83 results on '"Kyoichi Takaori"'
Search Results
2. Impact of vascular abnormality on contrast-enhanced CT and high C-reactive protein levels on postoperative pancreatic hemorrhage after pancreaticoduodenectomy: A multi-institutional, retrospective analysis of 590 consecutive cases
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Kenzo Nakano, Toshihiko Masui, Asahi Sato, Yuichiro Uchida, Shinji Uemoto, Kyoichi Takaori, Kazuyuki Nagai, Takayuki Anazawa, Takafumi Machimoto, Kazuki Hashida, and Akitada Yogo
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Adult ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Postoperative Hemorrhage ,Gastroenterology ,Pancreaticoduodenectomy ,Pancreatic Fistula ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Predictive Value of Tests ,Risk Factors ,Internal medicine ,Ascites ,medicine ,Humans ,Aged ,Retrospective Studies ,Aged, 80 and over ,Hepatology ,biology ,business.industry ,C-reactive protein ,Perioperative ,Odds ratio ,Middle Aged ,medicine.disease ,C-Reactive Protein ,Pancreatic fistula ,030220 oncology & carcinogenesis ,biology.protein ,Blood Vessels ,Female ,030211 gastroenterology & hepatology ,Abnormality ,medicine.symptom ,Tomography, X-Ray Computed ,business ,Complication ,Aneurysm, False - Abstract
Background /Objectives: This study aimed to elucidate the efficacy of CT findings and perioperative characteristics to predict post-pancreatectomy hemorrhage (PPH): a critical complication after pancreaticoduodenectomy. Methods The records of 590 consecutive patients who underwent pancreaticoduodenectomy at three institutes between 2012 and 2018 were included. The presence of a vascular wall abnormality or ascites with high density (vascular abnormality) on postoperative day (POD) 5–10 contrast-enhanced CT (early CT), perioperative characteristics, and any PPH or pseudoaneurysm formation (PPH events) were analyzed through a multivariate analysis. Results PPH events occurred in 48 out of 590 patients (8%). The vascular abnormality on early CT and the C-reactive protein (CRP) value on POD 3 were independent risk factors for PPH events after POD5 (vascular abnormality: odds ratio 6.42, p = 0.001; CRP on POD 3: odds ratio 1.17, p = 0.016). The sensitivity of vascular abnormality for PPH events was 24% (7/29), and the positive predictive value was 30% (7/23). The combination of vascular abnormality and a high CRP value (≥15.5 mg/dL) on postoperative day 3 had a higher positive predictive value of 64% (7/11) than the vascular abnormality alone. None of the seven PPH events that occurred more than one month after surgery were foreseen via early CT. Conclusion The combination of vascular abnormality and high CRP value was associated with increasing risk of PPH events after pancreaticoduodenectomy, but the low sensitivity of early CT must be noted as an important shortcoming. The normal findings on early CT could not eliminate the risk of late PPH.
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- 2021
3. Postoperative pancreatic fistulas decrease the survival of pancreatic cancer patients treated with surgery after neoadjuvant chemoradiotherapy: A retrospective analysis
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Toshihiko Masui, Takayuki Anazawa, Kazuyuki Nagai, Kyoichi Takaori, Yuichiro Uchida, Takashi Mizowaki, Norimitsu Uza, Shinji Uemoto, and Michio Yoshimura
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Male ,medicine.medical_specialty ,medicine.medical_treatment ,Pancreatic Fistula ,Pancreatectomy ,Postoperative Complications ,Pancreatic cancer ,medicine ,Retrospective analysis ,Humans ,Neoadjuvant therapy ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Chemoradiotherapy ,Middle Aged ,Prognosis ,medicine.disease ,University hospital ,Combined Modality Therapy ,Neoadjuvant Therapy ,Surgery ,Pancreatic Neoplasms ,Survival Rate ,Oncology ,Pancreatic fistula ,Female ,Complication ,business ,Follow-Up Studies ,Neoadjuvant chemoradiotherapy - Abstract
Background and objectives A postoperative pancreatic fistula (POPF) is a critical complication after surgery for pancreatic cancer. Whether a POPF affects the long-term prognosis of pancreatic cancer cases remains controversial. This study aimed to clarify the effect of a POPF on the long-term prognosis of pancreatic cancer patients, especially after neoadjuvant chemoradiotherapy (NACRT). Methods Patients who underwent curative pancreatectomy for pancreatic cancer between January 2012 and June 2019 at Kyoto University Hospital were retrospectively investigated. A fistula ≥ Grade B was considered a POPF. Results During the study period, 148 patients underwent upfront surgery (Upfront group), and 52 patients underwent surgery after NACRT (NACRT group). A POPF developed in 16% of patients in the Upfront group and 13% in the NACRT group (p = 0.824). In the Upfront group, development of a POPF did not have a significant effect on recurrence-free survival (p = 0.766) or overall survival (p = 0.863). However, in the NACRT group, development of a POPF significantly decreased recurrence-free survival (HR 5.856, p = 0.002) and overall survival (HR 7.097, p = 0.020) on multivariate analysis. Conclusions The development of a POPF decreases the survival of pancreatic cancer patients treated by surgery after NACRT.
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- 2020
4. Left-posterior approach for artery-first en bloc resection in laparoscopic distal pancreatectomy for left-sided pancreatic cancer
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Akitada Yogo, Kazuyuki Nagai, Kyoichi Takaori, Gozo Kiguchi, Shintaro Yagi, Kojiro Taura, Takayuki Anazawa, and Toshihiko Masui
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Male ,medicine.medical_specialty ,medicine.medical_treatment ,Pancreatic Intraepithelial Neoplasia ,030230 surgery ,Splenic artery ,03 medical and health sciences ,Pancreatectomy ,0302 clinical medicine ,Mesenteric Artery, Superior ,medicine.artery ,Pancreatic cancer ,medicine ,Humans ,Superior mesenteric artery ,Pancreas ,Gastric emptying ,business.industry ,medicine.disease ,Surgery ,Pancreatic Neoplasms ,medicine.anatomical_structure ,Pancreatic fistula ,030220 oncology & carcinogenesis ,Female ,Laparoscopy ,Lymphadenectomy ,business - Abstract
We describe a “left-posterior approach” in which the important steps in laparoscopic distal pancreatectomy (LDP) for left-sided pancreatic cancer are accomplished in the direction caudal and dorsal to the pancreas. The patients who underwent LDP with a left-posterior approach at our hospital from January 2016 to April 2020 were reviewed to evaluate the short-term postoperative outcomes. In LDP, we first dissected retroperitoneal tissues above the left renal vein and superior mesenteric artery, yielding the mobilization of the pancreatic body widely. Then, the splenic artery was divided behind the ventrally lifted pancreas as an artery-first approach. The regional lymphadenectomy was performed in an en bloc manner consecutively in the same operative field. The neck of the pancreas was transected with a linear stapler after mobilization of the spleen. In nine patients (five men and four women) aged 76 years (range: 64–82 years), the operative time was 398 min (276–482 min) with the estimated blood loss of 40 ml (0–80 ml). No patients developed grade B/C pancreatic fistula or delayed gastric emptying. Postoperative complications classified as grade III in the Clavien–Dindo classification occurred in one patient (abdominal abscess). The pathology confirmed R0 resection in all patients who had pancreatic cancer (n = 5), IPMNs (n = 3), and high-grade pancreatic intraepithelial neoplasia (PanIN) (n = 1). The number of retrieved lymph nodes was 35 (11–49). The procedure with a left-posterior approach is a rational surgical technique in LDP for left-sided pancreatic cancer.
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- 2020
5. Usefulness of 18 F‐FDG‐PET/CT in the diagnosis and prediction of recurrence of pancreatic neuroendocrine neoplasms
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Yuji Nakamoto, Asahi Sato, Takayuki Anazawa, Yuichiro Uchida, Akitada Yogo, Kazuyuki Nagai, Kyoichi Takaori, Shinji Uemoto, Kenzo Nakano, and Toshihiko Masui
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Oncology ,medicine.medical_specialty ,Univariate analysis ,Multivariate analysis ,Hepatology ,business.industry ,Disease ,Neuroendocrine tumors ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,030211 gastroenterology & hepatology ,Surgery ,Avidity ,Fdg pet ct ,Pancreas ,business ,Pathological - Abstract
Background Although 18 F-FDG-PET/CT is a widely used diagnostic tool for several malignancies, its efficacy in diagnosing pancreatic neuroendocrine tumors is reported to be controversial because of the short-term follow-up. Methods We retrospectively compared demographics and pathological features between 18 F-FDG-positive and -negative diseases. Additionally, we evaluated whether the avidity of 18 F-FDG-PET/CT affected earlier recurrence after curative treatment of non-functioning tumors. The median duration of observation was 65.6 months. Results Seventy-two patients were enrolled. 18 F-FDG-positive diseases were pathologically advanced and significantly associated with metastatic behavior. In a multivariate analysis, metastatic behavior and WHO tumor grade was independently associated with 18 F-FDG accumulation. Only 25% of functional tumors (4/16) and 8% of insulinomas (1/12) were 18 F-FDG-positive. In a Kaplan-Meier analysis in patients with non-functioning tumors (n = 56), 18 F-FDG-positivity was significantly correlated with poorer recurrence-free survival (RFS) but had no correlation with overall survival. In univariate analysis of factors associated with shorter RFS, male gender, prevalence of nodal metastasis, WHO tumor grade ≥G2, or 18 F-FDG-positive disease were significantly higher in patients with shorter RFS, whereas only 18 F-FDG-positivity was associated with shorter RFS in multivariate analyses. Conclusions The avidity of 18 F-FDG-PET/CT was associated with metastatic behavior of pancreatic neuroendocrine tumors and recurrence after treatment of non-functioning tumors.
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- 2020
6. Prediction of the Probability of Malignancy in Mucinous Cystic Neoplasm of the Pancreas With Ovarian-Type Stroma
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Kei Ito, Hiroshi Yamaguchi, Yasuhiro Shimizu, Takahiro Urata, Naoto Gotohda, Susumu Hijioka, Takeshi Aoki, Tsuyoshi Sano, Kenji Yamao, Kyoichi Takaori, Masahiro Serikawa, Kojun Okamoto, Wataru Kimura, Kousei Ishigami, Kazuichi Okazaki, Emiri Kita, Minoru Tanabe, Minoru Tada, Keiji Hanada, Hiroyuki Isayama, Akio Katanuma, Michiaki Unno, Takao Ohtsuka, Yuichi Nagakawa, Masanori Sugiyama, Yoshitaka Gotoh, Masafumi Nakamura, and Seiko Hirono
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,CA-19-9 Antigen ,Endocrinology, Diabetes and Metabolism ,Malignancy ,Sensitivity and Specificity ,Gastroenterology ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Carcinoembryonic antigen ,Japan ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Pathological ,Aged ,Probability ,Aged, 80 and over ,Hepatology ,biology ,Receiver operating characteristic ,business.industry ,Ovary ,Area under the curve ,Odds ratio ,Middle Aged ,medicine.disease ,Carcinoembryonic Antigen ,Cystic Neoplasm ,Pancreatic Neoplasms ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,biology.protein ,Female ,030211 gastroenterology & hepatology ,Stromal Cells ,Neoplasms, Cystic, Mucinous, and Serous ,Pancreas ,business - Abstract
OBJECTIVE The aim of the study was to develop a formula for predicting the probability of malignancy of mucinous cystic neoplasm (MCN) of the pancreas with ovarian-type stroma. METHODS A total of 364 patients were enrolled. A total score was calculated as the sum of the approximate integers of the odds ratios of the predictive factors identified by multivariate analysis. The relationship between the total score and pathological results was assessed. RESULTS A total of 321 patients had benign MCN and 43 had malignant MCN. Five possible predictive factors were analyzed: 56 years or older, high serum carcinoembryonic antigen level, high carbohydrate antigen 19-9 level, tumor size of 51 mm or greater, and the presence of mural nodules. The total score was significantly higher in patients with malignant MCN (median, 24; range, 0-37) compared with benign MCN (median, 5; range, 0-33; P < 0.001). Receiver operating characteristic curve analysis demonstrated that the area under the curve was 0.86, and the sensitivity and specificity of the total score for discriminating malignant MCNs were 72% and 83%, respectively, using a cut-off value of 22. CONCLUSIONS The current simple formula can predict the malignancy of MCN and may thus contribute to the adequate management of patients with MCN.
