197 results on '"T. Ioka"'
Search Results
2. Lower-extremity venous stasis during laparoscopic cholecystectomy as assessed using color Doppler ultrasound
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K. Kimura, T. Suzuki, Yoshimi Hirayama, Y. Taniguchi, N. Isoda, N. Nagamine, C. Kawamoto, T. Ioka, M. Kumagai, and Kenichi Ido
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Male ,Insufflation ,medicine.medical_specialty ,Supine position ,medicine.medical_treatment ,Posture ,Femoral vein ,Hemodynamics ,Venous stasis ,Monitoring, Intraoperative ,Humans ,Medicine ,Ultrasonography, Doppler, Color ,Intraoperative Complications ,Laparoscopy ,medicine.diagnostic_test ,business.industry ,Femoral Vein ,Middle Aged ,medicine.disease ,Surgery ,Cholecystectomy, Laparoscopic ,Venous Insufficiency ,Female ,Cholecystectomy ,business ,Blood Flow Velocity ,Abdominal surgery - Abstract
Lower-extremity venous stasis during laparoscopic cholecystectomy was evaluated in 16 patients by monitoring the blood velocity in the femoral vein and the femoral vein size (cross-sectional area) using color Doppler ultrasonography. The blood velocity in the femoral vein decreased significantly after the start of 10-mmHg abdominal insufflation in the supine position. When the patients were placed in a reverse Trendelenburg position during 10-mmHg insufflation, blood velocity in the femoral vein further decreased. However, velocity returned to the baseline after deflation. The cross-sectional area of the femoral vein was significantly elevated after the start of 10 mm Hg insufflation in the supine position. When patients were placed in the reverse Trendelenburg position during 10-mmHg insufflation, this parameter was further elevated, but returned to the baseline soon after deflation. These results indicate that femoral vein stasis during laparoscopic cholecystectomy can be minimized by reducing the pressure of abdominal insufflation and avoiding elevation of the patient's head as much as possible.
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- 1995
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3. PP015—Chronotherapy with docetaxel, cisplatin, and 5-fluorouracil (5-FU) in patients with oral squamous cell carcinoma
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T. Ioka, K. Ushijima, Y. Ioka, Akio Fujimura, Mikio Kusama, Y.J Imbu, and Tadahide Noguchi
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Cisplatin ,Oncology ,Pharmacology ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,02 engineering and technology ,030204 cardiovascular system & hematology ,Chronotherapy (treatment scheduling) ,03 medical and health sciences ,020210 optoelectronics & photonics ,0302 clinical medicine ,Docetaxel ,Fluorouracil ,Internal medicine ,0202 electrical engineering, electronic engineering, information engineering ,medicine ,In patient ,Basal cell ,Pharmacology (medical) ,business ,medicine.drug - Published
- 2013
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4. Confirmation of a 'safety zone' by intraoperative cholangiography during laparoscopic cholecystectomy
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K. Ido, N. Isoda, C. Kawamoto, T. Suzuki, T. Ioka, N. Nagamine, Y. Taniguchi, M. Kumagai, and K. Kimura
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Surgery - Published
- 1996
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5. Hepatobiliary Pancreatic Cancer: Cutting-Edge Drug Therapy
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T. Ioka
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Oncology ,medicine.medical_specialty ,endocrine system diseases ,Combination therapy ,business.industry ,FOLFIRINOX ,medicine.medical_treatment ,Hematology ,medicine.disease ,Gemcitabine ,Radiation therapy ,Regimen ,Internal medicine ,Pancreatic cancer ,Medicine ,Erlotinib ,business ,Chemoradiotherapy ,medicine.drug - Abstract
Chemotherapy appears to prolong survival in patients with advanced pancreatic cancer (PC) or biliary tract cancer (BTC) and can take clinical benefits and improve quality of life since the clinical use of gemcitabine (Gem) in 1999 in Japan [1]. Many investigators have struggled to prove the superiority of Gem-contained combination therapy to Gem monotherapy for PC patients. Unfortunately, they all failed to prove the better survival benefit except Gem plus Erlotinib (GE) [2]. GE therapy demonstrate to be superior both in metastatic and locally advanced PC (HR 0.81). Many patients with GE therapy suffer from skin rush, and sometimes are afraid of a risk of Interstitial lung diseases (ILD). French investigators created a new standard chemotherapy which does not contain Gem: FOLFIRINOX. FORFIRINOX regimen can deliver a much better survival benefit rather than Gem monotherapy in metastatic PC, although it increased both hematological and non-hematological adverse effects (AE). Gem plus S1 (GS) showed both good survival benefits and anti-tumor effect in previous phase II studies [3,4]. We carried phase III study called GEST trial in Japan and Taiwan, which aimed to make sure the superiority of GS to Gem and non-inferiority of S1 to Gem. However, we can prove only non-inferiority of S1 to Gem in OS both in metastatic and locally advanced PC [5]. It is not clear whether radiotherapy should be useful or beneficial for locally advanced PC. Moreover, we do not have a good answer which drug we should administer when we plan the chemoradiotherapy for PC. Currently, there are some randomized phase II studies of chemoradiotherapy for PC in Japan, one is a study of chemoradiotherapy using GS combination compared with GS therapy, and the other is a study of Gem monotherapy followed by S1-chemoradiothrapy compared with S1-chemoradiotherapy. We need a well-designed phase II or phase III trial to prove a benefit of radiotherapy in PC near the future. But it is difficult to standardize a procedure of radiotherapy in many institutions even only in Japan. Gem plus cisplatin (CisGem) showed a better OS compared with Gem6) in BTC [6]. Kanai et al. study a phase I study of CisGem plus S1 in BTC (KHBO1002) [7]. We need to develop much more chemotherapy or chemoradiotherapy in PC or BTC, because we do not have enough agents to administer and there are many clinical questions still.
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- 2012
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6. Chlamydia pneumoniae infection and accelerated development of coronary artery disease in patients with chronic renal failure
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H, Song, H, Tasaki, A, Yashiro, M, Okazaki, T, Ioka, H, Taniguchi, and Y, Nakashima
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Blood Glucose ,Male ,Cholesterol, HDL ,Coronary Artery Disease ,Chlamydophila pneumoniae ,Middle Aged ,Coronary Angiography ,Antibodies, Bacterial ,Severity of Illness Index ,Antibodies, Anti-Idiotypic ,Immunoglobulin A ,Risk Factors ,Immunoglobulin G ,Prevalence ,Humans ,Kidney Failure, Chronic ,Female ,Chlamydophila Infections ,Serum Albumin ,Triglycerides ,Aged ,Lipoprotein(a) - Abstract
This study examined the relationship between Chlamydia pneumoniae (C. pneumoniae) infection and the accelerated development of coronary artery disease (CAD) in patients with chronic renal failure (CRF).Two-hundred and fourteen patients undergoing coronary angiography, including 67 controls and 147 patients with CAD (97 without CRF and 50 with CRF), were enrolled in this study. Anti-C. pneumoniae specific IgG and IgA antibodies were measured using an enzyme-linked immunosorbent assay (ELISA).Coronary artery disease (expressed as CAD score) was more severe in patients with than without CRF (14.9 +/- 6.0 vs. 11.3 +/- 6.0, p0.01). Seropositive rates of IgG and IgA antibodies against C. pneumoniae were higher in all CAD patients than in the controls (76.2% vs. 44.8%, p0.001 for IgG; 59.9% vs. 40.3%, p0.01 for IgA). In both CAD subgroups, IgG seropositive rates were similarly elevated (82.0% and 73.2% vs. 44.8% for control, p0.001, respectively), whereas those of IgA were significantly elevated only in CAD with CRF (68.0% vs. 55.7% for control, p0.01). The mean antibody index of IgG was elevated in all CAD patients compared with the controls (1.9 +/- 1.0 vs. 1.3 +/- 0.9, p0.0001), but that of IgA was not (1.5 +/- 1.0 vs. 1.2 +/- 0.9). Levels of IgG were elevated in all patients with CAD compared with the control (2.4 +/- 1.1 and 1.8 +/- 1.0 vs. 1.3 +/- 0.9, p0.001 and p0.001, respectively), whereas those of IgA were elevated only in CAD with CRF (1.8 +/- 1.1 vs. 1.2 +/- 0.9, p0.05). Stepwise logistic regression analysis revealed that the elevated IgG antibody index was an independent risk factor for CAD regardless of CRF (odds ratios 1.9, 1.8, and 2.3), whereas the IgA index was a risk factor only in CAD with CRF (odds ratio 1.7).Chlamydia pneumoniae infection may be related to the accelerated CAD in patients with CRF, which was specifically suggested by an elevated IgA level. In other words, the prevalence of active C. pneumoniae infection is higher in patients with CAD and CRF than that in those with CAD without CRF.
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- 2002
7. [Colorectal cancer prevention through lifestyle modification]
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H, Ishikawa, T, Suzuki, T, Ioka, and T, Otani
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Cohort Studies ,Clinical Trials as Topic ,Humans ,Colorectal Neoplasms ,Exercise ,Life Style ,Exercise Therapy - Published
- 2000
8. Reply
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S TSURUOKA, T IOKA, M WAKAUMI, A FUJIMURA, K SAKAMOTO, and H OOKAMI
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Pharmacology ,Pharmacology (medical) - Published
- 2006
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9. Laparoscopic transcystic cholangioscopic lithotripsy for common bile duct stones during laparoscopic cholecystectomy
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Norio Ueno, Ken Kimura, Y. Taniguchi, T. Ioka, N. Nagamine, T. Suzuki, M. Kumagai, N. Isoda, and Kenichi Ido
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Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Gallstones ,Lithotripsy ,Extracorporeal ,Postoperative Complications ,Cholelithiasis ,Sphincter of Oddi ,medicine ,Humans ,Laparoscopy ,Aged ,Aged, 80 and over ,Common bile duct ,medicine.diagnostic_test ,business.industry ,Gastroenterology ,Cystic Duct ,Length of Stay ,Middle Aged ,Surgery ,medicine.anatomical_structure ,Cholecystectomy, Laparoscopic ,Biliary tract ,Cystic duct ,Cholecystectomy ,Female ,business ,Follow-Up Studies - Abstract
Background and Study Aims : Following the recent introduction of laparoscopic cholecystectomy (LC) for cholecystolithiasis, treatment of concomitant common bile duct (CBD) stones has been evaluated by using laparoscopic choledochotomy, a transcystic approach, or by means of endoscopic sphincterotomy (ES) before or after LC. Patients and Methods : During laparoscopic cholecystectomy, we attempted lithotripsy of CBD stones using laparoscopic transcystic cholangioscopy with lithotripsy (LTCL), in 70 patients out of 950 laparoscopic cholecystectomies. Preparatory tests included laboratory values, ultrasound, and performance of endoscopic retrograde cholangiography (ERC) with placement of a nasobiliary tube (without sphincterotomy). Results : Introduction of the cholangioscope into the CBD was successful in 65 patients (92.9%) and CBD clearance was completely achieved by LTCL alone in 51 (78.5%). The overall success rate was therefore 73 %. The remaining 19 cases required postoperative procedures such as extracorporeal shock-wave lithotripsy without ERC or ES (successful in all). The average hospital stay period was 9.4 days for patients in whom CBD clearance was achieved by LTCL alone. This period did not differ significantly from that of patients who underwent LC alone (8.4 days). The operation time was about 70 minutes longer for the LTCL group (total time 174 minutes on average) than for the LC group (107 minutes). We did not observe any serious complications during or after LTCL (mean follow-up period : 34 months). Conclusion : LTCL in combination with LC allows shortening of the hospital stay and a swift return to work for patients with CBD stones. This procedure also preserves the function of the sphincter of Oddi, so that the long-term prognosis for patients is likely to be very good.
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- 1996
10. A case with metastatic liver cancer from malignant melanoma: dense deposit of melanin pigment possibly causes the high-echo level of the tumor
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T. Ioka, S. Tanaka, and K. Misu
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Oncology ,medicine.medical_specialty ,Acoustics and Ultrasonics ,Radiological and Ultrasound Technology ,business.industry ,Melanoma ,Echo (computing) ,Biophysics ,Metastatic liver cancer ,medicine.disease ,Malignant transformation ,Internal medicine ,Cancer research ,Medicine ,Radiology, Nuclear Medicine and imaging ,business ,Melanin pigment - Published
- 2003
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11. The Roles of Growth Arrest DNA Damage-Inducible Gene 45Γ (GADD45Γ) Expression in Sorafenib-Induced Apoptosis in Hepatocellular Carcinoma (HCC) Cells
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Y. Takeuchi, I. Ikai, Min-Shu Hsieh, H.-S. Han, Chung-Yi Huang, H. Anai, D.-L. Ou, S. M. Huang, M. Awane, H. Y. Kim, H.-H. Fan, H. Terajima, Y. Inaba, Sang Hyub Lee, T. Ochiai, Jin-Hyeok Hwang, T. Okusaka, K. Lee, Chih-Hung Hsu, M. Ikeda, A. Miyamoto, Z. L. Liang, T. Tsukamoto, S. J. Park, C-W Shiau, J. K. Kim, S. Takemura, Y. Arai, D. G. Lee, S. Ahn, S. E. Jang, C.-H. Hsu, H. Furuyama, D.-W. Ahn, S. Yamamoto, Yu-Yun Shao, Ban Seok Lee, N. Kuroda, Masashi Kanai, Y.-Y. Lin, Tetsuo Ajiki, K. Ikezawa, J.-M. Kim, Li-Chun Lu, T. Aramaki, H. Toyokawa, Deog-Yeon Jo, S. H. Kwon, D. W. Hwang, A-L Cheng, J.-K. Min, Hyo Jin Lee, J. Y. Cho, Y.-S. Yoon, S.-C. Liao, Y. S. Oh, Hiroaki Nagano, and T. Ioka
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Sorafenib ,MAPK/ERK pathway ,Gene knockdown ,medicine.diagnostic_test ,Gadd45 ,business.industry ,Hematology ,digestive system diseases ,Flow cytometry ,Blot ,Oncology ,Cell culture ,Apoptosis ,medicine ,Cancer research ,business ,neoplasms ,medicine.drug - Abstract
Background We previously found that GADD45b, which is associated with cellular stress response and apoptosis regulation, contributes to sorafenib resistance in HCC cells. The present study explored the role of GADD45γ, another GADD45 family protein, in HCC treatment. Methods HCC cell lines tested included Huh-7, HepG2, Hep3B, Huh-7R, HepG2R, the latter two sorafenib-resistant cell lines established by continuously exposure of Huh-7 and HepG2 cells to sorafenib. GADD45γ expression was examined by quantitative real-time PCR (qRT-PCR) and western blotting. Control of GADD45γ transcription was examined by luciferase reporter assay using a series of reporter plasmids with deletions or site-directed mutants of the 5′-flanking region of GADD45γ promoter. Apoptosis was analyzed by flow cytometry and western blotting. Expression of GADD45γ in human HCC tumor tissues was measured by qRT-PCR and immunohistochemistry. Results GADD45γ mRNA and protein levels were increased after sorafenib independent of cellular MEK/ERK activity. GADD45γ induction was more prominent in sorafenib-sensitive HCC cells (Huh-7 and HepG2, IC50 6-7 µM) than in sorafenib-resistant HCC cells (Hep3B, Huh-7R and HepG2R, IC50 12-15 µM). Knockdown of GADD45γ expression partially abrogated the pro-apoptotic effects of sorafenib in sorafenib-sensitive cells but not sorafenib-resistant cells. The region -449/ - 82 in the 5′-flanking region of GADD45γ promoter was found crucial for GADD45 gamma induction by sorafenib. Decreased GADD45γ expression in HCC tumor tissue was associated with worse overall survival in patients who underwent surgery for HCC. Conclusions Induction of GADD45γ expression contributes to sorafenib-induced apoptosis in HCC cells. The role of GADD45γ as a predictive biomarker for sorafenib sensitivity in HCC warrants further exploration. (Supported by grants NSC-100-2325-B-002 -042, NSC 100-2314-B-002 -058-MY3, DOH100-TD-B-111-001, and NHRI-EX101-9911BC.)
