, PhD, and Mitsuhiro Fujishiro, MD, PhD
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Published
- 2024
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3. Clinical meaning of sarcopenia in patients undergoing endoscopic treatment
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Hiroyuki Hisada, Yosuke Tsuji, Hikaru Kuribara, Ryohei Miyata, Kaori Oshio, Satoru Mizutani, Hideki Nakagawa, Rina Cho, Nobuyuki Sakuma, Yuko Miura, Hiroya Mizutani, Daisuke Ohki, Seiichi Yakabi, Yu Takahashi, Yoshiki Sakaguchi, Naomi Kakushima, Nobutake Yamamichi, and Mitsuhiro Fujishiro
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aged ,endoscopic submucosal dissection ,neoplasms ,prognosis ,sarcopenia ,Internal medicine ,RC31-1245 ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
With increasing global life expectancy, the significance of geriatric assessment parameters has increased. Sarcopenia is a crucial assessment parameter and is defined as the age-related loss of muscle mass and strength. Sarcopenia is widely acknowledged as a risk factor for postoperative complications in diverse advanced malignancies and has a detrimental effect on the long-term prognosis. While most studies have primarily concentrated on the correlation between sarcopenia and advanced cancer, more recent investigations have focused on the relationship between sarcopenia and early-stage cancer. Endoscopic submucosal dissection (ESD), which is less invasive than surgical intervention, is extensively employed in the management of early-stage cancer, although it is associated with complications such as bleeding and perforation. In recent years, several reports have revealed the adverse consequences of sarcopenia in patients with early-stage cancer undergoing ESD. This literature review briefly summarizes the recent studies on the association between sarcopenia and ESD.
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- 2024
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4. Metabolic Factors Associated with Endoscopic Atrophy, Intestinal Metaplasia, and Gastric Neoplasms in Helicobacter pylori-Positive Patients
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Junya Arai, Hiroaki Fujiwara, Tomonori Aoki, Ryota Niikura, Sozaburo Ihara, Nobumi Suzuki, Yoku Hayakawa, Masato Kasuga, and Mitsuhiro Fujishiro
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Helicobacter pylori ,gastric atrophy ,intestinal metaplasia ,gastric neoplasms ,fatty liver ,diabetes mellitus ,Medicine (General) ,R5-920 - Abstract
Background: Previous studies demonstrate an association between metabolic factors and Helicobacter pylori-related gastric cancer. However, the association of gastric atrophy or intestinal metaplasia (IM) with these factors remains unknown. Methods: Data on 1603 Helicobacter pylori-positive patients who underwent esophagogastroduodenoscopy between 2001 and 2021 were evaluated. The outcome measures were endoscopic atrophy, IM grade, and the incidence of endoscopically diagnosed and pathologically confirmed gastric neoplasms. Clinical factors associated with these findings were also determined. Results: Advanced age; successful Helicobacter pylori eradication; and comorbidities including diabetes mellitus (DM), hypertension, dyslipidemia, and fib4 index were significantly associated with endoscopic gastric atrophy grade. Male sex; advanced age; and comorbidities including DM, hypertension, dyslipidemia, hyperuricemia, fatty liver, aortic calcification, and fib4 index were also significantly associated with endoscopic IM grade, whereas advanced age, successful Helicobacter pylori eradication, DM, fatty liver, and fib4 index were significantly associated with the incidence of gastric neoplasms. Conclusion: Several metabolic disorders, including DM, hypertension, dyslipidemia, hyperuricemia, and fatty liver disease, are risk factors for advanced-grade gastric atrophy, intestinal metaplasia, and gastric neoplasms. Risk stratification according to these factors, particularly those with metabolic disorders, would affect EGD surveillance for Helicobacter pylori-positive patients.
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- 2024
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5. Probe-guided endoscopic system for 5-aminolevulinic acid-based photodynamic diagnosis in cholangiocarcinoma
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Hiroaki Fujiwara, Shiho Furudate, Naminatsu Takahara, Yousuke Nakai, Yuki Kodama, Junya Arai, Hayato Nakagawa, Tsuneo Ikenoue, Keisuke Tateishi, Masato Kasuga, and Mitsuhiro Fujishiro
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Cholangiocarcinoma ,5-Aminolevulinic acid ,Photodynamic diagnosis ,Cholangioscope ,Protoporphyrin IX ,Medicine (General) ,R5-920 - Abstract
Background and Aim: The diagnostic accuracy for cholangiocarcinoma (CCA) is inadequate, necessitating the exploration of novel diagnostic approaches. Protoporphyrin IX (Pp IX), a metabolic product of 5-aminolevulinic acid (5-ALA), emits red fluorescence upon blue light exposure. Because it accumulates selectively in cancer cells, photodynamic diagnosis using 5-ALA (5-ALA-PDD) has been integrated into clinical practice for diverse cancer types. Nevertheless, there is currently no device capable of capturing Pp IX-derived fluorescence for real-time 5-ALA-PDD within the biliary tract, largely due to challenges in device miniaturization. Methods: To investigate the feasibility of real-time 5ALA-PDD in CCA, we developed two essential components of the cholangioscopy system: a small-diameter flexible camera and a light guide for emitting blue light. We evaluated the detectability of Pp IX fluorescence using these devices in experimental gels and animal models. Results: Our camera and light guide were smoothly inserted into the lumen of existing cholangioscopes. Incorporating a long-pass filter at the camera tip enabled efficient detection of red fluorescence without significantly impacting white-light observation. The integration of these devices facilitated clear visualization of red fluorescence from gels containing Pp IX at concentrations of 5 μM or higher. Additionally, when observing subcutaneous human CCA tumor models in nude mice treated with 5-ALA, we successfully demonstrated distinct red fluorescence from Pp IX accumulation in tumors compared to peritumoral subcutaneous areas. Conclusion: The integration of our device combination holds promise for real-time 5-ALA-PDD in human CCA, potentially enhancing the diagnostic accuracy for this complex condition.
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- 2024
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6. The impact of COVID-19 on the diagnosis and treatment of HCC: analysis of a nationwide registry for advanced liver diseases (REAL)
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Kazuya Okushin, Ryosuke Tateishi, Shinya Hirakawa, Hisateru Tachimori, Koji Uchino, Ryo Nakagomi, Tomoharu Yamada, Takuma Nakatsuka, Tatsuya Minami, Masaya Sato, Mitsuhiro Fujishiro, Kiyoshi Hasegawa, Yuichiro Eguchi, Tatsuya Kanto, Hitoshi Yoshiji, Namiki Izumi, Masatoshi Kudo, and Kazuhiko Koike
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Medicine ,Science - Abstract
Abstract The number of cancer cases diagnosed during the coronavirus disease 2019 (COVID-19) pandemic has decreased. This study investigated the impact of the pandemic on the clinical practice of hepatocellular carcinoma (HCC) using a novel nationwide REgistry for Advanced Liver diseases (REAL) in Japan. We retrieved data of patients initially diagnosed with HCC between January 2018 and December 2021. We adopted tumor size as the primary outcome measure and compared it between the pre-COVID-19 (2018 and 2019) and COVID-19 eras (2020 and 2021). We analyzed 13,777 patients initially diagnosed with HCC (8074 in the pre-COVID-19 era and 5703 in the COVID-19 era). The size of the maximal intrahepatic tumor did not change between the two periods (mean [SD] = 4.3 [3.6] cm and 4.4 [3.6] cm), whereas the proportion of patients with a single tumor increased slightly from 72.0 to 74.3%. HCC was diagnosed at a similar Barcelona Clinic Liver Cancer stage. However, the proportion of patients treated with systemic therapy has increased from 5.4 to 8.9%. The proportion of patients with a non-viral etiology significantly increased from 55.3 to 60.4%. Although the tumor size was significantly different among the etiologies, the subgroup analysis showed that the tumor size did not change after stratification by etiology. In conclusion, the characteristics of initially diagnosed HCC remained unchanged during the COVID-19 pandemic in Japan, regardless of differences in etiology. A robust surveillance system should be established particularly for non-B, non-C etiology to detect HCC in earlier stages.
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- 2024
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7. Computed tomography-based prediction of pancreatitis following biliary metal stent placement with the convolutional neural network
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Tsuyoshi Hamada, Koichiro Yasaka, Yousuke Nakai, Rintaro Fukuda, Ryunosuke Hakuta, Kazunaga Ishigaki, Sachiko Kanai, Kensaku Noguchi, Hiroki Oyama, Tomotaka Saito, Tatsuya Sato, Tatsunori Suzuki, Naminatsu Takahara, Hiroyuki Isayama, Osamu Abe, and Mitsuhiro Fujishiro
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Pancreatobiliary (ERCP/PTCD) ,Strictures ,ERC topics ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Published
- 2024
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8. CA19-9-Positive Extracellular Vesicle Is a Risk Factor for Cancer-Associated Thrombosis in Pancreatic Cancer
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Chikako Shibata, Motoyuki Otsuka, Kazunaga Ishigaki, Takahiro Seimiya, Takahiro Kishikawa, and Mitsuhiro Fujishiro
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E-selectin ,Glycan ,Tissue Factor ,Coagulation ,Endothelial Cell ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background and Aims: Cancer-associated venous thromboembolism (VTE) is a frequent complication associated with high mortality in patients with cancer, particularly pancreatic cancer. While biological factors such as coagulation factors released from cancer cells may underlie the mechanisms of cancer-associated VTE, the detailed mechanisms have not been determined. Here, we aimed to determine whether extracellular vesicles carrying a glycan sialyl-Lewisa, known as carbohydrate antigen 19-9 (CA19-9), which is a clinically used serum tumor marker and selectin ligand, are a significant cause of cancer-associated VTE. Methods: Risk factors for cancer-associated VTE were determined using clinical data. EVs derived from CA19-9-deficient or overexpressing pancreatic cancer cells were characterized. The protein levels of coagulation factors on the surface of the EVs were quantified using our newly developed sensitive method. Results: Higher CA19-9 levels in the sera of patients were significantly associated with the occurrence of VTE. Using CA19-9-negative or overexpressing pancreatic cancer cells, we found that EVs derived from these cells interacted with E-selectin of endothelial cells in a CA19-9-dependent manner in cell-based assays and in vitro blood vessel models. EVs derived from cancer cells have higher tissue factor levels on their surfaces, and increased tissue factor activity is induced locally, where CA19-9-positive EVs bind to activated endothelial cells. Conclusion: These results suggest that the binding between CA19-9-positive EVs released from cancer cells and endothelial cell E-selectin explains the increased frequency of VTE in patients with pancreatic cancer.