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- 2020
7. Familial Pancreatic Cancer and Surveillance of High-Risk Individuals
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Chigusa Morizane, Yoshimi Kiyozumi, Hiroyuki Matsubayashi, and Kyoichi Takaori
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Diagnostic Imaging ,Oncology ,medicine.medical_specialty ,Antineoplastic Agents ,Review ,Germline ,03 medical and health sciences ,0302 clinical medicine ,Pharmacotherapy ,Genetic ,Risk Factors ,Pancreatic cancer ,Internal medicine ,Epidemiology ,Familial Pancreatic Cancer ,medicine ,Humans ,Genetic Predisposition to Disease ,Genetic Testing ,Healthy Lifestyle ,Family history ,Risk factor ,Polymerase inhibitor ,Germ-Line Mutation ,Surveillance ,Hepatology ,High risk ,business.industry ,Carcinoma ,Gastroenterology ,medicine.disease ,Pedigree ,Treatment ,Pancreatic Neoplasms ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Familial pancreatic cancer ,business ,Genes, Neoplasm - Abstract
Family history of pancreatic cancer (PC) is a risk factor for PC development, and the risk level correlates with the number of affected families. A case of PC with : 1 PC cases in the first-degree relative is broadly defined as familial pancreatic cancer (FPC) and accounts for 5% to 10% of total PC cases. FPC possesses several epidemiological, genetic and clinicopathological aspects that are distinct from those of conventional PCs. In Western countries, FPC registries have been established since the 1990s, and high-risk individuals are screened to detect early PCs. For the pharmacotherapy of FPC, especially in cases with germline pathogenic BRCA mutations, regimens using platinum and poly (ADP-ribose) polymerase inhibitor have recently been studied for their effectiveness. To date, the concept of FPC has prevailed in Western countries, and it has begun to infiltrate into Eastern countries. As the genetic background and environmental conditions vary in association with ethnicity and living area, we need to establish our own FPC registries and accumulate data in Asian countries. (Gut Liver 2019;13:498-505 )
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- 2019
8. Clinical and experimental studies of intraperitoneal lipolysis and the development of clinically relevant pancreatic fistula after pancreatic surgery
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Asahi Sato, Kyoichi Takaori, Yasuhiko Tabata, Toshihiko Masui, Yuichiro Uchida, Kazuyuki Nagai, Takayuki Anazawa, Shinji Uemoto, Kenzo Nakano, and Akitada Yogo
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Male ,medicine.medical_specialty ,Lipolysis ,Fistula ,Fatty Acids, Nonesterified ,Intra-Abdominal Fat ,Gastroenterology ,Pancreaticoduodenectomy ,Rats, Sprague-Dawley ,Pancreatic Fistula ,03 medical and health sciences ,chemistry.chemical_compound ,Pancreatectomy ,Postoperative Complications ,0302 clinical medicine ,Pancreatic Juice ,Risk Factors ,Internal medicine ,medicine ,Animals ,Humans ,Aged ,Triglyceride ,business.industry ,Lipase ,Middle Aged ,medicine.disease ,Disease Models, Animal ,Orlistat ,medicine.anatomical_structure ,chemistry ,Pancreatic fistula ,Obesity, Abdominal ,030220 oncology & carcinogenesis ,Lipase inhibitors ,Pancreatic juice ,Female ,030211 gastroenterology & hepatology ,Surgery ,Pancreas ,business ,medicine.drug - Abstract
Background Visceral obesity is one of the risk factors for clinically relevant pancreatic fistula after pancreatic resection. The objective of this study was to evaluate the impact of intraperitoneal lipolysis on postoperative pancreatic fistula. Methods The degree of intraperitoneal lipolysis was investigated by measuring the free fatty acid concentration in drain discharge in patients after pancreatic resection. An experimental pancreatic fistula model was prepared by pancreatic transection, and the impact of intraperitoneal lipolysis was evaluated by intraperitoneal administration of triolein (triglyceride) with, or without orlistat (lipase inhibitor). Results Thirty-three patients were included in the analysis. The free fatty acid concentration in drain discharge on postoperative day 1 was significantly associated with the development of a clinically relevant pancreatic fistula (P = 0·004). A higher free fatty acid concentration in drain discharge was associated with more visceral adipose tissue (P = 0·009). In the experimental model that included 98 rats, intraperitoneal lipolysis caused an increased amount of pancreatic juice leakage and multiple organ dysfunction. Intraperitoneal administration of a lipase inhibitor reduced lipolysis and prevented deterioration of the fistula. Conclusion Intraperitoneal lipolysis significantly exacerbates pancreatic fistula after pancreatic resection. Inhibition of lipolysis by intraperitoneal administration of a lipase inhibitor could be a promising therapy to reduce clinically relevant postoperative pancreatic fistula. Surgical relevance Clinically, there are two types of pancreatic fistula after pancreatic resections: harmless biochemical leak and harmful clinically relevant pancreatic fistula. Visceral obesity is one of the known risk factors for clinically relevant pancreatic fistula; however, the underlying mechanisms remained to be elucidated. Patients with clinically relevant pancreatic fistula had a higher free fatty acid concentration in the drain discharge, suggesting a relationship between intraperitoneal lipolysis and pancreatic fistula. The experimental model of pancreatic fistula demonstrated that intraperitoneal lipolysis caused deterioration in pancreatic fistula, suggesting that intraperitoneal lipolysis is one of the mechanisms that drives biochemical leakage to clinically relevant pancreatic fistula. Intraperitoneal administration of a lipase inhibitor prevented lipolysis as well as pancreatic fistula deterioration in the experimental model, suggesting a future clinical application for lipase inhibitors in prevention of clinically relevant pancreatic fistula.
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- 2019
9. Visualization of stem cell activity in pancreatic cancer expansion by direct lineage tracing with live imaging
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Kyoichi Takaori, Yukiko Hiramatsu, Shinji Uemoto, Akihisa Fukuda, Hiroshi Seno, Takahisa Maruno, Kozo Ikuta, Norihiro Goto, Satoshi Ogawa, Yuichi Yamaga, Dieter Saur, Takuto Yoshioka, Tsutomu Chiba, Yuki Nakanishi, and Motoyuki Tsuda
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0301 basic medicine ,cancer stem cells ,endocrine system diseases ,Mouse ,QH301-705.5 ,Science ,Pancreatic Intraepithelial Neoplasia ,Biology ,Adenocarcinoma ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Cancer stem cell ,In vivo ,Live cell imaging ,Pancreatic cancer ,medicine ,pancreatic adenocarcinoma ,Animals ,Humans ,Cell Lineage ,Epithelial–mesenchymal transition ,Biology (General) ,Neoplasm Metastasis ,Cancer Biology ,General Immunology and Microbiology ,Kinase ,General Neuroscience ,General Medicine ,live imaging ,medicine.disease ,digestive system diseases ,3. Good health ,ddc ,Pancreatic Neoplasms ,genetic lineage tracing ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,Neoplastic Stem Cells ,Medicine ,Stem cell ,Carcinoma, Pancreatic Ductal ,Research Article ,Human - Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease. Although rigorous efforts identified the presence of ‘cancer stem cells (CSCs)’ in PDAC and molecular markers for them, stem cell dynamics in vivo have not been clearly demonstrated. Here we focused on Doublecortin-like kinase 1 (Dclk1), known as a CSC marker of PDAC. Using genetic lineage tracing with a dual-recombinase system and live imaging, we showed that Dclk1+ tumor cells continuously provided progeny cells within pancreatic intraepithelial neoplasia, primary and metastatic PDAC, and PDAC-derived spheroids in vivo and in vitro. Furthermore, genes associated with CSC and epithelial mesenchymal transition were enriched in mouse Dclk1+ and human DCLK1-high PDAC cells. Thus, we provided direct functional evidence for the stem cell activity of Dclk1+ cells in vivo, revealing the essential roles of Dclk1+ cells in expansion of pancreatic neoplasia in all progressive stages.
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- 2020
10. Author response: Visualization of stem cell activity in pancreatic cancer expansion by direct lineage tracing with live imaging
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Tsutomu Chiba, Dieter Saur, Yukiko Hiramatsu, Shinji Uemoto, Hiroshi Seno, Satoshi Ogawa, Motoyuki Tsuda, Norihiro Goto, Kyoichi Takaori, Yuki Nakanishi, Takahisa Maruno, Yuichi Yamaga, Akihisa Fukuda, Kozo Ikuta, and Takuto Yoshioka
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Pathology ,medicine.medical_specialty ,Live cell imaging ,Lineage tracing ,Pancreatic cancer ,medicine ,Biology ,Stem cell ,medicine.disease ,Visualization - Published
- 2020
11. International consensus guidelines on surveillance for pancreatic cancer in chronic pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with the International Association of Pancreatology, the American Pancreatic Association, the Japan Pancreas Society, and European Pancreatic Club
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Carlos Fernandez-del Castillo, Julia Mayerle, William Greenhalf, Markus M. Lerch, Andrea Sheel, Philippe Lévy, Patrick Maisonneuve, Chris E. Forsmark, Maiken Thyregod Jørgensen, Vinciane Rebours, Jörg Kleeff, John P. Neoptolemos, Shuiji Isaji, Kyoichi Takaori, Christopher Halloran, Steve Pandol, Dhiraj Yadav, Pramod Kumar Garg, Thomas M. Gress, Péter Hegyi, Randall E. Brand, Suresh T. Chari, Marc G. Besselink, David C. Whitcomb, C. Mel Wilcox, Tooru Shimosegawa, Surgery, CCA - Cancer Treatment and Quality of Life, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism
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Male ,Endocrinology, Diabetes and Metabolism ,0302 clinical medicine ,Japan ,Trypsin ,EUS ,Aged, 80 and over ,Hereditary pancreatitis ,Evidence-Based Medicine ,Age Factors ,Gastroenterology ,Middle Aged ,medicine.anatomical_structure ,Trypsin Inhibitor, Kazal Pancreatic ,Population Surveillance ,030220 oncology & carcinogenesis ,Female ,030211 gastroenterology & hepatology ,Club ,Pancreas ,Adult ,CT scan ,medicine.medical_specialty ,Consensus ,Guidelines as Topic ,03 medical and health sciences ,Pancreatitis, Chronic ,Pancreatic cancer ,Internal medicine ,medicine ,Genetics ,Humans ,Genetic Predisposition to Disease ,In patient ,Life Style ,Aged ,Markers ,Hepatology ,business.industry ,Evidence-based medicine ,medicine.disease ,United States ,Pancreatic Neoplasms ,Treatment ,Increased risk ,Risk factors ,Pancreatitis ,Surgery ,business - Abstract
Background Patients with chronic pancreatitis (CP) have an increased risk of pancreatic cancer. We present the international consensus guidelines for surveillance of pancreatic cancer in CP. Methods The international group evaluated 10 statements generated from evidence on 5 questions relating to pancreatic cancer in CP. The GRADE approach was used to evaluate the level of evidence available per statement. The working group voted on each statement for strength of agreement, using a nine-point Likert scale in order to calculate Cronbach’s alpha reliability coefficient. Results In the following domains there was strong consensus: (1) the risk of pancreatic cancer in affected individuals with hereditary pancreatitis due to inherited PRSS1 mutations is high enough to justify surveillance; (2) the risk of pancreatic cancer in patients with CP associated with SPINK1 p. N34S is not high enough to justify surveillance; (3) surveillance should be undertaken in pancreatic specialist centers; (4) surveillance should only be introduced after the age of 40 years and stopped when the patient would no longer be suitable for surgical intervention. All patients with CP should be advised to lead a healthy lifestyle aimed at avoiding risk factors for progression of CP and pancreatic cancer. There was only moderate or weak agreement on the best methods of screening and surveillance in other types of environmental, familial and genetic forms of CP. Conclusions Patients with inherited PRSS1 mutations should undergo surveillance for pancreatic cancer, but the best methods for cancer detection need further investigation.
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- 2020
12. Risk factors for short recurrence-free survival after resection of pancreatic neuroendocrine tumor (PanNET) liver metastases: which patients should undergo resection?
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Takayuki Anazawa, Kyoichi Takaori, Akitada Yogo, Yoshiya Kawaguchi, Shinji Uemoto, Toshihiko Masui, Asahi Sato, Yosuke Kasai, Yuichiro Uchida, Kenzo Nakano, and Kazuyuki Nagai
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Surgical resection ,Curative resection ,Adult ,Male ,medicine.medical_specialty ,Pancreatic neuroendocrine tumor ,Neuroendocrine tumors ,Resection ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Recurrence free survival ,medicine ,Humans ,Aged ,business.industry ,Liver Neoplasms ,Gastroenterology ,Middle Aged ,medicine.disease ,Pancreatic Neoplasms ,Survival Rate ,Neuroendocrine Tumors ,medicine.anatomical_structure ,Ki-67 Antigen ,Logistic Models ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Female ,Radiology ,Neoplasm Recurrence, Local ,Pancreas ,business - Abstract
Background: In the treatment of metastatic pancreatic neuroendocrine tumors (PanNETs), surgical resection is the first choice if curative resection is expected. However, most patients develop recur...
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- 2020
13. Robotic-assisted pancreaticoduodenectomy with vascular resection. Description of the surgical technique and analysis of early outcomes
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Kyoichi Takaori, Marco Vito Marino, Francesco Giovinazzo, Manuel Gómez Fleitas, Marcos Gómez Ruiz, Mauro Podda, Mario Adelfio Latteri, Adolfo Pisanu, Marino M.V., Giovinazzo F., Podda M., Gomez Ruiz M., Gomez Fleitas M., Pisanu A., Latteri M., and Takaori K.
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Male ,medicine.medical_specialty ,Robotic assisted ,medicine.medical_treatment ,Operative Time ,Adenocarcinoma ,030230 surgery ,Pancreaticoduodenectomy ,03 medical and health sciences ,0302 clinical medicine ,Robotic Surgical Procedures ,Borderline resectable ,Pancreatic cancer ,Vascular reconstruction ,Humans ,Medicine ,Robotic surgery ,Vascular resection ,Aged ,business.industry ,Mortality rate ,Surgical outcomes ,Middle Aged ,medicine.disease ,Surgery ,Pancreatic Neoplasms ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,Initial phase ,Female ,business ,Vascular Surgical Procedures - Abstract
Background Despite the potential benefits, the adoption of the minimally invasive surgery for the treatment of borderline resectable pancreatic cancer is still in the initial phase. We investigated the safety and feasibility of the robotic pancreaticoduodenectomy with venous resection/reconstruction (RPD SMV/PV). Methods Since March 2013 to October 2019, a total of 73 RPD and 10 RPD SMV/PV were performed. The two groups were case-matched according to the preoperative characteristics. Results Mean operative times and estimated blood loss were less in the RPD group in comparison to that in the RPD with SMV-PV group (525 vs 642 min, p = 0.003 and 290 vs 620 ml, p = 0.002, respectively). The mean length of hospital stay was similar in the RPD group in comparison to that in the RPD with SMV-PV group (10 days vs 13 days, p = 0.313). The two groups had similar overall postoperative morbidity rate (57.5% vs 60%, p = 0.686), although the severe complication rate was lower in the RPD group (11% vs 40%, p = 0.004). Conclusions RPD with SMV-PV is associated with increased operative time, estimated blood loss, higher major complication rate compared with RPD.