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- 2012
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12. TH-302 + Gemcitabine (G + T) vs Gemcitabine (G) in Patients with Previously Untreated advanced Pancreatic Cancer (PAC)
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Alain Duhamel, A. Tsuburaya, Mali Okada, S. Kuwabara, H. Hasegawa, A.L. Cohn, Anne Thirot-Bidault, J.R. Delgado, O.U. Unal, J. Isaacson, S. Khudayorov, Sue Ward, N. Mueller, Riccardo Lencioni, Giovanni Abbadessa, D. Takahari, T. Watanabe, Luca Faloppi, Y. Hamamoto, Julia Hocke, Elwyn Loh, M. Aizawa, E. Trejo, A. Novarino, A. Ohtsu, K. Okita, M.J. Flor, Riccardo Giampieri, C. Rose, D. Gonzalez-De-Castro, H. Isayama, M. Esaki, Jean-Pierre Bronowicki, S. Cereda, S. Hironaka, A. Sawaki, I. Iwanicki-Caron, L. Ferrari, J. Stephenson, F. Gerevini, E. Francois, T. Okusaka, S. De Minicis, Cristian Loretelli, S.Y. Roh, A. González-Vicente, F. Richard, H. Tuyev, A. Laforest, K. Lin, M. Milic´evic´, Chunming Li, Wolfgang Eisterer, P. Basile, Mohamed Gasmi, S. Hazama, M. Botta, Seiji Kawazoe, Jean-Luc Raoul, Y. Jiang, I. Trouilloud, B. Nagy, E. del Valle, Satoshi Yuki, K.W. Park, Hanno Riess, M. Bartosiewicz, L. Rolfe, H. Fang, E. Gardner, A. Benedetti, A. Carrato, E. Vasile, Takayuki Kii, N. Suzuki, Y. Shimada, S.F. Ang, S. Fushida, V. Vaccaro, Y. Liu, E. Castanon Alvarez, Y. Ozaki, D. Mirabelli, Ozgur Ozyilkan, J.E. Battley, C.H.S. Kim, N. Weijl, B. Bui, J.C. Sabourin, M. Hejna, Raymond Miller, N. Besova, Jinhui Xu, Ian Chau, J.-L. Van Laethem, Eric Vibert, Philippe Mathurin, H. Yabusaki, Melissa Frizziero, J. Soberino García, S. Salvagni, M. Zhu, Christoph Schuhmacher, Y. Yamada, A. Hubert, R. Libener, S.T. Dimoudis, Jonathan Wadsley, J. Martinez-Galan, Coskun U, V. Karavasilis, Cem Parlak, N. Jain, T. Gamucci, Elisa Giovannetti, R. Gupta, Suleyman Buyukberber, Jose Javier Sanchez, Taro Tokui, Kenneth K. Tanabe, V. Nerich, G. Dyson, Y. Kawachi, J. Reis-Filho, Junichi Sakamoto, A. Mohar-Betancourt, Masahide Mori, Aytug Uner, S. Martin Algarra, C.-J. Yen, J.J. Critchfield, Y. Naomoto, Julien Taieb, Young Seon Hong, Hironori Yamaguchi, S. Jiao, Alan P. Venook, C. Pericay, R.H. Wilson, D. Ferrari, Peter R. Galle, S. Falcon, Emilio Bria, L. Paz-Ares, Anna Tomezzoli, S. Al-Batran, G. Luppi, Jean-Marie Boher, I. Park, F. De Vita, Roland Leung, M. Abdelwahab, A. Ravaioli, Takuya Suzuki, C. Szczylik, C. González-Rivas, Sarita Dubey, Y. Miyashita, J.Y. Lim, Y. Chen, F. El Hajbi, Ichinosuke Hyodo, Tsutomu Chiba, C. Kondo, S. Ye, Thomas Aparicio, M. Nesrine, T. Ganten, T. Nishina, G. Grazi, A.C. Dupont-Gossard, I. Oze, F. Nosrati, J.H. Yook, C. Yoo, N.A. Adu-Aryee, M. Choi, Narikazu Boku, P. Chan, John Bridgewater, A. Gimenez-Capitan, Hamim Zahir, R. Hela, T. Villegas, Stefano Barbi, György Bodoky, D. Degiovanni, Y. Honma, A. Croitoru, K. Koufuji, Lorenza Rimassa, A. Tsuji, Yueyang Shen, Nathan Bahary, S. Abdelwahab, N. Matsuura, Parsee Tomar, L. Yu, Mohammed Elbassiouny, B. Ryoo, S. Adachi, Jean-Robert Delpero, V.D.N.K. Vanderpuye, S.T. Oh, E. Samantas, Amit Bahl, N. Karachaliou, Thierry Lecomte, S. Yoshino, H. Hahn, A. Matsuki, K. Nakamura, D.S. Johnston, M. Del Prete, Per Stål, R. Greil, Dirk Arnold, K. Ridwelski, J. Zhao, K. Shirouzu, Meltem Baykara, G. De Manzoni, I. Lang, K. Aoyagi, A. Fukutomi, Joji Kitayama, Antonieta Salud, K. Beecham, Y. Inoue, Armando Santoro, R. Rosell, P. Malfertheiner, Tsutomu Fujii, Jeong-Yeol Park, S. Taylor, K. Nakajima, Matus Studeny, H. Jiang, M. Shimada, O. Abdelrhman, Camillo Porta, P. Ballesteros, S. Lecleire, K. Han, G. Svegliati Baroni, Michitaka Nagase, François Paye, W. Rodriguez Pantigoso, M.M. Eatock, H.C. Toh, M. Ikeda, Hironori Ishigami, N. Stankovic, H. Kumada, K. Shitara, X. Zhang, E. Arevalo, R. Poon, M. Allard, Y.-Y. Lin, D. Egamberdiev, Shin'ichi Miyamoto, P. Afchain, Harpreet Wasan, Mitesh J. Borad, J. Blay, Dong Sup Yoon, H. Kawai, L. Jin, Margaret Sheehan, T. Otsuji, M. Lichinitser, Ahmet Ozet, R. Savage, Heind Smith, L. Zubiri, Tim Meyer, Erkan Topkan, Ross C. Donehower, Joanne Chiu, T. Tsuda, P. Jimenez Fonseca, U. Selek, N. Musha, B. Liu, A. Magnusson, S.C. Sharma, C. Purcell, H. Wong, E. Lucchini, Jean-Marc Phelip, E. Jeon, J. Fujita, Kelly S. Oliner, W. Schelman, W. Mao, S. Hato, A-L Cheng, D.-L. Ou, Tarek Sahmoud, J. Waters, Jorge A. Marrero, David Malka, P. Xavier, M. Haibo, S. Takiguchi, Q. Pan, S. Ohkawa, J. Kizaki, I.P. Le, A. Roveta, D.H. Koo, H.J. Kim, H. Choi, T. Göhler, A. Gelibter, C. Borg, X. Qiang, Masaya Suenaga, Ozan Cem Guler, Niall C. Tebbutt, M. Emi, S. Ota, N. Nagata, S. Iwasa, Mira Ayadi, K. Matsuo, Henk M.W. Verheul, Christoph C. Zielinski, S. Choo, M.W. Büchler, René Adam, M. Pistelli, J.A. Gonzalez, Charles S. Fuchs, G. Vallati, G. Pentheroudakis, S. Tokunaga, U. Demirci, Lin Shen, B. Heyd, X. Zhou, T. Ioka, Toshiyoshi Fujiwara, O. Testori, Y.S. Park, A. Allen, Rakesh Kapoor, Bruno Daniele, T. Hirai, Z. Lakkis, I.B. Tan, Y-K Kang, S.A. Aledavood, N. Reynoso, F. Serejo, Sergio Ricci, Jennifer Gansert, M. Miyagi, S. Santi, A. Parthan, A C Wotherspoon, L. Chaigneau, Sumera Rizvi, M.G. Fabrini, Véronique Vendrely, W. Su, V. Shalenkov, L. Tu, G. Numico, Joon Seong Park, J.H. Kim, Hope E. Uronis, Mustafa Benekli, I. Aoyama, M. Gauthier, S. Lazzarelli, W. Liguigli, N. Atsushi, H. Kastrissios, J. Thaler, Z. Zou, T. Tsujinaka, S. Barbero, F. Fiteni, Irene Kührer, Aldo Scarpa, C. Desauw, J.F. Seitz, Takahiro Horimatsu, R. von Roemeling, T. Yamamoto, H.R. Alexander, Timothy Iveson, F.M. Negri, Ermek Tangsakar, Pascal Artru, Jia Zhang, S. Lee, Satoshi Morita, E. Garralda, M. Moore, J. Lee, M. Seilanian Tousi, J. Gornet, Yasuhiro Kodera, Werner Scheithauer, L. Marthey, D. Atanackovic, P. Zhao, D. Wang, I. Davidenko, T.S. Waddell, S. Takeda, N. Fan, R. Kawabata, M. Raponi, Giampaolo Tortora, M. Ogasawara, B. Gruenberger, Guido Gerken, Ivan Borbath, N. Fuse, Denis Smith, Emmanuel Mitry, Vikki Tang, I. Stilidi, Min-Hee Ryu, Tulay Akman, C. Saffery, Roopinder Gillmore, K. Ligier, R. Coriat, T. Namikawa, L. Sun, R. Xu, Gary Middleton, W. Tröger, F. Keil, Bruno Chauffert, K. Achilles, David Cunningham, H. Raies, M.Y. Teo, Y. Hamai, S. Tjulandin, I. Boukovinas, J. Kazakin, J. Beebe-Dimmer, Pippa Corrie, J.A. Ortega, A. Cueff, C. Costa, V. Da Prat, Y. Tanaka, F. Rivera, K. Hashimoto, Tianshu Liu, K. Kato, J.C. Plaza, G. Fountzilas, N. Chaiet, Byung Sik Kim, K. Ueda, Pierre Laurent-Puig, Y.-C. Cheng, Mendel Jansen, T. Salman, C. Papandreou, T. Carothers, H. Van Vlierberghe, M. Rios, S. Barni, Y. Arai, G. Afc, Julia Klech, Bryan C. Fuchs, S.T. Fan, A. Falcone, J-B. Bachet, Y. Fujiwara, S. Navruzov, Fumihiko Kanai, H. Shiah, J. Xia, N. Xu, X. Garcia del Muro, M. Lucchesi, Jae Yong Cho, A. Leon, W. Jin, C. Eng, A.U. Yilmaz, L.-T. Chen, Laurent Bedenne, I. Vynnychenko, Brian Schwartz, J. Ruíz Vozmediano, Toshihiro Tanaka, Jinwan Wang, F. Musante, C. Belli, K. Imanaka, W. Fang, J.P. Fusco, S. Gupta, Daniel H. Palmer, M. Ninomiya, N. Ryuge, M. Djuraev, B. Benzidane, H. Yasui, P.G. Betta, M. Sanon, J. Mizusawa, M. Hou, H. Pan, Y. Osaki, Darren Sigal, E. Schott, J. Rodriguez, E. Wöll, S. Nakamori, Anthony F. Shields, Yasuo Ohashi, M. Raikou, M.W. Bennett, Zhilong Zhao, G. Colucci, R. Stauber, M. Nakamura, T. Nguyen, Xin Li, C. Greco, K. Hanazaki, C. Mao, Y. Matsumura, S. Emoto, Maristella Bianconi, Yoon Ho Ko, E. Trusilova, J. Coombs, H. Iwase, V.A. Gorbunova, M. Lencioni, M. Svrcek, S. Leo, Mahmoud Ellithy, N. Silvestris, Y.H. Min, N. Urata, A. Sainato, K. Yoshimura, U. Boggi, D.C. Huang, T. Tsuzuki, S.H. Hong, K. Ikeda, Mohammed Shaker, Olivier Turrini, Arsene-Bienvenu Loembe, Jaffer A. Ajani, G. Pelletier, Stefano Cascinu, F. Bergamo, I.T. Unek, T. Di Palma, H. Li, Maria Lamar, H. Inagaki, M. Ratti, M. Iida, F. Pons Valladares, S. Caponi, A. Sa-Cunha, A. Passardi, J. Wei, S. Azevedo, W. Wang, S. Luelmo, M. Brighenti, A. Mezlini, Y. Zheng, S. Reddy, M. Milella, S. Nered, D. Li, Carsten Bokemeyer, Manabu Muto, C. Krüger, X.J. Sun, T. Ueno, M. Harrison, F. Cognetti, Y. Kida, M. Kobayashi, S. Akamaru, G. Leonard, Y. Inaba, A. Jayaram, Özgür Ekinci, Y. Bai, F. Subtil, Wasaburo Koizumi, M.A. Fridrik, Pierre Michel, R.C. Turkington, D. Galun, N. De Lio, A. Le Cesne, L. Toppo, Thorsten Füreder, R. Poli, V. Moiseyenko, Jean-Louis Jouve, Y. Lu, A. Babaev, N. Okumura, Isamu Okamoto, G.C. Ruiz, I. Oztop, T. Isobe, W. Fischbach, A. Takashima, Alessandro Bittoni, Y-C Chang, K. Yamaguchi, Vincent J. Picozzi, K. Muro, M. Sebagh, Y. Shindo, S. Beghelli, M. Skoblar Vidmar, Alessandra Mandolesi, M. Reni, K. Nishikawa, Marine Gilabert, Y. Maeda, Francesco Massari, E.B. Ruiz, K. Pan, H. Lou, H.S. Won, C. Diaz, J.P. O'Brien, Shuichi Kaneko, C. Gomez-Martin, J. Sgouros, A. Funakoshi, W. Figg, F. Chai, M.S. Pino, X. Pivot, K. Anvari, J. Turnes, M. Reif, F. Lopez-Rios, W. Cheung, David P. Ryan, M. Oka, I. Varthalitis, A. Deptala, Masatoshi Kudo, F. Romeder, J. Qian, J. Hihara, T. Shibata, T. Yamatsuji, B. Gonzalez-Astorga, B. Allani, Y. Tsuji, J. Liu, Thomas Yau, S. Lim, F. Grosso, Y.D. Zheng, R. Passalacqua, J. Chen, I. Sperduti, H. C. Kwon, C. Cappelli, C. Guettier, O. Nematov, Lanjun Zhou, C. Caparello, F. Bonnetain, R. Ferrara, A. Nashimoto, A. Schumann, Richard Martin Bambury, C. Mazzara, T. Aramaki, B. Saracino, M. Takagi, G. Di Lucca, Philip A. Philip, A. Aloui, Philippe Bachellier, N. Hirabayashi, S. Osanto, S. So, N. Fukushima, K.-H. Yeh, Y. Aoki, M. Baretti, Y-L. Gong, Koichiro Yamakado, C.-H. Hsu, R. Buder, D.G. Power, H. Matsumoto, Chiara Costantini, Y. Xu, G. Tomasello, A. Lopez Pousa, D.K. Lee, F. Di Fiore, O. Polat, K. Suzuki, L. Arbea, R. McDermott, S.-H. Kim, E. Toure, O. Bouche, A. Zaanan, T. Hamaguchi, Mary Geitona, M.H. Tan, M. Antonietti, Italo Bearzi, Juan W. Valle, D. Castaing, H. Shoji, Eylem Pınar Eser, Mario Scartozzi, R. Abdul Rahman, Yukinori Kurokawa, F. Pardo, T. Sasatomi, Y. Kimura, Suguru Yamada, K. El Ouagari, F. Mosca, Yuichiro Doki, A.O. Singh, Goro Nakayama, Lara Lipton, H.J. An, B. Kato, Y. Ezoe, M. Salem, Samantha Bersani, B. Paule, O.E. Carranza Rua, Gabriela Kornek, L. Gray, S. Tamura, J.-F. Blanc, and L. Ginocchi
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medicine.medical_specialty ,Gastrointestinal tumors ,Performance status ,business.industry ,Hematology ,Severe hypoxia ,Neutropenia ,medicine.disease ,Rash ,Gastroenterology ,Discontinuation ,Non colorectal ,Oncology ,Internal medicine ,Toxicity ,medicine ,medicine.symptom ,business - Abstract
Background TH-302 is a hypoxia targeted prodrug with a hypoxia-triggered 2-nitroimidazole component designed to release the DNA alkylator, bromo-isophosphoramide mustard (Br-IPM), when reduced in severe hypoxia. A randomized Phase 2B study (NCT01144455) was conducted to assess the benefit of G + T to standard dose G as first-line therapy of PAC. Materials and methods An open-label multi-center study of two dose levels of TH-302 (240 mg/m2 or 340 mg/m2) in combination with G versus G alone (randomized 1:1:1). G (1000 mg/m2) and T were administered IV over 30-60 minutes on Days 1, 8 and 15 of a 28-day cycle. Patients on the G could crossover after progression and be randomized to a G + T arm. The primary efficacy endpoint was a comparison of progression-free survival (PFS) between the combination arms and G alone (80% power to detect 50% improvement in PFS with one-sided alpha of 10%). Summary PFS outcome has previously been reported; more detailed PFS as well as the initial overall survival (OS) data are presented. Results 214 pts were treated; 164 (77%) Stage IV and 50 (23%) Stage IIIB. Median age 65 (range 29-86); 126 M/88 F; 40% ECOG 0/60% ECOG 1. Receiving 6 or more cycles: 32% G; 45% G + T240; 55% G + T340. Median PFS was 3.6 mo in G vs 5.5 mo in G + T240 (p = 0.031) and 6.0 mo in G + T340 (p = 0.008). Poorer prognostic factors (older age, poorer performance status, reduced albumin) were associated with larger treatment effect. Median OS was 7.0 mo in G vs 9.0 in G + T240 and 9.5 mo in G + T340. RECIST best response was 12% in G vs 17% in G + T240 and 27% in G + T340. CA19-9 decreases were significantly greater G + T340. A >50% CA19-9 decrease was 52% with G vs 50% with G + T240 and 70% with G + T340. AEs leading to discontinuation were: 16% G, 15% G + T240 and 11% G + T340. Rash (45% in G + T340) and stomatitis (36% in G + T340) were greater in combination, 4 pts Grade 3 rash. Grd 3/4 thrombocytopenia were 11% G, 39% G + T240 and 59% G + T340 and Grd 3/4 neutropenia were 28% G, 56% G + T240 and 59% G + T340. Conclusions The combination of G plus TH-302 improved the efficacy of G. A TH-302 dose of 340 mg2 was identified for future studies. Skin and mucosal toxicity and myelosuppression were the most common TH-302 related AEs with no increase in treatment discontinuation. Disclosure All authors have declared no conflicts of interest.
