915 results on '"Masafumi, Nakamura"'
Search Results
102. Effects of Telmisartan and Candesartan on the Metabolism of Lipids and Glucose in Kidney Transplant Patients: A Prospective, Randomized Crossover Study
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Yoshifumi Miura, MD, Hiroshi Noguchi, MD, PhD, Yasuhiro Okabe, MD, Kosuke Masutani, MD, PhD, Shoji Tokunaga, PhD, and Masafumi Nakamura, MD, PhD
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Surgery ,RD1-811 - Abstract
Background. The risk of cardiovascular events remains after kidney transplantation (KT). Abnormal glucose metabolism and hyperlipidemia contribute partly to this risk. Among angiotensin II type-1 receptor blockers, telmisartan alone has been shown to ameliorate these effects on glucose and lipid metabolism (GLM). We investigated the effects of telmisartan on GLM in KT patients. Methods. This trial had a crossover design. Forty-six KT patients with well-controlled hypertension under angiotensin II type-1 receptor blockers were randomized into telmisartan and candesartan groups. After a 12-week treatment, crossover was initiated, and additional 12-week treatment was administered without a washout period. We examined the laboratory parameters of GLM, blood pressure and graft function before and after each treatment period. Results. Forty patients completed the scheduled treatment regimen. Serum levels of triglyceride were significantly lower (114.3 ± 50.8 mg/dL vs 136.5 ± 66.8 mg/dL; P = 0.019), and the estimated glomerular filtration rate was significantly higher (50.4 ± 15.1 mL/min per 1.73 m2 vs 48.5 ± 12.5 mL/min per 1.73 m2; P = 0.038) after telmisartan treatment than after candesartan treatment. There were no significant differences between the 2 treatment groups with regard to the other parameters studied (including serum adiponectin levels and parameters of glucose metabolism). Conclusions. These data suggest that telmisartan can improve serum triglyceride levels and graft function for KT patients better than candesartan.
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- 2019
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103. <scp>RHAMM</scp> marks proliferative subpopulation of human colorectal cancer stem cells
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Michitaka Nakano, Ryosuke Taguchi, Yoshikane Kikushige, Taichi Isobe, Kohta Miyawaki, Shinichi Mizuno, Nobuhiro Tsuruta, Fumiyasu Hanamura, Kyoko Yamaguchi, Takuji Yamauchi, Hiroshi Ariyama, Hitoshi Kusaba, Masafumi Nakamura, Takahiro Maeda, Calvin J. Kuo, Eishi Baba, and Koichi Akashi
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Cancer Research ,Oncology ,General Medicine - Published
- 2023
104. Risks and benefits of pancreaticoduodenectomy in patients aged 80 years and over
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Naoki Ikenaga, Kohei Nakata, Toshiya Abe, Noboru Ideno, Nao Fujimori, Takamasa Oono, Nobuhiro Fujita, Kousei Ishigami, and Masafumi Nakamura
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Surgery - Published
- 2023
105. Volume‐ and quality‐controlled certification system promotes centralization of complex hepato‐pancreatic‐biliary surgery
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Yoshihiro Mise, Shinya Hirakawa, Hisateru Tachimori, Yoshihiro Kakeji, Yuko Kitagawa, Shohei Komatsu, Atsushi Nanashima, Masafumi Nakamura, Itaru Endo, and Akio Saiura
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Hepatology ,Surgery - Published
- 2023
106. Genetic medicine is accelerating in Japan
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Saori, Hayashi, Makoto, Kubo, Kazuhisa, Kaneshiro, Masaya, Kai, Mai, Yamada, Takafumi, Morisaki, Yuka, Takao, Akiko, Shimazaki, Sawako, Shikada, and Masafumi, Nakamura
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BRCA2 Protein ,Ovarian Neoplasms ,BRCA1 Protein ,Breast Neoplasms ,Triple Negative Breast Neoplasms ,General Medicine ,Japan ,Oncology ,Hereditary Breast and Ovarian Cancer Syndrome ,Humans ,Female ,Pharmacology (medical) ,Radiology, Nuclear Medicine and imaging ,Genetic Testing - Abstract
Background In 2018, BRACAnalysis® was covered by medical insurance in Japan as a companion diagnostic test for the poly ADP-ribose polymerase inhibitor olaparib. In April 2020, eligibility for BRCA1/2 genetic testing was expanded to the diagnosis of hereditary breast and ovarian cancer syndrome, and medical management including prophylactic surgery and surveillance were covered by public insurance for BRCA1/2 mutation carriers who developed breast or ovarian cancer. The amount of BRCA1/2 genetic testing has been increasing recently, but the number of subjects and the impact of testing for patients’ outcomes remain unclear. Patients and methods This study explored the potential number of patients who will be eligible for new insurance coverage for BRCA1/2 genetic testing. We analyzed 868 patients from 938 surgeries between January 2014 and September 2020 from our database. Results Overall, 372 patients (43%) were eligible for new insurance coverage for BRCA1/2 genetic testing. The most common category was family history of breast or ovarian cancer within third-degree relatives. We found that 202 patients (23%) had family history of breast or ovarian cancer. In addition, the progression-free survival was significantly lower in triple-negative breast cancer patients aged 60 years or younger compared with the other patients (P = 0.0005). Conclusion The genetic medicine for primary breast cancer patients with BRCA1/2 germline mutation is accelerating rapidly in Japan. Therefore, establishing a system for the genetic medicine would be urgent.
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- 2022
107. Abstract PD1-04: Estrogen-mediated mechanisms in estrogen receptor-positive breast cancer at the single cell level
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Hitomi Mori, Kohei Saeki, Gregory Chang, Jinhui Wang, Xiwei Wu, Pei-Yin Hsu, Noriko Kanaya, George Somlo, Masafumi Nakamura, Andrea Bild, and Shiuan Chen
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Cancer Research ,Oncology - Abstract
Background: Estrogen typically promotes the progression of hormone-dependent breast cancer through activation of estrogen receptor (ER)-α encoded by ESR1. While estrogen-induced tumor suppression in ER+ breast cancer has been clinically observed as an unexpected outcome of aromatase inhibitor (AI)-resistance, the molecular mechanisms have not yet been fully defined. Methods: Characterization of estrogen regulation in the two ER+ breast cancer patient-derived xenograft (PDX) models with opposite responses to estrogen offered us an unprecedented opportunity to assess how 17β-estradiol (E2) modulates ER+ cancer. We succeeded in establishing estrogen-stimulating (SC31) and estrogen-suppressing (GS3) PDX models. In vivo tumor promotion or suppression by estrogen was confirmed through experiments by implanting E2 pellets in mice carrying SC31/GS3, and then single cell analysis was performed using SC31/GS3 tumors. To investigate whether GS3 would change its response to E2, we performed intermittent E2 treatment every 28 days (E2 pellet on/off every 28 days) and whole-genome RNA sequencing using GS3 tumors. Results: SC31 and GS3 behaved oppositely regarding estrogen-mediated tumor growth. Immunohistochemistry indicated that the number of ERα+ cells and Ki-67+ cells were increased in SC31 and decreased in GS3 after E2 treatment, but progesterone receptor+ cells appeared in both SC31 and GS3 after E2 treatment at the protein level. The E2-induced suppression of GS3 involves ERα, not ERβ, which was wild-type and not amplified. Single cell RNA sequencing analysis of these PDXs had revealed that E2 upregulated the expression of estrogen-regulated genes (e.g., PGR and AREG) in both SC31 and GS3. However, E2 treatment induced cell cycle promotion in SC31, while E2 induced cell cycle arrest in GS3. These gene-expression changes occurred in both ESR1+ cells and ESR1- cells, demonstrating for the first time the influence of estrogen on ESR1- cells in ER+breast tumors. This result suggests that 100% ER positivity is not essential for endocrine response. E2 also upregulated a tumor suppressor gene, IL24, only in GS3. More IL24+ cells were ESR1+ and in G1 phase than IL24- cells. Hallmark apoptosis gene sets were upregulated and the hallmark G2M checkpoint gene set was downregulated in IL24+ cells after E2 treatment. After three rounds of intermittent E2 treatment on GS3, an E2 independent growth developed. Approximately 60% of genes in the intermittent E2-treated sample had the same trend as E2-treated samples (mainly ER target genes), in which 40% of the genes behaved similarly to the placebo-treated sample (mainly cell cycle progression genes). Furthermore, lower levels of IL24 were linked to estrogen independence. Conclusions: Estrogen/ERα signaling increases the expression of estrogen-regulated genes, but it can modulate HR+ tumor growth in different manners. While E2 should activate ERα and regulate ESR1+ cells, our findings regarding ESR1- cells were new and suggested crosstalk between ESR1+ cells and ESR1- cells in both estrogen-stimulating and -suppressing ER+ tumors. Furthermore, our studies demonstrate the potential roles of tumor suppressor gene, IL24 in HR+ cancer. Our findings point to the need to identify biomarkers for patients with estrogen-suppressing tumors who can benefit from E2 treatment after AI resistance; measurements of ER and PR expression are insufficient. Expression of IL24 in AI-resistant tumors may be one such indicator for favorable response to E2 therapy. Citation Format: Hitomi Mori, Kohei Saeki, Gregory Chang, Jinhui Wang, Xiwei Wu, Pei-Yin Hsu, Noriko Kanaya, George Somlo, Masafumi Nakamura, Andrea Bild, Shiuan Chen. Estrogen-mediated mechanisms in estrogen receptor-positive breast cancer at the single cell level [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD1-04.