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- 2020
14. A multicenter prospective registration study on laparoscopic pancreatectomy in Japan: report on the assessment of 1,429 patients
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Ichiro Uyama, Hirokazu Noshiro, Shigeru Marubashi, Takashi Takao, Kyoichi Takaori, Masafumi Inomata, Masanao Kurata, Minoru Tanabe, Masaru Tsuchiya, Hiromitsu Hayashi, Yutaka Takeda, Kenichi Hakamada, Masakazu Yamamoto, Nobutsugu Abe, Naoto Gotohda, Yoichiro Uchida, Takeyuki Misawa, Yusuke Kumamoto, Mamoru Morimoto, Hiroki Yamaue, Eiji Sakamoto, Hideyuki Yoshitomi, Takeshi Sudo, Tomoki Ryu, Masahiko Watanabe, Koji Amaya, Kenjiro Kimura, Munenori Tahara, Saiho Ko, Eiji Toyoda, Makoto Shinzeki, Goro Honda, Susumu Eguchi, Yuichi Nagakawa, Shinichiro Kameyama, Masayoshi Hioki, Masafumi Yasunaga, Masafumi Nakamura, Ryuichi Yoshida, Michiaki Unno, Yoshiharu Nakamura, Takao Ohtsuka, Yosuke Inoue, Toru Kojima, Atsuyuki Maeda, Kenji Kitahara, Kazuki Hashida, Yasuji Seyama, Kengo Fukuzawa, Yasunari Kawabata, Hidetoshi Eguchi, Hideo Baba, Daisuke Ichikawa, Masayuki Sho, Hiroyoshi Matsukawa, Kiyoshi Hasegawa, Ippei Matsumoto, Shin Nakahira, Akihiro Murata, and Hirochika Toyama
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medicine.medical_specialty ,Patient characteristics ,030230 surgery ,03 medical and health sciences ,Pancreatectomy ,Postoperative Complications ,0302 clinical medicine ,Japan ,Blood loss ,Humans ,Medicine ,Operation time ,Prospective Studies ,Prospective cohort study ,Hepatology ,business.industry ,Mortality rate ,General surgery ,Laparoscopic pancreatectomy ,Postoperative complication ,Length of Stay ,medicine.disease ,Pancreatic Neoplasms ,Treatment Outcome ,Pancreatic fistula ,030220 oncology & carcinogenesis ,Laparoscopy ,Surgery ,business - Abstract
Background Prospective studies are needed to understand the safety and feasibility of laparoscopic pancreatectomy. The aim of the present study was to describe laparoscopic pancreatectomy currently undertaken in Japan, using a prospective registration system. Methods Patient characteristics and planned operations were registered preoperatively, and then the performed operation and outcomes were reported using an online system. Collected data were also compared between institutions based on their level of experience. This study was registered with UMIN000022836. Results Available data were obtained from 1,429 patients at 100 Japanese institutions, including 1,197 laparoscopic distal pancreatectomies (LDPs) and 232 laparoscopic pancreatoduodenectomies (LPDs). The rates of completion for planned operations were 92% for LDP and 91% for LPD. Postoperative complication rates after LDP and LPD were 17% and 30%, and 90-day mortality rates were 0.3% and 0.4%, respectively. Shorter operation time, less blood loss, and lower incidence of pancreatic fistula were observed in institutions experienced in LDP. A higher rate of pure laparoscopic procedure and shorter operation time were noted in institutions experienced with LPD. Conclusion LDPs and LPDs are performed safely in Japan, especially in experienced institutions. Our data could support the next challenges in the field of laparoscopic pancreatectomy.
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- 2019
15. Association between homologous recombination repair gene mutations and response to oxaliplatin in pancreatic cancer
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Tomohiro Sakuma, Hiroaki Mochizuki, Toshihiko Masui, Mayumi Kamada, Norimitsu Uza, Tadayuki Kou, Masahiko Nakatsui, Masashi Kanai, Tomohiro Kondo, Hidehiko Miyake, Yasushi Okuno, Shigemi Matsumoto, Manabu Muto, Kyoichi Takaori, and Yuzo Kodama
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,FOLFIRINOX ,precision medicine ,PALB2 ,BRCA ,pancreatic cancer ,Gene mutation ,homologous recombination repair ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Pancreatic cancer ,medicine ,CHEK2 ,business.industry ,oxaliplatin ,medicine.disease ,Oxaliplatin ,Transplantation ,MRE11A ,030104 developmental biology ,030220 oncology & carcinogenesis ,business ,human activities ,Research Paper ,medicine.drug - Abstract
// Tomohiro Kondo 1 , Masashi Kanai 1 , Tadayuki Kou 1 , Tomohiro Sakuma 2 , Hiroaki Mochizuki 2 , Mayumi Kamada 3 , Masahiko Nakatsui 3 , Norimitsu Uza 4 , Yuzo Kodama 4 , Toshihiko Masui 5 , Kyoichi Takaori 5 , Shigemi Matsumoto 1 , Hidehiko Miyake 6 , Yasushi Okuno 3 and Manabu Muto 1 1 Department of Medical Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan 2 Biomedical Department, Mitsui Knowledge Industry Co., Ltd., Tokyo, Japan 3 Department of Biomedical Data Intelligence, Graduate School of Medicine, Kyoto University, Kyoto, Japan 4 Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan 5 Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan 6 Clinical Genetics Unit, Kyoto University Hospital, Kyoto, Japan Correspondence to: Masashi Kanai, email: kanai@kuhp.kyoto-u.ac.jp Keywords: BRCA; homologous recombination repair; oxaliplatin; pancreatic cancer; precision medicine Received: August 24, 2017 Accepted: March 15, 2018 Published: April 13, 2018 ABSTRACT Objectives: We aimed to examine the association between homologous recombination repair (HRR)-related gene mutations and efficacy of oxaliplatin-based chemotherapy in patients with pancreatic ductal adenocarcinoma (PDAC). Results: Non-synonymous mutations in HRR-related genes were found in 13 patients and only one patient had a family history of pancreatic cancer. Eight patients with HRR-related gene mutations (group A) and nine without HRR-related gene mutations (group B) received oxaliplatin-based chemotherapy. Median progression-free survival after initiation of oxaliplatin-based chemotherapy was significantly longer in group A than in group B (20.8 months vs 1.7 months, p = 0.049). Interestingly, two patients with inactivating HRR-related gene mutations who received FOLFIRINOX as first-line treatment showed exceptional responses with respect to progression-free survival for > 24 months. Materials and Methods: Complete coding exons of 12 HRR-related genes ( ATM, ATR, BAP1, BRCA1, BRCA2, BLM, CHEK1, CHEK2, FANCA, MRE11A, PALB2, and RAD51 ) were sequenced using a Clinical Laboratory Improvement Amendment-certified multiplex next-generation sequencing assay. Thirty consecutive PDAC patients who underwent this assay between April 2015 and July 2017 were included. Conclusions: Our results suggest that inactivating HRR-related gene mutations are predictive of response to oxaliplatin-based chemotherapy in patients with PDAC.
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- 2018
16. Computer tomographic assessment of postoperative peripancreatic collections after distal pancreatectomy
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Yuichiro Uchida, Shinji Uemoto, Takayuki Anazawa, Kyoichi Takaori, Toshihiko Masui, Kazuyuki Nagai, and Asahi Sato
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Adult ,Male ,medicine.medical_specialty ,030230 surgery ,Risk Assessment ,Disease-Free Survival ,Cohort Studies ,Hospitals, University ,Pancreatic Fistula ,03 medical and health sciences ,Imaging, Three-Dimensional ,Pancreatectomy ,Postoperative Complications ,Sex Factors ,0302 clinical medicine ,Japan ,Humans ,Medicine ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Age Factors ,Odds ratio ,Middle Aged ,Vascular surgery ,Prognosis ,medicine.disease ,Survival Analysis ,Confidence interval ,Cardiac surgery ,Pancreatic Neoplasms ,Cardiothoracic surgery ,Pancreatic fistula ,030220 oncology & carcinogenesis ,Drainage ,Female ,Surgery ,Radiology ,Tomography, X-Ray Computed ,business ,Distal pancreatectomy ,Abdominal surgery - Abstract
Peripancreatic collections occur frequently after distal pancreatectomy. However, the sequelae of peripancreatic collections vary from case to case, and their clinical impact is uncertain. In this study, the correlations between CT findings of peripancreatic collections and complications after distal pancreatectomy were investigated. Ninety-six consecutive patients who had undergone distal pancreatectomy between 2010 and 2015 were retrospectively investigated. The extent and heterogeneity of peripancreatic collections and background clinicopathological characteristics were analyzed. The extent of peripancreatic collections was calculated based on three-dimensional computed tomography images, and the degree of heterogeneity of peripancreatic collections was assessed based on the standard deviation of their density on computed tomography. Of 85 patients who underwent postoperative computed tomography imaging, a peripancreatic collection was detected in 77 (91%). Patients with either a large extent or a high degree of heterogeneity of peripancreatic collection had a significantly higher rate of clinically relevant pancreatic fistula than those without (odds ratio 5.95, 95% confidence interval 2.12–19.72, p = 0.001; odds ratio 8.0, 95% confidence interval 2.87–24.19, p = 0.0001, respectively). A large and heterogeneous peripancreatic collection was significantly associated with postoperative complications, especially clinically relevant postoperative pancreatic fistula. A small and homogenous peripancreatic collection could be safely observed.
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- 2018
17. Visceral Adiposity and Sarcopenic Visceral Obesity are Associated with Poor Prognosis After Resection of Pancreatic Cancer
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Shinya Okumura, Shinji Uemoto, Hisaya Shirai, Naoko Kamo, Atsushi Kobayashi, Hideaki Okajima, Kyoichi Takaori, Toshimi Kaido, Yuhei Hamaguchi, Siyuan Yao, Etsuro Hatano, and Shintaro Yagi
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Male ,Sarcopenia ,medicine.medical_specialty ,Intra-Abdominal Fat ,medicine.medical_treatment ,Adipose tissue ,Gastroenterology ,Body Mass Index ,03 medical and health sciences ,Pancreatectomy ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Pancreatic cancer ,medicine ,Humans ,Obesity ,Muscle, Skeletal ,Survival rate ,Aged ,Retrospective Studies ,business.industry ,Hazard ratio ,Middle Aged ,Prognosis ,medicine.disease ,Pancreatic Neoplasms ,Survival Rate ,Endocrinology ,Adipose Tissue ,Oncology ,030220 oncology & carcinogenesis ,Body Composition ,Female ,030211 gastroenterology & hepatology ,Surgery ,Neoplasm Recurrence, Local ,business ,Body mass index ,Follow-Up Studies - Abstract
Visceral fat accumulation and muscle depletion have been identified as poor prognostic factors for various cancers. However, the significance of visceral adiposity and sarcopenic visceral obesity on outcomes after resection of pancreatic cancer remains unclear. A retrospective analysis of 301 patients who underwent resection for localized pancreatic cancer between 2004 and 2015 was performed. The extent of visceral adiposity [visceral to subcutaneous adipose tissue area ratio (VSR)] and visceral obesity [visceral fat area (VFA)] were measured on preoperative computed tomography images, together with skeletal muscle index (SMI) and muscle attenuation (MA). The impacts of these body composition parameters on outcomes after pancreatic resection were investigated. The overall survival (OS) and recurrence-free survival (RFS) rates in patients with high VSR were significantly lower than those in patients with low VSR (P = 0.001, P = 0.007, respectively). There were no differences in OS and RFS between high VFA and low VFA group; however, when analyzed together with sarcopenic factors, OS and RFS rates of the patients with sarcopenic visceral obesity were significantly lower compared with those of the others. Multivariate analyses revealed that high VSR was an independent risk factor for mortality (hazard ratio (HR) 1.58, P = 0.009) and recurrence (HR 1.41, P = 0.026) together with low SMI, low MA, high CA19-9, microvascular invasion, and nodal metastasis. Visceral adiposity and sarcopenic visceral obesity, as well as low muscle mass and quality, were closely associated with mortality and recurrence after resection of pancreatic cancer.
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- 2017
18. Validation of Lymphocyte-to-Monocyte Ratio as a Prognostic Factor in Advanced Pancreatic Cancer
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Peng Xue, Junjie Hang, Masashi Kanai, Weiyi Huang, Shaobo Li, Kyoichi Takaori, Ning Li, Lifei Zhu, Yuzo Kodama, and Shigemi Matsumoto
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Adult ,Male ,0301 basic medicine ,Oncology ,China ,medicine.medical_specialty ,Pathology ,Prognostic factor ,Endocrinology, Diabetes and Metabolism ,Lymphocyte ,Kaplan-Meier Estimate ,Monocytes ,Leukocyte Count ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Japan ,Internal medicine ,Pancreatic cancer ,Internal Medicine ,medicine ,Humans ,Lymphocytes ,Aged ,Retrospective Studies ,Aged, 80 and over ,Hepatology ,business.industry ,Monocyte ,Palliative Care ,Reproducibility of Results ,Retrospective cohort study ,Palliative chemotherapy ,Middle Aged ,Prognosis ,medicine.disease ,Pancreatic Neoplasms ,030104 developmental biology ,medicine.anatomical_structure ,Multicenter study ,030220 oncology & carcinogenesis ,Female ,business ,Cohort study - Abstract
Although the prognostic value of lymphocyte-to-monocyte ratio (LMR) has been recently demonstrated in solid tumors, little is known of its impact on advanced pancreatic cancer (APC). This study evaluates and validates the cutoff value of LMR for predicting palliative chemotherapy outcome using a transnational cohort of APC patients.A total of 405 APC patients receiving first-line palliative chemotherapy were retrospectively reviewed. Of these, 153 patients were from Shanghai General Hospital (training set) and 252 patients were from Kyoto University Hospital (validation set). The optimal cutoff value of LMR was determined by a generating receiver operating characteristic curve for the training set. The association between LMR and survival was evaluated using log-rank tests, and a Cox regression model was used to validate the independent prognostic significance of LMR in APC patients.The optimal cutoff value of LMR was 2.8. Overall survival was significantly longer in patients with LMR of 2.8 or greater than those with LMR of less than 2.8 (P0.001). Cox regression analysis showed that LMR was an independent prognostic factor. The impact of LMR was widely observed in all subgroups except the performance status 2 subgroup.Lymphocyte-to-monocyte ratio may be considered as a promising prognostic marker for APC patients receiving palliative chemotherapy.