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- 2012
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13. A Randomized Phase II Study of Gemcitabine 1000mg/msq and Concurrent Radiotherapy Comparing Gemcitabine Alone for Unresectable Locally Advanced Pancreatic Adenocarcinoma
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T. Ioka, K. Nishiyama, and Satoaki Nakamura
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Oncology ,Cancer Research ,medicine.medical_specialty ,Radiation ,business.industry ,medicine.medical_treatment ,Locally advanced ,Phases of clinical research ,medicine.disease ,Gemcitabine ,Radiation therapy ,Internal medicine ,medicine ,Adenocarcinoma ,Radiology, Nuclear Medicine and imaging ,business ,medicine.drug - Published
- 2010
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14. Evaluation of hepatic tumors by a multistep triggered method for dynamic sonography
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T. Ioka, R. Takakura, and Sachiko Tanaka
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Acoustics and Ultrasonics ,Radiological and Ultrasound Technology ,Biophysics ,Radiology, Nuclear Medicine and imaging - Published
- 2003
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15. Irregular vascular pooling: a finding in pancreatic ductal adenocarcinoma with dynamic ultrasound
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R. Takakura, S. Tanaka, and T. Ioka
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Dynamic ultrasound ,medicine.medical_specialty ,Pancreatic ductal adenocarcinoma ,Acoustics and Ultrasonics ,Radiological and Ultrasound Technology ,business.industry ,Pooling ,Biophysics ,Medicine ,Radiology, Nuclear Medicine and imaging ,Radiology ,business - Published
- 2003
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16. Phase II trial of combination therapy of gemcitabine plus anti-angiogenic vaccination of elpamotide in patients with advanced or recurrent biliary tract cancer
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Nobumasa Mizuno, T. Ioka, Tadanori Yamaguchi, Hiroshi Ishii, Tetsuo Ajiki, Masafumi Ikeda, Hiroki Yamaue, Junji Furuse, Masaru Miyazaki, H. Maguchi, Yasuo Ohashi, Yasutsuna Sasaki, S. Ohkawa, K. Eguchi, Wataru Ichikawa, Kenichi Hakamada, Masato Matsuyama, and M. Yamamoto
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Oncology ,Male ,Vascular Endothelial Growth Factor A ,medicine.medical_specialty ,Antimetabolites, Antineoplastic ,Combination therapy ,Phase II Studies ,Cancer vaccines ,Deoxycytidine ,Chemoimmunotherapy ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Pharmacology (medical) ,Survival rate ,Survival analysis ,Aged ,Pharmacology ,Biliary tract neoplasm ,business.industry ,Middle Aged ,Survival Analysis ,Vascular Endothelial Growth Factor Receptor-2 ,Gemcitabine ,Phase II clinical trial ,Peptide Fragments ,Surgery ,Regimen ,VEGFR2 ,Biliary Tract Neoplasms ,Biliary tract cancer ,Female ,Immunotherapy ,business ,medicine.drug - Abstract
SummaryBackground Elpamotide is an HLA-A*24:02-restricted epitope peptide of vascular endothelial growth factor receptor 2 (VEGFR-2) and induces cytotoxic T lymphocytes (CTLs) against VEGFR-2/KDR. Given the high expression of VEGFR-2 in biliary tract cancer, combination chemoimmunotherapy with elpamotide and gemcitabine holds promise as a new therapy. Patients and Methods Patients with unresectable advanced or recurrent biliary tract cancer were included in this single-arm phase II trial, with the primary endpoint of overall survival. Survival analysis was performed in comparison with historical control data. The patients concurrently received gemcitabine once a week for 3 weeks (the fourth week was skipped) and elpamotide once a week for 4 weeks. Results Fifty-five patients were registered, of which 54 received the regimen and were included in the full analysis set as well as the safety analysis set. Median survival was 10.1 months, which was longer than the historical control, and the 1-year survival rate was 44.4 %. Of these patients, injection site reactions were observed in 64.8 %, in whom median survival was significantly longer (14.8 months) compared to those with no injection site reactions (5.7 months). The response rate was 18.5 %, and all who responded exhibited injection site reactions. Serious adverse reactions were observed in five patients (9 %), and there were no treatment-related deaths. Conclusion Gemcitabine and elpamotide combination therapy was tolerable and had a moderate antitumor effect. For future development of therapies, it will be necessary to optimize the target population for which therapeutic effects could be expected.
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17. A prospective observational study of laparoscopic approaches for suspected gallbladder cancer in Yamaguchi (YPB-002 LAGBY).
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Tokumitsu Y, Kawaoka T, Matsukuma S, Harada E, Suenaga S, Tanabe M, Takahashi H, Shindo Y, Matsui H, Nakajima M, Ioka T, Takami T, Ito K, Tanaka H, Hamano K, and Nagano H
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We have previously reported laparoscopic total biopsy methods for suspected gallbladder cancer (GBC). The present prospective observational study evaluated the safety and feasibility of a novel two-stage algorithm using laparoscopic total biopsy methods. The two-stage algorithm was applied for 40 patients with suspected GBC between July 2018 and September 2022. Laparoscopic whole-layer cholecystectomy (LWLC) was performed for early-stage or suspected malignant lesions without liver invasion and laparoscopic gallbladder bed resection (LGBR) was performed for lesions with an unclear border between the gallbladder and liver. The appropriate strategy could be selected postoperatively depending on the final pathological diagnosis according to examination of permanent sections of gallbladder. If preoperative imaging reveals enlarged lymph nodes (LNs) with possible metastases, LN sampling with intraoperative pathological diagnosis is performed prior to gallbladder removal to determine whether to introduce neoadjuvant chemotherapy. As the first diagnostic procedure, we performed LWLC in 30 cases, LGBR in 8 cases, and LN sampling alone in 2 cases. Median operation time was 165 min and median blood loss was 5.5 ml. No bile leakage caused by intraoperative perforation of the gallbladder was observed. Histologically, GBC was diagnosed in 16 cases (pTis, n = 2; pT1a, n = 2; pT1b, n = 2; pT2, n = 6; pT3, n = 4). Seven of the 10 pT2/3 cases underwent additional open lymphadenectomy. The two-stage algorithm using laparoscopic total biopsy methods for suspected GBC appears to represent a safe, feasible procedure that could play an important role in the optimal treatment strategy., Competing Interests: Declarations. Conflict of interest: All authors have no conflicts of interest to disclose. Ethical approval: This study was approved by the Institutional Review Board of Yamaguchi University Hospital (approval no. H30-034). Informed consent: Written informed consent was obtained from all patients., (© 2025. Italian Society of Surgery (SIC).)
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- 2025
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18. Survival Analysis of 4 Different Age Groups of Pancreatic Ductal Adenocarcinoma After Radical Resection From Retrospective Multi-Center Analysis (YPB-003).
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Matsui H, Ioka T, Kawaoka T, Takahashi T, Inokuchi T, Harada E, Sakamoto K, Suto R, Maeda Y, Nishimura T, Shindo Y, Tokumitsu Y, Nakajima M, Kimura Y, Takami T, Ito K, Tanaka H, Hamano K, and Nagano H
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- Humans, Aged, Male, Female, Retrospective Studies, Aged, 80 and over, Age Factors, Middle Aged, Prognosis, Pancreatectomy, Chemotherapy, Adjuvant methods, Kaplan-Meier Estimate, Frailty, Survival Analysis, Carcinoma, Pancreatic Ductal surgery, Carcinoma, Pancreatic Ductal mortality, Carcinoma, Pancreatic Ductal pathology, Pancreatic Neoplasms surgery, Pancreatic Neoplasms mortality, Pancreatic Neoplasms pathology, Pancreatic Neoplasms drug therapy
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Aim: This study aimed to investigate the efficacy of radical resection and postoperative adjuvant chemotherapy on the survival benefit in patients with pancreatic ductal adenocarcinoma (PDAC), stratified by age, frailty, and other factors in actual clinical practice., Methods: We retrospectively analyzed the clinicopathological and follow-up data of 414 patients with PDAC who underwent surgical resection at nine institutions under the Yamaguchi Pancreat/Biliary Disease Study Group, between January 1997 and December 2016. Recurrence-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Associations between survival and prognostic factors were evaluated by univariate and multivariate analyses., Results: There were 30.5% of patients with PDAC who were aged < 65 years, 37.9% aged 65-74 years, 17.6% aged 75-79 years, and 14.0% aged ≥ 80 years. Notably, RFS declined with increasing age (median RFS: 12.9, 10.2, 9.4, and 7.4 months, respectively), although the differences were not significant (p = 0.223). OS significantly decreased with age (median OS: 21.6, 21.2, 17.0, and 13.9 months, respectively; p = 0.005). In patients aged < 75 years, independent prognostic factors identified by univariate and multivariate analyses included lymph node metastasis (hazard ratio [HR], 1.598; p = 0.007), tumor size (HR, 1.489; p = 0.043), R status (HR, 1.536; p = 0.011), and serum albumin levels (HR, 1.526; p = 0.031). In patients aged ≥ 75 years, a high modified frailty index (HR, 2.446; p = 0.012) emerged as an independent prognostic factor, along with lymph node metastasis, CA19-9 level (HR, 1.897; p = 0.017), and R status (HR, 2.087; p = 0.007)., Conclusion: The prognosis for older patients with PDAC was shorter than that of younger patients. Frailty may contribute to their poorer prognosis in older age., (© 2025 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2025
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19. Tasurgratinib in patients with cholangiocarcinoma or gastric cancer: Expansion part of the first-in-human phase I study.
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Morizane C, Ueno M, Ioka T, Tajika M, Ikeda M, Yamaguchi K, Hara H, Yabusaki H, Miyamoto A, Iwasa S, Muto M, Takashima T, Minashi K, Komatsu Y, Nishina T, Nakajima TE, Takeno A, Moriwaki T, Furukawa M, Sahara T, Ikezawa H, Nomoto M, Takashima S, Uehara T, Funasaka S, Yashiro M, and Furuse J
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- Humans, Male, Female, Middle Aged, Aged, Fibroblast Growth Factor-23, Adult, Receptors, Fibroblast Growth Factor antagonists & inhibitors, Receptors, Fibroblast Growth Factor genetics, Receptor, Fibroblast Growth Factor, Type 2 genetics, Receptor, Fibroblast Growth Factor, Type 2 antagonists & inhibitors, Protein Kinase Inhibitors therapeutic use, Protein Kinase Inhibitors pharmacokinetics, Protein Kinase Inhibitors adverse effects, Protein Kinase Inhibitors administration & dosage, Pyrimidines therapeutic use, Pyrimidines pharmacokinetics, Pyrimidines adverse effects, Pyrimidines administration & dosage, Cholangiocarcinoma drug therapy, Cholangiocarcinoma genetics, Stomach Neoplasms drug therapy, Stomach Neoplasms genetics, Stomach Neoplasms pathology, Bile Duct Neoplasms drug therapy, Bile Duct Neoplasms genetics
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Fibroblast growth factor receptors (FGFRs) are a highly conserved family of transmembrane receptor tyrosine kinases with multiple roles in the regulation of key cellular processes. Specific FGFR mutations have been observed in several types of cancers, including gastric carcinoma and cholangiocarcinoma. Dose escalation data of 24 Japanese patients with solid tumors treated with Tasurgratinib (previously known as E7090), a potent, selective FGFR1-3 inhibitor, was reported in a phase I, first-in-human, single-center study. Based on the safety, pharmacokinetic, and pharmacodynamic profiles observed in this study, the recommended dose of 140 mg once daily was selected for the expansion part (Part 2), a multicenter expansion of the dose-finding study restricted to patients with tumors harboring FGFR gene alterations. Safety and preliminary efficacy were assessed in Part 2. Pharmacodynamic pharmacogenomic markers (serum phosphate, FGF23, and 1,25-(OH)
2 -vitamin D, circulating tumor DNA) and pharmacokinetic profiles were also evaluated. A total of 16 patients were enrolled in Part 2, six with cholangiocarcinoma and 10 with gastric cancer. The most common treatment-emergent adverse events were hyperphosphatemia, palmar-plantar erythrodysesthesia syndrome, and paronychia. Five partial responses (83.3%) in cholangiocarcinoma patients and one partial response (11.1%) in gastric cancer patients were observed; median progression-free survival was 8.26 months (95% confidence interval [CI] 3.84, not evaluable [NE]) and 3.25 months (95% CI 0.95, 4.86), and overall survival was 22.49 months (95% CI 6.37, NE) and 4.27 months (95% CI 2.23, 7.95), respectively, in the two groups. In conclusion, Tasurgratinib 140 mg has a tolerable safety profile with good clinical efficacy in patients with cholangiocarcinoma harboring FGFR2 gene rearrangements., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)- Published
- 2025
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20. [A Case of Pancreatic Cancer with Concomitant Pancreatic Metastasis of Renal Cell Carcinoma].