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- 2022
108. Extensive (subtotal) distal pancreatectomy for pancreatic ductal adenocarcinoma: a propensity score matched cohort study of short- and long-term outcomes compared with those of conventional distal pancreatectomy
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Yusuke, Watanabe, Kohei, Nakata, Yasuhisa, Mori, Noboru, Ideno, Naoki, Ikenaga, Takao, Ohtsuka, and Masafumi, Nakamura
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Cohort Studies ,Male ,Pancreatic Neoplasms ,Pancreatectomy ,Treatment Outcome ,Humans ,Female ,Laparoscopy ,Surgery ,Propensity Score ,Carcinoma, Pancreatic Ductal ,Retrospective Studies - Abstract
Extensive distal pancreatectomy (ExDP) can transect the pancreatic parenchyma more from the right side than conventional distal pancreatectomy (CDP) can. This study aimed to evaluate the short- and long-term outcomes of ExDP for pancreatic ductal adenocarcinoma (PDAC) of the pancreatic body, located adjacent to the portal vein (PV).Medical records of 98 patients who underwent ExDP (n = 15) or CDP (n = 83) for PDAC were retrospectively reviewed. Short- and long-term outcomes of the two groups were compared. Propensity score matched analysis was additionally performed to minimize the impact of treatment allocation bias.In the total cohort, the CDP group had a significantly higher proportion of pancreatic tail lesions (P 0.01), higher proportion of males, and larger tumor size. Of the 15 patients who underwent ExDP, 11 could be matched. These differences of patients' characteristics were not observed after matching. Before and after matching, the duration of surgery, blood loss, rate of morbidity including pancreatic fistula, and postoperative course were comparable between the groups. The rate of recurrence and recurrence pattern were also not significantly different between the groups. ExDP for PDAC of the pancreatic body near the PV did not increase local or lymph node recurrence. The disease-free and overall survival did not differ between the groups.Surgical and oncological outcomes after ExDP for PDAC were acceptable and comparable to those after CDP. ExDP is a feasible procedure, and could be an option for the treatment of PDAC of the pancreatic body near PV.
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- 2022
109. Early Detection of Pancreatic Cancer: Role of Biomarkers in Pancreatic Fluid Samples
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Noboru Ideno, Yasuhisa Mori, Masafumi Nakamura, and Takao Ohtsuka
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pancreatic cancer ,pancreatic juice ,duodenal juice/fluid ,Medicine (General) ,R5-920 - Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths worldwide. Most patients with PDAC present with symptomatic, surgically unresectable disease. Therefore, the establishment of strategies for the early detection is urgently needed. Molecular biomarkers might be useful in various phases of a strategy to identify high-risk individuals in the general population and to detect high-risk lesions during intense surveillance programs combined with imaging modalities. However, the low sensitivity and specificity of biomarkers currently available for PDAC, such as carbohydrate 19-9 (CA19-9), contribute to the late diagnosis of this deadly disease. Although almost all classes of biomarker assays have been studied, most of them are used in the context of symptomatic diseases. Compared to other body fluids, pancreatic juice and duodenal fluid are better sources of DNA, RNA, proteins, and exosomes derived from neoplastic cells and have the potential to increase the sensitivity/specificity of these biomarkers. The number of studies using duodenal fluid with or without secretin stimulation for DNA/protein marker tests have been increasing because of the less-invasiveness in comparison to pancreatic juice collection by endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). Genomic analyses have been very well-studied, and based on PDAC progression model, mutations detected in pancreatic juice/duodenal fluid seem to indicate the presence of microscopic precursors and high-grade dysplasia/invasive cancer. In addition to known proteins overexpressed both in precursors and PDACs, such as CEA and S100P, comprehensive proteomic analysis of pancreatic juice from patients with PDAC identified many proteins which were not previously described. A novel technique to isolate exosomes from pancreatic juice was recently invented and identification of exosomal microRNA’s 21 and 155 could be biomarkers for diagnosis of PDAC. Since many studies have explored biomarkers in fluid samples containing pancreatic juice and reported excellent diagnostic accuracy, we need to discuss how these biomarker assays can be validated and utilized in the strategy of early detection of PDAC.
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- 2020
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110. Clinicopathologic Features and Genetic Alterations in Mixed-Type Ampullary Carcinoma
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Jun Kawata, Yutaka Koga, Shoko Noguchi, Yuki Shimada, Yutaka Yamada, Takeo Yamamoto, Koji Shindo, Masafumi Nakamura, and Yoshinao Oda
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Pathology and Forensic Medicine - Published
- 2023
111. Insights from managing clinical issues in distal pancreatectomy with en bloc coeliac axis resection: experiences from 626 patients.
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Toru Nakamura, Ken-Ichi Okada, Masayuki Ohtsuka, Ryota Higuchi, Hidenori Takahashi, Kazuyuki Nagai, Michiaki Unno, Yoshiaki Murakami, Atsushi Oba, Moriaki Tomikawa, Atsushi Kato, Akihiko Horiguchi, Masafumi Nakamura, Shintaro Yagi, Sohei Satoi, Itaru Endo, Ryosuke Amano, Ippei Matsumoto, Ito, Yoichi M., and Takukazu Nagakawa
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PANCREATECTOMY ,SPLENIC artery ,PROPENSITY score matching ,SURGERY ,PANCREATIC surgery ,THERAPEUTIC embolization - Abstract
Background: Distal pancreatectomy with en bloc coeliac axis resection (DP-CAR) for pancreatic body cancer has been reported increasingly. However, its large-scale outcomes remain undocumented. This study aimed to evaluate DP-CAR volume and mortality, preoperative arterial embolization for ischaemic gastropathy, the oncological benefit for resectable tumours close to the bifurcation of the splenic artery and coeliac artery using propensity score matching, and prognostic factors in DP-CAR. Methods: In a multi-institutional analysis, 626 DP-CARs were analysed retrospectively and compared with 1325 distal pancreatectomies undertaken in the same interval. Results: Ninety-day mortality was observed in 7 of 21 high-volume centres (1 or more DP-CARs per year) and 1 of 41 low-volume centres (OR 20.00, 95 per cent c.i. 2.26 to 177.26). The incidence of ischaemic gastropathy was 19.2 per cent in the embolization group and 7.9 per cent in the no-embolization group (OR 2.77, 1.48 to 5.19). Propensity score matching analysis showed that median overall survival was 33.5 (95 per cent c.i. 27.4 to 42.0) months in the DP-CAR and 37.9 (32.8 to 53.3) months in the DP group. Multivariable analysis identified age at least 67 years (HR 1.40, 95 per cent c.i. 1.12 to 1.75), preoperative tumour size 30 mm or more (HR 1.42, 1.12 to 1.80), and preoperative carbohydrate antigen 19-9 level over 37 units/ml (HR 1.43, 1.11 to 1.83) as adverse prognostic factors. Conclusion: DP-CAR can be performed safely in centres for general pancreatic surgery regardless of DP-CAR volume, and preoperative embolization may not be required. This procedure has no oncological advantage for resectable tumour close to the bifurcation of the splenic artery, and should be performed after appropriate patient selection. [ABSTRACT FROM AUTHOR]
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- 2023
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112. Nonmass-forming type anorectal cancer with pagetoid spread: A report of two cases.
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Masahiro Yamamoto, Yusuke Mizuuchi, Koji Tamura, Masafumi Sada, Kinuko Nagayoshi, Kohei Nakata, Kenoki Ohuchida, Yoshinao Oda, and Masafumi Nakamura
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METASTASIS ,LYMPHADENECTOMY ,ABDOMINOPERINEAL resection ,SKIN biopsy ,CELL proliferation - Abstract
Pagetoid spread (PS) of anorectal cancer is relatively rare and associated with poor prognosis. While a primary tumorous lesion is usually obvious in most PS cases, we experienced two cases of nonmass-forming type anorectal cancer with PS. It remains challenging to decide strategies. In both cases, histological findings of a perianal skin biopsy showed proliferation of atypical cells that were positive for cytokeratin (CK) 7, CK20, and caudal type homeobox 2 and negative for Gross cystic disease fluid protein 15, suggesting PS. Abdominoperineal resection (APR) with extensive anal skin resection was performed in both patients. The pathological diagnosis in each was nonmass-forming type anorectal cancer with PS. Neither has experienced recurrence in postoperative courses. Even nonmass-forming type anorectal cancer with PS could have high malignant potentials. APR with lymph nodes dissection and wide skin excision and regular surveillance might be necessary. [ABSTRACT FROM AUTHOR]
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- 2023
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113. Repeated robotic pancreatectomy for recurrent pancreatic metastasis of mesenchymal chondrosarcoma: A case report.
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Sayuri Hayashida, Naoki Ikenaga, Kohei Nakata, So Nakamura, Toshiya Abe, Noboru Ideno, Makoto Endo, Shoko Noguchi, Yoshinao Oda, and Masafumi Nakamura
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CHONDROSARCOMA ,PANCREATECTOMY ,SPLENIC artery ,TUMOR surgery ,ROBOTICS ,SURGICAL robots - Abstract
Mesenchymal chondrosarcoma is a rare subset of sarcomas accounting for 3%-10% of all cases of chondrosarcomas. Radical resection is the only curative strategy, even in patients with metastatic tumors. However, data regarding treatment strategies remain limited owing to the small number of cases. Herein, we report a patient who underwent repeated robotic pancreatectomy for recurrent pancreatic metastasis originating from extraskeletal mesenchymal chondrosarcoma of the pelvis. First, robotic pancreaticoduodenectomy with a reconstruction of pancreaticogastrostomy was performed for synchronous pancreatic metastasis 5 months after the primary resection of mesenchymal chondrosarcoma. Ten months after robotic pancreaticoduodenectomy, tumor recurrence was observed at the tail end of the pancreas, which was removed by reperforming robotic distal pancreatectomy. Given the precise tissue manipulation that can be achieved with robotic articulated forceps, the peripheral splenic artery and pancreas were easily isolated and divided in close proximity to the tumor. The central part of the pancreas was preserved. Robotic surgery allowed safe and effective resection of the reconstructed remnant pancreas. The patient survived for 28 months after primary tumor resection. Repeated pancreatectomy with minimally invasive techniques is a feasible and curative treatment for metastatic mesenchymal chondrosarcoma. [ABSTRACT FROM AUTHOR]
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- 2023
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114. Cancer-derived cholesterol sulfate is a key mediator to prevent tumor infiltration by effector T cells
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Takaaki Tatsuguchi, Takehito Uruno, Yuki Sugiura, Daiji Sakata, Yoshihiro Izumi, Tetsuya Sakurai, Yuko Hattori, Eiji Oki, Naoto Kubota, Koshiro Nishimoto, Masafumi Oyama, Kazufumi Kunimura, Takuto Ohki, Takeshi Bamba, Hideaki Tahara, Michiie Sakamoto, Masafumi Nakamura, Makoto Suematsu, and Yoshinori Fukui
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Neoplasms ,T-Lymphocytes ,Immunology ,Tumor Microenvironment ,Humans ,Immunology and Allergy ,Cholesterol Esters ,Immunotherapy ,Oxysterols ,General Medicine - Abstract
Effective tumor immunotherapy requires physical contact of T cells with cancer cells. However, tumors often constitute a specialized microenvironment that excludes T cells from the vicinity of cancer cells, and its underlying mechanisms are still poorly understood. DOCK2 is a Rac activator critical for migration and activation of lymphocytes. We herein show that cancer-derived cholesterol sulfate (CS), a lipid product of the sulfotransferase SULT2B1b, acts as a DOCK2 inhibitor and prevents tumor infiltration by effector T cells. Using clinical samples, we found that CS was abundantly produced in certain types of human cancers such as colon cancers. Functionally, CS-producing cancer cells exhibited resistance to cancer-specific T-cell transfer and immune checkpoint blockade. Although SULT2B1b is known to sulfate oxysterols and inactivate their tumor-promoting activity, the expression levels of cholesterol hydroxylases, which mediate oxysterol production, are low in SULT2B1b-expressing cancers. Therefore, SULT2B1b inhibition could be a therapeutic strategy to disrupt tumor immune evasion in oxysterol-non-producing cancers. Thus, our findings define a previously unknown mechanism for tumor immune evasion and provide a novel insight into the development of effective immunotherapies.