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- 2017
19. The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 Years After
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William Traverso, Mustapha Adam, John P. Neoptolemos, Roberto Salvia, Carlos Fernandez-del Castillo, Dirk J. Gouma, Horacio J. Asbun, M.W. Büchler, Charles J. Yeo, Sarr Mg, Claudio Bassi, C. Vollmer, Laureano Fernández-Cruz, Attila Oláh, Mohammad Abu Hilal, Christopher L. Wolfgang, Shailesh V. Shrikhande, Marc G. Besselink, Christos Dervenis, Abe Fingerhut, Marco Del Chiaro, Tadahiro Takada, Giovanni Marchegiani, Helmut Friess, Kevin C. Conlon, Keith D. Lillemoe, Thilo Hackert, Richard D. Schulick, Roland Andersson, Massimo Falconi, Peter J. Allen, Kyoichi Takaori, Jakob R. Izbicki, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Surgery, CCA -Cancer Center Amsterdam, and APH - Methodology
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medicine.medical_specialty ,Percutaneous ,business.industry ,030230 surgery ,Normal serum ,medicine.disease ,Severity of Illness Index ,Surgery ,Postoperative management ,Acs nsqip ,Pancreatic surgery ,Clinical Practice ,Pancreatic Fistula ,03 medical and health sciences ,Postoperative Complications ,0302 clinical medicine ,Pancreatic fistula ,030220 oncology & carcinogenesis ,medicine ,Humans ,business ,Grading (education) - Abstract
Background In 2005, the International Study Group of Pancreatic Fistula developed a definition and grading of postoperative pancreatic fistula that has been accepted universally. Eleven years later, because postoperative pancreatic fistula remains one of the most relevant and harmful complications of pancreatic operation, the International Study Group of Pancreatic Fistula classification has become the gold standard in defining postoperative pancreatic fistula in clinical practice. The aim of the present report is to verify the value of the International Study Group of Pancreatic Fistula definition and grading of postoperative pancreatic fistula and to update the International Study Group of Pancreatic Fistula classification in light of recent evidence that has emerged, as well as to address the lingering controversies about the original definition and grading of postoperative pancreatic fistula. Methods The International Study Group of Pancreatic Fistula reconvened as the International Study Group in Pancreatic Surgery in order to perform a review of the recent literature and consequently to update and revise the grading system of postoperative pancreatic fistula. Results Based on the literature since 2005 investigating the validity and clinical use of the original International Study Group of Pancreatic Fistula classification, a clinically relevant postoperative pancreatic fistula is now redefined as a drain output of any measurable volume of fluid with an amylase level >3 times the upper limit of institutional normal serum amylase activity, associated with a clinically relevant development/condition related directly to the postoperative pancreatic fistula. Consequently, the former “grade A postoperative pancreatic fistula” is now redefined and called a “biochemical leak,” because it has no clinical importance and is no longer referred to a true pancreatic fistula. Postoperative pancreatic fistula grades B and C are confirmed but defined more strictly. In particular, grade B requires a change in the postoperative management; drains are either left in place >3 weeks or repositioned through endoscopic or percutaneous procedures. Grade C postoperative pancreatic fistula refers to those postoperative pancreatic fistula that require reoperation or lead to single or multiple organ failure and/or mortality attributable to the pancreatic fistula. Conclusion This new definition and grading system of postoperative pancreatic fistula should lead to a more universally consistent evaluation of operative outcomes after pancreatic operation and will allow for a better comparison of techniques used to mitigate the rate and clinical impact of a pancreatic fistula. Use of this updated classification will also allow for more precise comparisons of surgical quality between surgeons and units who perform pancreatic surgery.
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- 2017
20. Familial pancreatic cancer: Concept, management and issues
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Kyoichi Takaori, Masami Suzuki, Hiroyuki Maguchi, Risa Usui, Nobumasa Mizuno, Chigusa Morizane, Masaki Mizumoto, Keita Wada, Hideaki Takahashi, Masayuki Kitano, Shinichi Yachida, Masamichi Mizuma, Yuzo Kodama, Toru Shimosegawa, Hiroyuki Matsubayashi, Masayuki Furukawa, Keiji Hanada, Susumu Hijioka, Ken Kawabe, Hiroko Hosoi, Masako Torishima, Takeshi Terashima, Toru Furukawa, Makoto Ueno, Yoshimi Kiyozumi, Junji Furuse, Yoshiyuki Majima, Takamitsu Sato, Reiko Ashida, and Takahisa Kawaguchi
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Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Pancreatic Intraepithelial Neoplasia ,Antineoplastic Agents ,Review ,familial pancreatic cancer ,high risk ,registry ,Familial adenomatous polyposis ,Cancer syndrome ,03 medical and health sciences ,Pancreatectomy ,0302 clinical medicine ,Japan ,Risk Factors ,Internal medicine ,Pancreatic cancer ,medicine ,Humans ,Genetic Predisposition to Disease ,Early Detection of Cancer ,BRCA2 Protein ,Hereditary pancreatitis ,BRCA1 Protein ,business.industry ,Incidence ,Carcinoma ,Gastroenterology ,General Medicine ,medicine.disease ,United States ,Lynch syndrome ,Europe ,Pancreatic Neoplasms ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Mutation ,surveillance ,030211 gastroenterology & hepatology ,genetic ,Pancreas ,business - Abstract
Familial pancreatic cancer (FPC) is broadly defined as two first-degree-relatives with pancreatic cancer (PC) and accounts for 4%-10% of PC. Several genetic syndromes, including Peutz-Jeghers syndrome, hereditary pancreatitis, hereditary breast-ovarian cancer syndrome (HBOC), Lynch syndrome, and familial adenomatous polyposis (FAP), also have increased risks of PC, but the narrowest definition of FPC excludes these known syndromes. When compared with other familial tumors, proven genetic alterations are limited to a small proportion (< 20%) and the familial aggregation is usually modest. However, an ethnic deviation (Ashkenazi Jewish > Caucasian) and a younger onset are common also in FPC. In European countries, “anticipation” is reported in FPC families, as with other hereditary syndromes; a trend toward younger age and worse prognosis is recognized in the late years. The resected pancreases of FPC kindred often show multiple pancreatic intraepithelial neoplasia (PanIN) foci, with various K-ras mutations, similar to colorectal polyposis seen in the FAP patients. As with HBOC patients, a patient who is a BRCA mutation carrier with unresectable pancreatic cancer (accounting for 0%-19% of FPC patients) demonstrated better outcome following platinum and Poly (ADP-ribose) polymerase inhibitor treatment. Western countries have established FPC registries since the 1990s and several surveillance projects for high-risk individuals are now ongoing to detect early PCs. Improvement in lifestyle habits, including non-smoking, is recommended for individuals at risk. In Japan, the FPC study group was initiated in 2013 and the Japanese FPC registry was established in 2014 by the Japan Pancreas Society.
- Published
- 2017
21. Successful laparoscopic distal pancreatectomy for a large solid pseudopapillary neoplasm: A case report
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Toshihiko Masui, Kyoichi Takaori, Satoru Seo, Toshimi Kaido, Seiichiro Tada, Shinji Uemoto, Taku Iida, Takayuki Anazawa, and Shintaro Yagi
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Laparoscopic surgery ,medicine.medical_specialty ,Large tumor ,business.industry ,medicine.medical_treatment ,Splenectomy ,General Medicine ,Splenic artery ,medicine.disease ,Surgery ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Pancreatic tumor ,030220 oncology & carcinogenesis ,medicine.artery ,medicine ,Neoplasm ,030211 gastroenterology & hepatology ,Pancreas ,Distal pancreatectomy ,business - Abstract
A 30-year-old Japanese woman presented at our hospital with a pancreatic tumor. Contrast-enhanced CT revealed a tumor with a 12-cm diameter in the pancreatic body and tail. In the preoperative setting, endoscopic ultrasound-guided fine-needle aspiration permitted a histopathological diagnosis of solid pseudopapillary neoplasm. Twhe patient underwent laparoscopic distal pancreatectomy with splenectomy. Our procedure involved three steps. Firstly, the splenic artery was occluded to block inflow of blood to the tumor. Then, we transected the neck of the pancreas using radical antegrade modular pancreatosplenectomy. Finally, hand-assisted laparoscopic surgery allowed us to secure the operating field and easily handle the large tumor. This enabled us to accomplish laparoscopic distal pancreatectomy, and en-bloc resection was completed. The patient was discharged without major complications. Laparoscopic distal pancreatectomy for huge solid pancreatic tumors can be completed safely.
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- 2017
22. Japanese Familial Pancreatic Cancer Registry with the aim to early detection of pancreatic cancer
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Masaki Mizumoto, Susumu Hijioka, Chigusa Morizane, Keita Wada, Shinji Kosugi, Toru Furukawa, Junji Furuse, Masayuki Kitano, Tetsuhide Ito, Kyoichi Takaori, Terumi Kamisawa, Masamichi Mizuma, Hiroyuki Matsubayashi, and Yoshiyuki Majima
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Cancer ,Early detection ,medicine.disease ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,Pancreatic cancer ,Familial Pancreatic Cancer ,medicine ,030211 gastroenterology & hepatology ,business - Published
- 2017
23. Management of the pancreatic transection plane after left (distal) pancreatectomy: Expert consensus guidelines by the International Study Group of Pancreatic Surgery (ISGPS)
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Yi Miao, Zipeng Lu, Charles J. Yeo, Charles M. Vollmer, Carlos Fernandez-del Castillo, Paula Ghaneh, Christopher M. Halloran, Jörg Kleeff, Thijs de Rooij, Jens Werner, Massimo Falconi, Helmut Friess, Herbert J. Zeh, Jakob R. Izbicki, Jin He, Johanna Laukkarinen, Cees H. Dejong, Keith D. Lillemoe, Kevin Conlon, Kyoichi Takaori, Luca Gianotti, Marc G. Besselink, Marco Del Chiaro, Marco Montorsi, Masao Tanaka, Maximilian Bockhorn, Mustapha Adham, Attila Oláh, Roberto Salvia, Shailesh V. Shrikhande, Thilo Hackert, Tooru Shimosegawa, Amer H. Zureikat, Güralp O. Ceyhan, Yunpeng Peng, Guangfu Wang, Xumin Huang, Christos Dervenis, Claudio Bassi, John P. Neoptolemos, Markus W. Büchler, Anesthesiology, Surgery, AGEM - Digestive immunity, AGEM - Re-generation and cancer of the digestive system, Miao, Y, Lu, Z, Yeo, C, Vollmer, C, Fernandez-del Castillo, C, Ghaneh, P, Halloran, C, Kleeff, J, de Rooij, T, Werner, J, Falconi, M, Friess, H, Zeh, H, Izbicki, J, He, J, Laukkarinen, J, Dejong, C, Lillemoe, K, Conlon, K, Takaori, K, Gianotti, L, Besselink, M, Del Chiaro, M, Montorsi, M, Tanaka, M, Bockhorn, M, Adham, M, Olah, A, Salvia, R, Shrikhande, S, Hackert, T, Shimosegawa, T, Zureikat, A, Ceyhan, G, Peng, Y, Wang, G, Huang, X, Dervenis, C, Bassi, C, Neoptolemos, J, Buchler, M, RS: NUTRIM - R2 - Liver and digestive health, and MUMC+: MA Heelkunde (9)
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medicine.medical_specialty ,REMNANT CLOSURE ,medicine.medical_treatment ,fistula formation ,030230 surgery ,Anastomosis ,Pancreatic surgery ,law.invention ,03 medical and health sciences ,Pancreatic Fistula ,0302 clinical medicine ,Pancreatectomy ,Postoperative Complications ,Randomized controlled trial ,law ,medicine ,Humans ,Pancreas ,business.industry ,Expert consensus ,POLYGLYCOLIC ACID FELT ,stump closure ,STAPLE LINE REINFORCEMENT ,RANDOMIZED CONTROLLED-TRIAL ,medicine.disease ,soft coagulation ,Surgery ,hand-sewn closure ,medicine.anatomical_structure ,Pancreatic fistula ,030220 oncology & carcinogenesis ,RISK-FACTORS ,business ,Distal pancreatectomy ,TO-MUCOSA PANCREATICOGASTROSTOMY - Abstract
Background: The aim was to evaluate the various operative techniques and outcomes used to manage the pancreatic transection plane (or stump) during a left (distal) pancreatectomy and to develop expert consensus guidelines.Methods: Evidence-based, clinically relevant questions were discussed and then were circulated among members of the International Study Group of Pancreatic Surgery. After agreement on the questions and statements, voting in a 9-point Likert scale was used to gauge the level of objective support for each.Results: Studies using the International Study Group of Pancreatic Surgery definition of postoperative pancreatic fistula including 16 randomized trials were reviewed to generate a series of statements set into 14 domains. There was strong consensus in the following statements: there was no difference in the postoperative pancreatic fistula rate after left pancreatectomy between the handsewn and stapler techniques; a stapling technique could not be used in all cases of left pancreatectomy; the use of an energy-based tissue sealant or a chemical sealant device or combinations of these did not impact the postoperative pancreatic fistula rate; there was no difference in the postoperative pancreatic fistula rate between the open, laparoscopic, or robotic approaches; and there are 1 or more clinically important, patient-related risk factors associated with the postoperative pancreatic fistula rate. There was weak or conditional agreement on the use of prophylactic somatostatin analogs, stents, stump closure, stump anastomosis, and the role of abdominal drains.Conclusion: Areas of strong consensus suggests a change in clinical practice and priority setting. Eight domains with lower agreement will require novel approaches and large multicenter studies to determine future key areas of practice. (C) 2020 Elsevier Inc. All rights reserved.