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Yakabe A, Matsui H, Shindo Y, Tokumitsu Y, Nakajima M, Kimur Y, Watanabe Y, Tomochika S, Iida M, Ioka T, Takahashi H, and Nagano H
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- Humans, Male, Middle Aged, Drug Combinations, Tegafur administration & dosage, Tegafur therapeutic use, Oxonic Acid administration & dosage, Oxonic Acid therapeutic use, Antimetabolites, Antineoplastic therapeutic use, Pancreatic Neoplasms surgery, Pancreatic Neoplasms pathology, Pancreatic Neoplasms drug therapy, Kidney Neoplasms pathology, Kidney Neoplasms surgery, Kidney Neoplasms drug therapy, Carcinoma, Renal Cell surgery, Carcinoma, Renal Cell secondary, Carcinoma, Renal Cell pathology, Carcinoma, Renal Cell drug therapy, Pancreaticoduodenectomy
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A 52-year-old man presented with a postoperative abdominal ultrasound of left renal cell carcinoma, which revealed a dilated main pancreatic duct in the pancreatic body tail. A 15 mm tumor was noted in the pancreatic head-neck region on CT, and was diagnosed as invasive pancreatic cancer on EUS-FNA. The tumor was diagnosed as resectable pancreatic head-body cancer, and after neoadjuvant chemotherapy, a subtotal stomach-preserving pancreaticoduodenectomy was performed. Postoperative histopathology showed well-differentiated adenocarcinoma, TS1(9 mm), T1bN0M0, Stage Ⅰ, preoperative chemotherapy efficacy was Grade 2, and R0 resection was obtained. At the same time, a 4 mm-sized nodule was found in the center of the pancreatic head, far from the primary pancreatic cancer, and was diagnosed as renal cell carcinoma intrapancreatic metastasis. He received 4 courses of S-1 therapy as postoperative adjuvant chemotherapy for pancreatic cancer, and is alive 23 months postoperatively without recurrence. The coexistence of primary pancreatic cancer and pancreatic metastasis of renal cell carcinoma is extremely rare, and we report this case with a review of the literature.
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- 2024
21. Safety and Feasibility of Neoadjuvant-Modified FOLFIRINOX in Elderly Patients with Pancreatic Cancer.
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Shindo Y, Ioka T, Tokumitsu Y, Matsui H, Nakajima M, Kimura Y, Watanabe Y, Tomochika S, Nakagami Y, Tsunedomi R, Iida M, Takahashi H, and Nagano H
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The optimal treatment strategy for neoadjuvant chemotherapy in elderly patients with pancreatic cancer (PC) remains unclear. Hence, this study was aimed at evaluating the safety and feasibility of neoadjuvant-modified FOLFIRINOX (mFOLFIRINOX) in elderly patients with PC. We retrospectively collected data from 62 patients who received neoadjuvant mFOLFIRINOX between May 2015 and October 2023 and comparatively analyzed the clinicopathological data and outcomes between the non-elderly group (age: <75 years) and elderly group (age: >75 years). The non-elderly and elderly groups comprised 39 and 23 patients, respectively. Although elevated levels of aspartate aminotransferase ( p = 0.0173) and alanine aminotransferase ( p = 0.0378) and nausea ( p = 0.0177) were more frequent in the elderly group, the incidence of severe adverse events was similar between the groups. Intergroup differences in resection rate ( p = 0.3381), postoperative severe complication rates ( p = 0.2450), and postoperative hospital stay ( p = 0.3496) were not significant. Furthermore, no significant intergroup differences were found in survival in either the whole or the resection cohorts. The perioperative and postoperative outcomes of elderly patients treated with neoadjuvant mFOLFIRINOX were comparable with those of non-elderly patients. Neoadjuvant mFOLFIRINOX should be considered a feasible option for elderly patients with PC.
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- 2024
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22. Multicenter Prospective Cohort Study of Neoadjuvant Chemotherapy for Borderline Resectable Pancreatic Cancer (YPB-001).
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Matsui H, Ioka T, Takahashi T, Kawaoka T, Maeda Y, Yahara N, Kubo H, Nishimura T, Inokuchi T, Harada E, Shindo Y, Tokumitsu Y, Nakajima M, Takami T, Ito K, Tanaka H, Hamano K, and Nagano H
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- Humans, Aged, Female, Male, Prospective Studies, Middle Aged, Chemotherapy, Adjuvant methods, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Pancreatectomy methods, Pancreatectomy adverse effects, Treatment Outcome, Adult, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms surgery, Pancreatic Neoplasms mortality, Pancreatic Neoplasms pathology, Neoadjuvant Therapy methods
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Objectives: The present multicenter prospective observational study investigated the effectiveness and safety of neoadjuvant chemotherapy (NAC) for patients with borderline resectable pancreatic cancer (BRPC) and those with RPC contacting major vessels, with respect to a historical control of upfront surgery., Materials and Methods: Patients with BRPC and RPC contacting major vessels were prospectively registered and administered NAC with durations and regimens determined by the corresponding treating physician. Our primary aim was to assess the R0 resection rate, and secondary aim was to evaluate safety, resection rate, time to treatment failure, overall survival, and response rate., Results: Fifty of 52 enrolled patients were analyzed; 2 with serious comorbidities died during treatment. Thirty-one patients underwent resection, with R0 resection being achieved in 26 (52% of total and 84% of all resected cases). Univariate and multivariate analyses indicated age (≥75 years) as the only independent predictor of nonresection. Median progression-free survival and median survival time were longer in the prospective cohort than in the historical cohort., Conclusions: Overall, NAC for BRPC in real-world setting might yield R0 resection rates similar to those reported in previous clinical studies. Development of safe regimens and management strategies that can maintain treatment intensity in geriatric patients is warranted., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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23. Preventing Pneumonia in High-risk Patients After Esophageal Cancer Surgery: Mini-tracheostomy and Tazobactam/Piperacillin.
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Nishiyama M, Takeda S, Watanabe Y, Iida M, Yamamoto T, Nakashima C, Matsui H, Shindo Y, Tokumitsu Y, Tomochika S, Ioka T, and Nagano H
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- Humans, Male, Female, Aged, Middle Aged, Anti-Bacterial Agents therapeutic use, Anti-Bacterial Agents administration & dosage, Retrospective Studies, Risk Factors, Esophagectomy adverse effects, Esophagectomy methods, Esophageal Neoplasms surgery, Pneumonia prevention & control, Pneumonia etiology, Pneumonia epidemiology, Piperacillin, Tazobactam Drug Combination therapeutic use, Piperacillin, Tazobactam Drug Combination administration & dosage, Postoperative Complications prevention & control, Postoperative Complications etiology
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Background/aim: We evaluated the usefulness of prophylactic mini-tracheostomy (PMT) and perioperative administration of tazobactam/piperacillin (TAZ/PIPC) in high-risk patients after esophagectomy., Patients and Methods: We retrospectively studied 89 consecutive high-risk patients who underwent esophagectomy for esophageal cancer between January 2013 and December 2021. We defined patients with two or more of the following factors as high risk: age ≥70 years, performance status ≥1, respiratory dysfunction, liver dysfunction, cardiac dysfunction, renal dysfunction, diabetes mellitus, albumin <3.5 g/dl, and Brinkman index >600. Standard management was administered to the first 50 patients (standard group). PMT and TAZ/PIPC were administered to the next 39 patients (combination group). Patient characteristics and short-term outcomes were compared before and after propensity-score matching., Results: Before propensity-score matching, 24-hour urine creatinine clearance, retrosternal route, 3-field lymph node dissection, and open abdominal approach were more common, postoperative pneumonia (13% vs. 36%, p=0.045) and complications of grade ≥3b (2.6% vs. 22%, p=0.01) were less frequent, and the postoperative hospital stay was shorter (median: 23 vs. 28 days, p=0.022) in the combination group than in the standard group. In propensity-score matching, patient characteristics, except for 24-h creatinine clearance and reconstructive route, were matched for 23 paired patients. Postoperative pneumonia (8.7% vs. 39%, p=0.035) and complications of grade ≥3b (0% vs. 26%, p=0.022) were less frequent and postoperative hospital stay was shorter (median: 22 vs. 25 days, p=0.021) in the combination group than in the standard group., Conclusion: PMT with TAZ/PIPC can potentially prevent postoperative pneumonia in high-risk patients after esophagectomy., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
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- 2024
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24. Exosomal miR-141-3p Induces Gemcitabine Resistance in Biliary Tract Cancer Cells.
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Tokuhisa A, Tsunedomi R, Kimura Y, Nakajima M, Nishiyama M, Takahashi H, Ioka T, Kobayashi S, Eguchi H, and Nagano H
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- Humans, Cell Line, Tumor, Gene Expression Regulation, Neoplastic drug effects, Antimetabolites, Antineoplastic pharmacology, Cholangiocarcinoma genetics, Cholangiocarcinoma drug therapy, Cholangiocarcinoma pathology, Cholangiocarcinoma metabolism, Cell Survival drug effects, MicroRNAs genetics, Gemcitabine, Deoxycytidine analogs & derivatives, Deoxycytidine pharmacology, Exosomes metabolism, Exosomes genetics, Drug Resistance, Neoplasm genetics, Biliary Tract Neoplasms genetics, Biliary Tract Neoplasms drug therapy, Biliary Tract Neoplasms pathology, Biliary Tract Neoplasms metabolism
- Abstract
Background/aim: Gemcitabine (GEM)-based chemotherapy has been established as the core multimodal therapy for biliary tract cancer (BTC). However, the prognosis of BTC is unfavorable because of its resistance to GEM. Exosomes play important roles in the regulation of tumor progression and metastasis, immune dysregulation, and chemoresistance. This study investigated the effects of exosomes on GEM resistance in BTC., Materials and Methods: The human intrahepatic cholangiocarcinoma cell line CC-LP-1, its GEM-resistant (GR) derivative cell line CC-LP-1-GR, and the human intrahepatic cholangiocarcinoma cell lines HuCCA-1 and HuCCT1, were used. GEM resistance was examined by measuring cell viability in the presence of GEM using an MTS assay. Exosomes were isolated using ultracentrifugation and quantified using ELISA. Comprehensive expression analysis was performed using RNA sequencing. The effects of microRNAs were examined by miRNA mimic transfection., Results: The conditioned medium and exosomes derived from CC-LP-1-GR cells enhanced the GEM resistance of parental CC-LP-1 cells. In the presence of GEM, the p53 pathway was negatively enriched in CC-LP-1-GR and CC-LP-1 cells treated with exosomes from CC-LP-1-GR (rExo) compared to CC-LP-1 cells. The expression of miR-141-3p was higher in rExos than in CC-LP-1 cells. CC-LP-1 cells transfected with miR-141-3p mimic showed significantly (p<0.05) increased viability in the presence of GEM., Conclusion: A GEM-resistant human BTC cell line, CC-LP-1-GR, may acquire resistance to GEM by exosomes containing miR-141-3p., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
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- 2024
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25. High serum proteinase-3 levels predict poor progression-free survival and lower efficacy of bevacizumab in metastatic colorectal cancer.
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Furuya K, Nakajima M, Tsunedomi R, Nakagami Y, Xu M, Matsui H, Tokumitsu Y, Shindo Y, Watanabe Y, Tomochika S, Maeda N, Iida M, Suzuki N, Takeda S, Hazama S, Ioka T, Hoshii Y, Ueno T, and Nagano H
- Subjects
- Humans, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bevacizumab therapeutic use, Biomarkers, Fluorouracil, Peptide Hydrolases, Prognosis, Progression-Free Survival, Colonic Neoplasms drug therapy, Colorectal Neoplasms drug therapy, Colorectal Neoplasms genetics, Rectal Neoplasms drug therapy, Myeloblastin blood
- Abstract
Background: To improve the prognosis of patients with metastatic colorectal cancer (mCRC), investigating predictive biomarkers of their prognosis and chemotherapeutic responsiveness is necessary. This study aimed to analyze the clinical significance of serum proteinase-3 (PRTN3) as a predictor for prognosis and chemosensitivity, especially to bevacizumab therapy, in mCRC., Methods: This single-center retrospective observational study enrolled 79 patients with mCRC in our hospital and 353 patients with colorectal cancer in the TCGA database. Preoperative serum PRTN3 levels were measured using an enzyme-linked immunosorbent assay. The clinicopathological characteristics and prognosis according to serum PRTN3 levels were then evaluated. PRTN3 expression in tumor and stromal cells was evaluated immunohistochemically. The impact of PRTN3 levels on angiogenesis and bevacizumab sensitivity was evaluated using the tube formation assay., Results: Serum PRTN3 levels were an independent poor prognostic factor for progression-free survival (PFS) (hazard ratio, 2.082; 95% confidence interval, 1.118-3.647; P=0.010) in patients with mCRC. Similarly, prognostic analysis with TCGA data sets showed poorer overall survival in patients with PRTN3 expression than that in patients without PRTN3 expression, especially in patients with stage IV. Immunohistochemical analysis of resected specimens revealed that stromal neutrophils expressed PRTN3, and their expression level was significantly correlated with serum PRTN3 levels. Interestingly, the effectiveness of first-line chemotherapy was significantly poorer in the high serum PRTN3 level group. High serum PRTN3 was significantly associated with poor PFS (hazard ratio, 3.027; 95% confidence interval, 1.175-7.793; P=0.0161) in patients treated with bevacizumab, an anti-angiogenic inhibitor. The tube formation assay revealed that PRTN3 administration notably augmented angiogenesis while simultaneously attenuating the anti-angiogenic influence exerted by bevacizumab therapy., Conclusions: Serum PRTN3 levels could be a novel predictive biomarker of PFS of first-line chemotherapy, especially for bevacizumab therapy, in patients with mCRC., (© 2024. The Author(s).)
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- 2024
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26. Third Report of the Japan Diabetes Society/Japanese Cancer Association Joint Committee on Diabetes and Cancer: Summary of the results of a questionnaire survey of oncologists and diabetologists-Secondary publication.