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- 2022
115. Tumor progression by epithelial-mesenchymal transition in ARID1A- and SMARCA4-aberrant solid-type poorly differentiated gastric adenocarcinoma
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Taisuke Sasaki, Kenichi Kohashi, Shinichiro Kawatoko, Eikichi Ihara, Eiji Oki, Masafumi Nakamura, Yoshihiro Ogawa, and Yoshinao Oda
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Epithelial-Mesenchymal Transition ,DNA Helicases ,Nuclear Proteins ,Cell Biology ,General Medicine ,Adenocarcinoma ,Cadherins ,Pathology and Forensic Medicine ,DNA-Binding Proteins ,Stomach Neoplasms ,Biomarkers, Tumor ,Humans ,Molecular Biology ,beta Catenin ,Neoplastic Processes ,Transcription Factors - Abstract
Solid-type poorly differentiated adenocarcinoma (PDA) of the stomach is frequently associated with microsatellite instability (MSI) and aberrations of the SWI/SNF chromatin remodeling complex. Previous studies showed that aberrant ARID1A and SMARCA4 expression induces mesenchymal transition. We analyzed 51 primary-site cases and 209 metastatic lymph nodes among solid-type PDA for the expression of SWI/SNF complex subunits (ARID1A, SMARCA4, SMARCB1, SMARCC2) and epithelial-mesenchymal transition (EMT) markers (E-cadherin, β-catenin, Snail). We also analyzed 40 cases of non-solid-type PDA as a stage-matched control group. Aberrant expression of ARID1A (39%) and SMARCA4 (49%) was more common in solid-type PDA than in non-solid-type PDA (ARID1A, P = 0.0049; SMARCA4, P 0.0001). The group of solid-type PDA with aberrant ARID1A showed significantly longer overall and progression-free survival than the corresponding ARID1A-retained group (P = 0.0405 and P = 0.0296, respectively). Aberrant expression of EMT factors inducing mesenchymal transition in the groups with solid-type PDA at the primary site or metastatic lymph nodes with aberrant ARID1A was less common than in the corresponding groups with retained ARID1A (E-cadherin, primary site P = 0.0341, lymph node P 0.0001; β-catenin, primary site P = 0.0293, lymph node P = 0.0010; Snail, primary site P = 0.0169, lymph node P = 0.0828). Furthermore, N3 of the TNM classification was more frequently observed in the group with solid-type PDA with retained ARID1A than in the corresponding ARID1A-aberrant group (P = 0.0288). Mesenchymal transition was not induced in the ARID1A-aberrant group, in which patients had favorable prognosis, and preserved epithelial characteristics in EMT may play an important role in low tumor aggressiveness of solid-type PDA.
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- 2022
116. A Standardized Surgical Procedure Involving Dorsal Dissection from the Lateral Duodenojejunal Flexure in Patients with Splenic Flexure Colon Cancer
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Kinuko Nagayoshi, Haruka Mitsubuchi, Kan Watanabe, Kyoko Hisano, Koji Tamura, Masafumi Sada, Yusuke Mizuuchi, Shuntaro Nagai, and Masafumi Nakamura
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Gastroenterology ,Surgery - Published
- 2022
117. Preoperative prediction of malignancy and surgical treatment strategy in appendiceal tumors: multicenter review of 51 consecutive cases
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Koji Tamura, Takashi Ueki, Hiromichi Nakayama, Yusuke Watanabe, Masafumi Sada, Kinuko Nagayoshi, Yusuke Mizuuchi, Kenoki Ohuchida, Hitoshi Ichimiya, and Masafumi Nakamura
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Surgery - Published
- 2023
118. Relationship between prognostic impact of N3 lymph node metastasis at the root of the feeding artery and location of colon cancer
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Yusuke Mizuuchi, Yoshitaka Tanabe, Masafumi Sada, Koji Tamura, Kinuko Nagayoshi, Shuntaro Nagai, Yusuke Watanabe, Sadafumi Tamiya, Kenoki Ohuchida, Kohei Nakata, Toru Nakano, and Masafumi Nakamura
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Surgery - Published
- 2023
119. Effect of Biologics on the Risk of Advanced-Stage Inflammatory Bowel Disease-Associated Intestinal Cancer: A Nationwide Study
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Ryo, Seishima, Koji, Okabayashi, Hiroki, Ikeuchi, Motoi, Uchino, Kitaro, Futami, Tatsuki, Noguchi, Hiroki, Ohge, Yasuhito, Iseki, Kazuhiro, Watanabe, Michio, Itabashi, Kinya, Okamoto, Yuji, Toiyama, Takayuki, Ogino, Masafumi, Nakamura, Kazutaka, Yamada, Toshifumi, Wakai, Yu, Sato, Hideaki, Kimura, Kenichi, Takahashi, Koya, Hida, Yusuke, Kinugasa, Fumio, Ishida, Junji, Okuda, Koji, Daito, Fumikazu, Koyama, Hideki, Ueno, Takayuki, Yamamoto, Seiichiro, Yamamoto, Tsunekazu, Hanai, Atsuo, Maemoto, Junya, Arakaki, Koji, Komori, Yoshito, Akagi, Dai, Shida, Shigeki, Yamaguchi, Keiji, Matsuda, Kiyoshi, Maeda, Toshihiro, Noake, Riichiro, Nezu, Shin, Sasaki, Junichi, Hasegawa, Eiji, Sunami, Yukihide, Kanemitsu, Kenji, Katsumata, Kei, Uehara, Tomomichi, Kiyomatsu, Takeshi, Suto, Shinsuke, Kazama, Takeshi, Yamada, Takenori, Goi, Soichiro, Ishihara, Yoichi, Ajioka, and Kenichi, Sugihara
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Hepatology ,Gastroenterology - Abstract
The aim of this study was to evaluate the effect of biologics on the risk of advanced-stage inflammatory bowel disease (IBD)-associated intestinal cancer from a nationwide multicenter data set.The medical records of patients with Crohn's disease (CD) and ulcerative colitis (UC) diagnosed with IBD-associated intestinal neoplasia (dysplasia or cancer) from 1983 to 2020 were included in this study. Therapeutic agents were classified into 3 types: biologics, 5-aminosalicylic acid, and immunomodulators. The pathological cancer stage was compared based on the drug used in both patients with CD and UC.In total, 1,042 patients (214 CD and 828 UC patients) were included. None of the drugs were significantly associated with cancer stage in the patients with CD. In the patients with UC, an advanced cancer stage was significantly associated with less use of biologics (early stage: 7.7% vs advanced stage: 2.0%, P0.001), 5-aminosalicylic acid, and immunomodulators. Biologic use was associated with a lower incidence of advanced-stage cancer in patients diagnosed by regular surveillance (biologics [-] 24.5% vs. [+] 9.1%, P = 0.043), but this was not the case for the other drugs. Multivariate analysis showed that biologic use was significantly associated with a lower risk of advanced-stage disease (odds ratio = 0.111 [95% CI, 0.034-0.356], P0.001).Biologic use was associated with a lower risk of advanced IBD-associated cancer in patients with UC but not with CD. The mechanism of cancer progression between UC and CD may be different and needs to be further investigated.
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- 2023
120. Involvement of angiogenesis in cancer-associated acinar-to-ductal metaplasia lesion of pancreatic cancer invasive front
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Shuang Fei, Kenoki Ohuchida, Shin Kibe, Zilong Yan, Chika Iwamoto, Tomohiko Shinkawa, Bo Zhang, Jun Kawata, Toshiya Abe, Noboru Ideno, Naoki Ikenaga, Kohei Nakata, Yoshinao Oda, and Masafumi Nakamura
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Cancer Research ,Oncology ,General Medicine - Abstract
This study aimed to demonstrate the involvement of angiogenesis in cancer-associated acinar-to-ductal metaplasia (CA-ADM) lesion of invasive front pancreatic ductal adenocarcinoma (PDAC) and investigate the possible mechanism.Tissue samples from 128 patients with PDAC and 36 LSL-KrasAngiogenesis was significantly abundant in CA-ADM lesions compared with that in PDAC lesions in human and mouse tissues. High-level MVD in CA-ADM lesions was an independent predictor of poor prognosis (P = 0.0047) and the recurrence of liver metastasis (P = 0.0027). More CD68-positive and CD163-positive macrophages were detected in CA-ADM lesions than in PDAC. The percentage of CD68-positive macrophages was positively correlated with MVD in CA-ADM lesions. Multiplex-immunostaining revealed that MMP9 was expressed in CD68-positive macrophages of CA-ADM lesions. In CA-ADM lesions, the percentage of macrophages was positively correlated with MMP9 expression, which positively correlated with microvessel density.CA-ADM related angiogenesis is a promising predictive marker for poor prognosis of PDAC and may provide an attractive therapeutic target for PDAC.