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- 2019
24. Combination of postoperative C-reactive protein value and computed tomography imaging can predict severe pancreatic fistula after pancreatoduodenectomy
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Toshihiko Masui, Kyoichi Takaori, Kazuyuki Nagai, Yuichiro Uchida, Tomoaki Yoh, Kenzo Nakano, Akitada Yogo, Takayuki Anazawa, and Shinji Uemoto
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Adult ,Male ,medicine.medical_specialty ,Computed tomography ,030230 surgery ,Severity of Illness Index ,Pancreaticoduodenectomy ,03 medical and health sciences ,Pancreatic Fistula ,Young Adult ,0302 clinical medicine ,Postoperative Complications ,Predictive Value of Tests ,Risk Factors ,Medicine ,Humans ,Aged ,Retrospective Studies ,Aged, 80 and over ,Hepatology ,biology ,medicine.diagnostic_test ,business.industry ,C-reactive protein ,Gastroenterology ,Perioperative ,Middle Aged ,medicine.disease ,C-Reactive Protein ,ROC Curve ,Pancreatic fistula ,030220 oncology & carcinogenesis ,Amylases ,biology.protein ,Drainage ,Female ,Radiology ,business ,Tomography, X-Ray Computed - Abstract
Recent management after pancreatoduodenectomy recommends either omission of prophylactic drainage or early removal. This potentially makes the diagnosis of postoperative pancreatic fistula (POPF) difficult because the diagnosis is based on the amylase value of drain effluent. The aim of this study was to determine if severe POPF could be predicted independent of drainage information.Records of consecutive patients who underwent pancreatoduodenectomy between 2012 and 2018 were included for further analysis. The presence of a peripancreatic collection (PC) on routine postoperative (day7) computed tomography (early CT) and perioperative characteristics were analyzed.PC appeared in 82/211 patients (39%) and was associated with clinically relevant POPF (p 0.001). The C-reactive protein (CRP) on postoperative day5 was a good predictor of severe POPF (needing interventional therapy or Grade C) (area under the receiver operating characteristics curve, 0.802; 95% confidence interval, 0.702-0.875). Presence of a PC and a high CRP value were independent risk factors for severe POPF following multivariate analysis. The combination of CRP5.0 mg/dL on postoperative day 5 and the absence of a PC had 98% negative predictive value.The combination of CRP measurement and PC evaluation by early CT was useful in predicting severe POPF after pancreatoduodenectomy.
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- 2019
25. Predictive value of the Ki67 index for lymph node metastasis of small non-functioning pancreatic neuroendocrine neoplasms
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Kazuyuki Nagai, Kenzo Nakano, Akitada Yogo, Yuichiro Uchida, Toshihiko Masui, Asahi Sato, Takayuki Anazawa, Yoshiya Kawaguchi, Shinji Uemoto, and Kyoichi Takaori
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Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Lymph node metastasis ,Metastasis ,Surgical oncology ,Mesenteric Artery, Superior ,Predictive Value of Tests ,medicine.artery ,medicine ,Biomarkers, Tumor ,Humans ,Superior mesenteric artery ,Aged ,Aged, 80 and over ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Primary tumor ,Pancreatic Neoplasms ,Dissection ,Neuroendocrine Tumors ,Ki-67 Antigen ,Lymphatic Metastasis ,Ki67 index ,Lymph Node Excision ,Surgery ,Lymphadenectomy ,Female ,Radiology ,business ,Tomography, X-Ray Computed - Abstract
We evaluated the clinicopathological factors associated with lymph node metastasis in patients with non-functioning pancreatic neuroendocrine neoplasms (PanNENs), focusing on the risk factors and range of lymph node metastasis for tumors ≤ 2 cm in diameter. The subjects of this study were patients with PanNENs consecutively diagnosed at our hospital between January, 2000 and June, 2018. We analyzed 69 patients who underwent R0 resection of a non-functioning sporadic PanNEN with no distant metastasis, as well as 43 patients with tumors ≤ 20 mm in radiological diameter. Nineteen patients (27.5%), including 7 (16.3%) with a small PanNEN, had lymph node metastasis. A large radiological diameter, a high Ki67 index, and cyst formation correlated significantly with positive lymph node metastasis. In patients with tumors ≤ 20 mm in diameter, a high Ki67 index correlated significantly with lymph node metastasis. When we set the cut-off Ki67 index as 3.3%, 2 of 43 patients had lymph node metastasis. Tumors in the uncinate process readily metastasized to the region around the superior mesenteric artery. These findings suggest that a high Ki67 index indicates a risk of lymph node metastasis for tumors ≤ 20 mm in diameter and that lymphadenectomy should be performed in the region spatially adjacent to the primary tumor.
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- 2018
26. Concurrent gemcitabine+S-1 neoadjuvant chemotherapy contributes to the improved survival of patients with small borderline-resectable pancreatic cancer tumors
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Shinji Uemoto, Toshihiko Masui, Kyoichi Takaori, Takayuki Anazawa, Asahi Sato, Tatsuo Ito, Kenzo Nakano, Ryuichiro Doi, and Yoshiya Kawaguchi
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Adult ,Male ,Oncology ,medicine.medical_specialty ,Surgical margin ,medicine.medical_treatment ,030230 surgery ,Deoxycytidine ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Pancreatic cancer ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Stage (cooking) ,Aged ,Neoplasm Staging ,Tegafur ,Aged, 80 and over ,Chemotherapy ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Gemcitabine ,Neoadjuvant Therapy ,Pancreatic Neoplasms ,Survival Rate ,Drug Combinations ,Oxonic Acid ,Treatment Outcome ,Chemotherapy, Adjuvant ,Tumor progression ,030220 oncology & carcinogenesis ,Pancreatectomy ,Female ,Surgery ,business ,medicine.drug - Abstract
In the surgical treatment of pancreatic cancer, margin-negative status is one of the most important determinants of survival. We conducted this study to explore surgical margin status as well as other factors affecting the survival of borderline-resectable pancreatic cancer (BRPC) patients who received neoadjuvant chemotherapy with gemcitabine and S-1. Eighteen BRPC patients were prospectively treated with concurrent gemcitabine and S-1 neoadjuvant chemotherapy (NAC+) and 15 of these patients underwent resection. We evaluated the safety and efficacy of this treatment regimen by comparing the outcomes of these patients with those of 19 BRPC patients who did not receive neoadjuvant chemotherapy (NAC−) during the same period. Fifteen (83 %) of the NAC+ patients underwent pancreatectomy. The remaining three patients (17 %) had regional tumor progression or liver metastasis. Of the 15 NAC+ patients who underwent resection, 3 (20 %) had margin-positive status, whereas 9 of the 19 (43 %) NAC− patients had margin-positive status (p = 0.002). However, disease-free survival and overall survival were similar in the two groups (MST 21.7 vs. 21.1 months). NAC+ patients with tumors smaller than 30 mm had favorable overall survival (MST 43.9 vs. 23.1 months, p = 0.0321). Most recurrences developed at distant sites rather than locally in both groups. In the neoadjuvant setting, gemcitabine and S-1 improved the negative surgical margin rate in BRPC patients, but it did not improve survival. Thus, neoadjuvant chemotherapy should be given to BRPC patients at an earlier stage.
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- 2016
27. Artery-First Distal Pancreatectomy
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Kyoichi Takaori and Shinji Uemoto
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,Dissection (medical) ,030230 surgery ,Splenic artery ,03 medical and health sciences ,Pancreatectomy ,0302 clinical medicine ,Celiac artery ,medicine.artery ,Pancreatic cancer ,medicine ,Humans ,Laparoscopy ,Ligation ,medicine.diagnostic_test ,business.industry ,Dissection ,Gastroenterology ,medicine.disease ,Surgery ,Pancreatic Neoplasms ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Pancreas ,business ,Splenic Artery ,Artery - Abstract
Artery-first pancreatectomy is a technique to ligate the feeding artery before the division of the pancreas with intents to reduce the blood loss and to perform more oncologic resection; for example, the splenic artery (SA) is ligated first for artery-first distal pancreatectomy (DP). Potential merits of artery-first DP include early determination of resectability in the setting of pancreatic cancer with possible involvement of SA and/or celiac artery. However, due to difficulties in exposing the origin of SA, especially in open surgery, artery-first DP has been rarely performed. Through the experience of laparoscopic DP, we have developed a technique of artery-first DP by the ‘Tora-no-Ana' approach, which consists of posterior dissection of the pancreatic body thorough a division of the ligament of Treitz. A hanging maneuver of the pancreatic parenchyma with SA and vein is another key for a successful artery-first DP. By the hanging maneuver, the origin of SA is well visualized and clearly identified either by open, laparoscopic or robotic approach so that oncologic resection can be achieved. In conclusion, artery-first DP is safe and feasible if the surgical principals by the Tora-no-Ana approach and hanging maneuver of the pancreatic body are adhered.
- Published
- 2016
28. SETDB1 Inhibits p53-Mediated Apoptosis and Is Required for Formation of Pancreatic Ductal Adenocarcinomas in Mice
- Author
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Yuta Hanyu, Norihiro Goto, Satoshi Ogawa, Yukiko Hiramatsu, Tatsuaki Tsuruyama, Osamu Araki, Yuichi Fukunaga, Mohammed Salah Hussein, Makoto Sono, Shinji Uemoto, Takahisa Maruno, Akihisa Fukuda, Yoshihide Matsumoto, Motoyuki Tsuda, Kyoichi Takaori, Hiroshi Seno, Takaaki Yoshikawa, Munemasa Nagao, Yuki Nakanishi, and Tomonori Masuda
- Subjects
0301 basic medicine ,Programmed cell death ,endocrine system diseases ,Apoptosis ,medicine.disease_cause ,Proto-Oncogene Proteins p21(ras) ,03 medical and health sciences ,Histone H3 ,0302 clinical medicine ,Cell Line, Tumor ,Pancreatic cancer ,medicine ,Animals ,Humans ,Promoter Regions, Genetic ,Cell Proliferation ,Mice, Knockout ,Gene knockdown ,Binding Sites ,Hepatology ,Microarray analysis techniques ,Chemistry ,Gastroenterology ,Histone-Lysine N-Methyltransferase ,medicine.disease ,digestive system diseases ,Gene Expression Regulation, Neoplastic ,Pancreatic Neoplasms ,Disease Models, Animal ,Cell Transformation, Neoplastic ,030104 developmental biology ,Histone methyltransferase ,Cancer research ,030211 gastroenterology & hepatology ,Tumor Suppressor Protein p53 ,Carcinogenesis ,Chromatin immunoprecipitation ,Carcinoma, Pancreatic Ductal ,Signal Transduction ,Transcription Factors - Abstract
Background & Aims SETDB1, a histone methyltransferase that trimethylates histone H3 on lysine 9, promotes development of several tumor types. We investigated whether SETDB1 contributes to development of pancreatic ductal adenocarcinoma (PDAC). Methods We performed studies with Ptf1aCre; KrasG12D; Setdb1f/f , Ptf1aCre; KrasG12D; Trp53f/+; Setdb1f/f, and Ptf1aCre; KrasG12D; Trp53f/f; Setdb1f/f mice to investigate the effects of disruption of Setdb1 in mice with activated KRAS-induced pancreatic tumorigenesis, with heterozygous or homozygous disruption of Trp53. We performed microarray analyses of whole-pancreas tissues from Ptf1aCre; KrasG12D; Setdb1f/f, and Ptf1aCre; KrasG12D mice and compared their gene expression patterns. Chromatin immunoprecipitation assays were performed using acinar cells isolated from pancreata with and without disruption of Setdb1. We used human PDAC cells for SETDB1 knockdown and inhibitor experiments. Results Loss of SETDB1 from pancreas accelerated formation of premalignant lesions in mice with pancreata that express activated KRAS. Microarray analysis revealed up-regulated expression of genes in the apoptotic pathway and genes regulated by p53 in SETDB1-deficient pancreata. Deletion of Setdb1 from pancreas prevented formation of PDACs, concomitant with increased apoptosis and up-regulated expression of Trp53 in mice heterozygous for disruption of Trp53. In contrast, pancreata of mice with homozygous disruption of Trp53 had no increased apoptosis, and PDACs developed. Chromatin immunoprecipitation revealed that SETDB1 bound to the Trp53 promoter to regulate its expression. Expression of an inactivated form of SETDB1 in human PDAC cells with wild-type TP53 resulted in TP53-induced apoptosis. Conclusions We found that the histone methyltransferase SETDB1 is required for development of PDACs, induced by activated KRAS, in mice. SETDB1 inhibits apoptosis by regulating expression of p53. SETDB1 might be a therapeutic target for PDACs that retain p53 function.
- Published
- 2020
29. The Role of Laparoscopy and Peritoneal Cytology in the Management of Pancreatic Cancer
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Shinji Uemoto and Kyoichi Takaori
- Subjects
medicine.medical_specialty ,Peritoneal cytology ,medicine.diagnostic_test ,business.industry ,Cytology ,General surgery ,Pancreatic cancer ,medicine ,Peritonitis ,CA19-9 ,medicine.disease ,Laparoscopy ,business - Published
- 2018
30. Pancreaticoduodenectomy with the Superior Mesenteric Artery Approach: How I Do It
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Toshihiko Masui, Takayuki Anazawa, Kyoichi Takaori, and Shinji Uemoto
- Subjects
medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Nerve plexus ,Dissection (medical) ,medicine.disease ,Pancreaticoduodenectomy ,SMA ,medicine.anatomical_structure ,medicine.artery ,medicine ,Ligament ,Retroperitoneal space ,Superior mesenteric artery ,Radiology ,Pancreas ,business - Abstract
The superior mesenteric artery (SMA) approach to pancreaticoduodenectomy (PD) is considered extremely important for early determination of resectability with negative margins. In addition, transecting the feeding arteries, including the inferior pancreaticoduodenal (IPDA) and gastroduodenal (GDA) arteries, before division of the pancreas can reduce blood loss during surgery and is a reasonable method for performing oncologic resection. This approach has promoted the development of an “artery-first” technique. Several techniques have been described under the heading of “artery-first.” We use the “Tora-no-Ana” approach, which consists of division of the ligament of Treitz, an entry into the retroperitoneal space behind the pancreatic body, and circumferential dissection around the SMA, with preservation of the nerve plexus around the SMA to prevent intractable diarrhea. A hanging maneuver of the pancreatic body facilitates a good operative view through the “Tora-no-Ana” approach. The IPDA and GDA are divided before division of the pancreatic body. In this chapter, we describe our techniques of the “artery-first” approach to PD with a review of the literature.