- Author
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Goto A, Ohashi K, Noda M, Noto H, Ueki K, Inoue M, Nishimura R, Takahashi S, Ioka T, Oshima M, Fujibayashi K, Tsuji A, Kodaira M, Tamakoshi A, Mimori K, Tanabe Y, Hara E, Matsuo K, Murakami Y, and Watada H
- Subjects
- Humans, Japan epidemiology, Surveys and Questionnaires, Diabetes Mellitus epidemiology, Neoplasms epidemiology, Neoplasms therapy, Physicians, Oncologists
- Abstract
The Japan Diabetes Society and the Japan Cancer Association launched a joint committee and published their "First Joint Committee Report on Diabetes and Cancer" in 2013, compiling recommendations for physicians and health-care providers as well as for the general population. In 2016, the "Second Joint Committee Report on Diabetes and Cancer" summarized the current evidence on glycemic control and cancer risk in patients with diabetes. The current "Third Joint Committee Report on Diabetes and Cancer", for which the joint committee also enlisted the assistance of the Japanese Society of Clinical Oncology and the Japanese Society of Medical Oncology, reports on the results from the questionnaire survey, "Diabetes Management in Patients Receiving Cancer Therapy," which targeted oncologists responsible for cancer management and diabetologists in charge of glycemic control in cancer patients. The results of the current survey indicated that there is a general consensus among oncologists and diabetologists with regard to the need for guidelines on glycemic control goals, the relevance of glycemic control, and glycemic control during cancer therapy in cancer patients., (© 2023 The Japanese Cancer Association (JCA) and The Japan Diabetes Society (JDS). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
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- 2024
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27. Effect of Paxillin Expression and Phosphorylation on Colorectal Cancer Prognosis and Metastasis.
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Zheng H, Tsunedomi R, Xu M, Zhang Y, Kishi H, Kobayashi S, Tomochika S, Nakajima M, Matsui H, Tokumitsu Y, Shindo Y, Iida M, Ioka T, and Nagano H
- Subjects
- Humans, Cell Line, Tumor, Cell Movement, Cell Proliferation, Neoplasm Metastasis, Phosphorylation, Prognosis, Colorectal Neoplasms pathology, Gene Expression Regulation, Neoplastic, Paxillin genetics, Paxillin metabolism
- Abstract
Background/aim: Colorectal cancer (CRC) is the third most common cancer worldwide, and metastasis is strongly associated with poor prognosis in patients with CRC. We have previously found that the expression and phosphorylation of paxillin (PXN) play an important role in the metastatic potential of breast cancer. This study examined the potential role of PXN in CRC metastasis., Materials and Methods: Resected tumor specimens from 92 patients with CRC were subjected to immunohistochemical analysis of PXN levels. Three human CRC cell lines, HCT116, LoVo, and SW480 were used for scratch and transwell invasion assays to examine the effects of PXN over-expression. RNA sequencing was performed to obtain the expression profiles under PXN over-expression., Results: High levels of PXN were significantly correlated with advanced stage, higher carcinoembryonic antigen and carbohydrate antigen 19-9 levels, and poorer overall survival. The migration ability of CRC cells was enhanced by exogenous PXN over-expression, but this enhancement was not observed in cells harboring exogenously mutated PXN at Tyr31 or Tyr88 phosphorylation sites. In PXN-over-expressing cells, TNF-α signaling via NF-[Formula: see text]B was positively enriched., Conclusion: PXN expression and phosphorylation at Tyr31 or Tyr88 may influence the migration and invasion of CRC cells. PXN expression and phosphorylation at Tyr31 or Tyr88 are promising targets for evaluating prognosis and treating CRC., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
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- 2024
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28. Third Report of the Japan Diabetes Society (JDS)/Japanese Cancer Association (JCA) Joint Committee on diabetes and cancer: summary of the results of a questionnaire survey of oncologists and diabetologists-secondary publication.
- Author
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Goto A, Ohashi K, Noda M, Noto H, Ueki K, Inoue M, Nishimura R, Takahashi S, Ioka T, Oshima M, Fujibayashi K, Tsuji A, Kodaira M, Tamakoshi A, Mimori K, Tanabe Y, Hara E, Matsuo K, Murakami Y, and Watada H
- Abstract
The Japan Diabetes Society (JDS) and the Japan Cancer Association (JCA) launched a joint committee and published their "First Joint Committee Report on Diabetes and Cancer" in 2013, compiling recommendations for physicians and healthcare providers as well as for the general population. In 2016, the "Second Joint Committee Report on Diabetes and Cancer" summarized the current evidence on glycemic control and cancer risk in patients with diabetes. The current "Third Joint Committee Report on Diabetes and Cancer", for which the joint committee also enlisted the assistance of the Japanese Society of Clinical Oncology (JSCO) and the Japanese Society of Medical Oncology (JSMO), reports on the results from the questionnaire survey, "Diabetes Management in Patients Receiving Cancer Therapy," which targeted oncologists responsible for cancer management and diabetologists in charge of glycemic control in cancer patients. The results of the current survey demonstrated that there is a general consensus among oncologists and diabetologists with regard to the need for guidelines on glycemic control goals, the relevance of glycemic control, and glycemic control during cancer therapy in cancer patients., Competing Interests: Conflict of interestHiroshi Noto received Honoraria (Sumitomo Pharma, Eli Lilly Japan, Novo Nordisk Pharma), Research funding (Maruho). Kohjiro Ueki received Honoraria (Sumitomo Pharma, Novo Nordisk Pharma, Taisho Pharmaceutical, Eli Lilly Japan, Abbott, Bayer, Kowa, Boehringer Ingelheim, Daiichi Sankyo), Research funding (Sumitomo Pharma, Eli Lilly Japan, Boehringer Ingelheim, Novo Nordisk Pharma, Sanofi), Subsidies or Donations (Sumitomo Pharma, Boehringer Ingelheim, Mitsubishi Tanabe Pharma, Takeda Pharmaceutical, Daiichi Sankyo, Novo Nordisk Pharma, Kyowa Kirin, Ono Pharmaceutical). Rimei Nishimura received Honoraria (Sanofi, Japan Medtronic, Boehringer Ingelheim, Takeda Pharmaceutical, Kissei Pharmaceutical, Novartis Pharma, Eli Lilly Japan, Novo Nordisk Pharma, MSD, Astellas Pharma, Abbott, Teijin Pharma, Sumitomo Pharma, Ono Pharmaceutical, AstraZeneca), Research funding (Mitsubishi Electoronic), Subsidies or Donations (Taisho Pharmaceutical, Ono Pharmaceutical, Takeda Pharmaceutical, Boehringer Ingelheim, Sumitomo Pharma, Abbott). Family member of Rimei Nishimura from M.E.I.: Tatsuya Ioka received Honoraria (Taiho Pharmaceutical, Servier Japan, AstraZeneca), Masanobu Oshima received Research funding (Epsilon Molecular Engineering), Akihito Tsuji received Honoraria (Eli Lilly Japan, Taiho Pharmaceutical, Chugai Pharmaceutical, Merck Biopharma, Daiichi Sankyo), Subsidies or Donations (Taiho Pharmaceutical), Yuko Tanabe received Research funding (Daiichi Sankyo, Ono Pharmaceutical, Eli Lilly Japan, MSD), Eiji Hara received Research funding (Ezaki Glico, Suntory Wellness), Yoshinori Murakami received Employment/Leadership position/Advisory role (FUJIFILM chairperson of the ethical committee of biomedicul research), Research funding (Nippon Telegraph and Telephone, Ono Pharmaceutical), Endowed departments by commercial entities (Nippon Telegraph and Telephone), Hirotaka Watada received Honoraria (Mitsubishi Tanabe Pharma, Teijin Pharma, Bayer Pharma Japan, Sanofi, Novo Nordisk Pharma, Boehringer Ingelheim, Sumitomo Pharma, Daiichi Sankyo, Abbott, Kowa, Taisho Pharmaceutical, Astellas Pharma, Kissei Pharmaceutical, AstraZeneca, Ono Pharmaceutical, Sanwa Kagaku, Takeda Pharmaceuticals, Eli Lilly Japan), Research funding (Boehringer Ingelheim, Sumitomo Pharma, Biofermin Pharmaceutical), Subsidies or Donations (Takeda Pharmaceuticals, Boehringer Ingelheim, Kissei Pharmaceutical, Novo Nordisk Pharma, Mitsubishi Tanabe Pharma, Lifescan Japan, Kyowa Kirin, Sumitomo Pharma, Eli Lilly Japan, Teijin Pharma, Taisho Pharmaceutical, Abbott, Ono Pharmaceutical), Endowed departments by commercial entities (Takeda Pharmaceuticals, Sanwa Kagaku, Soiken, Sumitomo Pharma, Taisho Pharmaceutical, Mitsubishi Tanabe Pharma, Ono Pharmaceutical, Kowa, MSD, Boehringer Ingelheim). The other co-authors have no conflict of interest., (© The Japan Diabetes Society and the Japanese Cancer Association 2023.)
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- 2024
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29. Laparoscopic spleen-preserving distal pancreatectomy: A novel technique with splenic artery resection and splenic vein preservation.
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Shindo Y, Tokumitsu Y, Nakajima M, Kimura Y, Matsui H, Iida M, Suzuki N, Takeda S, Ioka T, and Nagano H
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- Female, Humans, Adult, Spleen surgery, Spleen blood supply, Splenic Vein surgery, Pancreatectomy methods, Splenic Artery diagnostic imaging, Splenic Artery surgery, Laparoscopy methods, Pancreatic Neoplasms diagnostic imaging, Pancreatic Neoplasms surgery
- Abstract
Introduction: Laparoscopic spleen-preserving distal pancreatectomy (LSDP) is widely performed to treat benign and low-grade malignant diseases. Although preservation of splenic vessels may be desirable considering the risk of postoperative complications, it is sometimes difficult due to tumor size, inflammation, and proximity of the tumor and splenic vessels. Herein, we present the first case of LSDP with splenic artery resection and splenic vein preservation., Materials and Surgical Technique: A 40-year-old woman with a pancreatic tumor was referred to our hospital. Contrast-enhanced computed tomography (CT) revealed a tumor in the pancreatic tail that was in contact with the splenic artery and distant from the splenic vein. The splenic artery and vein were separated from the pancreas near the dissection line. The splenic artery was resected after pancreatic dissection using a linear stapler. After the pancreatic tail was separated from the splenic hilum while preserving the splenic vein, the distal side of the splenic artery was resected, and the specimen was removed. The postoperative course was uneventful and the patient was discharged on postoperative Day 9. Four months after surgery, postoperative follow-up CT findings showed neither splenic infarction nor gastric varices., Discussion: This technique is an alternative method of splenic preservation when there is no attachment of the tumor to the splenic vein or uncontrolled expected bleeding of the splenic artery using the Kimura technique., (© 2023 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)
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- 2024
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30. Loss of myocardial Hey2/Hrt2 function disrupts rightward shift of atrioventricular cushion tissue and causes tricuspid atresia.
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Okumura K, Ioka T, and Sakabe M
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- Animals, Mice, Humans, Heart, Myocardium, Transcription Factors, Basic Helix-Loop-Helix Transcription Factors genetics, Repressor Proteins, Tricuspid Atresia, Endocardial Cushion Defects
- Abstract
Background: Endocardial cushion tissue is primordia of the valves and septa of the adult heart, and its malformation causes various congenital heart diseases (CHDs). Tricuspid atresia (TA) is defined as congenital absence or agenesis of the tricuspid valve caused by endocardial cushion defects. However, little is known about what type of endocardial cushion defect causes TA., Results: Using three-dimensional volume rendering image analysis, we demonstrated morphological changes of endocardial cushion tissue in developing Hey2/Hrt2 KO mouse embryos that showed malformation of the tricuspid valve, which resembled human TA at neonatal period. In control embryos, atrioventricular (AV) endocardial cushion tissues showed rightward shift to form a tricuspid valve. However, the rightward shift of endocardial cushion tissue was disrupted in Hey2/Hrt2 KO embryos, leading to the misalignment of AV cushions. We also found that muscular tissue filled up the space between the right atrium and ventricle, resulting in the absence of the tricuspid valve. Moreover, analysis using tissue-specific conditional KO mice showed that HEY2/HRT2-expressing myocardium may physically regulate the AV shift., Conclusion: Disruption of rightward cushion movement is an initial cue of TA phenotype, and myocardial HEY2/HRT2 is necessary for the regulation of proper alignment of AV endocardial cushion tissue., (© 2023 American Association for Anatomy.)
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- 2024
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31. Impact of Tumor Shrinkage Pattern with Biweekly Triplet Gemcitabine+Cisplatin+S-1 Regimen for Biliary Tract Cancers: Implications for Neoadjuvant Therapy from the Data of KHBO1401 (KHBO1401-1A Study).
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Kobayashi S, Wada H, Sakai D, Baba H, Kanai M, Kamachi H, Takayama T, Ueno M, Takahashi M, Sho M, Yoshimura K, Hatano E, Nagano H, and Ioka T
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Adult, Treatment Outcome, Gemcitabine, Deoxycytidine analogs & derivatives, Deoxycytidine administration & dosage, Cisplatin administration & dosage, Neoadjuvant Therapy, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biliary Tract Neoplasms drug therapy, Biliary Tract Neoplasms pathology, Biliary Tract Neoplasms mortality, Drug Combinations, Tegafur administration & dosage, Oxonic Acid administration & dosage
- Abstract
Introduction: The multicenter randomized phase III KHBO1401 study (gemcitabine+cisplatin+S-1 [GCS] vs. GC in biliary tract cancers [BTC]) demonstrated that GCS not only prolonged patient survival but also achieved a high response rate and that it should be good for neoadjuvant therapy. Therefore, to explore the possibilities of neoadjuvant therapy, we investigated the tumor shrinkage pattern., Methods: Among the total of 246 patients enrolled in the KHBO1401, the tumor shrinkage pattern and survival were investigated in patients with measurable BTC (n = 183, 74%; GCS, n = 91; GC, n = 92)., Results: The tumor shrinkage pattern could be divided into 4 categories based on the response at 100 days after enrollment: categories A (<-30% in size), B (-30-0%), C (0% to +20%), and D (>+20%). The GCS arm included more category A and B cases (61 [67%] vs. 33 [36%], p < 0.0001). Each category predicted the best response and overall survival (p < 0.0001). Category A showed sustained tumor response compared with category B; in GCS, the time to maximum tumor response was 165 ± 76 days in category A and 139 ± 78 in category B. Categories C and D did not achieve tumor shrinkage. The maximum tumor shrinkage size in category A was -53% in the GCS arm and -65% in the GC arm (p = 0.0892). Twenty percent of patients in the GCS showed tumor regrowth 154 ± 143 days later., Conclusion: GCS provided faster and greater tumor shrinkage with better survival in comparison to GC, although 20% of patients showed regrowth after 6 cycles., (© 2023 S. Karger AG, Basel.)
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- 2024
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32. [A Case of HER2-Positive Advanced Breast Cancer Who Was Able to Start and Continue Chemotherapy Despite Liver Damage Due to Diffuse Liver Metastasis].