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- 2024
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9. Gut Bacteria-derived Membrane Vesicles Induce Colonic Dysplasia by Inducing DNA Damage in Colon Epithelial CellsSummary
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Yu Miyakawa, Motoyuki Otsuka, Chikako Shibata, Takahiro Seimiya, Keisuke Yamamoto, Rei Ishibashi, Takahiro Kishikawa, Eri Tanaka, Takayuki Isagawa, Norihiko Takeda, Noriaki Kamio, Kenichi Imai, and Mitsuhiro Fujishiro
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A odontolyticus ,DNA Damage ,NF-κB ,Colon Cancer ,Mitochondria ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background & Aims: Colorectal cancer (CRC) is the third most common cancer in the world. Gut microbiota has recently been implicated in the development of CRC. Actinomyces odontolyticus is one of the most abundant bacteria in the gut of patients with very early stages of CRC. A odontolyticus is an anaerobic bacterium existing principally in the oral cavity, similar to Fusobacterium nucleatum, which is known as a colon carcinogenic bacterium. Here we newly determined the biological functions of A odontolyticus on colonic oncogenesis. Methods: We examined the induction of intracellular signaling by A odontolyticus in human colonic epithelial cells (CECs). DNA damage levels in CECs were confirmed using the human induced pluripotent stem cell-derived gut organoid model and mouse colon tissues in vivo. Results: A odontolyticus secretes membrane vesicles (MVs), which induce nuclear factor kappa B signaling and also produce excessive reactive oxygen species (ROS) in colon epithelial cells. We found that A odontolyticus secretes lipoteichoic acid-rich MVs, promoting inflammatory signaling via TLR2. Simultaneously, those MVs are internalized into the colon epithelial cells, co-localize with the mitochondria, and cause mitochondrial dysfunction, resulting in excessive ROS production and DNA damage. Induction of excessive DNA damage in colonic cells by A odontolyticus-derived MVs was confirmed in the gut organoid model and also in mouse colon tissues. Conclusions: A odontolyticus secretes MVs, which cause chronic inflammation and ROS production in colonic epithelial cells, leading to the initiation of CRC.
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- 2024
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10. Feasibility of comprehensive genomic profiling using endoscopic ultrasound‐guided tissue acquisition with a 22‐gauge Franseen needle
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Kazunaga Ishigaki, Yousuke Nakai, Go Endo, Kohei Kurihara, Kota Ishida, Shuichi Tange, Rintaro Fukuda, Shinya Takaoka, Yurie Tokito, Yukari Suzuki, Hiroki Oyama, Sachiko Kanai, Tatsunori Suzuki, Tatsuya Sato, Ryunosuke Hakuta, Tomotaka Saito, Tsuyoshi Hamada, Naminatsu Takahara, Aya Shinozaki‐Ushiku, and Mitsuhiro Fujishiro
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comprehensive genomic profiling ,endoscopic ultrasound‐guided fine needle aspiration ,Franseen needle ,image analysis ,pancreatobiliary cancer ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Aim Comprehensive genomic profiling (CGP) test for solid tumors is now increasingly utilized in clinical practice, especially in pancreatobiliary cancer, and specimens obtained by endoscopic ultrasound‐guided tissue acquisition (EUS‐TA) are often submitted for tissue‐based CGP test. In this study, we evaluated the feasibility of EUS‐TA using a 22‐gauge Franseen needle for the CGP test. Methods Consecutive patients with solid tumors who underwent EUS‐TA using a 22‐gauge Franseen needle, and whose tissue samples were pre‐checked for suitability for CGP test, were included in this single‐center, retrospective analysis. The success rates of appropriate sample collection for CGP evaluated by pathologists (1st quality control) and CGP test (2nd quality control) were evaluated. In addition, The EUS‐TA slides were evaluated for the tissue area and tumor area content, using the image software. Results A total of 50 cases, with 78% of pancreatic cancer, were included in the analysis. A median of 3 passes of EUS‐TA were performed with an adverse event rate of 4%. The success rates for 1st and 2nd quality control for CGP tests were 86% and 76%, respectively. The image analyses suggested EUS‐TA specimen did not always fulfill CGP test criteria, with 18% of tissue area ≥16 mm2 and 38% of tumor area content ≥20%, even in cases with successful CGP tests. The suction method yielded a significantly larger amount of DNA but without a significant difference in the multivariate analysis. Conclusions The present study demonstrated the feasibility of EUS‐TA using a 22‐gauge Franseen needle for CGP test.
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- 2024
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11. The impact of biliary stents on the diagnostic yield of endoscopic ultrasound‐guided fine needle aspiration for solid pancreatic lesions: A single‐center retrospective study and meta‐analysis
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Go Endo, Kazunaga Ishigaki, Tsuyoshi Hamada, Yousuke Nakai, Kota Ishida, Kohei Kurihara, Shuichi Tange, Shinya Takaoka, Yurie Tokito, Yukari Suzuki, Hiroki Oyama, Sachiko Kanai, Tatsunori Suzuki, Tatsuya Sato, Ryunosuke Hakuta, Tomotaka Saito, Naminatsu Takahara, and Mitsuhiro Fujishiro
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cholangiopancreatography ,endoscopic retrograde ,endoscopic ultrasound‐guided fine needle aspiration ,jaundice ,obstructive ,pancreatic neoplasms ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Background Endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) is widely used for the pathological diagnosis of solid pancreatic lesions but in cases with obstructive jaundice, transpapillary sampling can be performed during endoscopic retrograde cholangiopancreatography with transpapillary biliary stent placement. Thus, it is still controversial whether EUS‐FNA should be performed prior to endoscopic retrograde cholangiopancreatography with biliary stent placement or only after negative transpapillary sampling. Methods The accuracy, sensitivity, and specificity of EUS‐FNA for solid pancreatic lesions with or without indwelling biliary stents were retrospectively studied in patients undergoing EUS‐FNA between January 2017 and December 2021. We also conducted a meta‐analysis including our data to compare the accuracy and sensitivity of EUS‐FNA with or without biliary stents. Results A total of 509 patients (40 with biliary stents and 469 without biliary stents) were included. The accuracy (77.5% vs. 94.5%, p < 0.001) and sensitivity (71.0% vs. 91.7%, p < 0.001) were lower in EUS‐FNA with biliary stents. A meta‐analysis confirmed that accuracy (odds ratio [OR] of 0.43, 95% confidence interval [CI] 0.29–0.62, p < 0.001) and sensitivity (OR of 0.46, 95% CI 0.33–0.64, p < 0.001) were lower in EUS‐FNA with biliary stents. There were no statistically significant differences between plastic stents and self‐expandable metallic stents for accuracy or sensitivity. Conclusions The presence of biliary stents had a negative impact on the diagnostic performance of EUS‐FNA, and EUS‐FNA prior to endoscopic retrograde cholangiopancreatography with biliary stent placement should be considered in cases with obstructive jaundice.
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- 2024
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12. Severe obstructive colitis treated with repeated colonoscopic decompression
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Junya Arai, Nobumi Suzuki, Yoku Hayakawa, Hiroyuki Matzuzaki, Yuichiro Yokoyama, Tomonori Aoki, Rei Ishibashi, Nariaki Odawara, Sozaburo Ihara, Yosuke Tsuji, Soichiro Ishihara, and Mitsuhiro Fujishiro
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black colon ,bowel irrigation solution ,colonoscopic decompression ,diverticulosis ,obstructive colitis ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Obstructive colitis is an acute condition caused by colorectal strictures and requires a combination of therapeutic strategies, including surgery, endoscopic interventions, and medications. Here, we describe the case of a 69‐year‐old man who developed severe obstructive colitis owing to diverticular stenosis of the sigmoid colon. We immediately performed endoscopic decompression to avoid perforation. The mucosa of the dilated colon appeared black, suggesting severe ischemia. We considered surgical total colectomy owing to the extensive colitis. However, considering the invasiveness of the emergent surgery, we adopted a conservative approach as enhanced computed tomography demonstrated colonic dilation with maintained blood flow in the deeper layer of the colonic wall and no signs of colonic necrosis, such as peritoneal irritation sign or elevation of deviation enzymes, were observed. Moreover, the patient preferred a conservative approach, and surgeons in our team agreed with this conservative approach. While relapses of colonic dilation occurred several times, antibiotic treatment and repeated endoscopic decompression successfully suppressed the dilation and systemic inflammation. The colonic mucosa healed gradually, and we performed a colostomy without resecting a large portion of the colorectum. In conclusion, severe obstructive colitis with maintained blood flow can be treated with endoscopic decompression instead of emergent resection for a wide portion of the colorectum. Moreover, endoscopic images of improved colitic mucosa obtained through repeated colorectal procedures are rare and noteworthy.
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- 2024
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13. Verification of the increase in concomitant dysplasia and cancer with the size of sessile serrated lesions
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Daisuke Ohki, Yosuke Tsuji, Hiroyuki Hisada, Hideki Nakagawa, Satoru Mizutani, Kaori Oshio, Junichi Sato, Dai Kubota, Rina Cho, Yuko Miura, Hiroya Mizutani, Yoshiki Sakaguchi, Yu Takahashi, Seiichi Yakabi, Naomi Kakushima, Nobutake Yamamichi, Tetsuo Ushiku, and Mitsuhiro Fujishiro
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Endoscopy Upper GI Tract ,Endoscopic resection (ESD, EMRc, ...) ,Endoscopy Lower GI Tract ,Polyps / adenomas / ... ,Colorectal cancer ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Published
- 2024
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14. Gut insulin action protects from hepatocarcinogenesis in diabetic mice comorbid with nonalcoholic steatohepatitis
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Kotaro Soeda, Takayoshi Sasako, Kenichiro Enooku, Naoto Kubota, Naoki Kobayashi, Yoshiko Matsumoto Ikushima, Motoharu Awazawa, Ryotaro Bouchi, Gotaro Toda, Tomoharu Yamada, Takuma Nakatsuka, Ryosuke Tateishi, Miwako Kakiuchi, Shogo Yamamoto, Kenji Tatsuno, Koji Atarashi, Wataru Suda, Kenya Honda, Hiroyuki Aburatani, Toshimasa Yamauchi, Mitsuhiro Fujishiro, Tetsuo Noda, Kazuhiko Koike, Takashi Kadowaki, and Kohjiro Ueki
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Science - Abstract
Abstract Diabetes is known to increase the risk of nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). Here we treat male STAM (STelic Animal Model) mice, which develop diabetes, NASH and HCC associated with dysbiosis upon low-dose streptozotocin and high-fat diet (HFD), with insulin or phlorizin. Although both treatments ameliorate hyperglycemia and NASH, insulin treatment alone lead to suppression of HCC accompanied by improvement of dysbiosis and restoration of antimicrobial peptide production. There are some similarities in changes of microflora from insulin-treated patients comorbid with diabetes and NASH. Insulin treatment, however, fails to suppress HCC in the male STAM mice lacking insulin receptor specifically in intestinal epithelial cells (ieIRKO), which show dysbiosis and impaired gut barrier function. Furthermore, male ieIRKO mice are prone to develop HCC merely on HFD. These data suggest that impaired gut insulin signaling increases the risk of HCC, which can be countered by restoration of insulin action in diabetes.