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- 2023
121. Minimally invasive anatomic liver resection: Results of a survey of world experts
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Mamoru Morimoto, Kazuteru Monden, Taiga Wakabayashi, Naoto Gotohda, Yuta Abe, Goro Honda, Mohammed Abu Hilal, Takeshi Aoki, Horacio J. Asbun, Giammauro Berardi, Albert C.Y. Chan, Rawisak Chanwat, Kuo‐Hsin Chen, Yajin Chen, Daniel Cherqui, Tan To Cheung, Ruben Ciria, David Fuks, David A. Geller, Ho‐Seong Han, Kiyoshi Hasegawa, Etsuro Hatano, Osamu Itano, Yukio Iwashita, Hironori Kaneko, Yutaro Kato, Ji Hoon Kim, Rong Liu, Santiago López‐Ben, Fernando Rotellar, Yoshihiro Sakamoto, Atsushi Sugioka, Tomoharu Yoshizumi, Keiichi Akahoshi, Felipe Alconchel, Shunichi Ariizumi, Andrea Benedetti Cacciaguerra, Manuel Durán, Alain García Vázquez, Nicolas Golse, Yoshihiro Miyasaka, Yasuhisa Mori, Satoshi Ogiso, Chikara Shirata, Federico Tomassini, Takeshi Urade, Hitoe Nishino, Filipe Kunzler, Shingo Kozono, Hiroaki Osakabe, Chie Takishita, Daisuke Ban, Taizo Hibi, Norihiro Kokudo, Masayuki Ohtsuka, Yuichi Nagakawa, Takao Ohtsuka, Minoru Tanabe, Masafumi Nakamura, Masakazu Yamamoto, Akihiko Tsuchida, and Go Wakabayashi
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Hepatology ,Surveys and Questionnaires ,Liver Neoplasms ,Hepatectomy ,Humans ,Laparoscopy ,Surgery - Abstract
Although the number of minimally invasive liver resections (MILRs) has been steadily increasing in many institutions, minimally invasive anatomic liver resection (MIALR) remains a complicated procedure that has not been standardized. We present the results of a survey among expert liver surgeons as a benchmark for standardizing MIALR.We administered this survey to 34 expert liver surgeons who routinely perform MIALR. The survey contained questions on personal experience with liver resection, inflow/outflow control methods, and identification techniques of intersegmental/sectional planes (IPs).All 34 participants completed the survey; 24 experts (70%) had more than 11 years of experience with MILR, and over 80% of experts had performed over 100 open resections and MILRs each. Regarding the methods used for laparoscopic or robotic anatomic resection, the Glissonean approach (GA) was a more frequent procedure than the hilar approach (HA). Although hepatic veins were considered essential landmarks, the exposure methods varied. The top three techniques that the experts recommended for identifying IPs were creating a demarcation line, indocyanine green negative staining method, and intraoperative ultrasound.Minimally invasive anatomic liver resection remains a challenging procedure; however, a certain degree of consensus exists among expert liver surgeons.
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- 2021
122. Incidence and location of perioperative deep vein thrombosis in patients with bladder cancer undergoing radical cystectomy
- Author
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Ryo Yamashita, Masafumi Nakamura, Yukiko Okayama, Mizuki Kawase, Nao Muraoka, Ayano Fujita, Akifumi Notsu, Koiku Asakura, Akihito Hashizume, Hideo Shinsaka, Masato Matsuzaki, Masashi Niwakawa, and Mototsugu Oya
- Subjects
Venous Thrombosis ,Postoperative Complications ,Urinary Bladder Neoplasms ,Incidence ,Urology ,Humans ,Urinary Diversion ,Cystectomy - Abstract
To determine the incidence and location of lower extremity deep vein thrombosis in patients undergoing radical cystectomy.We performed radical cystectomy in 137 patients with bladder cancer between August 2014 and February 2020. Since 2014, we have had a policy to screen for deep vein thrombosis using lower extremity ultrasonography both before and after radical cystectomy. We determined the incidence and location of deep vein thrombosis and classified it as either proximal or distal type. Furthermore, we explored the incidence of pulmonary embolism within 3 months after radical cystectomy.After excluding six patients with a lack of ultrasonographic data, we evaluated 131 patients. Preoperative deep vein thrombosis (one proximal and 17 distal) was diagnosed in 18 patients (14%) with no symptoms. Postoperative deep vein thrombosis was diagnosed in 41 patients (31%; three proximal and 38 distal), of whom 26 (63%) had new-onset deep vein thrombosis after cystectomy. Three patients, two with proximal and one with distal type deep vein thrombosis, developed nonfatal pulmonary embolism postoperatively. Multivariate analysis showed that preoperative D-dimer levels (odds ratio 5.35, 95% confidence interval 1.74-16.50; P 0.003), type of urinary diversion (ileal neobladder; odds ratio 11.15, 95% confidence interval 2.16-57.55; P = 0.004), and preoperative deep vein thrombosis (odds ratio 15.93, 95% confidence interval 3.82-66.30; P 0.001) were significant risk factors for postoperative deep vein thrombosis.Pre- and post-radical cystectomy whole-leg ultrasonography can lead to an early perioperative diagnosis and immediate treatment of proximal deep vein thrombosis, thereby potentially preventing fatal pulmonary embolism.
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- 2021
123. Relationship between cellular morphology and abnormality of SWI/SNF complex subunits in pancreatic undifferentiated carcinoma
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Masafumi Nakamura, Yutaka Yamada, Shinichi Aishima, Takeo Yamamoto, Yutaka Koga, Kenichi Kohashi, Kukiko Sakihama, Jun Kawata, Yoshinao Oda, and Ryota Matsuda
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Cancer Research ,ARID1A ,Vimentin ,Adenocarcinoma ,Downregulation and upregulation ,Formaldehyde ,Humans ,RNA, Messenger ,Epithelial–mesenchymal transition ,SMARCB1 ,biology ,SWI/SNF complex ,DNA Helicases ,Nuclear Proteins ,General Medicine ,Cadherins ,Immunohistochemistry ,DNA-Binding Proteins ,Pancreatic Neoplasms ,Blot ,Oncology ,biology.protein ,Cancer research ,SMARCA4 ,Transcription Factors - Abstract
Pancreatic undifferentiated carcinoma (UDC) is a rare tumor with a worse prognosis than pancreatic ductal adenocarcinoma (PDAC). Recent study showed that UDC exhibits loss of SMARCB1, which is one of the subunits of the SWI/SNF complex. However, whether there are abnormalities of other SWI/SNF complex subunits in UDC has remained unknown. In this study, we attempted to clarify whether the loss of SWI/SNF complex subunits is related to the pathogenesis of UDC by comparing undifferentiated component (UC) and ductal adenocarcinoma component (DAC). Genetic analysis of the ten UCs and six DACs was performed. The expression of ARID1A, SMARCA2, SMARCA4, SMARCB1, SMARCC1, and SMARCC2 in formalin-fixed, paraffin-embedded tumor tissues collected by surgical resection from 18 UDC patients was evaluated immunohistochemically. Moreover, two pancreatic cell lines were evaluated for the effects of siARID1A on the mRNA and protein expression of E-cadherin, vimentin, and epithelial-mesenchymal transition (EMT)-related markers by qRT-PCR, western blotting, and immunofluorescence staining. UCs tended to have a higher frequency of mutation in ARID1A, SMARCA4, and SMARCC2 than DACs. Immunohistochemically, UCs revealed reduced/lost expression of ARID1A (72%), SMARCB1 (44%), SMARCC1 (31%), and SMARCC2 (67%). Reduced/lost expression of ARID1A, SMARCB1, and SMARCC2 was significantly more frequently observed in UCs than in DACs. In the pancreatic cell lines, western blotting and qRT-PCR showed that the downregulation of ARID1A increased the expression of vimentin and EMT-related markers. Our results suggest that the abnormality of SWI/SNF complex subunits, especially ARID1A, is one of the factors behind the morphological change of UDC.
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- 2021
124. Rectal Phenotype of Perianal Paget Disease: Rare Concomitant Phenomena
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Yuichi Yamada, Shinichiro Kawatoko, Yuki Tateishi, Masaki Mori, Yutaka Yamada, Takeo Yamamoto, Taisuke Sasaki, Masafumi Nakamura, Jun Kawata, and Yoshinao Oda
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Pathology ,medicine.medical_specialty ,business.industry ,Concomitant ,Paget Disease ,Medicine ,business ,Phenotype ,Research Article - Abstract
Aim: Classically, ‘Paget disease’ refers to a distinct histological pattern in breast carcinoma. Here, we review the clinicopathological features of anorectal adenocarcinoma with ‘pagetoid’ spread. Materials and Methods: Histological and immunohistochemical records for 11 cases of anorectal adenocarcinoma with pagetoid spread among 958 Japanese patients with primary rectal/anal carcinoma were reviewed. Results: Grossly, nine of 11 cases had areas of invasive carcinoma: Tubular adenocarcinoma in eight and neuroendocrine carcinoma in one. Pagetoid components were positive for cytokeratin 7 in eight cases, cytokeratin 20 and caudal type homeobox 2 in all 11 cases, and p63 in one case, but were negative for estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2), gross cystic disease fluid protein-15, and GATA binding protein 3. Conclusion: The prevalence of perianal Paget disease in this series was 1.1%, with two cases of genuine perianal Paget disease with a rectal phenotype without invasive carcinoma. The rectal phenotype of perianal Paget disease may not be associated with HER2 overexpression.