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Fujimoto T, Maeda N, Ioka T, and Nagano H
- Subjects
- Female, Humans, Receptor, ErbB-2, Antineoplastic Combined Chemotherapy Protocols adverse effects, Trastuzumab, Breast Neoplasms pathology, Liver Neoplasms drug therapy
- Abstract
49-year-old woman, who diagnosed advanced breast cancer with, ER-positive, HER2-positive, T4bN1M1, Stage Ⅳ. At the time of initial diagnosis, liver damage equivalent to Child-Pugh classification C due to diffuse liver metastasis was observed, but trastuzumab/pertuzumab(HP)and paclitaxel(PTX)adjusted according to liver function were administered every 3 weeks, resulting in rapid improvement of liver function, PR of the primary tumor(90% reduction), PR of the liver metastases(70% reduction), and improvement of tumor markers. Currently, chemotherapy has been switched to docetaxel (DTX)due to peripheral neuropathy caused by PTX, and treatment is continuing. In the case of HER2-positive breast cancer, good disease control may be achieved with aggressive treatment and intervention under dose adjustment and careful systemic management, even in the setting of liver injury.
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- 2023
33. [A Case of Malignant Lymphoma of the Bile Duct Mimicking Cholangiocarcinoma].
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Saeki S, Tokumitsu Y, Shindo Y, Matsui H, Nakajima M, Kimura Y, Iida M, Suzuki N, Takeda S, Ioka T, and Nagano H
- Subjects
- Male, Humans, Aged, Bile Ducts pathology, Bile Ducts, Intrahepatic pathology, Bile Duct Neoplasms diagnosis, Bile Duct Neoplasms surgery, Bile Duct Neoplasms pathology, Cholangiocarcinoma diagnosis, Lymphoma
- Abstract
During the postoperative follow-up for adrenal tumor for a 78-year-old male patient, a contrast-enhanced computed tomography scan revealed wall thickness with contrast effect in the cystic duct, enlarged lymph nodes along the ileocecal artery, and nodal shadow in the lower lobe of the left lung. First, the collected bile juice at ERC was submitted to cytology multiple times however, no malignant findings were noted. Next, a staging laparoscopy was performed; but the pathological findings of the enlarged lymph nodes and the abdominal lavage cytology showed no malignancy. A nodule in the lower lobe of the left lung was resected for diagnostic and therapeutic purposes, and the pathological diagnosis was primary adenocarcinoma of the lung. Finally the patient underwent exploratory laparotomy for diagnostic purposes. An intraoperative ultrasound- guided needle biopsy for mass lesion located in the medial section of the left liver was performed, and malignant lymphoma was suspected by the intraoperative pathological diagnosis. Cholecystectomy was performed to confirm the histological type, leading to the diagnosis of diffuse large B cell lymphoma. After surgery, the patient underwent 6 courses of rituximab plus CHOP therapy, and the bile duct stricture was improved.
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- 2023
34. Incidence and risk factors for venous thromboembolism in the Cancer-VTE Registry pancreatic cancer subcohort.
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Okusaka T, Saiura A, Shimada K, Ikeda M, Ioka T, Kimura T, Hosokawa J, Takita A, and Oba MS
- Subjects
- Humans, Incidence, Registries, Cerebral Infarction, Risk Factors, Venous Thromboembolism epidemiology, Venous Thromboembolism etiology, Ischemic Attack, Transient, Pancreatic Neoplasms complications, Pancreatic Neoplasms epidemiology
- Abstract
Background: This substudy of the Cancer-VTE Registry estimated venous thromboembolism (VTE) incidence and risk factors in pancreatic cancer patients., Methods: The Cancer-VTE Registry was an observational study that collected VTE data from patients with solid tumors across Japan. We measured baseline VTE prevalence, and at 1-year follow-up, the cumulative incidence of symptomatic and composite VTE (symptomatic VTE and incidental VTE requiring treatment), bleeding, cerebral infarction/transient ischemic attack (TIA)/systemic embolic event (SEE), and all-cause death., Results: Of 1006 pancreatic cancer patients, 86 (8.5%) had VTE at baseline, and seven (0.7%) had symptomatic VTE. Significant risk factors of baseline VTE were Eastern Cooperative Oncology Group performance status (ECOG PS) of 1, body mass index (BMI) ≥ 25 kg/m
2 , history of VTE, D-dimer > 1.2 µg/mL, and hemoglobin < 10 g/dL. At 1-year follow-up, the cumulative incidence of events was higher for pancreatic cancer vs other cancers. Pancreatic cancer patients with VTE vs those without VTE had significantly higher incidences of bleeding, cerebral infarction/TIA/SEE, and all-cause death. No significant risk factors for composite VTE were identified., Conclusions: The cumulative incidence of composite VTE during cancer treatment was higher in pancreatic cancer than in other cancer types. Some risk factors for VTE prevalence at cancer diagnosis were identified. Although VTE prevalence at cancer diagnosis did not predict the subsequent 1-year incidence of composite VTE, it was a significant predictor of other events such as all-cause death in pancreatic cancer patients., Trial Registration: UMIN Clinical Trials Registry; UMIN000024942., (© 2023. The Author(s).)- Published
- 2023
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35. [A Severe Case of Bleeding from Duodenal Invasion Due to Co-Morbid IPMC with Arcuate Ligament Syndrome and IPDA Aneurysm].
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Umeno H, Matsui H, Tokumitsu Y, Shindo Y, Nakajima M, Watanabe Y, Tomochika S, Iida M, Suzuki N, Takeda S, Ioka T, and Nagano H
- Subjects
- Aged, 80 and over, Humans, Male, Celiac Artery surgery, Duodenum, Hemorrhage therapy, Ligaments, Mesenteric Artery, Superior, Pancreas, Syndrome, Aneurysm complications, Aneurysm surgery, Embolization, Therapeutic
- Abstract
An 81-year-old man with a history of left hemiplegia due to a cerebral hemorrhage was admitted to a clinic because of tarry stools. Endoscopic findings revealed an ulcerative lesion with hemorrhage in the descending duodenum. The patient was transferred to our hospital for treatment. Because endoscopic hemostasis was impossible, interventional radiology(IVR) hemostasis was performed using coil embolization for the feeding artery. Simultaneously, angiography showed stenosis of the root of the celiac axis due to arch ligament syndrome and an aneurysm of the inferior pancreaticoduodenal artery (IPDA). Due to the risk of rebleeding, subtotal stomach-preserving pancreatoduodenectomy was performed after the patient's overall condition had stabilized. Despite dissecting the arcuate ligament, the hepatic artery flow did not improve. Hence, a direct arterial anastomosis between the middle colic artery and the gastroduodenal artery was performed. Furthermore, due to the proximity of the IPDA aneurysm to the superior mesenteric artery, IVR embolization for the IPDA aneurysm was performed on postoperative day 8, and he was transferred to a rehabilitation hospital on postoperative day 57. The pathological result was invasive intraductal papillary mucinous carcinoma(IPMC). The patient has been an outpatient with no recurrence 12 months postoperatively.
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- 2023
36. Efficacy of Staging Laparoscopy in Patients With Pancreatic Cancer: A Single Center Prospective Cohort Study.
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Shindo Y, Tokumitsu Y, Matsui H, Nakajima M, Kimura Y, Iida M, Suzuki N, Takeda S, Ioka T, and Nagano H
- Subjects
- Humans, Male, Aged, Female, Prospective Studies, Neoplasm Staging, Retrospective Studies, Pancreatic Neoplasms diagnosis, Pancreatic Neoplasms surgery, Pancreatic Neoplasms pathology, Laparoscopy methods
- Abstract
Background/aim: Staging laparoscopy (SL) for pancreatic cancer (PC) is considered useful to improve accuracy of staging and resectability. However, given the current accuracy of preoperative imaging, the routine application of SL remains unclear. Therefore, we aimed to investigate the importance of SL in patients with PC without radiological distant metastasis., Patients and Methods: This was a prospective, cohort, observational study. SL was performed in all patients with PC without radiological distant metastasis before pancreatectomy or chemotherapy at the Yamaguchi University Hospital., Results: Between July 2020 and March 2023, 55 patients underwent SL with peritoneal cytology. The median age was 71, with 53% male patients. SL revealed occult metastasis in six (11%) patients including positive peritoneal cytology (n=6), and peritoneal dissemination (n=1). The resectability of unresectable locally advanced (UR-LA) was associated with a significantly increased risk of occult metastasis (p=0.0211). The median operative time was 40 min, and the median volume of blood loss was 3 ml. There were no severe complications (Clavien-Dindo III or higher)., Conclusion: SL with peritoneal cytology regardless of previous abdominal surgery is safe and effective to determine accurate staging. Therefore, SL with peritoneal cytology should be considered for patients with PC without radiological distant metastasis, especially in those with UR-LA., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
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- 2023
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37. A novel prediction model of pancreatic fistula after pancreaticoduodenectomy using only preoperative markers.
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Matsui H, Shindo Y, Yamada D, Ogihara H, Tokumitsu Y, Nakajima M, Iida M, Suzuki N, Takeda S, Nakagami Y, Kobayashi S, Eguchi H, Ioka T, Hamamoto Y, and Nagano H
- Subjects
- Humans, Pancreatic Fistula diagnosis, Pancreatic Fistula etiology, Pancreaticoduodenectomy adverse effects, Bayes Theorem, Risk Factors, Retrospective Studies, Postoperative Complications diagnosis, Postoperative Complications etiology, Postoperative Complications surgery, Pancreatic Neoplasms surgery, Pancreatic Neoplasms complications, Carcinoma, Pancreatic Ductal surgery
- Abstract
Background: Since clinically relevant postoperative pancreatic fistula (CR-POPF) can cause intra-abdominal hemorrhage and abscesses, leading to surgery-related deaths after pancreaticoduodenectomy (PD), its preoperative prediction is important to develop strategies for surgical procedures and perioperative management. This study aimed to establish a novel prediction model for CR-POPF using preoperative markers., Methods: On a training set of 180 patients who underwent PD at the Yamaguchi University Hospital, a combination of CR-POPF predictors were explored using the leave-one-out method with a unique discrete Bayes classifier. This predictive model was confirmed using a validation set of 366 patients who underwent PD at the Osaka University Hospital., Results: In the training set, CR-POPF occurred in 60 (33%) of 180 patients and 130 (36%) of 366 patients in the validation set using selected markers. In patients with pancreatic ductal adenocarcinoma (PDAC), the main pancreatic duct (MPD) index showed the highest prognostic performance and could differentiate CR-POPF with 87% sensitivity and 81% specificity among 84 patients in the training set. In the validation set, the sensitivity and specificity of the MPD index-based model for 130 PDAC samples were 93% and 87%, respectively. In patients with non-PDAC, the MPD index/body mass index (BMI) combination showed the highest prognostic performance and could differentiate CR-POPF with 84% sensitivity and 57% specificity among 96 patients in the training set. In the validation set, the sensitivity and specificity of the MPD index/BMI-based model for 236 non-PDAC samples were 85% and 53%, respectively., Conclusion: We developed a novel prediction model for pancreatic fistulas after PD using only preoperative markers. The MPD index and MPD index/BMI combination will be useful for CR-POPF assessment in PDAC and non-PDAC samples, respectively., (© 2023. BioMed Central Ltd., part of Springer Nature.)
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- 2023
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38. IL-6 Levels Correlate with Prognosis and Immunosuppressive Stromal Cells in Patients with Colorectal Cancer.
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Yamamoto T, Tsunedomi R, Nakajima M, Suzuki N, Yoshida S, Tomochika S, Xu M, Nakagami Y, Matsui H, Tokumitsu Y, Shindo Y, Watanabe Y, Iida M, Takeda S, Hazama S, Tanabe T, Ioka T, Hoshii Y, Kiyota A, Takizawa H, Kawakami Y, Ueno T, and Nagano H
- Subjects
- Humans, Forkhead Transcription Factors metabolism, Interleukin-6, Lymphocytes, Tumor-Infiltrating, Prognosis, Tumor Microenvironment, Colorectal Neoplasms metabolism, Interleukin-10 metabolism
- Abstract
Background: The prognosis for patients with colorectal cancer (CRC) is determined by tumor characteristics as well as the host immune response. This study investigated the relationship between an immunosuppressive state and patient prognosis by evaluating the systemic and tumor microenvironment (TME) interleukin (IL)-6 levels., Methods: Preoperative serum IL-6 levels were measured using an electrochemiluminescence assay. Expression of IL-6 in tumor and stromal cells was evaluated immunohistochemically in 209 patients with resected CRC. Single-cell analysis of tumor-infiltrating immune cells was performed using mass cytometry in 10 additional cases., Results: Elevated serum IL-6 levels were associated with elevated stromal IL-6 levels and a poor prognosis for patients with CRC. High IL-6 expression in stromal cells was associated with low-density subsets of CD3
+ and CD4+ T cells as well as FOXP3+ cells. Mass cytometry analysis showed that IL-6+ cells among tumor-infiltrating immune cells were composed primarily of myeloid cells and rarely of lymphoid cells. In the high-IL-6-expression group, the percentages of myeloid-derived suppressor cells (MDSCs) and CD4+ FOXP3high CD45RA- effector regulatory T cells (eTreg) were significantly higher than in the low-IL-6-expression group. Furthermore, the proportion of IL-10+ cells in MDSCs and that of IL-10+ or CTLA-4+ cells in eTregs correlated with IL-6 levels., Conclusion: Elevated serum IL-6 levels were associated with stromal IL-6 levels in CRC. High IL-6 expression in tumor-infiltrating immune cells also was associated with accumulation of immunosuppressive cells in the TME., (© 2023. Society of Surgical Oncology.)- Published
- 2023
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39. Effect of systemic inflammatory response on induction chemotherapy followed by chemoradiotherapy for locally advanced pancreatic cancer: an exploratory subgroup analysis on systemic inflammatory response in JCOG1106.
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Mizuno N, Ioka T, Ogawa G, Nakamura S, Hiraoka N, Ito Y, Katayama H, Takada R, Kobayashi S, Ikeda M, Miwa H, Okano N, Kuramochi H, Sekimoto M, Okusaka T, Ozaka M, Todaka A, Gotoh K, Tobimatsu K, Yamaguchi H, Nakagohri T, Kajiura S, Sudo K, Okamura K, Shimizu S, Shirakawa H, Kato N, Sano K, Iwai T, Fujimori N, Ueno M, Ishii H, and Furuse J
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- Humans, Induction Chemotherapy, Chemoradiotherapy adverse effects, Chemoradiotherapy methods, Systemic Inflammatory Response Syndrome drug therapy, Systemic Inflammatory Response Syndrome etiology, Antineoplastic Combined Chemotherapy Protocols adverse effects, C-Reactive Protein metabolism, Pancreatic Neoplasms drug therapy
- Abstract
Objective: JCOG1106, a randomized phase II trial conducted to compare chemoradiotherapy (S-1 concurrent radiotherapy) with (Arm B) or without (Arm A) induction chemotherapy using gemcitabine in patients with locally advanced pancreatic cancer, showed a more favorable long-term survival in Arm A. This study was aimed at exploring whether some subgroups classified by the systemic inflammatory response might derive greater benefit from either treatment., Methods: All subjects eligible for JCOG1106 were included in this analysis (n = 51/49 in Arm A/B). This exploratory subgroup analysis was performed by Cox regression analysis to investigate the impact of the systemic inflammatory response, as assessed based on the serum C-reactive protein, serum albumin (albumin), Glasgow Prognostic Score and derived neutrophil-lymphocyte ratio, at the baseline on overall survival. P values <0.1 for the interaction were regarded as denoting significant association., Results: Glasgow prognostic score showed significant treatment interactions for overall survival. Hazard ratios of Arm B to Arm A were 1.35 (95% confidence interval, 0.82-2.23) in the Glasgow Prognostic Score 0 (C-reactive protein ≤10 mg/L and albumin ≥35 g/L) (n = 44/34 in Arm A/B) and 0.59 (95% confidence interval, 0.24-1.50) in the Glasgow Prognostic Score 1/2 (C-reactive protein >10 mg/L and/or albumin <35 g/L) (n = 7/15) (P-interaction = 0.06). C-reactive protein alone and albumin alone also showed significant treatment interactions for overall survival., Conclusions: Survival benefits of induction chemotherapy in chemoradiotherapy for locally advanced pancreatic cancer were observed in patients with elevated Glasgow Prognostic Score, high C-reactive protein and low albumin. These results suggest that systemic inflammatory response might be considered to apply induction chemotherapy preceding chemoradiotherapy., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)
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- 2023
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40. Impact of conversion surgery after chemotherapy in patients with initially unresectable and recurrent biliary tract cancer.