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- 2023
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15. Post‐operative mortality and recurrence patterns in pancreatic cancer according to KRAS mutation and CDKN2A, p53, and SMAD4 expression
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Yohei Masugi, Manabu Takamatsu, Mariko Tanaka, Kensuke Hara, Yosuke Inoue, Tsuyoshi Hamada, Tatsunori Suzuki, Junichi Arita, Yuki Hirose, Yoshikuni Kawaguchi, Yousuke Nakai, Atsushi Oba, Naoki Sasahira, Gaku Shimane, Tsuyoshi Takeda, Keisuke Tateishi, Sho Uemura, Mitsuhiro Fujishiro, Kiyoshi Hasegawa, Minoru Kitago, Yu Takahashi, Tetsuo Ushiku, Kengo Takeuchi, Michiie Sakamoto, and for the GTK Pancreatic Cancer Study Group in Japan
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cohort studies ,oncogenes ,pancreatectomy ,pancreatic ductal adenocarcinoma ,outcome ,Pathology ,RB1-214 - Abstract
Abstract Alterations in KRAS, CDKN2A (p16), TP53, and SMAD4 genes have been major drivers of pancreatic carcinogenesis. The clinical course of patients with pancreatic cancer in relation to these driver alterations has not been fully characterised in large populations. We hypothesised that pancreatic carcinomas with different combinations of KRAS mutation and aberrant expression of CDKN2A, p53, and SMAD4 might show distinctive recurrence patterns and post‐operative survival outcomes. To test this hypothesis, we utilised a multi‐institutional cohort of 1,146 resected pancreatic carcinomas and assessed KRAS mutations by droplet digital polymerase chain reaction and CDKN2A, p53, and SMAD4 expression by immunohistochemistry. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for disease‐free survival (DFS) and overall survival (OS) were computed according to each molecular alteration and the number of altered genes using the Cox regression models. Multivariable competing risks regression analyses were conducted to assess the associations of the number of altered genes with specific patterns of recurrence. Loss of SMAD4 expression was associated with short DFS (multivariable HR, 1.24; 95% CI, 1.09–1.43) and OS times (multivariable HR, 1.27; 95% CI, 1.10–1.46). Compared to cases with 0–2 altered genes, cases with three and four altered genes had multivariable HRs for OS of 1.28 (95% CI, 1.09–1.51) and 1.47 (95% CI, 1.22–1.78), respectively (ptrend
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- 2023
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16. Association of probiotic use with nivolumab effectiveness against various cancers: A multicenter retrospective cohort study
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Junya Arai, Ryota Niikura, Yoku Hayakawa, Nobumi Suzuki, Tetsuro Honda, Takuma Okamura, Kenkei Hasatani, Naohiro Yoshida, Tsutomu Nishida, Tetsuya Sumiyoshi, Shu Kiyotoki, Takashi Ikeya, Masahiro Arai, Narikazu Boku, and Mitsuhiro Fujishiro
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CBM588 ,gastric cancer ,nivolumab ,probiotics ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Previous studies have revealed an association between probiotic use and effectiveness of immune checkpoint inhibitors in renal and lung cancers. However, little is known regarding other cancers, including gastrointestinal cancer. Methods To address this issue, we conducted a multicenter retrospective cohort study and the duration of nivolumab treatment for various cancers was compared between probiotic users and non‐users. Results and Conclusions In total, 488 patients who received nivolumab therapy were included. In all cancers, no significant differences in treatment duration of nivolumab were observed between probiotic users and non‐users (median 62.0 vs. 56.0, hazard ratio = 1.02, p = 0.825), whereas probiotic use, compared with non‐use, in patients with gastric cancer was significantly associated with a longer duration of nivolumab treatment (55.0 vs. 31.0 days, hazard ratio = 0.69, p = 0.039). In conclusion, probiotics may improve the response to nivolumab and potentially prolong progression‐free survival in patients with gastric cancer.
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- 2023
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17. Treatment and outcome of hepatorenal syndrome in Japan: a retrospective cohort study using a national inpatient database
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Kazuya Okushin, Hayato Yamana, Ryosuke Tateishi, Masaya Sato, Takeya Tsutsumi, Hiroki Matsui, Kiyohide Fushimi, Hideo Yasunaga, Kazuhiko Koike, and Mitsuhiro Fujishiro
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Hepatorenal syndrome ,Liver cirrhosis ,Renal insufficiency ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Background Hepatorenal syndrome (HRS) is a life-threatening complication of end-stage liver disease. This study aimed to clarify the status of HRS in Japan by analyzing the Japanese Diagnosis Procedure Combination database. Methods Patients hospitalized for cirrhosis and HRS from July 2010 to March 2019 were sampled. They were divided into two groups according to their prognosis upon discharge: the transplant-free survival group and the death or liver transplantation group. The two groups’ baseline patient characteristics and treatments were compared. Results The mean age of the 1,412 participants was 67.3 years (standard deviation: 12.3 years), and 65.4% were male. The Child–Pugh grades was B and C in 18.8% and 81.2%, respectively. Hepatocellular carcinoma was present in 27.1% of the patients, and the proportion of spontaneous bacterial peritonitis was 2.3%. Albumin, noradrenaline, and dopamine were administered to 57.9%, 8.0%, and 14.9% of the patients, respectively; 7.0% of the patients underwent renal replacement therapy; and 5.0% were admitted to the intensive care unit. Intravenous antibiotics were administered to 30.8% of the patients. A total of 925 patients (65.5%) died or underwent liver transplantation. In addition to a higher proportion of patients with poor baseline liver function, the death or liver transplantation group included more males, patients with hepatocellular carcinoma, and those with spontaneous bacterial peritonitis. Conclusions HRS in Japan has a high mortality rate. Albumin was administered to over 50% of participants. Although noradrenaline is recommended in Japanese clinical guidelines, dopamine was more frequently used as a vasoconstrictor in clinical practice.
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- 2023
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18. Non-Helicobacter pylori Gastric Microbiome Modulates Prooncogenic Responses and Is Associated With Gastric Cancer Risk
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Ryota Niikura, Yoku Hayakawa, Naoyoshi Nagata, Tohru Miyoshi-Akiayama, Koji Miyabayashi, Mayo Tsuboi, Nobumi Suzuki, Masahiro Hata, Junya Arai, Ken Kurokawa, Sohei Abe, Chie Uekura, Kotaro Miyoshi, Sozaburo Ihara, Yoshihiro Hirata, Atsuo Yamada, Hiroaki Fujiwara, Tetsuo Ushiku, Susan L. Woods, Daniel L. Worthley, Masanori Hatakeyama, Yiping W. Han, Timothy C. Wang, Takashi Kawai, and Mitsuhiro Fujishiro
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16SrRNA ,Gastric Microbiota ,Dysbiosis ,Fusobacterium ,Neisseria ,DNA damage ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background and Aims: Although Helicobacter pylori is the most important bacterial carcinogen in gastric cancer (GC), GC can emerge even after H. pylori eradication. Studies suggest that various constituents of the gastric microbiome may influence GC development, but the role of individual pathogens is unclear. Methods: Human gastric mucosal samples were analyzed by 16SrRNA sequencing to investigate microbiome composition and its association with clinical parameters, including GC risk. Identified bacteria in the stomach were cocultured with gastric epithelial cells or inoculated into mice, and transcriptomic changes, DNA damage, and inflammation were analyzed. Bacterial reads in GC tissues were examined together with transcriptomic and genetic sequencing data in the cancer genome atlas dataset. Results: Patients after Helicobacter pylori eradication formed 3 subgroups based on the microbial composition revealed by 16SrRNA sequencing. One dysbiotic group enriched with Fusobacterium and Neisseria species was associated with a significantly higher GC incidence. These species activated prooncogenic pathways in gastric epithelial cells and promoted inflammation in mouse stomachs. Sugar chains that constitute gastric mucin attenuate host-bacteria interactions. Metabolites from Fusobacterium species were genotoxic, and the presence of the bacteria was associated with an inflammatory signature and a higher tumor mutation burden. Conclusion: Gastric microbiota in the dysbiotic stomach is associated with GC development after H. pylori eradication and plays a pathogenic role through direct host-bacteria interaction.