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- 2021
125. PIK3CB is involved in metastasis through the regulation of cell adhesion to collagen I in pancreatic cancer
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Kenoki Ohuchida, Stephen Jun Fei Chong, Jianhua Qu, Haimin Feng, Rui Liang, Xianbin Zhang, Zhong Liu, Kengo Shirahane, Biao Zheng, Peng Gong, Kazuhiro Mizumoto, and Masafumi Nakamura
- Subjects
0301 basic medicine ,Medicine (General) ,Science (General) ,Class I Phosphatidylinositol 3-Kinases ,Mice, Nude ,Adenocarcinoma ,Malignancy ,Metastasis ,03 medical and health sciences ,Mice ,Q1-390 ,0302 clinical medicine ,R5-920 ,Downregulation and upregulation ,In vivo ,Pancreatic cancer ,Cell Line, Tumor ,medicine ,Cell Adhesion ,Animals ,Humans ,Cell adhesion ,ComputingMethodologies_COMPUTERGRAPHICS ,Multidisciplinary ,Oncogene ,business.industry ,PIK3CB ,medicine.disease ,Collagen I ,Pancreatic Neoplasms ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,Adhesion ,Medicine ,Collagen ,business - Abstract
Graphical abstract, Highlights • PIK3CB is highly expressed in PAAD. • PIK3CB is involved in PAAD progression and metastasis. • PIK3CB-depletion does not significantly affect cell viability, migration or invasion capabilities of human PAAD cells in vitro. • PIK3CB-depletion does not significantly influence growth or hepatic colonization abilities of human PAAD cells in vivo. • PIK3CB influences cell invasiveness via cell-to-collagen I interaction in human PAAD cells in vitro., Introduction Pancreatic adenocarcinoma (PAAD) is an aggressive malignancy, with a major mortality resulting from the rapid progression of metastasis. Unfortunately, no effective treatment strategy has been developed for PAAD metastasis to date. Thus, unraveling the mechanisms involved in PAAD metastatic phenotype may facilitate the treatment for PAAD patients. Objectives PIK3CB is an oncogene implicated in cancer development and progression but less is known about whether PIK3CB participates in PAAD metastasis. Therefore, the objective of this study is to explore the mechanism(s) of PIK3CB in PAAD metastasis. Methods In our study, we examined the PIK3CB expression pattern using bioinformatic analysis and clinical material derived from patients with PAAD. Subsequently, a series of biochemical experiments were conducted to investigate the role of PIK3CB as potential mechanism(s) underlying PAAD metastasis in vivo using nude mice and in vitro using cell lines. Results We observed that PIK3CB was involved in PAAD progression. Notably, we identified that PIK3CB was involved in PAAD metastasis. Downregulation of PIK3CB significantly reduced PAAD metastatic potential in vivo. Furthermore, a series of bioinformatic analyses showed that PIK3CB was involved in cell adhesion in PAAD. Notably, PIK3CB depletion inhibited invasion potential specifically via suppressing cell adhesion to collagen I in PAAD cells. Conclusion Collectively, our findings indicate that PIK3CB is involved in PAAD metastasis through cell-matrix adhesion. We proposed that PIK3CB is a potential therapeutic target for PAAD therapy.
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- 2021
126. Predicting Operation Time and Creating a Difficulty Scoring System in Donor Nephrectomy
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Keizo Kaku, Yu Hisadome, Yu Sato, Yasuhiro Okabe, Takanori Mei, Hiroshi Noguchi, and Masafumi Nakamura
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medicine.medical_specialty ,Scoring system ,Urology ,medicine.medical_treatment ,030232 urology & nephrology ,MEDLINE ,Kidney ,Nephrectomy ,03 medical and health sciences ,0302 clinical medicine ,Text mining ,Living Donors ,medicine ,Humans ,Operation time ,Laparoscopy ,Kidney transplantation ,Retrospective Studies ,medicine.diagnostic_test ,business.industry ,General surgery ,Middle Aged ,medicine.disease ,humanities ,030220 oncology & carcinogenesis ,Tissue and Organ Harvesting ,Female ,business - Abstract
Background: To determine predictive formulas for operation time and surgical difficulty in laparoscopic living-donor kidney transplantation. Methods: We retrospectively analyzed data for 222 living...
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- 2021
127. Minimally invasive pancreatic resection for patients with benign to low-grade malignancies
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Kohei Nakata and Masafumi Nakamura
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medicine.medical_specialty ,business.industry ,medicine ,Radiology ,business ,Pancreatic resection - Published
- 2021
128. ANALYSIS OF THE ASSOCIATION BETWEEN IMMUNE-RELATED ADVERSE EVENTS AND THE EFFICACY OF PEMBROLIZUMAB IN PATIENTS WITH METASTATIC UROTHELIAL CARCINOMA
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Akihito, Hashizume, Ryo, Yamashita, Hideo, Shinsaka, Masafumi, Nakamura, Masato, Matsuzaki, and Masashi, Niwakawa
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Urology - Abstract
(Objectives) We evaluated the association between immune-related adverse events (irAEs) and the efficacy of pembrolizumab therapy in patients with metastatic urothelial carcinoma. (Methods) Data of 42 patients with metastatic urothelial carcinoma treated with pembrolizumab between May 2018 and February 2020 were retrospectively analyzed to determine the association between irAEs and objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). (Results) IrAEs were observed in 19 patients (45.2%). Objective response was observed in 15 patients (35.7%). Thirteen (68.4%) of 19 patients who experienced irAEs showed an objective response, whereas two (8.70%) of 23 patients who did not experience irAEs (odds ratio: 15.0, 95% confidence interval [CI]: 1.70-738, P=0.006). PFS and OS in the irAE group were longer than those in the non-irAE group (PFS: hazard ratio: 0.24, 95% CI: 0.11-0.54, P0.001; OS: hazard ratio: 0.11, 95% CI: 0.03-0.37, P0.001). (Conclusions) During pembrolizumab treatment, the occurrence of irAEs was significantly associated with higher response and survival prolongation in patients with metastatic urothelial carcinoma.
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- 2021
129. Contribution of pre-existing neoantigen-specific T cells to a durable complete response after tumor-pulsed dendritic cell vaccine plus nivolumab therapy in a patient with metastatic salivary duct carcinoma
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Masayo Umebayashi, Muneyuki Masuda, Norihiro Koya, Yusuke Nakamura, Masafumi Nakamura, Poh Yin Yew, Hiroto Tanaka, Shu Ichimiya, Hideya Onishi, Shinichiro Nakagawa, Takashi Morisaki, Ryuji Yasumatsu, Akiko Fujimura, Sachiko Yoshimura, and Shogo Masuda
- Subjects
Combination therapy ,Immunology ,Cancer Vaccines ,Metastasis ,Salivary duct carcinoma ,Antigens, Neoplasm ,medicine ,Humans ,Salivary Ducts ,Cytotoxic T cell ,Retrospective Studies ,business.industry ,ELISPOT ,Carcinoma ,Dendritic Cells ,General Medicine ,Dendritic cell ,medicine.disease ,Vaccine therapy ,Carcinoma, Ductal ,Nivolumab ,Leukocytes, Mononuclear ,Cancer research ,Peptides ,business - Abstract
Although immune checkpoint inhibitors (ICIs) have emerged as new therapeutic options for refractory cancer, they are only effective in select patients. Tumor antigen-pulsed dendritic cell (DC) vaccine therapy activates tumor-specific cytotoxic T lymphocytes, making it an important immunotherapeutic strategy. Salivary ductal carcinoma (SDC) carries a poor prognosis, including poor long-term survival after metastasis or recurrence. In this study, we reported a case of refractory metastatic SDC that was treated with a tumor lysate-pulsed DC vaccine followed by a single injection of low-dose nivolumab, and a durable complete response was achieved. We retrospectively analyzed the immunological factors that contributed to these long-lasting clinical effects. First, we performed neoantigen analysis using resected metastatic tumor specimens obtained before treatment. We found that the tumor had 256 non-synonymous mutations and 669 class I high-affinity binding neoantigen peptides. Using synthetic neoantigen peptides and ELISpot analysis, we found that peripheral blood mononuclear leukocytes cryopreserved before treatment contained pre-existing neoantigen-specific T cells, and the cells obtained after treatment exhibited greater reactivity to neoantigens than those obtained before treatment. Our results collectively suggest that the rapid and long-lasting effect of this combination therapy in our patient may have resulted from the presence of pre-existing neoantigen-specific T cells and stimulation and expansion of those cells following tumor lysate-pulsed DC vaccine and ICI therapy.
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- 2021
130. A Case of Laparoscopy and Endoscopy Cooperative Surgery for Duodenal Neoplasm of a Gastric Phenotype
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Kohei Nakata, Shoko Noguchi, Koji Shindo, Shin Fujioka, Takehiro Torisu, Taiki Moriyama, Hidetaka Yamamoto, Takahito Matsuyoshi, Masafumi Nakamura, Shuntaro Nagai, Shinichiro Kawatoko, and Kenoki Ohuchida
- Subjects
medicine.medical_specialty ,Gastric phenotype ,medicine.diagnostic_test ,business.industry ,Gastroenterology ,Medicine ,Surgery ,business ,Laparoscopy ,Duodenal Neoplasm ,Endoscopy - Published
- 2021
131. Prognostic implications of the coexisting precursor lesion types in invasive gallbladder cancer
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Ryota Matsuda, Yuichi Yamada, Tetsuyuki Miyazaki, Yutaka Koga, Naoki Mochidome, Yoshihiro Ohishi, Shinichi Aishima, Masafumi Nakamura, and Yoshinao Oda
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Risk Assessment ,Gastroenterology ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Ribonucleoproteins, Small Nucleolar ,Risk Factors ,Internal medicine ,Biomarkers, Tumor ,medicine ,Carcinoma ,Humans ,CDX2 Transcription Factor ,Neoplasm Invasiveness ,Clinical significance ,Papillary pattern ,Gallbladder cancer ,Cyclin-Dependent Kinase Inhibitor p16 ,Aged ,business.industry ,Precursor lesion ,Gallbladder ,Mucins ,Middle Aged ,Prognosis ,medicine.disease ,Immunohistochemistry ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Biliary Intraepithelial Neoplasia ,Female ,Gallbladder Neoplasms ,Tumor Suppressor Protein p53 ,business ,Precancerous Conditions - Abstract
Invasive gallbladder carcinoma (GBC) is preceded by two main types of precursor lesions: intracholecystic papillary-tubular neoplasms (ICPNs) and biliary intraepithelial neoplasias (BilINs). Invasive GBCs with an ICPN component have more favorable prognoses than those without an ICPN component. Some BilINs show a relatively exophytic papillary pattern but do not meet the ICPN criteria; at our institution, we call these papillary neoplasias. To clarify the clinical significance of papillary neoplasia, we herein examined 80 invasive GBCs and classified them into three groups based on the type of preinvasive lesions: those with ICPN (ICPN group, n = 35), those with papillary neoplasia (pap-neoplasia group, n = 13), and those without ICPN/papillary neoplasia (group without ICPN/pap-neoplasia, n = 32). We then compared the prognostic differences and characterized the tumors of each group by determining the immunohistochemical expressions of various biomarkers. The overall survival periods of the ICPN and pap-neoplasia groups were significantly longer than that of the group without ICPN/pap-neoplasia (P 0.0001, P = 0.0036, respectively). Multivariate analysis revealed that lacking ICPN/papillary neoplasia was independently associated with poor prognosis (P = 0.0007), as were poor differentiation (P = 0.0395), presence of preoperative symptoms (P = 0.0488), and advanced stage (P = 0.0234). Invasive components of the ICPN and pap-neoplasia groups were characterized by higher expressions of p16 and p53 compared with those of the group without ICPN/pap-neoplasia. The prognoses of the invasive GBCs with either papillary neoplasia or ICPN were thus more favorable than those of the invasive GBCs without ICPN/pap-neoplasia. Invasive GBCs with exophytic papillary preinvasive lesions (ICPN and papillary neoplasia) may be biologically different from those without such lesions.