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Nakamura I, Hatano E, Baba H, Kamei K, Wada H, Shimizu J, Kanai M, Yoshimura K, Nagano H, and Ioka T
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Purpose: Gemcitabine, cisplatin, and S-1 chemotherapy was superior to gemcitabine and cisplatin chemotherapy for progression-free survival and overall survival for unresectable and recurrent biliary tract cancer in a randomized phase III trial (KHBO1401). This study aimed to evaluate the outcome of conversion surgery after chemotherapy in biliary tract cancer patients (ancillary study, KHBO1401-3C)., Methods: A total of 246 patients were enrolled in KHBO1401. We compared progression-free and overall survivals between the conversion surgery and non-conversion surgery groups., Results: Eight patients (3.3%) underwent conversion surgery with chemotherapy, seven of whom were diagnosed with unresectable disease and one with recurrence. Six and two patients received gemcitabine, cisplatin, and S-1 chemotherapy as well as gemcitabine and cisplatin chemotherapy, respectively. Three patients in the conversion surgery group who received gemcitabine, cisplatin, and S-1 chemotherapy showed no disease progression and survived without postoperative chemotherapy. Preoperative carbohydrate antigen 19-9 (CA19-9) level was a prognostic factor for conversion surgery. After correcting for immortal time bias, 1-year progression-free survival rates in the conversion surgery and non-conversion surgery groups were 50.0% and 19.0%, respectively (hazard ratio 0.343, 95% confidence interval 0.286-0.843, p = 0.0092). One-year overall survival rates in the conversion surgery and non-conversion surgery groups were 87.5% and 56.0%, respectively (hazard ratio 0.222, 95% confidence interval 0.226-0.877, p = 0.0197)., Conclusions: Conversion surgery might be an option for the treatment of unresectable and recurrent biliary tract cancer in patients with normal preoperative CA19-9 level., Competing Interests: E.H. received lecture fees from Taiho, and E.H. and T.I. received research expenses, scholarship donations (grants) from Taiho. H.B. and H.N. are editorial board members of the Annals of Gastroenterological Surgery., (© 2023 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery.)
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- 2023
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41. Phase I study of a novel therapeutic vaccine as perioperative treatment for patients with surgically resectable hepatocellular carcinoma: The YCP02 trial.
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Nakajima M, Hazama S, Tokumitsu Y, Shindo Y, Matsui H, Matsukuma S, Nakagami Y, Tamada K, Udaka K, Sakamoto M, Saito A, Kouki Y, Uematsu T, Xu M, Iida M, Tsunedomi R, Suzuki N, Takeda S, Ioka T, Doi S, and Nagano H
- Abstract
Aim: Developing effective adjuvant therapies is essential for improving the surgical outcomes in patients with hepatocellular carcinoma (HCC). Immunotherapy against HCC has become a promising strategy; however, only approximately 30% of all HCC patients respond to immunotherapy. Previously, we generated the novel therapeutic vaccine comprising multi-human leukocyte antigen-binding heat shock protein 70/glypican-3 peptides with a novel adjuvant combination of hLAG-3Ig and poly-ICLC. We also confirmed the safety of this vaccination therapy, as well as its capacity for the effective induction of immune responses in a previous clinical trial., Methods: In this phase I study, we administered this vaccine intradermally six times before surgery, and 10 times after surgery to patients with untreated, surgically resectable HCC (stage II to IVa). The primary end-points of this study were the safety and feasibility of this treatment. We also analyzed the resected tumor specimens pathologically using hematoxylin-eosin staining and immunohistochemistry for heat shock protein 70, glypican 3, CD8 and programmed death-1., Results: A total of 20 human leukocyte antigen-matched patients received this vaccination therapy with an acceptable side-effect profile. All patients underwent planned surgery without vaccination-related delay. Immunohistochemical analyses revealed that potent infiltration of CD8
+ T cells into tumors with target antigen expression was observed in 12 of 20 (60%) patients., Conclusions: This novel therapeutic vaccine was safe as perioperative immunotherapy for patients with HCC, and has the potential to strongly induce CD8+ T cells infiltration into tumors., (© 2023 Japan Society of Hepatology.)- Published
- 2023
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42. Current progress in perioperative chemotherapy for biliary tract cancer.
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Ioka T, Shindo Y, Ueno M, and Nagano H
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Biliary tract cancer (BTCs) is a heterogeneous malignancy divided into cholangiocarcinoma, gallbladder cancer, and ampullary cancer. Due to little or no symptoms, most patients with BTCs are diagnosed with unresectable or metastatic disease. Only 20%-30% of all BTCs are suitable for potentially resectable diseases. Although radical resection with a negative surgical margin is the only potentially curative method for BTCs, most patients develop postoperative recurrence, which is associated with poor prognosis. Therefore, perioperative treatment is necessary to improve survival. There are very few randomized phase III clinical trials of perioperative chemotherapy due to the relative rarity of BTCs. Adjuvant chemotherapy with S-1 for patients with resected BTC significantly increased overall survival compared with upfront surgery in a recent ASCOT trial. In East Asia, S-1 is currently considered the standard adjuvant chemotherapy, while capecitabine may still be used in other areas. Since then, our phase III trial (KHBO1401), gemcitabine and cisplatin plus S-1 (GCS) has become the standard chemotherapy for advanced BTCs. GCS not only improved overall survival but demonstrated a high response rate. The efficacy of GCS as a preoperative neoadjuvant chemotherapy for resectable BTCs has been investigated in a randomized phase III trial (JCOG1920) in Japan. In this review, we summarize the current and ongoing clinical trials focusing on adjuvant and neoadjuvant chemotherapy for BTCs., Competing Interests: MU has received research funding from Taiho, Incyte, AstraZeneca, Merck, MSD, Astellas, Eisai, and Ono, and honoraria from Taiho, Yakult, Chugai, Incyte, AstraZeneca, MSD, Eisai, and Ono. Hiroaki Nagano is an editorial member of the Annals of Gastroenterological Surgery. The other authors declare no conflicts of interest., (© 2023 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery.)
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- 2023
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43. Overexpression of GRK2 in vascular smooth muscle leads to inappropriate hypertension and acute heart failure as in clinical scenario 1.
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Yano H, Onoue K, Tokinaga S, Ioka T, Ishihara S, Hashimoto Y, Nakada Y, Nakagawa H, Ueda T, Seno A, Nishida T, Watanabe M, and Saito Y
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- Mice, Male, Animals, Muscle, Smooth, Vascular metabolism, G-Protein-Coupled Receptor Kinase 2 genetics, G-Protein-Coupled Receptor Kinase 2 metabolism, Heart, Receptors, Adrenergic, beta, Heart Failure, Hypertension genetics
- Abstract
Clinical scenario 1 (CS1) is acute heart failure (HF) characterized by transient systolic blood pressure (SBP) elevation and pulmonary congestion. Although it is managed by vasodilators, the molecular mechanism remains unclear. The sympathetic nervous system plays a key role in HF, and desensitization of cardiac β-adrenergic receptor (AR) signaling due to G protein-coupled receptor kinase 2 (GRK2) upregulation is known. However, vascular β-AR signaling that regulates cardiac afterload remains unelucidated in HF. We hypothesized that upregulation of vascular GRK2 leads to pathological conditions similar to CS1. GRK2 was overexpressed in vascular smooth muscle (VSM) of normal adult male mice by peritoneally injected adeno-associated viral vectors driven by the myosin heavy chain 11 promoter. Upregulation of GRK2 in VSM of GRK2 overexpressing mice augmented the absolute increase in SBP (+ 22.5 ± 4.3 mmHg vs. + 36.0 ± 4.0 mmHg, P < 0.01) and lung wet weight (4.28 ± 0.05 mg/g vs. 4.76 ± 0.15 mg/g, P < 0.01) by epinephrine as compared to those in control mice. Additionally, the expression of brain natriuretic peptide mRNA was doubled in GRK2 overexpressing mice as compared to that in control mice (P < 0.05). These findings were similar to CS1. GRK2 overexpression in VSM may cause inappropriate hypertension and HF, as in CS1., (© 2023. The Author(s).)
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- 2023
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44. FIGHT-102: A phase 1 study of pemigatinib in Japanese patients with advanced malignancies.
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Fujiwara Y, Kuboki Y, Furukawa M, Mizuno N, Hara H, Ioka T, Ueno M, Takahashi Y, Takahashi S, Takeuchi S, Lihou C, Ji T, Tian C, and Shimizu T
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- Adult, Humans, Young Adult, East Asian People, Neoplasms drug therapy, Morpholines therapeutic use, Pyrimidines therapeutic use, Pyrroles therapeutic use
- Abstract
Background: FIGHT-102 was a phase 1, dose-escalation, dose-expansion study of pemigatinib in Japanese patients with advanced solid tumors. Here, we report safety, tolerability, and preliminary efficacy of pemigatinib from FIGHT-102., Methods: Patients (≥20 years old) self-administered oral pemigatinib 9, 13.5, or 18 mg QD on intermittent dosing (Part 1) or 13.5 mg QD intermittent or continuous dosing (Part 2). A dosing cycle was 21 days (2 weeks on/1 week off or 21 continuous days). Primary endpoint was safety. Secondary endpoints were pharmacokinetics, pharmacodynamics, and preliminary efficacy., Results: Forty-four patients (Part 1, n = 14; Part 2, n = 30) were enrolled; most common tumors, cholangiocarcinoma, n = 8; esophageal, n = 6; 26 patients had confirmed FGF/FGFR alterations (Part 1, n = 3; Part 2, n = 23); 70.5% had ≥3 prior systemic therapies. Maximum tolerated dose was not identified. The recommended phase 2 dosage was determined to be 13.5 mg QD. Most common treatment-emergent adverse events (TEAEs) were hyperphosphatemia (81.8%), dysgeusia (45.5%), stomatitis (43.2%), and alopecia (38.6%); most frequent Grade ≥3 TEAEs were anemia and decreased appetite (9.1% each). In Part 1, no patient achieved partial response (PR) or complete response, and 7 (50.0%) patients had stable disease (SD). In Part 2, 5 (16.7%) patients achieved PR (one each with cholangiocarcinoma, gall bladder cancer, breast cancer, urothelial tract/bladder cancer, and sweat gland carcinoma) and 6 (20%) had SD. Median duration of response was 9.56 months (95% CI: 4.17, 14.95)., Conclusions: Pemigatinib demonstrated manageable adverse events, consistent pharmacokinetics and pharmacodynamics profiles, and preliminary efficacy in Japanese patients with advanced solid tumors., (© 2023 Incyte Corporation and The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2023
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45. Napabucasin plus nab-paclitaxel with gemcitabine versus nab-paclitaxel with gemcitabine in previously untreated metastatic pancreatic adenocarcinoma: an adaptive multicentre, randomised, open-label, phase 3, superiority trial.