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- 2023
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19. Transcriptome of sessile serrated adenoma/polyps is associated with MSI‐high colorectal cancer and decreased expression of CDX2
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Daisuke Ohki, Nobutake Yamamichi, Yoshiki Sakaguchi, Yu Takahashi, Natsuko Kageyama‐Yahara, Mitsue Yamamichi, Chihiro Takeuchi, Yosuke Tsuji, Yasuhiro Sakai, Kouhei Sakurai, Shuta Tomida, Kazuhiko Koike, and Mitsuhiro Fujishiro
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CDX2 ,comprehensive gene expression analysis ,microsatellite instability‐high colorectal cancer ,sessile serrated adenoma/polyp ,transcriptome analysis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract The objective of this study was to elucidate the molecular background of sessile serrated adenoma/polyp (SSA/P) endoscopically resected with comprehensive gene expression analysis. Gene expression profiling was performed for 10 tumor‐normal pairs of SSA/P. Cluster analysis, gene set enrichment analysis (GSEA), and consensus molecular subtype (CMS) classification of colorectal cancer (CRC) were applied to our transcriptome analysis. Unsupervised cluster analysis showed that the gene expression profile of SSA/Ps is different from that of adjacent normal epithelial cells, even in the very early stage of tumorigenesis. According to the CMS classification, our microarray data indicated that SSA/Ps were classified as CMS1. GSEA demonstrated a strong association between SSA/P and microsatellite instability‐high (MSI‐H) CRC (p
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- 2022
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20. Fibrosis-4 index efficiently predicts chronic hepatitis and liver cirrhosis development based on a large-scale data of general population in Japan
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Nobutake Yamamichi, Takeshi Shimamoto, Kazuya Okushin, Takako Nishikawa, Hirotaka Matsuzaki, Seiichi Yakabi, Mami Takahashi, Ryoichi Wada, Kazuhiko Koike, and Mitsuhiro Fujishiro
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Medicine ,Science - Abstract
Abstract A non-invasive method to evaluate the fibrosis stage and the risk stratification of non-alcoholic fatty liver disease (NAFLD) is required. A total of 416,066 generally healthy subjects who underwent health check-ups between 1990 and 2019 were investigated. Fatty liver prevalence greatly increased from the 1990s (21.9%) to the 2000s (37.1%) but showed no considerable change between 2001–2010 (39.2%) and 2011–2019 (35.5%). During the 30 years, the rate of high FIB-4 index (≥2.67) and mean body mass index (BMI) did not markedly change. Fatty liver was significantly associated with BMI, but not with alcohol intake or FIB-4 index. Cox regression analyses for development of chronic hepatitis or liver cirrhosis identified that the risk of developing chronic hepatitis and liver cirrhosis was higher in subjects without fatty liver than in those with it (hazard ratio [HR]=0.09; 95% confidence interval [CI], 0.03–0.22, p
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- 2022
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21. The transnasal decompression tube versus self-expanding metallic stents for right-sided obstructive colorectal cancer
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Yuichiro Yokoyama, Rei Ishibashi, Mitsuhiro Fujishiro, and Soichiro Ishihara
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Surgery ,RD1-811 - Published
- 2023
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22. The role of EUS elastography-guided fine needle biopsy in the histological diagnosis of solid pancreatic lesions: a prospective exploratory study
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Eizaburo Ohno, Hiroki Kawashima, Takuya Ishikawa, Yasuyuki Mizutani, Tadashi Iida, Ryo Nishio, Kota Uetsuki, Jun Yashika, Kenta Yamada, Masakatsu Yoshikawa, Noriaki Gibo, Toshinori Aoki, Kunio Kataoka, Hiroshi Mori, Yoshihisa Takada, Hironori Aoi, Hidekazu Takahashi, Takeshi Yamamura, Kazuhiro Furukawa, Masanao Nakamura, Yoshie Shimoyama, Yoshiki Hirooka, and Mitsuhiro Fujishiro
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Medicine ,Science - Abstract
Abstract This study aimed to evaluate the feasibility and efficacy of Endoscopic ultrasound elastography-guided fine needle biopsy (EUS-EG-FNB) for the diagnosis of pancreatic mass lesions. EUS-EG images were classified into heterogeneous and homogeneous groups. For the heterogeneous group, EUS-FNB was separately performed in both hard areas and soft areas. Only samples obtained during the first two passes (hard/soft areas) were used to compare the diagnostic accuracy as well as the quality and quantity of the specimens. We investigated the association of EUS-EG findings using strain histogram analysis with the histological findings. Fifty-five patients were enrolled including 25 patients with heterogeneous group. The homogeneous group had significantly lower mean strain value (hard) lesions. The adequate sampling rates from hard and soft areas were 88 and 92%, respectively (P = 0.6374). Comparison of the diagnostic accuracy and the quality and quantity of the histological core between hard and soft areas showed no significant differences. In pancreatic adenocarcinoma cases, the proportion of fibrous stroma in the core tissue was significantly correlated with the elasticity of the region. (R2 = 0.1226: P = 0.0022) EUS-EG may reflect tissue composition in pancreatic tumors, however, EUS-EG did not affect either the quality and quantity of the tissues obtained. Clinical Trial Registry No: UMIN-000033073.
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- 2022
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23. Improved prognosis of hepatitis C‐related hepatocellular carcinoma in the era of direct‐acting antivirals
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Tsuyoshi Fukumoto, Tatsuya Minami, Makoto Moriyama, Tomoharu Yamada, Taijiro Wake, Mizuki Nishibatake Kinoshita, Naoto Fujiwara, Ryo Nakagomi, Takuma Nakatsuka, Masaya Sato, Kenichiro Enooku, Hayato Nakagawa, Mitsuhiro Fujishiro, Shuichiro Shiina, Kazuhiko Koike, and Ryosuke Tateishi
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract The prognostic impact of direct‐acting antivirals (DAAs) on patients with hepatitis C‐related hepatocellular carcinoma (C‐HCC) is still unclear. This study aimed to evaluate the prognosis of C‐HCC in the DAA era. We enrolled 1237 consecutive patients with treatment‐naive C‐HCC who underwent radical radiofrequency ablation between 1999 and 2019. We also enrolled 350 patients with nonviral HCC as controls. We divided these patients into three groups according to the year of initial treatment: 1999–2005 (cohort 1), 2006–2013 (cohort 2), and 2014–2019 (cohort 3). The use of antiviral agents and their effect in patients with C‐HCC was investigated. Overall survival was evaluated for each cohort using the Kaplan‐Meier method and a multivariable Cox proportional hazards regression model. Sustained virologic response (SVR) was achieved in 52 (10%), 157 (26%), and 102 (74%) patients with C‐HCC in cohorts 1–3, respectively. The 3‐ and 5‐year survival rates of patients with C‐HCC were 82% and 59% in cohort 1; 80% and 64% in cohort 2; and 86% and 78% in cohort 3, respectively (p = 0.003). Multivariable analysis adjusted for age, liver function, and tumor extension showed that the prognosis of C‐HCC improved in cohort 3 compared to cohort 1 (adjusted hazard ratio [aHR], 0.49; 95% confidence interval [CI], 0.32–0.73; p
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- 2022
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24. Endoscopic Treatment of Superficial Gastric Cancer: Present Status and Future
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Hiroyuki Hisada, Yoshiki Sakaguchi, Kaori Oshio, Satoru Mizutani, Hideki Nakagawa, Junichi Sato, Dai Kubota, Miho Obata, Rina Cho, Sayaka Nagao, Yuko Miura, Hiroya Mizutani, Daisuke Ohki, Seiichi Yakabi, Yu Takahashi, Naomi Kakushima, Yosuke Tsuji, Nobutake Yamamichi, and Mitsuhiro Fujishiro
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gastric cancer ,endoscopic diagnosis ,endoscopic submucosal dissection ,endoscopic resection ,curability assessment ,endoscopic screening ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Although the mortality rates of gastric cancer (GC) are gradually declining, gastric cancer is still the fourth leading cause of cancer-related death worldwide. This may be due to the high rate of patients who are diagnosed with GC at advanced stages. However, in countries such as Japan with endoscopic screening systems, more than half of GCs are discovered at an early stage, enabling endoscopic resection (ER). Especially after the introduction of endoscopic submucosal dissection (ESD) in Japan around 2000, a high en bloc resection rate allowing pathological assessment of margin and depth has become possible. While ER is a diagnostic method of treatment and may not always be curative, it is widely accepted as standard treatment because it is less invasive than surgery and can provide an accurate diagnosis for deciding whether additional surgery is necessary. The curability of ER is currently assessed by the completeness of primary tumor removal and the possibility of lymph node metastasis. This review introduces methods, indications, and curability criteria for ER of EGC. Despite recent advances, several problems remain unsolved. This review will also outline the latest evidence concerning future issues.
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- 2022
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25. Fecal microbiota transplantation in the treatment of irritable bowel syndrome: a single-center prospective study in Japan
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Motonobu Hamazaki, Tsunaki Sawada, Takeshi Yamamura, Keiko Maeda, Yasuyuki Mizutani, Eri Ishikawa, Satoshi Furune, Kenta Yamamoto, Takuya Ishikawa, Naomi Kakushima, Kazuhiro Furukawa, Eizaburo Ohno, Takashi Honda, Hiroki Kawashima, Masatoshi Ishigami, Masanao Nakamura, and Mitsuhiro Fujishiro
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Fecal microbiota transplantation ,Irritable bowel syndrome ,Microbiome ,Gastrointestinal endoscopy ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Background Fecal microbiota transplantation (FMT) is a potential treatment for irritable bowel syndrome (IBS), but its efficacy in Japanese IBS patients is unknown. This study aimed to evaluate the efficacy, side effects, and microbiome changes following FMT in Japanese IBS patients. Methods Seventeen Japanese patients with refractory IBS received FMT (4 donors) under colonoscopy. Responders were defined by an improvement in the IBS severity index (IBS-SI) of 50 points or more after 12 weeks. We evaluated the IBS-SI and Bristol Stool Form Scale (BSFS) and compared the diversity and microbiome before and 12 weeks after FMT. For the microbiome, we analyzed the V3–V4 region of the 16S rRNA gene. Results IBS-SI decreased an average of 115.58 points after 12 weeks, and 10 patients (58.8%) were considered responders. Eight patients with diarrhea (66.7%) and three patients with constipation (60.0%) showed improvement in the BSFS. Two patients complained of mild abdominal pain, but there were no cases with severe side-effects. α-diversity was increased only in the responder group (p = 0.017). Patients who closely paralleled the donor microbiome had a higher rate of IBS-SI improvement. The relative abundance of Neisseria and Akkermansia increased and Desulfovibrio and Delftia were decreased in the responder group after FMT. Conclusions Following FMT, about 60% of Japanese patients with IBS showed improvement in both the IBS-SI and BSFS, without severe side effects. Increased α-diversity and similarity to the donor microbiome after FMT may be associated with better treatment effects. Trial registration: This study was registered in the University Hospital Medical Information Network Clinical Trial Registration (UMIN000026363). Registered 31 May 2017, https://rctportal.niph.go.jp/s/detail/um?trial_id=UMIN000026363 . The study was registered prospectively.