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- 2021
132. Bile peritonitis after placement of a metallic stent in endoscopic ultrasound-guided hepaticogastrostomy: A pitfall and the rescue technique
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Akihisa Ohno, Nao Fujimori, Toshiya Abe, Masafumi Nakamura, and Yoshihiro Ogawa
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Gastroenterology - Published
- 2022
133. ASO Visual Abstract: A Prospective, Multicenter, Phase II, Trial of Neoadjuvant Chemotherapy with Gemcitabine Plus Nab-Paclitaxel for Borderline Resectable Pancreatic Cancer with Arterial Involvement
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Naoki, Ikenaga, Yoshihiro, Miyasaka, Takao, Ohtsuka, Kohei, Nakata, Tomohiko, Adachi, Susumu, Eguchi, Kazuyoshi, Nishihara, Masafumi, Inomata, Hiroshi, Kurahara, Toru, Hisaka, Hideo, Baba, Hiroaki, Nagano, Toshiharu, Ueki, Hirokazu, Noshiro, Shoji, Tokunaga, Kousei, Ishigami, and Masafumi, Nakamura
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- 2022
134. Preoperative Prediction of Malignancy and Surgical Treatment Strategy for Appendiceal Tumors: Multicenter Review of 51 Consecutive Cases
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Koji Tamura, Takashi Ueki, Hiromichi Nakayama, Yusuke Watanabe, Masafumi Sada, Kinuko Nagayoshi, Yusuke Mizuuchi, Kenoki Ohuchida, Hitoshi Ichimiya, and Masafumi Nakamura
- Abstract
Purpose: A diagnostic and treatment strategy for appendiceal tumors (ATs) has not been established. We aimed to evaluate our treatment strategy for ATs including laparoscopic surgery (LS) and to identify preoperative malignancy predictors. Methods: A total of 51 patients were retrospectively reviewed. Data including tumor markers and imaging findings were compared between carcinoma and non-carcinoma patients. Validity of planned operation was evaluated based on pathological diagnosis. Results: Twenty-five patients were diagnosed with carcinoma, 13 with low-grade mucinous neoplasm, and 13 with other diseases. Symptoms were more commonly present in carcinoma patients than in non-carcinoma patients (68.0% vs. 23.1%, p=0.001). Elevated CEA and CA19-9 were more frequently observed in carcinoma patients than in non-carcinoma patients (pp=0.04, respectively). Five carcinoma patients had malignancy on biopsy, compared with zero non-carcinoma patients. Significant differences were noted in the percentages of carcinoma and non-carcinoma patients with solid enhanced mass (41.7% vs. 0%, pp=0.03) on imaging. Although the sensitivity was not high, the specificity and positive predictive value of these findings were 100%. Forty-two patients (82.4%) underwent LS as minimally invasive exploratory tool and/or radical operation, of whom 2 were converted to open surgery for invasion of adjacent organ. None of the patients had intraoperative complications or postoperative mortality. Conclusion: Clinical symptoms, elevated tumor markers, and worrisome features of solid enhanced mass and tumor wall irregularity on imaging can be malignancy predictors. For management of AT patients, LS is feasible and useful for diagnosis and treatment.
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- 2022
135. ASO Author Reflections: Novel Evidence on Neoadjuvant Chemotherapy for Borderline Resectable Pancreatic Cancer with Arterial Involvement
- Author
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Naoki Ikenaga, Yoshihiro Miyasaka, Takao Ohtsuka, and Masafumi Nakamura
- Subjects
Pancreatic Neoplasms ,Oncology ,Humans ,Surgery ,Arteries ,Neoadjuvant Therapy - Published
- 2022
136. Framework for Training in Minimally Invasive Pancreatic Surgery: An International Delphi Consensus Study
- Author
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Maarten, Korrel, Sanne, Lof, Adnan A, Alseidi, Horacio J, Asbun, Ugo, Boggi, Melissa E, Hogg, Jin-Young, Jang, Masafumi, Nakamura, Marc G, Besselink, Mohammad, Abu Hilal, and Amer, Zureikat
- Subjects
Surgeons ,Consensus ,Delphi Technique ,Humans ,Minimally Invasive Surgical Procedures ,Surgery ,Clinical Competence - Abstract
BACKGROUND: Previous reports suggest that structured training in minimally invasive pancreatic surgery (MIPS) can ensure a safe implementation into standard practice. Although some training programs have been constructed, worldwide consensus on fundamental items of these training programs is lacking. This study aimed to determine items for a structured MIPS training program using the Delphi consensus methodology. STUDY DESIGN: The study process consisted of 2 Delphi rounds among international experts in MIPS, identified by a literature review. The study committee developed a list of items for 3 key domains of MIPS training: (1) framework, (2) centers and surgeons eligible for training, and (3) surgeons eligible as proctor. The experts rated these items on a scale from 1 (not important) to 5 (very important). A Cronbach's α of 0.70 or greater was defined as the cut-off value to achieve consensus. Each item that achieved 80% or greater of expert votes was considered as fundamental for a training program in MIPS. RESULTS: Both Delphi study rounds were completed by all invited experts in MIPS, with a median experience of 20 years in MIPS. Experts included surgeons from 31 cities in 13 countries across 4 continents. Consensus was reached on 38 fundamental items for the framework of training (16 of 35 items, Cronbach's α = 0.72), centers and surgeons eligible for training (19 of 30 items, Cronbach's α = 0.87), and surgeons eligible as proctor (3 of 10 items, Cronbach's α = 0.89). Center eligibility for MIPS included a minimum annual volume of 10 distal pancreatectomies and 50 pancreatoduodenectomies. CONCLUSION: Consensus among worldwide experts in MIPS was reached on fundamental items for the framework of training and criteria for participating surgeons and centers. These items act as a guideline and intend to improve training, proctoring, and safe worldwide dissemination of MIPS.
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- 2022
137. Clinical impact of remnant lymphatic invasion on the recurrence of esophageal squamous cell carcinoma after esophagectomy with neoadjuvant chemotherapy
- Author
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Sho Okuda, Kenoki Ohuchida, Koji Shindo, Taiki Moriyama, Jun Kawata, Koji Tamura, Masafumi Sada, Kinuko Nagayoshi, Yusuke Mizuuchi, Naoki Ikenaga, Kohei Nakata, Yoshinao Oda, and Masafumi Nakamura
- Subjects
Cancer Research ,Oncology - Abstract
For stage II and III esophageal squamous cell carcinoma (ESCC), neoadjuvant chemotherapy (NAC) followed by esophagectomy is recommended in the Japanese guidelines for the diagnosis and treatment of esophageal cancer. However, recurrence of ESCC is common regardless of the NAC regimen and surgical method, and NAC demonstrates limited efficacy against recurrence. Therefore, the present study was conducted to identify risk factors of recurrence of ESCC with surgery after NAC. The outcomes of 51 patients who underwent esophagectomy for ESCC after NAC from 2010 to 2017 at Kyushu University Hospital were retrospectively analyzed. A total of 52 patients with ESCC without NAC followed by esophagectomy from 2001 to 2017 were selected for comparison. Among patients who underwent NAC followed by surgery, only lymphatic invasion (LY; hazard ratio, 2.761; 95% CI, 1.86-6.43, P=0.018) was an independent factor significantly associated with 3-year recurrence-free survival in the multivariate analysis. In patients with pathologic lymph node metastasis (pN) and no LY after NAC, there was significantly less recurrence compared with patients with pN and LY (P=0.0085), whereas in patients without LY after NAC, the presence of pN was not significantly associated with recurrence (P=0.2401). There were significantly fewer LY (+) patients in the NAC (+) group (P=0.0158) compared with those in the NAC (-) group. The presence of LY was an independent risk factor for recurrence of ESCC after esophagectomy following NAC. Overall, adjuvant treatment after surgery may be required in cases with remnant LY after NAC.