- Published
- 2018
31. A Prospective Study of Intensity-modified Radiation Therapy in Comparison with Conventional 3D-RT for BR Pancreatic Cancer Patients with Arterial Involvement
- Author
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Kenzo Nakano, Toshihiko Masui, Keiko Shibuya, Yuichiro Uchida, Hiroyoshi Isoda, Satoshi Itasaka, Asahi Sato, Kyoichi Takaori, Takayuki Anazawa, Masashi Kanai, Shinji Uemoto, Yoko Goto, Masaki Mizumoto, Shigemi Matsumoto, Akitada Yogo, Yuzo Kodama, and Yoshiya Kawaguchi
- Subjects
Male ,Cancer Research ,medicine.medical_treatment ,03 medical and health sciences ,0302 clinical medicine ,Pancreatic cancer ,Adjuvant therapy ,Humans ,Medicine ,Prospective Studies ,Prospective cohort study ,Pancreas ,Neoadjuvant therapy ,Aged ,business.industry ,Cumulative dose ,Therapeutic effect ,Arteries ,Chemoradiotherapy ,General Medicine ,Middle Aged ,medicine.disease ,Survival Analysis ,Neoadjuvant Therapy ,Intensity (physics) ,Pancreatic Neoplasms ,Radiation therapy ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,Female ,Radiotherapy, Intensity-Modulated ,Radiotherapy, Conformal ,business ,Nuclear medicine - Abstract
Background/aim Intensity-modulated radiation therapy (IMRT) is a form of radiation therapy that allows accurate irradiation with reduced damage to surrounding tissues. Here, we analyzed borderline-resectable pancreatic cancer (BRPC) with arterial abutment (BR-A) patients with IMRT as neoadjuvant therapy and performed comparisons with patients with conventional RT to clarify the advantages of IMRT as a neoadjuvant therapy. Patients and methods Thirty BR-A patients treated at our hospital between January 2012 and December 2015 were divided into two groups: 12 patients underwent conventional 3D-RT before resection (RT group); and 18 patients underwent IMRT before resection (IMRT group). We analyzed safety, tumor resection rate, histological classification of the tumor and overall survival. Results The R0 rate was 84% for the IMRT group and 83% for the RT group. Local therapeutic effects as assessed by Evans classification showed a higher local control rate in the IMRT group (Grade: 1, 0%; 2a, 25%; 2b, 41.6%; 3, 17%; 4, 8%) than in the RT group (Grade: 1, 17%; 2a, 50%; 2b, 17%; 3, 17%; 4, 0%). The cumulative dose of S1 treatment as adjuvant therapy was much smaller in the RT group (18.3%) compared to that in the IMRT group (57.1%, p=0.047), and with better subsequent overall survival rate (MST 32 months vs. 13.8 months, p=0.0273). Conclusion The IMRT group showed a better control rate than the RT group. The neoadjuvant IMRT has advantages of higher completion rate of adjuvant chemotherapy with better nutritional status and better subsequent overall survival rate (OS).
- Published
- 2017
32. Screening for Pancreatic Cancer
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Keita Wada, Kyoichi Takaori, and L. William Traverso
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Systemic disease ,medicine.medical_specialty ,Intraductal papillary mucinous neoplasm ,business.industry ,medicine.medical_treatment ,General surgery ,Pancreatic Intraepithelial Neoplasia ,Autopsy ,medicine.disease ,Adenocarcinoma, Mucinous ,Risk Assessment ,Carcinoma, Papillary ,Pancreatic Neoplasms ,Pancreatectomy ,Risk Factors ,Pancreatic cancer ,medicine ,Humans ,Surgery ,CA19-9 ,Stage (cooking) ,business ,Early Detection of Cancer ,Carcinoma, Pancreatic Ductal - Abstract
Neither extended surgery nor extended indication for surgery has improved survival in patients with pancreatic cancer. According to autopsy studies, presumably 90% are metastatic. The only cure is complete removal of the tumor at an early stage before it becomes a systemic disease or becomes invasive. Early detection and screening of individuals at risk is currently under way. This article reviews the evidence and methods for screening, either familial or sporadic. Indication for early-stage surgery and precursors are discussed. Surgeons should be familiar with screening because it may provide patients with a chance for cure by surgical resection.
- Published
- 2015
33. Impact of preoperative quality as well as quantity of skeletal muscle on survival after resection of pancreatic cancer
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Toshihiko Masui, Masaki Mizumoto, Akira Mori, Yuhei Hamaguchi, Shinji Uemoto, Yasuhiro Fujimoto, Kyoichi Takaori, Toshimi Kaido, Ahmed Hammad, and Shinya Okumura
- Subjects
Adult ,Male ,Sarcopenia ,medicine.medical_specialty ,Adipose tissue ,Risk Assessment ,Gastroenterology ,Disease-Free Survival ,Cohort Studies ,Pancreatectomy ,Japan ,Predictive Value of Tests ,Internal medicine ,Pancreatic cancer ,Preoperative Care ,medicine ,Humans ,Survival analysis ,Abdominal Muscles ,Aged ,Retrospective Studies ,Aged, 80 and over ,Analysis of Variance ,business.industry ,Hazard ratio ,Skeletal muscle ,Retrospective cohort study ,Organ Size ,Middle Aged ,medicine.disease ,Survival Analysis ,Surgery ,Pancreatic Neoplasms ,Treatment Outcome ,medicine.anatomical_structure ,Predictive value of tests ,Female ,Neoplasm Recurrence, Local ,Tomography, X-Ray Computed ,business ,Follow-Up Studies - Abstract
[Background]Skeletal muscle depletion, referred to as sarcopenia, is predictive of mortality in patients undergoing digestive operations. The impact of muscle quality on outcomes, however, is unclear. This retrospective study investigated the impact of preoperative skeletal muscle quantity and quality on survival in patients undergoing resection of pancreatic cancer. [Methods]We investigated 230 patients who underwent resection of pancreatic cancer between 2004 and 2013. The quantity and quality of skeletal muscle, indicated by psoas muscle mass index (PMI) and intramuscular adipose tissue content (IMAC), were measured in preoperative computed tomography images. Overall survival (OS) and recurrence-free survival (RFS) rates were compared according to PMI and IMAC, and prognostic factors after pancreatic resection were assessed.[Results]The OS and RFS rates in patients with low PMI were lesser than in those with normal/high PMI (P < .001, P < .001), with a mean survival time of 17.7 and 33.2 months, respectively. The OS and RFS rates in patients with high IMAC also were less than in those with normal/low IMAC (P < .001, P = .003) (mean survival time = 21.5 and 56.5 months, respectively). Low PMI (low muscle mass) and high IMAC (low muscle quality) were independent prognostic factors of poor OS (hazard ratio [HR] = 1.999, P < .001; HR = 2.527, P < .001) and RFS (HR = 1.607, P = .007; HR = 1.640, P = .004), respectively. [Conclusion]Preoperative sarcopenia, indicating low quality and quantity of skeletal muscle, is closely related to mortality after resection of pancreatic cancer.
- Published
- 2015
34. Nardilysin inhibits pancreatitis and suppresses pancreatic ductal adenocarcinoma initiation in mice
- Author
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Shinji Uemoto, Kyoichi Takaori, Norihiro Goto, Tsutomu Chiba, Satoshi Ogawa, Yuto Kimura, Kiyoto Nishi, Yoshito Kimura, Akihisa Fukuda, Motoyuki Tsuda, Yoshihide Matsumoto, Shigeo Takaishi, Eiichiro Nishi, Kenji Masuo, Yukiko Hiramatsu, Takahisa Maruno, Keitaro Kanda, Kozo Ikuta, and Hiroshi Seno
- Subjects
0301 basic medicine ,Cre recombinase ,Context (language use) ,Biology ,medicine.disease_cause ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Pancreatic cancer ,Nardilysin ,medicine ,Animals ,Gastroenterology ,Metalloendopeptidases ,medicine.disease ,Pancreatic Neoplasms ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Pancreatitis ,Cancer research ,Immunohistochemistry ,030211 gastroenterology & hepatology ,KRAS ,Pancreas ,Carcinoma, Pancreatic Ductal - Abstract
ObjectiveNardilysin (NRDC), a zinc peptidase, exhibits multiple localisation-dependent functions including as an enhancer of ectodomain shedding in the extracellular space and a transcriptional coregulator in the nucleus. In this study, we investigated its functional role in exocrine pancreatic development, homeostasis and the formation of pancreatic ductal adenocarcinoma (PDA).DesignWe analysedPtf1a-Cre; Nrdcflox/floxmice to investigate the impact ofNrdcdeletion. Pancreatic acinar cells were isolated fromNrdcflox/floxmice and infected with adenovirus expressing Cre recombinase to examine the impact ofNrdcinactivation. Global gene expression inNrdc-cKOpancreas was analysed compared with wild-type pancreas by microarray analysis. We also analysedPtf1a-Cre; KrasG12D; Nrdcflox/floxmice to investigate the impact ofNrdcdeletion in the context of oncogenic Kras. A total of 51 human samples of pancreatic intraepithelial lesions (PanIN) and PDA were examined by immunohistochemistry for NRDC.ResultsWe found that pancreatic deletion ofNrdcleads to spontaneous chronic pancreatitis concomitant with acinar-to-ductal conversion, increased apoptosis and atrophic pancreas in mice. Acinar-to-ductal conversion was observed mainly through a non-cell autonomous mechanism, and the expression of several chemokines was significantly increased inNrdc-null pancreatic acinar cells. Furthermore, pancreatic deletion ofNrdcdramatically acceleratedKrasG12D-driven PanIN and subsequent PDA formation in mice. These data demonstrate a previously unappreciated anti-inflammatory and tumour suppressive functions of Nrdc in the pancreas in mice. Finally, absence of NRDC expression was observed in a subset of human PanIN and PDA.ConclusionNrdc inhibits pancreatitis and suppresses PDA initiation in mice.
- Published
- 2017
35. Henoch-Schönlein Purpura After Living Donor Liver Transplantation: Report of the First Case
- Author
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Hideaki Okajima, Shintaro Yagi, Vusal Aliyev, Amr Badawy, Ahmed Hammad, Toshimi Kaido, Kyoichi Takaori, Kojiro Taura, and S. Uemoto
- Subjects
Immunoglobulin A ,Male ,medicine.medical_specialty ,Henoch-Schonlein purpura ,IgA Vasculitis ,medicine.medical_treatment ,Arthritis ,Liver transplantation ,Gastroenterology ,Postoperative Complications ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Living Donors ,Humans ,Transplantation ,biology ,business.industry ,Glomerulonephritis ,Glomerulonephritis, IGA ,Middle Aged ,medicine.disease ,Liver Transplantation ,Purpura ,biology.protein ,Surgery ,medicine.symptom ,business ,Nephritis ,Systemic vasculitis - Abstract
Henoch-Schonlein purpura (HSP) is a systemic vasculitis affecting the small vessels that mainly presents in children and young adults. It is characterized by tissue deposition of immunoglobulin A (IgA) immune complexes with the classic manifestations of purpura, arthritis, arthralgia, and gastrointestinal and renal involvements. We report a case of HSP nephritis that occurred 2 years after living-donor liver transplantation (LDLT). After pulse steroid administration, the patient's symptoms disappeared and blood markers normalized. To the best of our knowledge, this is the first HSP case to be reported in a liver transplant recipient.
- Published
- 2017
36. 'Revisions of the International Consensus Fukuoka Guidelines for the Management of IPMN of the Pancreas': Progress for twelve years
- Author
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Kyoichi Takaori
- Subjects
medicine.medical_specialty ,Internationality ,Endocrinology, Diabetes and Metabolism ,Consensus Development Conferences as Topic ,MEDLINE ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Internal medicine ,medicine ,Carcinoma ,Humans ,Hepatology ,business.industry ,General surgery ,medicine.disease ,Adenocarcinoma, Mucinous ,Carcinoma, Papillary ,Pancreatic Neoplasms ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Practice Guidelines as Topic ,Adenocarcinoma ,030211 gastroenterology & hepatology ,Pancreas ,business ,Carcinoma, Pancreatic Ductal - Published
- 2017
37. A case of successful conversion from everolimus to surgical resection of a giant pancreatic neuroendocrine tumor
- Author
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Toshihiko Masui, Asahi Sato, Yoshiya Kawaguchi, Nao Sankoda, Yuichiro Uchida, Takayuki Anazawa, Kyoichi Takaori, Shinji Uemoto, and Kenzo Nakano
- Subjects
Surgical resection ,medicine.medical_specialty ,Pancreatic neuroendocrine tumor ,medicine.medical_treatment ,lcsh:Surgery ,Case Report ,Neuroendocrine tumors ,Sunitinib malate ,03 medical and health sciences ,0302 clinical medicine ,Neuroendocrine tumor ,Pancreatic cancer ,medicine ,Everolimus ,Pathological ,Neoadjuvant therapy ,business.industry ,lcsh:RD1-811 ,medicine.disease ,68Ga-DOTATOC-PET/CT ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Radiology ,business ,medicine.drug - Abstract
Background Although pancreatic neuroendocrine tumors generally have a far better prognosis relative to pancreatic cancer, the varied manifestations lead to treatment-related challenges. Everolimus therapy is generally recommended for patients with advanced pancreatic neuroendocrine tumors; however, its efficacy in a neoadjuvant setting remains unclear. Here we present a case of a giant pancreatic neuroendocrine tumor with a portal tumor thrombus that became resectable after everolimus therapy. Case presentation A 62-year-old woman was admitted to our hospital for surgical resection of a giant pancreatic neuroendocrine tumor in the left upper abdomen. Unfortunately, she was ineligible for surgery because the tumor had extended near the hepatic hilus in the portal vein, and she was administered everolimus (10 mg/day). After 2 years of this therapy, the extent of portal vein involvement had decreased, despite the lack of significant changes in the tumor size, and the hepatic hilus became free of disease. She was subsequently referred to us for resection via distal pancreatectomy with portal vein reconstruction because the tumor had begun to grow slowly. Pathological review identified a grade 2 neuroendocrine tumor with no lymph node metastasis. The patient’s postoperative course was uneventful, and she has remained recurrence-free for 27 months, despite a lack of additional treatment. Conclusions Our experience suggests that everolimus could be useful for neoadjuvant therapy in cases of locally advanced pancreatic neuroendocrine tumor.