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- 2022
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26. Magnifying endoscopy with narrow-band imaging is useful in differentiating gastric cancer from matched adenoma in white light imaging
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Naoki Tamura, Yoshiki Sakaguchi, Wakiko Furutani, Maki Matsui, Sayaka Nagao, Nobuyuki Sakuma, Kazushi Fukagawa, Yuko Miura, Hiroya Mizutani, Daisuke Ohki, Yosuke Kataoka, Itaru Saito, Masayoshi Ono, Chihiro Minatsuki, Yosuke Tsuji, Satoshi Ono, Shinya Kodashima, Hiroyuki Abe, Tetsuo Ushiku, Nobutake Yamamichi, Kazuhiko Koike, and Mitsuhiro Fujishiro
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Medicine ,Science - Abstract
Abstract This study assessed the effect of magnifying endoscopy with narrow-band imaging (M-NBI) on the endoscopic differential diagnosis between intramucosal gastric carcinomas and adenomas with matched characteristics. Associations between magnified endoscopic findings and pathological high-grade cellular and architectural atypia were also investigated. In total, the records of 50 adenomas and 50 intramucosal well-differentiated adenocarcinomas matched by tumor size (≥ 20 mm or
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- 2022
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27. Increased risk of biliary infection after biliary stent placement in users of proton pump inhibitors
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Ryunosuke Hakuta, Yousuke Nakai, Hiroki Oyama, Kensaku Noguchi, Sachiko Kanai, Yusuke Nomura, Tatsunori Suzuki, Kazunaga Ishigaki, Kei Saito, Tomotaka Saito, Tsuyoshi Hamada, Naminatsu Takahara, Suguru Mizuno, Hirofumi Kogure, Kyoji Moriya, and Mitsuhiro Fujishiro
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cholangitis ,cholecystitis ,endoscopic retrograde cholangiopancreatography ,proton pump inhibitors ,stents ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Objectives Proton pump inhibitors (PPIs) are widely prescribed medications for gastric acid‐induced diseases. Despite the effectiveness of PPIs, recent evidence suggested an increased risk of various bacterial infections in PPI users. The current study was conducted to evaluate the risk of biliary infection after endoscopic biliary stent placement in regular users of PPIs. Methods Consecutive patients with a native papilla who underwent endoscopic retrograde cholangiopancreatography and stent placement for biliary stricture between January 2010 and August 2019 were included in this retrospective study. The cumulative incidences of biliary infection were compared between regular and non‐regular PPI users. Results During the study period, 270 regular PPI users and 146 non‐regular PPI users were included in the analyses. Age, gender, and indication of endoscopic retrograde cholangiopancreatography were not different between the two groups. The incidences of biliary infection were 43% in regular PPI users and 36% in non‐regular PPI users but the time to biliary infection was significantly shorter in regular PPI users than in non‐regular users (28 vs. 87 days, p = 0.01). The cumulative incidence of biliary infection was significantly higher in regular PPI users compared with non‐regular users (p = 0.008). The multivariable Cox regression analysis also showed a significantly higher hazard ratio of biliary infection in regular PPI users (1.62 [95% confidence interval 1.16–2.26; p = 0.005]). Conclusions Regular PPI use was associated with a higher risk of biliary infection after endoscopic biliary drainage. Inappropriate PPI use should be avoided.
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- 2023
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28. Electrosurgical knife with the water‐jet function of tip‐type during endoscopic treatment injection
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Satoshi Ono, Yasuko Kurihara, Fumiya Hirose, Hajime Aoki, Kyohei Maejima, Shun Ito, Shun Osumi, Seika Hatori, Kazushi Fukagawa, Shosuke Hosaka, Miho Matsukawa, Ryosuke Kobayashi, Nobuyoshi Yamazaki, and Mitsuhiro Fujishiro
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desktop experiment ,electrosurgical knife ,endoscopic submucosal dissection ,injection ,porcine model ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Objectives This study aimed to objectively evaluate the water‐jet‐functioned electrosurgical knife injection performances in a desktop experiment. Methods Five types of water‐jet‐functioned electrosurgical knives, including two injection styles of sheath‐type (A: DualKnife J, KD‐655L; B: FlushKnife, DK2620‐J‐B20S; C: Splash M‐Knife, DN‐D2718B; D: ISSEN, SN1650‐20) and tip‐type (E: ORISE ProKnife, M00519361) were evaluated. These knives were compared with an injection needle (Control: SuperGrip 25G) as a control. The injection speed under constant pressure and the injection efficiency for each knife against prepared porcine stomach mucosa were evaluated. The additional clear gel injections using an injection needle were observed using an indigo blue‐colored gel to evaluate the difference between the locations of water‐jet holes. Results Four types of knives, except for A, showed significantly higher water‐jet speeds (A: 0.79 ± 0.03 g/20 s, B: 2.56 ± 0.05 g/20 s, C: 3.09 ± 0.06 g/20 s, D: 2.86 ± 0.05 g/20 s, and E: 1.79 ± 0.03 g/20 s) compared to that of the control (1.21 ± 0.03 g/20 s). Meanwhile, significantly higher efficacy of injection was found in the tip‐type water‐jet function knife, second to the injection needle (Control: 37.2% ± 35.5%, A: 20.9% ± 20.2%, B: 1.1% ± 2.2%, C: 6.2% ± 12.6%, D: 12.5% ± 15.6%, and E: 33.3% ± 32.2%). An additional injection experiment revealed that the injection with a piercing tip into the gel could achieve sufficient additional injection inside the stacked clear gel. Conclusions The tip‐type water‐jet function electrosurgical knife is preferable for effective submucosal injection during endoscopic treatments.
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- 2023
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29. Patients with low muscle mass have characteristic microbiome with low potential for amino acid synthesis in chronic liver disease
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Kenta Yamamoto, Yoji Ishizu, Takashi Honda, Takanori Ito, Norihiro Imai, Masanao Nakamura, Hiroki Kawashima, Yasuyuki Kitaura, Masatoshi Ishigami, and Mitsuhiro Fujishiro
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Medicine ,Science - Abstract
Abstract Sarcopenia is thought to be related to the microbiome, but not enough reports in chronic liver disease (CLD) patients. In addition to the differences in microbiome, the role of the microbiome in the gut is also important to be clarified because it has recently been shown that the microbiome may produce branched-chain amino acids (BCAAs) in the body. In this single-center study, sixty-nine CLD patients were divided by skeletal muscle mass index (SMI) into low (L-SMI: n = 25) and normal (N-SMI: n = 44). Microbiome was analyzed from stool samples based on V3-4 region of bacterial 16S rRNA). L-SMI had a lower Firmicutes/Bacteroidetes ratio than N-SMI. At the genus level, Coprobacillus, Catenibacterium and Clostridium were also lower while the Bacteroides was higher. Predictive functional profiling of the L-SMI group showed that genes related to nitrogen metabolism were enriched, but those related to amino acid metabolism, including BCAA biosynthesis, were lower. The genes related to 'LPS biosynthesis' was also higher. The microbiome of CLD patients with low muscle mass is characterized not only by high relative abundance of gram-negative bacteria with LPS, but also by the possibility of low potential for amino acid synthesis including BCAAs.
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- 2022
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30. Safety and efficacy of MIKE-1 in patients with advanced pancreatic cancer: a study protocol for an open-label phase I/II investigator-initiated clinical trial based on a drug repositioning approach that reprograms the tumour stroma
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Yasuyuki Mizutani, Tadashi Iida, Eizaburo Ohno, Takuya Ishikawa, Fumie Kinoshita, Yachiyo Kuwatsuka, Miwa Imai, Shinobu Shimizu, Toshihisa Tsuruta, Atsushi Enomoto, Hiroki Kawashima, and Mitsuhiro Fujishiro
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Cancer stroma ,Tumour microenvironment ,Cancer-associated fibroblasts ,Cancer-restraining CAFs ,Meflin ,ISLR ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Cancer-associated fibroblasts (CAFs) are an important component of the tumour microenvironment. Recent studies revealed CAFs are heterogeneous and CAF subset(s) that suppress cancer progression (cancer-restraining CAFs [rCAFs]) must exist in addition to well-characterised cancer-promoting CAFs (pCAFs). However, the identity and specific markers of rCAFs are not yet reported. We recently identified Meflin as a specific marker of rCAFs in pancreatic and colon cancers. Our studies revealed that rCAFs may represent proliferating resident fibroblasts. Interestingly, a lineage tracing experiment showed Meflin-positive rCAFs differentiate into α-smooth muscle actin-positive and Meflin-negative CAFs, which are generally hypothesised as pCAFs, during cancer progression. Using a pharmacological approach, we identified AM80, a synthetic unnatural retinoid, as a reagent that effectively converts Meflin-negative pCAFs to Meflin-positive rCAFs. We aimed to investigate the efficacy of a combination of AM80 and gemcitabine (GEM) and nab-paclitaxel (nab-PTX) in patients with advanced pancreatic cancer. Methods The phase I part is a 3 + 3 design, open-label, and dose-finding study. The dose-limiting toxicity (DLT) of these combination therapies would be evaluated for 4 weeks. After the DLT evaluation period, if no disease progression is noted based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or if the patient has no intolerable toxicity, administration of AM80 with GEM and nab-PTX would be continued for up to 24 weeks. The phase II part is an open-label, single-arm study. The maximum tolerated dose (MTD) of AM80 with GEM and nab-PTX, determined in phase I, would be administered until intolerable toxicity or disease progression occurs, up to a maximum of 24 weeks, to confirm efficacy and safety. The primary endpoints are frequency of DLT and MTD of AM80 with GEM and nab-PTX in the phase I part and response rate based on the RECIST in the phase II part. Given the historical control data, we hope that the response rate will be over 23% in phase II. Discussion Strategies to convert pCAFs into rCAFs have been developed in recent years. We hypothesised that AM80 would be a promising enhancer of chemosensitivity and drug distribution through CAF conversion in the stroma. Trial registration Clinicaltrial.gov: NCT05064618 , registered on 1 October 2021. jRCT: jRCT2041210056 , registered on 27 August 2021.
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- 2022
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31. Kluyvera georgiana Bacteremia Due to Acute Cholangitis: A Report of the First Known Case and a Literature Review.