- Published
- 2022
138. Extracellular volume fraction determined by dual-layer spectral detector CT: Possible role in predicting the efficacy of preoperative neoadjuvant chemotherapy in pancreatic ductal adenocarcinoma
- Author
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Nobuhiro Fujita, Yasuhiro Ushijima, Masahiro Itoyama, Daisuke Okamoto, Keisuke Ishimatsu, Noriaki Wada, Seiichiro Takao, Ryo Murayama, Nao Fujimori, Kohei Nakata, Masafumi Nakamura, Takeo Yamamoto, Yoshinao Oda, and Kousei Ishigami
- Subjects
Radiology, Nuclear Medicine and imaging ,General Medicine - Published
- 2023
139. Impact of Recipient Age on Outcomes After Pancreas Transplantation
- Author
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Masafumi Nakamura, Yasuhiro Okabe, Hiroshi Noguchi, Takanori Mei, Yu Sato, Keizo Kaku, and Yu Hisadome
- Subjects
Adult ,medicine.medical_specialty ,medicine.medical_treatment ,Pancreas graft ,Pancreas transplantation ,Risk Factors ,medicine ,Humans ,Risk factor ,Survival rate ,Proportional Hazards Models ,Retrospective Studies ,Transplantation ,Receiver operating characteristic ,business.industry ,Graft Survival ,Transplant Recipients ,Confidence interval ,Surgery ,Survival Rate ,Treatment Outcome ,medicine.anatomical_structure ,Pancreas Transplantation ,Pancreas ,business - Abstract
Few reports have provided the ages of pancreas transplant recipients. The aim of this study was to determine whether recipient age affects survival of pancreatic grafts after transplantation.We analyzed 73 patients who had undergone pancreas transplantation at our institution from August 2001 to March 2020 and assessed the effects of recipient age on pancreas graft survival within 5 years after pancreas transplantation.The cutoff value for recipient age established by receiver operating characteristic curve was 35 years. The pancreas graft survival rate of recipients aged 35 years or younger (1, 3, and 5 years: 72.9%, 41.7%, and 41.7%, respectively) was significantly lower than that of recipients aged over 35 years (1, 3, and 5 years: 93.2%, 88.4%, and 88.4%, respectively). Multivariate Cox hazard regression analysis showed that recipient age 35 years or younger (hazard ratio = 3.60; 95% confidence interval, 1.04-12.50; P = .044) and solitary pancreas transplantation (hazard ratio = 10.72; 95% confidence interval, 2.72-42.28; P.001) were significant risk factors for pancreas graft loss within 5 years.Our data suggest that younger recipient age is a risk factor for pancreas graft loss after transplantation.
- Published
- 2021
140. Two Cases of Mediastinal Cavernous Hemangioma in Which the Preoperative Diagnosis Was Difficult
- Author
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Satoko Koga, Seitaro Fujimoto, Yasutaka Hachiya, Seiichi Odate, Kazuki Tamura, Masafumi Nakamura, Yoshinao Oda, and Kei Miyoshi
- Subjects
Pulmonary and Respiratory Medicine ,Oncology - Published
- 2021
141. What are the Appropriate Surgery and Postoperative Surveillance for Intraductal Papillary Mucinous Neoplasm?
- Author
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Masafumi Nakamura, Kohei Nakata, and Noboru Ideno
- Subjects
medicine.medical_specialty ,Intraductal papillary mucinous neoplasm ,business.industry ,medicine ,medicine.disease ,business ,Surgery - Published
- 2021
142. Neoantigens elicit T cell responses in breast cancer
- Author
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Jae-Hyun Park, Sachiko Yoshimura, Mai Yamada, Masafumi Nakamura, Masayo Umebayashi, Poh Yin Yew, Takafumi Morisaki, Makoto Kubo, Yoshinao Oda, Takashi Morisaki, Yusuke Nakamura, Kazuma Kiyotani, and Masaya Kai
- Subjects
Adult ,T cell ,Science ,Immunology ,Breast Neoplasms ,Human leukocyte antigen ,Biology ,Article ,Immune system ,Breast cancer ,Lymphocytes, Tumor-Infiltrating ,Antigen ,Antigens, Neoplasm ,Exome Sequencing ,medicine ,Cytotoxic T cell ,Humans ,Cancer ,Aged ,Immunity, Cellular ,Multidisciplinary ,integumentary system ,ELISPOT ,Dendritic Cells ,Middle Aged ,medicine.disease ,Computational biology and bioinformatics ,medicine.anatomical_structure ,Oncology ,Cancer research ,Medicine ,Female ,Ex vivo ,T-Lymphocytes, Cytotoxic - Abstract
Neoantigens are tumor-specific antigens that arise from non-synonymous mutations in tumor cells. However, their effect on the immune responses in tumor microenvironment are still unclear in breast cancer.We performed whole exome and RNA sequencing of 31 fresh breast cancer tissues and neoantigen prediction on the non-synonymous single nucleotide variants (nsSNVs) among exonic mutations. Neoantigen profiles were determined by predictive HLA binding affinity (IC50ex vivo. These results suggest that neoantigen analysis may show utility in developing strategies to elicit T cell responses.
- Published
- 2021
143. Management of postoperative pancreatic fistula after pancreatoduodenectomy: Analysis of 600 cases of pancreatoduodenectomy patients over a 10-year period at a single institution
- Author
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Yusuke Watanabe, Yasuhisa Mori, Naoki Ikenaga, Takao Ohtsuka, Yoshihiro Miyasaka, Noboru Ideno, Masafumi Nakamura, and Kohei Nakata
- Subjects
Adult ,Male ,Reoperation ,medicine.medical_specialty ,Percutaneous ,Postoperative Hemorrhage ,030230 surgery ,Pancreaticoduodenectomy ,Pancreatic Fistula ,Young Adult ,03 medical and health sciences ,Pseudoaneurysm ,0302 clinical medicine ,medicine ,Humans ,Local anesthesia ,Hospital Mortality ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Mortality rate ,Retrospective cohort study ,Surgical wound ,Middle Aged ,medicine.disease ,Surgery ,Pancreatic fistula ,030220 oncology & carcinogenesis ,Drainage ,Female ,business ,Complication - Abstract
Background Although postoperative pancreatic fistula (POPF) is a common and critical complication of pancreatoduodenectomy (PD), effective strategies to prevent POPF have not yet been completely developed. Because appropriate management of POPF is important to reduce the mortality rate after PD, in this study we aimed to evaluate our approach for the management of POPF after PD, including the postoperative course. Methods This retrospective study included 605 consecutive patients who underwent PD at our hospital between 2010 and 2020. All patients who developed POPF were first managed conservatively, with drainage tubes placed during surgery retained to manage POPF. In cases wherein conservative treatment was unsuccessful, open drainage, followed by continuous negative pressure and continuous irrigation, was used. For open drainage, the surgical wound was opened bluntly (approximate length, 5 cm) under local anesthesia, and the fluid was directly and completely drained. Results The prevalence of POPF of grades B and C was 15.4% (n = 93) and 0.33% (n = 2), respectively. Of these patients, 1 required reoperation, 43 recovered with conservative management only, 47 required open drainage, and 4 required image-guided percutaneous drainage. Postoperative hemorrhage with a pseudoaneurysm was identified in 3 (0.66%) patients. The postoperative in-hospital mortality rate was low (n = 1, 0.16%). The rate of successful POPF management was 98.9%. Conclusion Based on our high success rate in POPF management, we consider open drainage to be a safe primary management method for POPF.
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- 2021
144. Passive Air Sampling of PCDD/Fs, PCBs, PAEs, DEHA, and PAHs from Informal Electronic Waste Recycling and Allied Sectors in Indian Megacities
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Masafumi Nakamura, Scott N, Harish Gadhavi, Moitraiyee Mukhopadhyay, Paromita Chakraborty, Sanjenbam Nirmala Khuman, and Balasubramanian Prithiviraj
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Pollutant ,Air Pollutants ,Air sampling ,Polychlorinated Dibenzodioxins ,Adipates ,India ,General Chemistry ,Dibenzofurans, Polychlorinated ,010501 environmental sciences ,Polychlorinated Biphenyls ,01 natural sciences ,Electronic waste recycling ,Article ,Electronic Waste ,Megacity ,Environmental chemistry ,Environmental Chemistry ,Environmental science ,New delhi ,Cities ,Dibenzofurans ,Transect ,Environmental Monitoring ,0105 earth and related environmental sciences - Abstract
Xenobiotic chemical emissions from the informal electronic waste recycling (EW) sector are emerging problem for developing countries, with scale and impacts that are yet to be evaluated. We report an intensive polyurethane foam disk passive air sampling study in four megacities in India to investigate atmospheric organic pollutants along five transects viz., EW, information technology (IT), industrial, residential, and dumpsites. Intraurban emission sources were estimated and attributed by trajectory modeling and positive matrix factorization (PMF). ∑(17)PCDD/Fs, ∑(25)PCBs, ∑(7)plasticizers, and ∑(15)PAHs concentrations ranged from 3.1 to 26 pg/m(3) (14 ± 7; Avg ± SD), 0.5–52 ng/m(3) (9 ± 12); 7.5–520 ng/m(3), (63 ± 107) and 6–33 ng/m(3) (17 ± 6), respectively. EW contributed 45% of total PCB concentrations in this study and was evidenced as a major factor by PMF. The dominance of dioxin-like PCBs (dl-PCBs), particularly PCB-126, reflects combustion as the possible primary emission source. PCDD/Fs, PCBs and plasticizers were consistently highest at EW transect, while PAHs were maximum in industrial transect followed by EW. Concentrations of marker plasticizers (DnBP and DEHP) released during EW activities were significantly higher (p < 0.05) in Bangalore than in other cities. Toxic equivalents (TEQs) due to dl-PCBs was maximum in the EW transect and PCB-126 was the major contributor. For both youth and adult, the highest estimated inhalation risks for dl-PCBs and plasticizers were seen at the EW transect in Bangalore, followed by Chennai and New Delhi.
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- 2021
145. Learning curves in laparoscopic distal pancreatectomy: a different experience for each generation.
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van Ramshorst, Tess M. E., Edwin, Bjørn, Ho-Seong Han, Masafumi Nakamura, Yoo-Seok Yoon, Takao Ohtsuka, Tholfsen, Tore, Besselink, Marc G., and Hilal, Mohammad Abu
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Background: Learning curves of laparoscopic distal pancreatectomy (LDP) are mostly based on 'self-taught' surgeons who acquired sufficient proficiency largely through self-teaching. No learning curves have been investigated for 'trained' surgeons who received training and built on the experience of the 'self-taught' surgeons. This study compared the learning curves and outcome of LDP between 'self-taught' and 'trained' surgeons in terms of feasibility and proficiency using short-term outcomes. Materials and methods: Data of consecutive patients with benign or malignant disease of the left pancreas who underwent LDP by four 'self-taught' and four 'trained' surgeons between 1997 and 2019 were collected, starting from the first patient operated by a contributing surgeon. Risk-adjusted cumulative sum (RA-CUSUM) analyses were performed to determine phase-1 feasibility (operative time) and phase-2 proficiency (major complications) learning curves. Outcomes were compared based on the inflection points of the learning curves. Results: The inflection points for the feasibility and proficiency learning curves were 24 and 36 procedures for 'trained' surgeons compared to 64 and 85 procedures for 'self-taught' surgeons, respectively. In 'trained' surgeons, operative time was reduced after completion of the learning curves (230.5-203 min, P= 0.028). In 'self-taught' surgeons, operative time (240-195 min, P ≤0.001), major complications (20.6-7.8%, P= 0.008), and length of hospital stay (9-5 days, P ≤0.001) reduced after completion of the learning curves. Conclusion: This retrospective international cohort study showed that the feasibility and proficiency learning curves for LDP of 'trained' surgeons were at least halved as compared to 'self-taught' surgeons. [ABSTRACT FROM AUTHOR]
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- 2023
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146. Utilization of the Pancreas From Donors With an Extremely High Pancreas Donor Risk Index: Report of the National Registry of Pancreas Transplantation.