- Published
- 2017
38. Comparison of Recurrence Between Pancreatic and Duodenal Neuroendocrine Neoplasms After Curative Resection: A Single-Institution Analysis
- Author
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Akitada Yogo, Shinji Uemoto, Kenzo Nakano, Toshihiko Masui, Takayuki Anazawa, Asahi Sato, Yuichiro Uchida, Kyoichi Takaori, Kazuyuki Nagai, and Yoshiya Kawaguchi
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Neuroendocrine tumors ,Gastroenterology ,Pancreaticoduodenectomy ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Pancreatectomy ,Duodenal Neoplasms ,Internal medicine ,medicine ,Humans ,Neoplasm Invasiveness ,Child ,Survival rate ,Duodenal Neoplasm ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Prognosis ,Pancreatic Neoplasms ,Survival Rate ,Neuroendocrine Tumors ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Lymphatic Metastasis ,030211 gastroenterology & hepatology ,Surgery ,Female ,Lymph ,Neoplasm Recurrence, Local ,business ,Pancreas ,Follow-Up Studies - Abstract
The primary site of a neuroendocrine neoplasms (NEN) around the head of the pancreas is sometimes difficult to assess before resection, and the characteristics of the primary site around this region have not been elucidated for recurrence after curative resection. In this study, the clinicopathologic characteristics of pancreatic NEN (PanNEN) and duodenal NEN (DuNEN) were evaluated, and the risk factors as well as the recurrence types after resection were investigated. Consecutively diagnosed NEN patients at the authors’ hospital from January 2000 to July 2016 were evaluated in this study. For 117 PanNEN patients and 31 non-ampullary DuNEN patients, R0 resection was achieved. The median follow-up period was 8.1 years. In this study, 27 PanNEN patients (23.1%) had recurrences, with a median disease-free survival (DFS) of 133 months, whereas 11 DuNEN patients (35.5%) had recurrences, with a median DFS of 156 months. The PanNEN patients tended to have primary recurrence in the liver (85.2%), followed by lymph nodes (11.1%). The independent risk factors for short DFS were lymph node metastasis at resection (p = 0.001) and microvascular invasion (p = 0.048). In contrast, the DuNEN patients were likely to have lymph node metastasis (81.8%). The independent risk factors for short DFS were lymph node metastasis at resection (p = 0.003) and large diameter (p = 0.013). Most initial recurrences of PanNEN occurred in the liver, whereas those of DuNEN appeared in lymph nodes, suggesting that proper diagnosis of the primary site and appropriate imaging methods for surveillance after resection are necessary.
- Published
- 2017
39. Streptozocin chemotherapy for advanced/metastatic well-differentiated neuroendocrine tumors: an analysis of a multi-center survey in Japan
- Author
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Takeshi Takamoto, Izumi Komoto, Takuji Okusaka, Wataru Kimura, Takuya Hashimoto, Keiji Sano, Norihiro Kokudo, Kyoichi Takaori, Masayuki Imamura, Chigusa Morizane, Tetsuhide Ito, and Taku Aoki
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,endocrine system diseases ,medicine.medical_treatment ,Neuroendocrine tumors ,Streptozocin ,Disease-Free Survival ,Metastasis ,Young Adult ,Progression-free survival rate ,Japan ,Surgical oncology ,Internal medicine ,medicine ,Humans ,Survival rate ,Aged ,Retrospective Studies ,Original Article—Liver, Pancreas, and Biliary Tract ,Chemotherapy ,Antibiotics, Antineoplastic ,business.industry ,Gastroenterology ,nutritional and metabolic diseases ,Retrospective cohort study ,Middle Aged ,Hepatology ,medicine.disease ,Multi-center survey ,Surgery ,Pancreatic Neoplasms ,Survival Rate ,Neuroendocrine Tumors ,Treatment Outcome ,Female ,Tumor response ,business - Abstract
Background Neuroendocrine tumors (NETs) are believed to be relatively rare and to follow a generally indolent course. However, liver metastases are common in NET patients and the outcome of NET liver metastasis is poor. In Western countries, streptozocin (STZ) has been established as a first-line anticancer drug for unresectable NET; however, STZ cannot be used in daily practice in Japan. The aim of the present study was to determine the status of STZ usage in Japan and to evaluate the effectiveness and safety of STZ chemotherapy in Japanese NET patients. Methods A retrospective multi-center survey was conducted. Five institutions with experience performing STZ chemotherapy participated in the study. The patient demographics, tumor characteristics, context of STZ chemotherapy, and patient outcome were collected and assessed. Results Fifty-four patients were enrolled. The main recipients of STZ chemotherapy were middle-aged patients with pancreatic NET and unresectable liver metastases. The predominant regimen was the weekly/bi-weekly intravenous administration of STZ combined with other oral anticancer agents. STZ monotherapy was used in one-fourth of the patients. The median progression-free and overall survival periods were 11.8 and 38.7 months, respectively, and sustained stable disease was obtained in some selected patients. The adverse events profile was mild and tolerable. Conclusions Our survey showed the clinical benefit and safety of STZ therapy for Japanese patients with unresectable NET. Therefore, we recommend that STZ, which is the only cytotoxic agent available against NET, should be used in daily practice in Japan. Electronic supplementary material The online version of this article (doi:10.1007/s00535-014-1006-3) contains supplementary material, which is available to authorized users.
- Published
- 2014
40. Radiotherapy for patients with isolated local recurrence of primary resected pancreatic cancer
- Author
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Yukinori Matsuo, Shinji Uemoto, Yoshiya Kawaguchi, Kyoichi Takaori, Takashi Mizowaki, Michio Yoshimura, Satoshi Itasaka, Keiko Shibuya, Akira Nakamura, and Masahiro Hiraoka
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Ileus ,medicine.medical_treatment ,Favorable prognosis ,Deoxycytidine ,Gastroenterology ,Disease-Free Survival ,Pancreatectomy ,Pancreatic cancer ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Aged ,Pain Measurement ,Tegafur ,Tumor marker ,Aged, 80 and over ,Disease free interval ,business.industry ,Palliative Care ,Radiotherapy Dosage ,Chemoradiotherapy, Adjuvant ,Middle Aged ,Prognosis ,medicine.disease ,Combined Modality Therapy ,Gemcitabine ,Pancreatic Neoplasms ,Radiation therapy ,Drug Combinations ,Oxonic Acid ,Toxicity ,Female ,Neoplasm Recurrence, Local ,business ,medicine.drug - Abstract
To evaluate the treatment outcomes of radiotherapy and prognostic factors for recurrent pancreatic cancer. The study comprised 30 patients who developed a locoregional recurrence of primarily resected pancreatic cancer and received radiotherapy between 2000 and 2013 with a median dose of 54 Gy (range, 39–60 Gy). Concurrent chemotherapy included gemcitabine for 18 patients and S-1 for seven patients. The treatment outcomes and prognostic factors were retrospectively analyzed. The median follow-up after radiotherapy was 14.6 months. The 1-year overall survival, local control, and progression-free survival rates were 69 %, 67 %, and 32 %, respectively. The median overall survival and progression-free survival rates were 15.9 and 6.9 months, respectively. Tumor marker reduction and ≥ 50 % reduction were observed in 18 and two patients, respectively. Of the seven patients who exhibited pain symptoms, four and two patients were partly and completely relieved, respectively. Late grade 3 ileus and gastroduodenal bleeding were observed in one patient each. Among the clinicopathological factors evaluated, only a disease-free interval of greater than 18.9 months exhibited a significant association with improved overall survival (p = 0.017). Radiotherapy for isolated locally recurrent pancreatic cancer resulted in encouraging local control, overall survival, and palliative effects with mild toxicity, particularly in patients with a prolonged disease-free interval. This treatment strategy should be prospectively evaluated.
- Published
- 2014
41. Neutrophil‐to‐lymphocyte ratio for predicting palliative chemotherapy outcomes in advanced pancreatic cancer patients
- Author
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Yuzo Kodama, Takafumi Nishimura, Masashi Kanai, Peng Xue, Shinji Uemoto, Tsutomu Chiba, Kyoichi Takaori, Shigemi Matsumoto, Yukiko Mori, Yoshiya Kawaguchi, and Norimitsu Uza
- Subjects
Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Palliative care ,Neutrophils ,medicine.medical_treatment ,pancreatic cancer ,Deoxycytidine ,NLR ,Cohort Studies ,Erlotinib Hydrochloride ,Internal medicine ,Pancreatic cancer ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Chemotherapy ,Radiology, Nuclear Medicine and imaging ,Lymphocytes ,Prospective Studies ,Neutrophil to lymphocyte ratio ,prognostic factor ,Prospective cohort study ,Survival analysis ,Aged ,Tegafur ,Original Research ,Predictive marker ,business.industry ,Palliative Care ,fungi ,Cancer ,Prognosis ,medicine.disease ,Survival Analysis ,Gemcitabine ,Surgery ,Pancreatic Neoplasms ,Drug Combinations ,Oxonic Acid ,Treatment Outcome ,inflammation ,Quinazolines ,Female ,business ,Carcinoma, Pancreatic Ductal - Abstract
Several previous studies reported that the neutrophil-to-lymphocyte ratio (NLR) could be a promising prognostic factor for patients with cancer. We aimed to determine the prognostic value of NLR in patients with advanced pancreatic cancer (APC) following palliative chemotherapy. We retrospectively reviewed 252 consecutive APC patients receiving palliative chemotherapy between January 2006 and December 2012. We classified the patients according to the pretreatment NLR values (≤5 or >5) into two groups and investigated the difference in treatment outcomes, including time to treatment failure (TTF) and overall survival (OS). A total of 212 patients had pretreatment NLR values of ≤5 (group A), while 40 patients had an NLR of >5 (group B). TTF and OS were significantly shorter in group B than in group A (3.1 vs. 8.7 months and 6.0 vs. 12.8 months, respectively; both P 5. Our results support the idea that NLR can be a promising prognostic and predictive marker for APC patients receiving palliative chemotherapy.
- Published
- 2014
42. Expression of SOX9 in Intraductal Papillary Mucinous Neoplasms of the Pancreas
- Author
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Kyoichi Takaori, Michiya Kawaguchi, Toshihiko Masui, Yoshiya Kawaguchi, Shinji Uemoto, Tatsuo Ito, and Fanbin Meng
- Subjects
Male ,endocrine system ,Pathology ,medicine.medical_specialty ,animal structures ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,SOX9 ,Endocrinology ,stomatognathic system ,Internal Medicine ,Carcinoma ,medicine ,Humans ,Aged ,Hepatology ,biology ,business.industry ,CD44 ,SOX9 Transcription Factor ,Middle Aged ,medicine.disease ,Adenocarcinoma, Mucinous ,Immunohistochemistry ,Carcinoma, Papillary ,Pancreatic Neoplasms ,Hyaluronan Receptors ,Testis determining factor ,medicine.anatomical_structure ,Dysplasia ,embryonic structures ,biology.protein ,Adenocarcinoma ,Female ,Pancreas ,business ,Carcinoma, Pancreatic Ductal - Abstract
Objectives SRY (sex determining region Y) box 9 (SOX9) plays a key role in the embryologic development, differentiation, and maintenance of organs in the pancreas as well as progression of several kinds of tumors. The aim of the present study was to evaluate the expression and potential role of SOX9 in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Methods The authors selected 27 pathological tissues from 19 IPMN cases to assess the expression of SOX9 by means of immunohistochemistry and analyzed the expression pattern of SOX9 with 78 lesions obtained from these tissues stained by SOX9. Results SOX9 was expressed in the normal pancreas, IPMN, and pancreatic ductal adenocarcinoma. SOX9-positive cells were confined to the lower portions of the papillary structures of IPMN. However, SOX9 was expressed in the entire epithelium once the neoplasms advanced to high-grade dysplasia and invasive carcinoma. The expression pattern of SOX9 was similar to that of CD44 in the normal pancreas and IPMN. Double staining of SOX9 and CD44 detected colocalization of SOX9 and CD44 in IPMN. Conclusions Changes in the SOX9 expression pattern may be involved in the mechanisms of the malignant progression of IPMN.
- Published
- 2014
43. Genetics and biology of pancreatic cancer and its precursor lesions: lessons learned from human pathology and mouse models
- Author
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Hiroshi Seno, Akihisa Fukuda, Kyoichi Takaori, and Motoyuki Tsuda
- Subjects
Genetics ,congenital, hereditary, and neonatal diseases and abnormalities ,Diagnostic methods ,Pancreatic ductal adenocarcinoma ,health care facilities, manpower, and services ,Endocrinology, Diabetes and Metabolism ,Genomic sequencing ,education ,Biology ,medicine.disease ,Transcriptome ,Endocrinology ,Oncology ,Late diagnosis ,health services administration ,Pancreatic cancer ,Internal Medicine ,medicine ,Treatment strategy ,Human Pathology - Abstract
Pancreatic ductal adenocarcinoma (PDA) is one of the most fatal malignancies; it has an extremely poor prognosis due to its late diagnosis and limited response to conventional treatments. To improve PDA prognosis, new diagnostic and treatment strategies are urgently required. Recent genomic sequencing analyses revealed several mutated core signaling pathways and transcriptomic subtypes in PDA. A better understanding of PDA biology based on these genetic insights would promote the future development of novel diagnostic methods and treatments. In this review, we summarize our current understanding of PDA genetics and biology, predominantly via insights from mouse model studies.