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Go Endo, Sachiko Kanai, Hiroto Nishio, Hideki Hashimoto, Yoshimi Higurashi, Yusuke Nomura, Yousuke Nakai, and Mitsuhiro Fujishiro
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- 2024
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32. Changes in the gut microbiota after hepatitis C virus eradication
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Takashi Honda, Masatoshi Ishigami, Kenta Yamamoto, Tomoaki Takeyama, Takanori Ito, Yoji Ishizu, Teiji Kuzuya, Masanao Nakamura, Hiroki Kawashima, Ryoji Miyahara, Tetsuya Ishikawa, Yoshiki Hirooka, and Mitsuhiro Fujishiro
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Medicine ,Science - Abstract
Abstract The gut microbiota interacts with infectious diseases and affects host immunity. Liver disease is also reportedly associated with changes in the gut microbiota. To elucidate the changes in the gut microbiota before and after hepatitis C virus (HCV) eradication through direct-acting antiviral (DAA) treatment in patients with chronic hepatitis C (CHC), we investigated 42 samples from 14 patients who received DAA therapy for HCV. Fecal samples were obtained before treatment (Pre), when treatment ended (EOT), and 24 weeks after treatment ended (Post24). The target V3–4 region of the 16S rRNA gene from fecal samples was amplified using the Illumina Miseq sequencing platform. The diversity of the gut microbiota did not significantly differ between Pre, EOT, and Post24. Principal coordinates analysis showed that for each patient, the values at Pre, EOT, and Post24 were concentrated within a small area. The linear discriminant analysis of effect size showed that the relative abundances of Faecalibacterium and Bacillus increased at EOT, further increased at Post24, and were significantly increased at Post24 compared to Pre. These suggest that changes in the gut microbiota should be considered as among the various effects observed on living organisms after HCV eradication.
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- 2021
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33. Lipolysis by pancreatic cancer‐derived extracellular vesicles in cancer‐associated cachexia via specific integrins
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Chikako Shibata, Motoyuki Otsuka, Takahiro Seimiya, Takahiro Kishikawa, Kazunaga Ishigaki, and Mitsuhiro Fujishiro
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Medicine (General) ,R5-920 - Published
- 2022
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34. Roles of circular RNAs in the pathogenesis and treatment of pancreatic cancer
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Takahiro Seimiya, Motoyuki Otsuka, and Mitsuhiro Fujishiro
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circular RNA ,circRNA ,pancreatic cancer ,biomarker ,treatment ,Biology (General) ,QH301-705.5 - Abstract
Circular RNAs are single-stranded RNAs with a covalently closed structure formed by the process of back-splicing. Aberrant expression of circular RNAs contributes to the pathogenesis of a wide range of cancers. Pancreatic cancer is one of the most lethal cancers due to diagnostic difficulties and limited therapeutic options. Circular RNAs are emerging as novel diagnostic biomarkers and therapeutic targets for pancreatic cancer. Moreover, recent advances in the therapeutic application of engineered circular RNAs have provided a promising approach to overcoming pancreatic cancer. This review discusses the roles of circular RNAs in the pathogenesis of pancreatic cancer and in potential treatment applications and their usefulness as diagnostic biomarkers.
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- 2022
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35. Conditioned medium from stem cells derived from human exfoliated deciduous teeth ameliorates NASH via the Gut-Liver axis
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Hisanori Muto, Takanori Ito, Taku Tanaka, Shinya Yokoyama, Kenta Yamamoto, Norihiro Imai, Yoji Ishizu, Keiko Maeda, Takashi Honda, Tetsuya Ishikawa, Asuka Kato, Taichi Ohshiro, Fumiya Kano, Akihito Yamamoto, Kiyoshi Sakai, Hideharu Hibi, Masatoshi Ishigami, and Mitsuhiro Fujishiro
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Medicine ,Science - Abstract
Abstract Non-alcoholic steatohepatitis (NASH) occurrence has been increasing and is becoming a major cause of liver cirrhosis and liver cancer. However, effective treatments for NASH are still lacking. We examined the benefits of serum-free conditioned medium from stem cells derived from human exfoliated deciduous teeth (SHED-CM) on a murine non-alcoholic steatohepatitis (NASH) model induced by a combination of Western diet (WD) and repeated administration of low doses of carbon tetrachloride intraperitoneally, focusing on the gut-liver axis. We showed that repeated intravenous administration of SHED-CM significantly ameliorated histological liver fibrosis and inflammation in a murine NASH model. SHED-CM inhibited parenchymal cell apoptosis and reduced the activation of inflammatory macrophages. Gene expression of pro-inflammatory and pro-fibrotic mediators (such as Tnf-α , Tgf-β, and Ccl-2) in the liver was reduced in mice treated with SHED-CM. Furthermore, SHED-CM protected intestinal tight junctions and maintained intestinal barrier function, while suppressing gene expression of the receptor for endotoxin, Toll-like receptor 4, in the liver. SHED-CM promoted the recovery of Caco-2 monolayer dysfunction induced by IFN-γ and TNF-α in vitro. Our findings suggest that SHED-CM may inhibit NASH fibrosis via the gut-liver axis, in addition to its protective effect on hepatocytes and the induction of macrophages with unique anti-inflammatory phenotypes.
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- 2021
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36. Gauze extension method for specimens resected by endoscopic submucosal dissection
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Satoshi Ono, MD, PhD, Daiki Nemoto, MD, PhD, Yoshikazu Hayashi, MD, PhD, and Mitsuhiro Fujishiro, MD, PhD
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Published
- 2022
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37. Measurement of fasting breath hydrogen concentration as a simple diagnostic method for pancreatic exocrine insufficiency
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Kota Uetsuki, Hiroki Kawashima, Eizaburo Ohno, Takuya Ishikawa, Tadashi Iida, Kenta Yamamoto, Kazuhiro Furukawa, Masanao Nakamura, Takashi Honda, Masatoshi Ishigami, Yoshiki Hirooka, and Mitsuhiro Fujishiro
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Pancreatic exocrine insufficiency ,Fasting breath hydrogen concentration ,Pancreatic disease ,Non-invasive measurement ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Background Pancreatic exocrine insufficiency (PEI) is associated with the outcome of pancreatic disease. However, there is no method for assessing PEI that can be used noninvasively and easily for outpatient. It has been reported that changes in intestinal bacteria caused by PEI may increase breath hydrogen concentration (BHC) levels during glucose or lactose loading. We have evaluated the usefulness of fasting breath hydrogen concentration (FBHC) measurement without glucose loading for the evaluation of PEI. Methods Sixty patients underwent FBHC measurement, BT-PABA testing, and microbiome analysis. They were classified into PEI group (PABA excretion rate
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- 2021
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38. Immunohistochemical staining for IMP3 in patients with duodenal papilla tumors: assessment of the potential for diagnosing endoscopic resectability and predicting prognosis
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Hiroyuki Tanaka, Hiroki Kawashima, Eizaburo Ohno, Takuya Ishikawa, Tadashi Iida, Eri Ishikawa, Kazuhiro Furukawa, Masanao Nakamura, Takashi Honda, Yoshie Shimoyama, Ryoji Miyahara, Naoto Kawabe, Teiji Kuzuya, Senju Hashimoto, Masatoshi Ishigami, Yoshiki Hirooka, and Mitsuhiro Fujishiro
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IMP3 protein ,Ampulla of Vater ,Sphincter of Oddi ,Pancreaticoduodenectomy ,Endoscopic papillectomy ,Prognosis ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Background Endoscopic papillectomy of duodenal papillary tumors (PT) is indicated for adenomas or well-differentiated adenocarcinomas that do not involve the sphincter of Oddi. However, there is currently no reliable pre-operative method to diagnose the infiltration in the sphincter of Oddi.’ Insulin-like growth factor 2 mRNA protein 3 (IMP3) staining is reportedly associated with advanced disease stage and clinical outcomes in many carcinomas. The aim of this retrospective study was to investigate the ability of diagnosing sphincter of Oddi involvement in PT and predicting the prognoses using IMP3 immunohistochemistry. Methods Twenty-five resected specimens from patients with PT and 24 biopsy specimens from the same patients excluding one were immunostained for IMP3. The percentage of positive cells in the tumor was evaluated and compared with the final pathological diagnosis and prognosis. Results The final pathological diagnoses were adenoma in 5 patients and adenocarcinoma in 20 patients (no sphincter of Oddi involvement in 5 and involvement in 15). The ability to diagnose sphincter of Oddi involvement based on the percentage of IMP3-positive cells in resected specimens and tissue biopsies was the area under the curve 0.8 and 0.78, respectively, of the receiver operating characteristic curve, and the accuracies were 80.0% and 75.0% (cutoff value: 10%), respectively. Moreover, patients with an IMP3-positive cell rate of ≥ 10% had a significantly worse prognosis (log-rank test P = 0.01). Conclusion IMP3 immunostaining of resected and biopsy specimens from PT patients enables the diagnosis of sphincter of Oddi involvement objectively and is also effective in predicting the prognosis.
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- 2021
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39. Inhibiting SCAP/SREBP exacerbates liver injury and carcinogenesis in murine nonalcoholic steatohepatitis
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Satoshi Kawamura, Yuki Matsushita, Shigeyuki Kurosaki, Mizuki Tange, Naoto Fujiwara, Yuki Hayata, Yoku Hayakawa, Nobumi Suzuki, Masahiro Hata, Mayo Tsuboi, Takahiro Kishikawa, Hiroto Kinoshita, Takuma Nakatsuka, Masaya Sato, Yotaro Kudo, Yujin Hoshida, Atsushi Umemura, Akiko Eguchi, Tsuneo Ikenoue, Yoshihiro Hirata, Motonari Uesugi, Ryosuke Tateishi, Keisuke Tateishi, Mitsuhiro Fujishiro, Kazuhiko Koike, and Hayato Nakagawa
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Gastroenterology ,Medicine - Abstract
Enhanced de novo lipogenesis mediated by sterol regulatory element–binding proteins (SREBPs) is thought to be involved in nonalcoholic steatohepatitis (NASH) pathogenesis. In this study, we assessed the impact of SREBP inhibition on NASH and liver cancer development in murine models. Unexpectedly, SREBP inhibition via deletion of the SREBP cleavage–activating protein (SCAP) in the liver exacerbated liver injury, fibrosis, and carcinogenesis despite markedly reduced hepatic steatosis. These phenotypes were ameliorated by restoring SREBP function. Transcriptome and lipidome analyses revealed that SCAP/SREBP pathway inhibition altered the fatty acid (FA) composition of phosphatidylcholines due to both impaired FA synthesis and disorganized FA incorporation into phosphatidylcholine via lysophosphatidylcholine acyltransferase 3 (LPCAT3) downregulation, which led to endoplasmic reticulum (ER) stress and hepatocyte injury. Supplementation with phosphatidylcholines significantly improved liver injury and ER stress induced by SCAP deletion. The activity of the SCAP/SREBP/LPCAT3 axis was found to be inversely associated with liver fibrosis severity in human NASH. SREBP inhibition also cooperated with impaired autophagy to trigger liver injury. Thus, excessively strong and broad lipogenesis inhibition was counterproductive for NASH therapy; this will have important clinical implications in NASH treatment.