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Keizo Kaku, Yasuhiro Okabe, Shinsuke Kubo, Yu Sato, Takanori Mei, Hiroshi Noguchi, Yoshito Tomimaru, Toshinori Ito, Takashi Kenmochi, and Masafumi Nakamura
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PANCREAS transplantation ,PANCREAS ,GRAFT survival ,PROGNOSIS - Abstract
Pancreas transplants from expanded criteria donors are performed widely in Japan because there is a shortage of brain-dead donors. However, the effectiveness of this strategy is unknown. We retrospectively studied 371 pancreas transplants to evaluate the possibility of pancreas transplantation from expanded criteria donors by the Pancreas Donor Risk Index (PDRI). Patients were divided into five groups according to quintiles of PDRI values (Q1-Q5). The 1-year pancreas graft survival rates were 94.5% for Q1, 91.9% for Q2, 90.5%for Q3, 89.3% for Q4, and 79.6% for Q5, and were significantly lower with a lower PDRI (p = 0.04). A multivariate analysis showed that the PDRI, donor hemoglobin A1c values, and pancreas transplantation alone significantly predicted 1-year pancreas graft survival (all p < 0.05). Spline curve analysis showed that the PDRI was incrementally associated with an increased risk of 1-year graft failure. In the group with a PDRI ≥ 2.87, 8/56 patients had graft failures within 1 month, and all were due to graft thrombosis. The PDRI is a prognostic factor related to the 1-year graft survival rate. However, pancreas transplantation from high-PDRI donors shows acceptable results and could be an alternative when the donor pool is insufficient. [ABSTRACT FROM AUTHOR]
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- 2023
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147. Solid Pseudopapillary Neoplasm of the Pancreas in Young Male Patients: Three Case Reports
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Akira Aso, Eikichi Ihara, Kazuhiko Nakamura, Irina Sudovykh, Tetsuhide Ito, Masafumi Nakamura, Tetsuo Ikeda, Nobuyoshi Takizawa, Yoshinao Oda, and Shuji Shimizu
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
A preoperative diagnosis of solid pseudopapillary neoplasms (SPNs) in young male patients is difficult to achieve using radiological images. We herein present three cases of young male patients with relatively small SPNs. Endoscopic ultrasound (EUS) showed well-encapsulated, smooth-surfaced, heterogeneous solid lesions in all patients, and all preoperative diagnoses were achieved by EUS-guided fine needle aspiration (EUS-FNA). The final pathological diagnosis after surgery was an SPN with a Ki-67 labeling index of
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- 2017
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148. GPR125 (ADGRA3) is an autocleavable adhesion GPCR that traffics with Dlg1 to the basolateral membrane and regulates epithelial apicobasal polarity
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Tsubasa Sakurai, Sachiko Kamakura, Junya Hayase, Akira Kohda, Masafumi Nakamura, and Hideki Sumimoto
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Mammals ,Cell Membrane ,Amino Acid Motifs ,Cell Polarity ,Cell Biology ,Biochemistry ,Receptors, G-Protein-Coupled ,Cell Line ,Discs Large Homolog 1 Protein ,Dogs ,HEK293 Cells ,Gene Knockdown Techniques ,Cell Adhesion ,Animals ,Humans ,Molecular Biology ,Zebrafish ,Protein Binding - Abstract
The adhesion family of G protein-coupled receptors (GPCRs) is defined by an N-terminal large extracellular region that contains various adhesion-related domains and a highly-conserved GPCR-autoproteolysis-inducing (GAIN) domain, the latter of which is located immediately before a canonical seven-transmembrane domain. These receptors are expressed widely and involved in various functions including development, angiogenesis, synapse formation, and tumorigenesis. GPR125 (ADGRA3), an orphan adhesion GPCR, has been shown to modulate planar cell polarity in gastrulating zebrafish, but its biochemical properties and role in mammalian cells have remained largely unknown. Here, we show that human GPR125 likely undergoes cis-autoproteolysis when expressed in canine kidney epithelial MDCK cells and human embryonic kidney HEK293 cells. The cleavage appears to occur at an atypical GPCR proteolysis site within the GAIN domain during an early stage of receptor biosynthesis. The products, i.e., the N-terminal and C-terminal fragments, seem to remain associated after self-proteolysis, as observed in other adhesion GPCRs. Furthermore, in polarized MDCK cells, GPR125 is exclusively recruited to the basolateral domain of the plasma membrane. The recruitment likely requires the C-terminal PDZ-domain-binding motif of GPR125 and its interaction with the cell polarity protein Dlg1. Knockdown of GPR125 as well as that of Dlg1 results in formation of aberrant cysts with multiple lumens in Matrigel 3D culture of MDCK cells. Consistent with the multilumen phenotype, mitotic spindles are incorrectly oriented during cystogenesis in GPR125-KO MDCK cells. Thus, the basolateral protein GPR125, an autocleavable adhesion GPCR, appears to play a crucial role in apicobasal polarization in epithelial cells.
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- 2022
149. [Primary cutaneous anaplastic large cell lymphoma with systemic progression responding to low-dose methotrexate therapy]
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Ryohei, Sumitani, Takeshi, Harada, Masafumi, Nakamura, Makiko, Mizuguchi, Masahiro, Oura, Kimiko, Sogabe, Tomoko, Maruhashi, Mamiko, Takahashi, Shiro, Fujii, Shingen, Nakamura, Hirokazu, Miki, Kumiko, Kagawa, Mio, Yada, Yoshihiro, Matsudate, Hisanori, Uehara, and Masahiro, Abe
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Male ,Lymphoma, Primary Cutaneous Anaplastic Large Cell ,Methotrexate ,Skin Neoplasms ,Lymphomatoid Papulosis ,Humans ,Lymphoma, Large-Cell, Anaplastic ,Immunotherapy ,Aged - Abstract
The standard therapies for primary cutaneous anaplastic large cell lymphoma (pcALCL) in an advanced stage remain undefined. A 71-year-old man presented with multiple erythema and nodules. He was diagnosed with lymphomatoid papulosis (LyP) through a skin biopsy from the left postauricular area. All skin lesions achieved complete response by electron beam irradiation. However, nodular lesions appeared in both inner canthi 5 months later. Histopathological evaluation of the lesional biopsy revealed dominant infiltration of CD30-positive large cells. Positron emission tomography/computed tomography revealed fluorodeoxyglucose-positive cervical and inguinal lymph node swelling and right tonsillitis, followed by the diagnosis of pcALCL and TNM classification T3bN3M0. Since the patient had severe chronic obstructive pulmonary disease and recurrent pneumonia, he received low-dose methotrexate (MTX) (15 mg/week) therapy. Low-dose MTX effectively debulked the lymphadenopathies over time without particular adverse effects. Although the standard therapies for pcALCL are not established, low-dose MTX was effective and considered safe for patients with frailty and compromised respiratory function. Further study is warranted on the pathophysiology of pcALCL after the development of LyP and mechanisms of action of low-dose MTX against LyP and pcALCL.
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- 2022
150. Reliability, validity, and responsiveness of the Japanese version of the EORTC QLQ-ELD14 in evaluating the health-related quality of life of elderly patients with cancer
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Yumiko Kinoshita, Rieko Izukura, Junji Kishimoto, Maki Kanaoka, Hayato Fujita, Koji Ando, Shuntaro Nagai, Sayuri Akiyoshi, Tetsuzo Tagawa, Makoto Kubo, Junichi Inokuchi, Kenoki Ohuchida, Eiji Oki, Kentaro Tanaka, Masatoshi Eto, Tomoharu Yoshizumi, Masafumi Nakamura, and Akiko Chishaki
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Cancer Research ,Oncology ,General Medicine - Abstract
This study evaluated the reliability, validity, and responsiveness of the Japanese version of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-ELD14 and measured the health-related quality of life (HRQOL) of elderly Japanese patients with cancer aged ≥ 60 and ≥ 70 years.The study recruited elderly Japanese patients with cancer aged ≥ 60 (≥ 70) years (n = 1803 [n = 1236]). The EORTC QLQ-ELD14 was evaluated for reliability, validity, responsiveness, and correlations of changes in score between the EORTC QLQ-ELD14 and the EORTC QLQ-C30 before and after the commencement of the COVID-19 pandemic.In both age groups, the proportion of missing items was low ( 3%). Cronbach's α was good at ≥ 0.70, except for two of the seven items. All the intraclass coefficient constants were good at ≥ 0.70. The concurrent validity was good but correlation with the EORTC QLQ-C30 was not strong, except for the hypothesis items. Regarding the assessment of responsiveness, only one item ("maintaining purpose") of the EORTC QLQ-ELD14 worsened (- 6.14 ± 29.20, standard response of mean 0.2) after the commencement of the COVID-19 pandemic. The changes in score between the EORTC QLQ-ELD14 and the "global health status/QOL" and "summary score" of the EORTC QLQ-C30 had moderate-to-high negative correlations for all items, except two. Hypotheses to evaluate construct validity were accepted at 90%, while responsiveness was accepted at 80%.The Japanese version of the EORTC QLQ-ELD14 questionnaire appears to have acceptable reliability, validity, and responsiveness to evaluate HRQOL in elderly Japanese people with cancer.
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- 2022
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