- Published
- 2019
44. GPR119 expression in normal human tissues and islet cell tumors: evidence for its islet-gastrointestinal distribution, expression in pancreatic beta and alpha cells, and involvement in islet function
- Author
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Ken Ebihara, Kyoichi Takaori, Shinji Odori, Junji Fujikura, Ryuichiro Doi, Yoshiharu Sakai, Yoshiya Kawaguchi, Shinji Uemoto, Kiminori Hosoda, Tsutomu Tomita, Kazuwa Nakao, and Toru Kusakabe
- Subjects
Adult ,Male ,medicine.medical_specialty ,endocrine system ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,Glucagonoma ,Biology ,Receptors, G-Protein-Coupled ,Mice ,Young Adult ,Endocrinology ,Free fatty acid receptor 1 ,Internal medicine ,Insulin-Secreting Cells ,Gene expression ,medicine ,Animals ,Humans ,RNA, Messenger ,Gastrointestinal hormones ,Insulinoma ,Aged ,geography ,geography.geographical_feature_category ,Reverse Transcriptase Polymerase Chain Reaction ,Pancreatic islets ,Insulin secretion ,Middle Aged ,Islet ,medicine.disease ,Gastrointestinal Tract ,Gene Expression Regulation, Neoplastic ,Mice, Inbred C57BL ,Pancreatic Neoplasms ,medicine.anatomical_structure ,Glucagon-Secreting Cells ,Duodenum ,Regression Analysis ,Female ,Pancreas - Abstract
Objective GPR119 is reportedly involved in regulating glucose metabolism and food intake in rodents, but little is known about its expression and functional significance in humans. To begin to assess the potential clinical importance of GPR119, the distribution of GPR119 gene expression in humans was examined. Materials/Methods Expression of GPR119 mRNA in fresh samples of normal human pancreas ( n= 19) and pancreatic islets ( n =3) and in insulinomas ( n =2) and glucagonomas ( n =2), all collected at surgery, was compared with the mRNA expression of various receptors highly expressed and operative in human pancreatic islets. Results GPR119 mRNA was most abundant in the pancreas, followed by the duodenum, stomach, jejunum, ileum and colon. Pancreatic levels of GPR119 mRNA were similar to those of GPR40 mRNA and were higher than those of GLP1R and SUR1 mRNA, which are strongly expressed in human pancreatic islets. Moreover, levels of GPR119 mRNA in pancreatic islets were more than 10 times higher than in adjacent pancreatic tissue, as were levels of GPR40 mRNA. GPR119 mRNA was also abundant in two cases of insulinoma and two cases of glucagonoma, but was undetectable in a pancreatic acinar cell tumor. Similar results were obtained with mouse pancreatic islets, MIN6 insulinoma cells and alpha-TC glucagonoma cells. Conclusions The results provide evidence of an islet-gastrointestinal distribution of GPR119, its expression in pancreatic beta and alpha cells, and its possible involvement in islet function. They also provide the basis for a better understanding of the potential clinical importance of GPR119.
- Published
- 2013
45. Overview of 'International Consensus Guidelines for Management of Intraductal Papillary Mucinous Neoplasm 2012' and prospects for the future from an international point of view
- Author
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Kyoichi Takaori
- Subjects
medicine.medical_specialty ,biology ,Point (typography) ,Intraductal papillary mucinous neoplasm ,business.industry ,General surgery ,GNAS complex locus ,biology.protein ,medicine ,Robotic surgery ,medicine.disease ,business - Published
- 2013
46. P-220Clinical evaluation of intensity-modulated radiotherapy for locally advanced pancreatic cancer
- Author
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S. Matsumoto, Yuzo Kodama, Keiko Shibuya, Masahiro Hiraoka, Yoko Goto, Takashi Mizowaki, Satoshi Itasaka, Kyoichi Takaori, Takahiro Kishi, Akira Nakamura, and Katsuyuki Sakanaka
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Hematology ,Intensity-modulated radiation therapy ,medicine.disease ,Locally advanced pancreatic cancer ,Radiation therapy ,Abstracts ,Internal medicine ,Pancreatic cancer ,medicine ,Intensity modulated radiotherapy ,business - Published
- 2016
47. International Association of Pancreatology (IAP)/European Pancreatic Club (EPC) consensus review of guidelines for the treatment of pancreatic cancer
- Author
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Francesco Sclafani, Colin D. Johnson, Thomas Brunner, John P. Neoptolemos, Massimo Falconi, Marc Giovannini, Andrew V. Biankin, Koji Yamaguchi, Francisco X. Real, David Cunningham, Adam E Frampton, William H. Nealon, Richard J. Jackson, Christopher L. Wolfgang, Ivana Cataldo, Kyoichi Takaori, Junji Furuse, Claudio Bassi, John A. Windsor, Akira Nakamura, Aldo Scarpa, and Fiona Campbell
- Subjects
medicine.medical_specialty ,Future studies ,Endocrinology, Diabetes and Metabolism ,Chemotherapy ,Guidelines ,Pancreatic cancer ,Pathology ,Radiation ,Surgery ,Antineoplastic Agents ,English language ,030230 surgery ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Intensive care medicine ,Hepatology ,business.industry ,High mortality ,medicine.disease ,Pancreatic Neoplasms ,030220 oncology & carcinogenesis ,Practice Guidelines as Topic ,Level evidence ,Club ,Active treatment ,business - Abstract
Background Pancreatic cancer is one of the most devastating diseases with an extremely high mortality. Medical organizations and scientific societies have published a number of guidelines to address active treatment of pancreatic cancer. The aim of this consensus review was to identify where there is agreement or disagreement among the existing guidelines and to help define the gaps for future studies. Methods A panel of expert pancreatologists gathered at the 46th European Pancreatic Club Meeting combined with the 18th International Association of Pancreatology Meeting and collaborated on critical reviews of eight English language guidelines for the clinical management of pancreatic cancer. Clinical questions (CQs) of interest were proposed by specialists in each of nine areas. The recommendations for the CQs in existing guidelines, as well as the evidence on which these were based, were reviewed and compared. The evidence was graded as sufficient, mediocre or poor/absent. Results Only 4 of the 36 CQs, had sufficient evidence for agreement. There was also agreement in five additional CQs despite the lack of sufficient evidence. In 22 CQs, there was disagreement regardless of the presence or absence of evidence. There were five CQs that were not addressed adequately by existing guidelines. Conclusion The existing guidelines provide both evidence- and consensus-based recommendations. There is also considerable disagreement about the recommendations in part due to the lack of high level evidence. Improving the clinical management of patients with pancreatic cancer, will require continuing efforts to undertake research that will provide sufficient evidence to allow agreement.
- Published
- 2016
48. 4. Current Therapies for IPMN and MCN
- Author
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Kyoichi Takaori
- Subjects
Oncology ,medicine.medical_specialty ,Pathology ,Intraductal papillary mucinous neoplasm ,business.industry ,General Medicine ,medicine.disease ,Cystic Neoplasm ,medicine.anatomical_structure ,Pancreatic tumor ,Internal medicine ,medicine ,Pancreas ,business - Published
- 2012
49. A revised classification system and recommendations from the Baltimore consensus meeting for neoplastic precursor lesions in the pancreas
- Author
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Michio Shimizu, Andrew V. Biankin, Irene Esposito, Olca Basturk, Noriyoshi Fukushima, Alyssa M. Krasinskas, Lodewijk A.A. Brosens, Daniel S. Longnecker, Hanno Matthaei, Jorge Albores-Saavedra, Seung-Mo Hong, David S. Klimstra, Toru Furukawa, Yo Kato, N. Volkan Adsay, Laura D. Wood, Günter Klöppel, Michael Goggins, Shinichi Yachida, Benoit Terris, Kyoichi Takaori, G. Johan A. Offerhaus, and Ralph H. Hruban
- Subjects
Pathology ,medicine.medical_specialty ,Consensus ,endocrine system diseases ,Biopsy ,International Cooperation ,precursor ,Pancreatic Intraepithelial Neoplasia ,pancreatic intraepithelial neoplasia (PanIN) ,Research Support ,Article ,N.I.H ,Pathology and Forensic Medicine ,Research Support, N.I.H., Extramural ,Predictive Value of Tests ,Terminology as Topic ,intraductal papillary mucinous neoplasm (IPMN) ,medicine ,Carcinoma ,Atypia ,Journal Article ,Humans ,Neoplasm Invasiveness ,Cooperative Behavior ,adenocarcinoma ,Intraductal papillary mucinous neoplasm ,business.industry ,Carcinoma in situ ,Extramural ,Consensus Development Conference ,medicine.disease ,Cystic Neoplasm ,Tumor Burden ,atypical flat lesions (AFL) ,Pancreatic Neoplasms ,Dysplasia ,mucinous cystic neoplasm (MCN) ,Adenocarcinoma ,Surgery ,Neoplasm Grading ,Anatomy ,business ,Neoplasms, Cystic, Mucinous, and Serous ,Precancerous Conditions ,Carcinoma in Situ ,Carcinoma, Pancreatic Ductal - Abstract
International experts met to discuss recent advances and to revise the 2004 recommendations for assessing and reporting precursor lesions to invasive carcinomas of the pancreas, including pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm, and other lesions. Consensus recommendations include the following: (1) To improve concordance and to align with practical consequences, a 2-tiered system (low vs. high grade) is proposed for all precursor lesions, with the provision that the current PanIN-2 and neoplasms with intermediate-grade dysplasia now be categorized as low grade. Thus, "high-grade dysplasia" is to be reserved for only the uppermost end of the spectrum ("carcinoma in situ"-type lesions). (2) Current data indicate that PanIN of any grade at a margin of a resected pancreas with invasive carcinoma does not have prognostic implications; the clinical significance of dysplasia at a margin in a resected pancreas with IPMN lacking invasive carcinoma remains to be determined. (3) Intraductal lesions 0.5 to 1 cm can be either large PanINs or small IPMNs. The term "incipient IPMN" should be reserved for lesions in this size with intestinal or oncocytic papillae or GNAS mutations. (4) Measurement of the distance between an IPMN and invasive carcinoma and sampling of intervening tissue are recommended to assess concomitant versus associated status. Conceptually, concomitant invasive carcinoma (in contrast with the "associated" group) ought to be genetically distinct from an IPMN elsewhere in the gland. (5) "Intraductal spread of invasive carcinoma" (aka, "colonization") is recommended to describe lesions of invasive carcinoma invading back into and extending along the ductal system, which may morphologically mimic high-grade PanIN or even IPMN. (6) "Simple mucinous cyst" is recommended to describe cysts >1 cm having gastric-type flat mucinous lining at most minimal atypia without ovarian-type stroma to distinguish them from IPMN. (7) Human lesions resembling the acinar to ductal metaplasia and atypical flat lesions of genetically engineered mouse models exist and may reflect an alternate pathway of carcinogenesis; however, their biological significance requires further study. These revised recommendations are expected to improve our management and understanding of precursor lesions in the pancreas.
- Published
- 2015
50. Identification of S-acyl glutathione conjugates of bile acids in human bile by means of LC/ESI-MS
- Author
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Alan F. Hofmann, Shigeo Ikegawa, Toshiaki Shimizu, Naohiro Hori, Kuniko Mitamura, Hiroshi Nittono, Kyoichi Takaori, Mitsuyoshi Suzuki, Hajime Takikawa, and Takashi Iida
- Subjects
Adult ,Spectrometry, Mass, Electrospray Ionization ,Lithocholic acid ,Electrospray ionization ,Clinical Biochemistry ,Biochemistry ,Bile duct cancer ,Bile Acids and Salts ,chemistry.chemical_compound ,Endocrinology ,Biotransformation ,Liquid chromatography–mass spectrometry ,medicine ,Animals ,Bile ,Humans ,Molecular Biology ,Aged ,Pharmacology ,Chromatography ,Organic Chemistry ,Infant ,Glutathione ,Middle Aged ,medicine.disease ,Ursodeoxycholic acid ,Orders of magnitude (mass) ,Rats ,chemistry ,Chromatography, Liquid ,medicine.drug - Abstract
Previous work from this laboratory has reported the biotransformation of bile acids (BA) into the thioester-linked glutathione (GSH) conjugates via the intermediary metabolites formed by BA:CoA ligase and shown that such GSH conjugates are excreted into the bile in healthy rats as well as rats dosed with lithocholic acid or ursodeoxycholic acid. To examine whether such novel BA–GSH conjugates are present in human bile, we determined the concentration of the GSH conjugates of the five BA that predominate in human bile. Bile was obtained from three infants (age 4, 10, and 13 months) and the BA–GSH conjugates quantified by means of liquid chromatography (LC)/electrospray ionization (ESI)-linear ion trap mass spectrometry (MS) in negative-ion scan mode, monitoring characteristic transitions of the analytes. By LC/ESI-MS, only primary BA were present in biliary BA, indicating that the dehydroxylating flora had not yet developed. GSH conjugates of chenodeoxycholic and lithocholic acid were present in concentrations ranging from 27 to 1120 pmol/ml, several orders of magnitude less than those of natural BA N-acylamidates. GSH conjugates were not present, however, in the ductal bile obtained from 10 adults (nine choledocholithiasis, one bile duct cancer). Our results indicate that BA–GSH conjugates are formed and excreted in human bile, at least in infants, although this novel mode of conjugation is a very minor pathway.
- Published
- 2011
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