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- 2022
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40. Snare devices with thinner loop wire may provide higher performance for cold snare polypectomy in an experimental model
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Satoshi Ono, Kyohei Maejima, Shun Ito, Shosuke Hosaka, Kiyotaka Umeki, Shin-ichiro Sato, Kota Akamine, Daichi Asai, and Mitsuhiro Fujishiro
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background and study aims Snare devices play an important role in treatment of intestinal polyps. However, there are no objective measurements for the characteristics of the various types of snare devices. Materials and methods Seven types of snare devices from four manufacturers were evaluated based on original measurements. The evaluated factors were stiffness, cutting quality, and change in force required for cutting depending on sheath shape. The latter two factors were evaluated by measuring the force required to cut 20 % gelatin cylinders, which simulated intestinal polyps. The cutting sharpness was evaluated by observing the sectional surface of cut gelatin cylinders using a stereomicroscope. The correlations between these measurements and characteristics of the snare devices were investigated. Results A strong positive correlation, with an R2 value of 0.863, was shown between the force required to cut gelatin cylinders and loop wire diameter. Loop wire diameter also had a strong correlation, with an R2 value of 0.7997, with the change in force required for cutting gelatin cylinders depending on sheath shape. No correlations were detected between loop stiffness and characteristics of snare devices. The edge-enhanced image revealed that the rougher surfaces of the gelatin cylinders were cut by snares with a thicker diameter. Conclusions Thinner loop wire may provide higher performance in cold snare polypectomy in an experimental model.
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- 2022
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41. Variability measurements provide additional value to shear wave elastography in the diagnosis of pancreatic cancer
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Masakatsu Yoshikawa, Takuya Ishikawa, Eizaburo Ohno, Tadashi Iida, Kazuhiro Furukawa, Masanao Nakamura, Takashi Honda, Masatoshi Ishigami, Fumie Kinoshita, Hiroki Kawashima, and Mitsuhiro Fujishiro
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Medicine ,Science - Abstract
Abstract Shear wave elastography (SWE) is a technique to non-invasively and quantitatively evaluate tissue stiffness. We aimed to investigate whether we can differentiate pancreatic cancer (PC) from normal pancreatic parenchyma (NPP) by SWE using transabdominal ultrasound. We investigated a total of 106 patients (84 with NPP and 22 with PC) whose pancreatic elastic modulus was measured by two-dimensional SWE (2D-SWE). Intra-rater reliability in this study was examined, and three measurements were sufficiently reliable. There were no differences between the two groups in factors that could affect SWE measurements. The median value of the elastic modulus was 5.70 kPa in the PC patients and 5.66 kPa in the NPP group, which was not significantly different (P = 0.785). On the contrary, the range was 8.64 kPa and 4.72 kPa, with a significantly greater range in the PC patients (P = 0.001). In conclusion, the median elastic modulus measured by 2D-SWE was not significantly different between PC and NPP, and evaluating the obtained elastic modulus itself is not useful in differentiation. However, the variability was significantly greater in PC than in NPP. Evaluating the range of elasticities will provide additional information in SWE, which may be useful in the diagnosis of PC.
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- 2021
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42. Diagnostic yield of colon capsule endoscopy for Crohn’s disease lesions in the whole gastrointestinal tract
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Keisaku Yamada, Masanao Nakamura, Takeshi Yamamura, Keiko Maeda, Tsunaki Sawada, Yasuyuki Mizutani, Eri Ishikawa, Takuya Ishikawa, Naomi Kakushima, Kazuhiro Furukawa, Eizaburo Ohno, Hiroki Kawashima, Takashi Honda, Masatoshi Ishigami, and Mitsuhiro Fujishiro
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Colon capsule endoscopy ,Crohn’s disease ,Diagnostic yield ,Retention ,Whole gastrointestinal tract ,Prospective study ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Background Crohn’s disease (CD) can involve the upper gastrointestinal (GI) tract as well as the small and large bowel. PillCam colon capsule endoscopy (PCCE-2) enables observation of the whole GI tract, but its diagnostic yield for CD lesions in the whole GI tract remains unknown. Aim To elucidate the diagnostic yield of PCCE-2 in patients with CD. Methods Patients with CD who underwent PCCE-2 and double-balloon endoscopy (DBE) using oral and anal approaches were evaluated for CD lesions in the whole GI tract. We divided the small bowel into three segments (jejunum, ileum, and terminal ileum), and the large bowel into four segments (right colon, transverse colon, left colon, rectum). Detection of ulcer scars, erosion, ulcers, bamboo joint-like appearance, and notch-like appearance was assessed in each segment. The diagnostic yield of PCCE-2 was analyzed based on the DBE results as the gold standard. Results Of the total 124 segments, the sensitivities of PCCE-2 for ulcer scars, erosion, and ulcers were 83.3%, 93.8%, and 88.5%, respectively, and the specificities were 76.0%, 78.3%, and 81.6%, respectively. For the 60 small bowel segments, the sensitivities were 84.2%, 95.5%, and 90.0%, respectively, and the specificities were 63.4%, 86.8%, and 87.5%, respectively. For the 64 large bowel segments, the sensitivities were 80.0%, 90.0%, and 83.3%, respectively, and the specificities were 84.7%, 72.2%, and 77.6%, respectively. Conclusion PCCE-2 provides a high diagnostic yield for lesions in the whole GI tract of patients with CD. Thus, we recommend its use as a pan-enteric tool in clinical settings.
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- 2021
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43. Performing the ABC Method Twice for Gastric Cancer Risk Stratification: A Retrospective Study Based on Data from a Large-Scale Screening Facility
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Satoru Mizutani, Yu Takahashi, Takeshi Shimamoto, Hideki Nakagawa, Hiroyuki Hisada, Kaori Oshio, Dai Kubota, Hiroya Mizutani, Daisuke Ohki, Yoshiki Sakaguchi, Seiichi Yakabi, Keiko Niimi, Naomi Kakushima, Yosuke Tsuji, Ryoichi Wada, Nobutake Yamamichi, and Mitsuhiro Fujishiro
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ABC method ,gastric cancer ,H. pylori ,pepsinogen ,risk stratification ,Medicine (General) ,R5-920 - Abstract
The ABC method is a classification method used for stratifying the risk of gastric cancer. However, whether the ABC method should be performed only once or multiple times throughout an individual’s lifetime remains unclear. Therefore, this study aimed to analyze whether performing ABC screening twice in a lifetime is useful. We retrospectively analyzed the data of individuals who participated in health checkups in 2010 and 2015. We collected data on patient characteristics, pepsinogen levels, anti-Helicobacter pylori antibody titers, and the presence of gastric cancer. Overall, 7129 participants without a history of H. pylori eradication were included in this study. The participants’ average age in 2010 was 48.4 ± 8.3 years, and 58.1% were male. In addition, 11 and 20 cases of new H. pylori infection (0.15%) and spontaneous eradication (0.28%), respectively, were recorded. No significant difference was found in the incidence of gastric cancer between participants who underwent the ABC method once and those who underwent it twice (Group A: 0.16% vs. 0.16%; Group B: 0.47% vs. 0.39%; and Group C + D: 1.97% vs. 1.82%). Therefore, performing the ABC method twice, 5 years apart, does not significantly improve gastric cancer risk stratification.
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- 2023
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44. Proteomic Analysis Reveals Changes in Tight Junctions in the Small Intestinal Epithelium of Mice Fed a High-Fat Diet
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Hisanori Muto, Takashi Honda, Taku Tanaka, Shinya Yokoyama, Kenta Yamamoto, Takanori Ito, Norihiro Imai, Yoji Ishizu, Keiko Maeda, Tetsuya Ishikawa, Shungo Adachi, Chikara Sato, Noriko M. Tsuji, Masatoshi Ishigami, Mitsuhiro Fujishiro, and Hiroki Kawashima
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non-alcoholic fatty liver disease ,intestinal epithelial cells ,proteomic analysis ,tight junctions ,Cldn 7 ,Epcam ,Nutrition. Foods and food supply ,TX341-641 - Abstract
The impact of a high-fat diet (HFD) on intestinal permeability has been well established. When bacteria and their metabolites from the intestinal tract flow into the portal vein, inflammation in the liver is triggered. However, the exact mechanism behind the development of a leaky gut caused by an HFD is unclear. In this study, we investigated the mechanism underlying the leaky gut related to an HFD. C57BL/6J mice were fed an HFD or control diet for 24 weeks, and their small intestine epithelial cells (IECs) were analyzed using deep quantitative proteomics. A significant increase in fat accumulation in the liver and a trend toward increased intestinal permeability were observed in the HFD group compared to the control group. Proteomics analysis of the upper small intestine epithelial cells identified 3684 proteins, of which 1032 were differentially expressed proteins (DEPs). Functional analysis of DEPs showed significant enrichment of proteins related to endocytosis, protein transport, and tight junctions (TJ). Expression of Cldn7 was inversely correlated with intestinal barrier function and strongly correlated with that of Epcam. This study will make important foundational contributions by providing a comprehensive depiction of protein expression in IECs affected by HFD, including an indication that the Epcam/Cldn7 complex plays a role in leaky gut.