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Bekaii-Saab T, Okusaka T, Goldstein D, Oh DY, Ueno M, Ioka T, Fang W, Anderson EC, Noel MS, Reni M, Choi HJ, Goldberg JS, Oh SC, Li CP, Tabernero J, Li J, Foos E, Oh C, and Van Cutsem E
- Abstract
Background: Compared with normal cells, tumour cells contain elevated levels of reactive oxygen species (ROS). Increased levels of the antioxidant protein NAD(P)H:quinone oxidoreductase 1 (NQO1) and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) correlate negatively with the survival of patients with pancreatic cancer. Napabucasin is an investigational, orally administered ROS generator bioactivated by NQO1., Methods: In the open-label, phase 3 CanStem111P study (NCT02993731), adults with previously untreated metastatic pancreatic adenocarcinoma (mPDAC) were randomised (1:1) to napabucasin plus nab-paclitaxel with gemcitabine or nab-paclitaxel with gemcitabine alone. The primary endpoint was overall survival (OS). In exploratory analyses, OS was evaluated in the subgroup of patients with tumours positive for pSTAT3 (biomarker-positive)., Findings: Between 30 January 2017 and 20 February 2019, a total of 1779 patients were screened across 165 study sites in Austria, Australia, Belgium, Canada, China, Czech Republic, France, Germany, Italy, Japan, Korea, Netherlands, Poland, Portugal, Russia, Singapore, Spain, Taiwan, Ukraine, and the US. Of the 565 and 569 patients randomised to the napabucasin and control treatment arms, respectively, 206 and 176 were biomarker-positive. Median (95% confidence interval [CI]) OS in the napabucasin and control treatment arms was 11.4 (10.5-12.2) and 11.7 (10.7-12.7) months, respectively (hazard ratio, 1.07; 95% CI, 0.93-1.23). Due to the lack of OS improvement in the napabucasin arm, CanStem111P was terminated due to futility. In the biomarker-positive subgroup, no difference between treatment arms was found for OS. Grade ≥3 adverse events were reported in 85.4% and 83.9% of napabucasin-treated and control-treated patients, respectively. The incidence of gastrointestinal-related grade ≥3 events was higher with napabucasin (diarrhoea: 11.6% vs 4.9%; abdominal pain: 10.0% vs 4.8%)., Interpretation: Our findings suggested that although the addition of napabucasin to nab-paclitaxel with gemcitabine did not improve efficacy in patients with previously untreated mPDAC, the safety profile of napabucasin was consistent with previous reports. CanStem111P represents the largest cohort of patients with mPDAC administered nab-paclitaxel with gemcitabine in the clinical trial setting. Our data reinforce the value of nab-paclitaxel plus gemcitabine as a platform for novel therapeutics approaches in mPDAC., Funding: The Sumitomo Pharma Oncology, Inc., Competing Interests: Tanios Bekaii-Saab has received research funding (paid to institution) from Agios, Arys, Arcus, Atreca, Boston Biomedical, Bayer, Amgen, Merck, Celgene, Lilly, Ipsen, Clovis, Seattle Genetics, Genentech, Novartis, Mirati, Merus, Abgenomics, Incyte, Pfizer, and Bristol Myers Squibb; served as a consultant (paid to institution) to Ipsen, Array, Pfizer, Seattle Genetics, Bayer, Genentech, Incyte, and Merck; served as a consultant (paid to self) to AbbVie, Boehringer Ingelheim, Janssen, Eisai, Daichii Sankyo, Natera, TreosBio, Celularity, Exact Science, Sobi, Beigene, Xilis, AstraZeneca, and Foundation Medicine; served on independent data monitoring committees/data and safety monitoring boards (paid to self) for AstraZeneca, Exelixis, Lilly, PanCan, and 1Globe; participated in advisory boards for Imugene, Immuneering, and Sun Biopharma; and holds the following inventions/patents: WO/2018/183488 and WO/2019/055687. Takuji Okusaka has received research grants (paid to self and institution) from Eisai, Eli Lilly, Sumitomo Dainippon Pharma Oncology, AstraZeneca, Chugai, Bristol Myers Squibb, Merck Sharp & Dohme, Baxter, and Taiho; participates in advisory boards for Sumitomo Pharma Oncology, Bristol Myers Squibb, and Nihon Servier; and has been a member of speakers' bureaus at Eisai, Novartis, Eli Lilly, Sumitomo Pharma Oncology, AstraZeneca, Chugai, Bristol Myers Squibb, Merck Sharp & Dohme, Taiho, Nihon Servier, Ono, Yakult Honsha, Daiichi Sankyo, Nippon Shinyaku, Pfizer, and Mundipharma. Do-Youn Oh participates in advisory boards (paid to self) for AstraZeneca, Novartis, Genentech/Roche, 13 Merck Serono, Bayer, Taiho, ASLAN, Halozyme, Zymeworks, Bristol Myers Squibb/Celgene, BeiGene, Basilea, Turning Point, Yuhan, Arcus Biosciences and IQVIA and has received research grants (paid to institution) from AstraZeneca, Novartis, Array, Eli Lilly, 15 Servier, BeiGene, Merck Sharp & Dohme, and Handok. Makoto Ueno has been an invited speaker (paid to self) for Taiho, Yakult Honsha, AstraZeneca, Merck, Eisai, Merck Sharp & Dohme, Servier, and Chugai and has received research grants (paid to institution) from Astellas, Taiho, Eisai, AstraZeneca, Ono, Merck Sharp & Dohme, Merck, Incyte, and Chugai. Tatsuya Ioka is a member of speakers’ bureaus at and serves as an advisor to Taiho (paid to self), is on the advisory board (paid to self) at Incyte, and has received research grants (paid to institution) from AstraZeneca, Incyte, Eisai, and Astellas. Michele Reni has participated in advisory boards (paid to self) for Eli Lilly, Celgene, AstraZeneca, Shire, Baxter, Servier, SOTIO, Viatris, and Merck Sharp & Dohme. Hye Jin Choi has received consulting fees (paid to self) from AstraZeneca and Roche. Josep Tabernero has participated in advisory boards (paid to self) for Array, AstraZeneca, Avvinity, Bayer, Boehringer, Chugai, Daiichi Sankyo, F. Hoffman La Roche, Genentech, HalioDx, Hutinson, Ikena Oncology, IQVIA, Lily, Menarini, Merck Serono, Merus, Merck Sharp & Dohme, Mirati, Neophore, Novartis, Orion, Peptomyc, Pfizer, Pierre Fabre, Samsung Biologics, Sanofi, Seattle Genomics, Servier, Taiho, Tessa, and Theramyc. Jian Li is a salaried employee of Sumitomo Pharma Oncology. Emma Foos was a salaried employee of Sumitomo Pharma Oncology at the time that these analyses were undertaken. Cindy Oh was a salaried employee of Sumitomo Pharma Oncology at the time that these analyses were undertaken. Eric Van Cutsem has participated in advisory boards Abbvie, ALX, Amgen, Array, Astellas, Astrazeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi, GSK, Incyte, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Mirati, Novartis, Nordic, Pierre Fabre, Pfizer, Roche, Seattle Genetics, Servier, Takeda, Terumo, Taiho, Zymeworks. His institution has also received research grants from Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Roche, Servier. Weijia Fang, Eric C. Anderson, Jonathan S. Goldberg, Sang Cheul Oh, David Goldstein, Marcus Noel, and Chung-Pin Li have nothing to disclose., (© 2023 The Author(s).)
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- 2023
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46. Anti-VEGF and Anti-EGFR Antibody Therapy on T-Cell Infiltration and TCR Variation in Metastatic Colorectal Cancer.
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Xu M, Tsunedomi R, Kiyotani K, Tomochika S, Furuya K, Nakajima M, Matsui H, Tokumitsu Y, Shindo Y, Yoshida S, Iida M, Suzuki N, Takeda S, Ioka T, Hazama S, and Nagano H
- Subjects
- Humans, T-Lymphocytes, Antibodies, Monoclonal pharmacology, Receptors, Antigen, T-Cell, alpha-beta, Receptors, Antigen, T-Cell, Antineoplastic Agents therapeutic use, Colorectal Neoplasms drug therapy, Liver Neoplasms drug therapy
- Abstract
Background/aim: Chemotherapy combined with anti-EGFR or anti-VEGF monoclonal antibodies (mAb) is widely used to treat patients with metastatic colorectal cancer (mCRC). Here, we investigated the effects of these antibodies on T-cell infiltration and T-cell receptor (TCR) repertoire variation in CRC liver metastases., Materials and Methods: Ten patients with mCRC received chemotherapy in combination with anti-EGFR (n=6) or anti-VEGF (n=4) mAb. T-cell infiltration was examined for CD3 and CD8 by carrying out immunohistochemistry on biopsy or surgical specimens from liver metastases before and after treatment. TCR repertoire analysis was carried out on specimens with post-treatment CD3
+ T-cell infiltration., Results: T-cell infiltrations were approximately 83% (5/6) and 50% (2/4), following treatment with anti-EGFR or anti-VEGF mAb, respectively. TCR repertoire analysis revealed higher clonality and lower diversity of TCR alpha and beta (TRA and TRB) in the anti-VEGF mAb group than that in the anti-EGFR group mAb. Furthermore, the percentage of the common TCR clones between infiltrating T cells and T cells in peripheral blood was significantly lower in the anti-VEGF mAb group compared to that in the anti-EGFR mAb group., Conclusion: The population of T cells infiltrating liver metastases in the anti-VEGF mAb group differed from that in the anti-EGFR mAb group., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)- Published
- 2023
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47. A prospective multicenter phase II study of FOLFIRINOX as a first-line treatment for patients with advanced and recurrent biliary tract cancer.
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Takahara N, Nakai Y, Isayama H, Sasaki T, Morine Y, Watanabe K, Ueno M, Ioka T, Kanai M, Kondo S, Okano N, and Koike K
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- Humans, Antineoplastic Combined Chemotherapy Protocols adverse effects, Prospective Studies, Neoplasm Recurrence, Local drug therapy, Pancreatic Neoplasms drug therapy, Biliary Tract Neoplasms drug therapy, Biliary Tract Neoplasms pathology, Neutropenia, Gastrointestinal Neoplasms drug therapy, Thrombocytopenia
- Abstract
Given the promising activity and tolerability of FOLFIRINOX as a second-line treatment for advanced biliary tract cancer (BTC), it can be an attractive first-line treatment option as well. This is a single-arm, open-label, multicenter phase II study to evaluate the safety and efficacy of FOLFIRINOX as a first-line treatment for patients with advanced BTC. Primary endpoint was progression-free survival (PFS), and the secondary endpoints included overall survival (OS), tumor response and safety. This study defined primary endpoint might be met when the lower limit value of 80% confidence interval [CI] of the median PFS ≥ 6.0 months. Between June 2016 and March 2020, 35 BTC patients (21 intrahepatic, 10 extrahepatic, 2 gallbladder, 2 ampulla) including 26 unresectable and 9 recurrent disease were enrolled. After a median follow-up of 13.9 months, the median PFS and OS were 7.4 (80% CI, 5.5-7.5) and 14.7 (80% CI, 11.8-15.7) months, respectively. Complete response was achieved in 1 (2.9%) and partial response in 10 (28.6%), giving an objective response rate of 31.4% and disease control rate of 74.3%. Major grade 3-4 adverse events included neutropenia (54.3%), leukopenia (34.4%), febrile neutropenia (17.1%), thrombocytopenia (8.6%), cholangitis (8.6%), anemia, nausea, diarrhea, and peripheral sensory neuropathy (2.9% each). FOLFIRINOX was well tolerable in patients with advanced BTC, however, this study did not meet the primary endpoint to conduct a phase III trial. Thus, further explorations are required to find a subset of patients and/or certain clinical scenario which might be beneficial from FOLFIRINOX., (© 2022. The Author(s).)
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- 2023
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48. Association between a single nucleotide polymorphism in the R3HCC1 gene and irinotecan toxicity.
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Kanesada K, Tsunedomi R, Hazama S, Ogihara H, Hamamoto Y, Shindo Y, Matsui H, Tokumitsu Y, Yoshida S, Iida M, Suzuki N, Takeda S, Ioka T, and Nagano H
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- Humans, Irinotecan, Polymorphism, Single Nucleotide, Camptothecin adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Fluorouracil, Leucovorin adverse effects, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms genetics, Colorectal Neoplasms drug therapy, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, Colonic Neoplasms drug therapy, Neutropenia chemically induced, Rectal Neoplasms drug therapy
- Abstract
Objective: Irinotecan is a useful anticancer drug for colorectal cancer treatment. UGT1A1*28 and *6 gene polymorphisms are known risk factors for irinotecan-associated toxicity. However, severe adverse effects due to irinotecan have been observed even in patients who do not harbor UGT1A1*28 or *6. We investigated gene polymorphisms in the whole exome to identify useful biomarkers for irinotecan toxicity other than UGT1A., Methods: A total of 178 patients with metastatic colorectal cancer (mCRC) and 87 patients with pancreatic cancer were treated with FOLFIRI, FOLFOX, FOLFOXIRI, modified FOLFIRINOX, or gemcitabine plus nab-paclitaxel. Genome-wide screening was performed using whole-exome sequencing (WES), and validation analysis was performed using qPCR with a hydrolysis probe., Results: Using WES after a doublet chemotherapy regimen comprising irinotecan and 5-fluorouracil (n = 15), seven single nucleotide polymorphisms (SNPs) were identified as candidate biomarkers for irinotecan-associated toxicity of neutropenia. Among the seven SNPs, an SNP in R3H domain and coiled-coil containing 1 (R3HCC1; c.919G > A, rs2272761) showed a significant association with neutropenia (>grade 3) after doublet chemotherapy. Patients receiving irinotecan including triplet chemotherapy, FOLFOXIRI for mCRC (n = 23) or modified FOLFIRINOX for pancreatic cancer (n = 40), also showed significant linear trends between R3HCC1 polymorphism and neutropenia (p = 0.017 and 0.046, respectively). No significant association was observed in patients treated with irinotecan-free regimens, FOLFOX for mCRC (n = 66), and gemcitabine plus nab-paclitaxel for pancreatic cancer (n = 47)., Conclusion: Thus, an SNP in the R3HCC1 gene may be a useful biomarker for the toxicity of irinotecan-containing chemotherapy for mCRC and pancreatic cancer., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2023
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49. Clinical outcomes of second‑line chemotherapy after gemcitabine and cisplatin plus S‑1 treatment for patients with advanced biliary tract cancer in the KHBO1401‑3A study.
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Shindo Y, Nagano H, Kanai M, Kobayashi S, Wada H, Sakai D, Eguchi H, Baba H, Kamachi H, Takayama T, Ueno M, Takahashi M, Nakagami Y, Yoshimura K, Hatano E, and Ioka T
- Subjects
- Humans, Gemcitabine, Cisplatin, Deoxycytidine, Retrospective Studies, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Treatment Outcome, Biliary Tract Neoplasms drug therapy, Bile Duct Neoplasms drug therapy
- Abstract
Since the completion of the KHBO1401 study, which evaluated the efficacy of the combination of gemcitabine (GEM) and cisplatin (GC) compared with GC plus S‑1 (GCS), GCS has become a standard chemotherapy for patients with advanced biliary tract cancer (BTC). However, there are currently no data revealing second‑line therapy options after GCS. The present study aimed to evaluate the survival outcomes of patients receiving second‑line chemotherapy for advanced BTC, refractory or intolerant to GCS, using data from the KHBO1401 study. Patients who received a second‑line treatment after GCS chemotherapy between July 2014 and February 2016 were retrospectively studied. Overall survival (OS) was calculated from the day of GCS treatment failure or the first day of second‑line chemotherapy to the final follow‑up date or until death from any cause. Among 83 patients refractory or intolerant to GCS chemotherapy, 51 (61%) received second‑line chemotherapy, including GCS (n=8), GC (n=15), GEM (n=6), GEM plus S‑1 (GS) (n=4) and S‑1 (n=18). The 6‑ and 12‑month OS rates were 66.7 and 44.4%, respectively, following second‑line chemotherapy, and 6.3 and 3.1%, respectively, in the best supportive care group (P<0.0001). In addition, the 12‑ and 24‑month OS rates were 59.3 and 36.2%, respectively, in the multidrug chemotherapy group, and 26.9 and 9.0%, respectively, in the single‑agent chemotherapy group (P=0.0191). These results suggested that second‑line combination chemotherapy is a viable treatment option for patients with advanced BTC that is refractory or intolerant to first‑line GCS therapy.
- Published
- 2023
- Full Text
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50. Liposomal irinotecan with fluorouracil and leucovorin after gemcitabine-based therapy in Japanese patients with metastatic pancreatic cancer: additional safety analysis of a randomized phase 2 trial.
- Author
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Furuse J, Ueno M, Ikeda M, Okusaka T, Teng Z, Furuya M, and Ioka T
- Subjects
- Humans, Irinotecan adverse effects, Leucovorin adverse effects, East Asian People, Fluorouracil therapeutic use, Liposomes therapeutic use, Diarrhea chemically induced, Diarrhea drug therapy, Antineoplastic Combined Chemotherapy Protocols adverse effects, Camptothecin adverse effects, Gemcitabine, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms pathology
- Abstract
Background: Nanoliposomal irinotecan (nal-IRI) was recently authorized in Japan for unresectable pancreatic cancer after disease progression following chemotherapy. Physicians now consider certain aspects of nal-IRI safety profile as slightly different from conventional irinotecan. This report aims to explore additional aspects of the nal-IRI safety in Japanese phase 2 study., Methods: We analyzed the incidence, time to first onset, and time to resolution for adverse events that require special attention and other selected toxicities in the nal-IRI combination group (n = 46)., Results: Leukopenia/neutropenia (76.1%/71.7%), diarrhea (58.7%) and hepatic dysfunction (41.3%) were the most commonly reported treatment-emergent adverse events, with a median time to onset of 21.0 days (range: 8, 97), 9.0 days (1, 61) and 22.0 days (2, 325), respectively, and a median time to resolution of 8.0 days (95% confidence intervals: 8, 9), 4.0 days (4, 8) and 40.0 days (9, -), respectively. Eight patients experienced Grade ≥ 3 diarrhea and their symptoms were well controlled by dose modification except one patient who had drug withdrawal. The median time to resolution for Grade ≥ 3 and Grade ≤ 2 diarrhea was 17.5 days (95% confidence intervals: 1, 31) and 4 days (3, 7), respectively. Anorexia occurred in 28/46 patients (60.9%) with a median time to onset of 4.0 days (range: 2, 132) and a median time to resolution of 12.0 days (95% confidence intervals: 6, 26)., Conclusions: We explored safety profile of nal-IRI combination regimen recognized as effective and tolerable treatment for Japanese unresectable pancreatic cancer patients. Although the treatment-emergent adverse events occurred were controllable, patients with prolonged toxicities should be closely managed., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)
- Published
- 2023
- Full Text
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