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- 2023
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45. Improved Object Detection Artificial Intelligence Using the Revised RetinaNet Model for the Automatic Detection of Ulcerations, Vascular Lesions, and Tumors in Wireless Capsule Endoscopy
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Ayako Nakada, Ryota Niikura, Keita Otani, Yusuke Kurose, Yoshito Hayashi, Kazuya Kitamura, Hiroyoshi Nakanishi, Seiji Kawano, Testuya Honda, Kenkei Hasatani, Tetsuya Sumiyoshi, Tsutomu Nishida, Atsuo Yamada, Tomonori Aoki, Tatsuya Harada, Takashi Kawai, and Mitsuhiro Fujishiro
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artificial intelligence ,small intestine erosions and ulcers ,small intestine tumors ,small intestine vascular lesions ,wireless capsule endoscopy ,Biology (General) ,QH301-705.5 - Abstract
The use of computer-aided detection models to diagnose lesions in images from wireless capsule endoscopy (WCE) is a topical endoscopic diagnostic solution. We revised our artificial intelligence (AI) model, RetinaNet, to better diagnose multiple types of lesions, including erosions and ulcers, vascular lesions, and tumors. RetinaNet was trained using the data of 1234 patients, consisting of images of 6476 erosions and ulcers, 1916 vascular lesions, 7127 tumors, and 14,014,149 normal tissues. The mean area under the receiver operating characteristic curve (AUC), sensitivity, and specificity for each lesion were evaluated using five-fold stratified cross-validation. Each cross-validation set consisted of between 6,647,148 and 7,267,813 images from 217 patients. The mean AUC values were 0.997 for erosions and ulcers, 0.998 for vascular lesions, and 0.998 for tumors. The mean sensitivities were 0.919, 0.878, and 0.876, respectively. The mean specificities were 0.936, 0.969, and 0.937, and the mean accuracies were 0.930, 0.962, and 0.924, respectively. We developed a new version of an AI-based diagnostic model for the multiclass identification of small bowel lesions in WCE images to help endoscopists appropriately diagnose small intestine diseases in daily clinical practice.
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- 2023
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46. Optimal age to discontinue long-term surveillance of intraductal papillary mucinous neoplasms: comparative cost-effectiveness of surveillance by age.
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Tsuyoshi Hamada, Hiroki Oyama, Igarashi, Ataru, Yoshikuni Kawaguchi, Mihye Lee, Hiroki Matsui, Nobuaki Michihata, Yousuke Nakai, Kiyohide Fushimi, Hideo Yasunaga, and Mitsuhiro Fujishiro
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PANCREATIC cysts ,PANCREATIC surgery ,PANCREATECTOMY ,INFORMED consent (Medical law) ,TUMORS ,COST effectiveness ,ABO blood group system - Published
- 2024
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47. Amino Acid Polymorphism in Hepatitis B Virus Associated With Functional CureSummary
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Takashi Honda, Norie Yamada, Asako Murayama, Masaaki Shiina, Hussein Hassan Aly, Asuka Kato, Takanori Ito, Yoji Ishizu, Teiji Kuzuya, Masatoshi Ishigami, Yoshiki Murakami, Tomohisa Tanaka, Kohji Moriishi, Hironori Nishitsuji, Kunitada Shimotohno, Tetsuya Ishikawa, Mitsuhiro Fujishiro, Masamichi Muramatsu, Takaji Wakita, and Takanobu Kato
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HBc ,cccDNA ,HBVcc ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background & Aims: To provide an adequate treatment strategy for chronic hepatitis B, it is essential to know which patients are expected to have a good prognosis and which patients do not require therapeutic intervention. Previously, we identified the substitution of isoleucine to leucine at amino acid 97 (I97L) in the hepatitis B core region as a key predictor among patients with stable hepatitis. In this study, we attempted to identify the point at which I97L affects the hepatitis B virus (HBV) life cycle and to elucidate the underlying mechanisms governing the stabilization of hepatitis. Methods: To confirm the clinical features of I97L, we used a cohort of hepatitis B e antigen–negative patients with chronic hepatitis B infected with HBV-I97 wild-type (wt) or HBV-I97L. The effects of I97L on viral characteristics were evaluated by in vitro HBV production and infection systems with the HBV reporter virus and cell culture-generated HBV. Results: The ratios of reduction in hepatitis B surface antigen and HBV DNA were higher in patients with HBV-I97L than in those with HBV-I97wt. HBV-I97L exhibited lower infectivity than HBV-I97wt in both infection systems with reporter HBV and cell culture-generated HBV. HBV-I97L virions exhibiting low infectivity primarily contained a single-stranded HBV genome. The lower efficiency of cccDNA synthesis was demonstrated after infection of HBV-I97L or transfection of the molecular clone of HBV-I97L. Conclusions: The I97L substitution reduces the level of cccDNA through the generation of immature virions with single-stranded genomes. This I97L-associated low efficiency of cccDNA synthesis may be involved in the stabilization of hepatitis.
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- 2021
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48. Clinical characteristics and long-term prognosis of autoimmune pancreatitis with renal lesions
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Takuya Ishikawa, Hiroki Kawashima, Eizaburo Ohno, Tadashi Iida, Hirotaka Suzuki, Kota Uetsuki, Jun Yashika, Kenta Yamada, Masakatsu Yoshikawa, Noriaki Gibo, Toshinori Aoki, Kunio Kataoka, Hiroshi Mori, Takeshi Yamamura, Kazuhiro Furukawa, Masanao Nakamura, Yoshiki Hirooka, and Mitsuhiro Fujishiro
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Medicine ,Science - Abstract
Abstract Autoimmune pancreatitis (AIP) is recognized as the pancreatic manifestation of a systemic IgG4-related disease that can involve various organs, including the kidney. However, renal lesions tend to be overlooked when AIP is diagnosed, and the clinical characteristics and long-term prognosis of AIP with renal lesions are unclear. We retrospectively reviewed 153 patients with AIP diagnosed at our hospital with a median follow-up period of 41 months (interquartile range, 10–86) and classified them into two groups: the KD group (n = 17), with characteristic renal imaging features, and the non-KD group (n = 136). Serum IgG4 levels were significantly higher in the KD group (663 vs. 304.5 mg/dl, P = 0.014). No differences were observed between the two groups in terms of steroid treatment [14/17 (82.4%) vs. 112/136 (82.4%), P = 1] or in the number of patients who exhibited exacerbation of renal function during treatment [1/17 (5.9%) vs. 8/136 (5.9%), P = 1]. However, the cumulative relapse rate was significantly higher in the KD group [61% vs. 21.9% (3 years), P
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- 2021
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49. A novel Lugol’s iodine staining technique to visualize the upper margin of the surgical anal canal intraoperatively for Hirschsprung disease: a case series
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Kazuki Yokota, Hizuru Amano, Toyoki Kudo, Takeshi Yamamura, Yujiro Tanaka, Takahisa Tainaka, Chiyoe Shirota, Wataru Sumida, Satoshi Makita, Aitaro Takimoto, Masanao Nakamura, Mitsuhiro Fujishiro, Akinari Hinoki, and Hiroo Uchida
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Hirschsprung disease ,Aganglionosis ,Lugol’s iodine staining ,Surgical anal canal ,Transanal pull-through ,Surgery ,RD1-811 - Abstract
Abstract Background In cases of Hirschsprung disease, complete and reproducible resection of the aganglionic bowel is ideal to achieve good postoperative bowel function. Reliable identification of the upper margin of the surgical anal canal, which is the squamous-columnar junction, is necessary during transanal pull-through. Here, we describe a novel staining technique using Lugol’s iodine stain to visualize the upper margin of the surgical anal canal. Methods Lugol’s iodine staining was performed in five patients with Hirschsprung disease treated using a single-stage laparoscopic transanal pull-through modified Swenson procedure. In two of these patients, endocytoscopic observation with ultra-high magnification was performed using methylene blue and crystal violet to mark the border of the squamous epithelium at 1 week before surgery. The alignment between the incisional line, which was revealed using Lugol’s iodine staining and endocytoscopic marking, was evaluated. Complications, including postoperative bowel dysfunction, were evaluated. Results In all cases, Lugol’s iodine staining produced a well-demarcated line. The endocytoscopic marking of the upper margin of the surgical anal canal was aligned with the line revealed by Lugol’s iodine staining. There were no complications associated with the transanal pull-through procedure, including postoperative bowel dysfunction. Conclusions Lugol’s iodine staining could be a safe and practical method to visualize the upper margin of the surgical anal canal intraoperatively. This finding may be useful for surgeons to make a consistent removal of the aganglionic bowel during surgery for Hirschsprung disease.
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- 2020
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50. Endoscopic ultrasonography‐guided tissue acquisition for small solid pancreatic lesions: Does the size matter?
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Yousuke Nakai, Tsuyoshi Hamada, Ryunosuke Hakuta, Kazunaga Ishigaki, Kei Saito, Tomotaka Saito, Naminatsu Takahara, Suguru Mizuno, Hirofumi Kogure, Kazuhiko Koike, and Mitsuhiro Fujishiro
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endoscopic ultrasound ,fine needle aspiration ,fine needle biopsy ,pancreatic lesions ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Endoscopic ultrasonography‐guided tissue acquisition (EUS‐TA) is now an established technique to obtain the pathological diagnosis of solid pancreatic lesions (SPLs), but the diagnosis of small SPLS by EUS‐TA can still be difficult. We conducted a literature review and a meta‐analysis on the diagnostic yield of EUS‐TA according to the tumor size. In a meta‐analysis of 33 studies with 6883 cases, a pooled odds ratio (OR) of sensitivity was significantly higher in SPLs of >20 mm (OR 1.64, p = 0.02) and in SPLs of >10 mm (OR 3.05, p = 0.01), but not in SPLs of >30 mm (OR 1.18, p = 0.46). The meta‐analysis of accuracy also showed a similar trend: OR of 1.59 in SPLs of >20 mm (p < 0.01) and OR of 3.27 in SPLs of >10 mm (p < 0.01) and OR of 1.03 in SPLs of >30 mm (p = 0.87). The use of a 25‐gauge needle tended to improve sensitivity in small SPLs, though not statistically significant: OR of 1.25 and 2.82 in studies with and without a 25‐gauge needle (p = 0.08). The use of fine needle biopsy needles, slow pull method, and rapid on‐site evaluation did not significantly improve sensitivity in small SPLs. EUS‐TA for small SPLs, especially neuroendocrine neoplasms, is reported to have a high risk of adverse events. In summary, the diagnostic yield and safety of EUS‐TA for small (
- Published
- 2022
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