Annual Report 2020

Department of Pathology and Clinical Laboratories

Masato Sugano, Reiko Watanabe, Tokiko Nakai, Saori Miyazaki, Tetsuro Taki, Motohiro Kojima, Shingo Sakashita, Naoya Sakamoto, Takeshi Kuwata, Atsushi Ochiai, Takashi Kuroe, Shohei Murata, Satoshi Fujii, Yuko Kinowaki

Introduction

 The Department of Pathology and Clinical Laboratories (DPCL) conducts routine hospital services and supports research activities based on the requirement of ISO15189. The number of samples examined at the department in 2020 is shown in Table 1. We supported pathological diagnoses including 13,274 biopsy specimens, 3,222 intraoperative tissue specimens, 4,986 cytology specimens and 4 autopsy cases this year.

 Clinicopathological conferences are held regularly with each clinical department/section. Members participate in expert panel meetings every Thursday to medically interpret the results of a cancer gene panel test on.

Table. Number of pathology and cytology samples examined at the Pathology Division in 2020

The Team and What We Do

 We contribute to the provision of optimal medical care through quality-assured pathological diagnosis. We develop novel methods to perform translational research on the pathogenesis, diagnosis, and treatment of cancer. Some team members belong to both DPCL and the Division of Pathology/Division of Innovative Pathology and Laboratory Medicine, National Cancer Center Exploratory Oncology Research & Clinical Trial Center (EPOC), and are engaged in research aimed at understanding the biological characteristics of cancer and developing new therapies.

 We also support biobank construction (tissue preparation and tissue microarray construction).

Research activities

 The following are the major research results from this year.

1. Absence of definitive morphological features in a biopsy sample could be a useful predictor of the efficacy of pembrolizumab in NSq NSCLC patients with tumor PD-L1 scores ≥ 50%.

2. Using machine learning, we confirmed that the predominant stroma subtype was an independent factor for prognosis, suggesting that the ratio of the stromal component correlates with the malignant potential of SqCC of the lung.

3. We determined the optimal method for measuring pathological invasive size that predicts prognosis in invasive mucinous adenocarcinoma of the lung.

4. We found lymph node status and morphology are affected by differences in tumor histology. Moreover, the lymph node minor axis is a reliable parameter for the prediction of lymph node metastasis and has more utility as a predictive marker in pNENs than in PDACs.

5. We found that EGFR mutated lung cancer cells could develop EGFR-TKI resistance by Col I uptake via macropinocytosis.

6. We have shown that histological and radiological assessment of tumor necrosis is important in predicting the prognosis of PDAC.

7. Some biological functions of cancer stem cells might become evident only within the fibrous tumor microenvironment.

8. Water volumetry and tape measurement at 5 cm distal to the cubital fossa were useful to assess lymphedema in ISL stage II cases.

9. We contributed to the industry-university collaborative national genome screener SCRUM-Japan using histopathological specimens.

Clinical trials

 Pathological testing strengthens the quality control and quality assurance of clinical tests performed in the NCCHE's clinical trials.

Education

 The staff of the Clinical Laboratory Division regularly attend study sessions and lectures to improve their expertise and testing technique based on the requirement of ISO 15189.

 Clinicopathological conferences are held regularly with each clinical department/section. Conference-style training sessions are open weekly for the NCCHE residents.

 Staff members give lectures on diagnostic training and pathological research training to clinical residents in the NCCHE. They also offer professional guidance for NCCHE doctoral students of Juntendo University. Some staff are faculty members of the Graduate School of Frontier Sciences, University of Tokyo and instruct students in masters and doctoral courses.

Future Prospects

 Pathological diagnoses and laboratory tests play a fundamental role not just in routine hospital procedures but also in medical research. We acquired international standard ISO15189 authorization, and we aim to make advances in pathological diagnosis, laboratory tests, and clinical studies.

 In 2022, we will acquire CAP (College of American Pathologists) certification to form the basis for research and development at East Hospital and to be actively involved in the development of new therapies.

 We are strengthening the promotion of translational research of cancer diagnosis and treatment. We will strongly promote our research on how morphology is related to the malignant potential, genomic profile and immunophenotype of cancer cells.

List of papers published in 2020

Journal

1. Shirasawa M, Yoshida T, Horinouchi H, Kitano S, Arakawa S, Matsumoto Y, Shinno Y, Okuma Y, Goto Y, Kanda S, Watanabe R, Yamamoto N, Watanabe SI, Ohe Y, Motoi N. Prognostic impact of peripheral blood neutrophil to lymphocyte ratio in advanced-stage pulmonary large cell neuroendocrine carcinoma and its association with the immune-related tumour microenvironment. Br J Cancer, 124:925-932, 2021

2. Fujitani K, Nakamura K, Mizusawa J, Kuwata T, Shimoda T, Katayama H, Kushima R, Taniguchi H, Yoshikawa T, Boku N, Terashima M, Fukuda H, Sano T, Sasako M. Posttherapy topographical nodal status, ypN-site, predicts survival of patients who received neoadjuvant chemotherapy followed by curative surgical resection for non-type 4 locally advanced gastric cancer: supplementary analysis of JCOG1004-A. Gastric Cancer, 24:197-204, 2021

3. Hasegawa H, Taniguchi H, Nakamura Y, Kato T, Fujii S, Ebi H, Shiozawa M, Yuki S, Masuishi T, Kato K, Izawa N, Moriwaki T, Oki E, Kagawa Y, Denda T, Nishina T, Tsuji A, Hara H, Esaki T, Nishida T, Kawakami H, Sakamoto Y, Miki I, Okamoto W, Yamazaki K, Yoshino T. FMS-like tyrosine kinase 3 (FLT3) amplification in patients with metastatic colorectal cancer. Cancer Sci, 112:314-322, 2021

4. Yagishita S, Kato K, Takahashi M, Imai T, Yatabe Y, Kuwata T, Suzuki M, Ochiai A, Ohtsu A, Shimada K, Nishida T, Hamada A, Mano H. Characterization of the large-scale Japanese patient-derived xenograft (J-PDX) library. Cancer Sci, 112:2454-2466, 2021

5. Mukohara T, Hosono A, Mimaki S, Nakayama A, Kusuhara S, Funasaka C, Nakao T, Fukasawa Y, Kondoh C, Harano K, Naito Y, Matsubara N, Tsuchihara K, Kuwata T. Effects of Ado-Trastuzumab Emtansine and Fam-Trastuzumab Deruxtecan on Metastatic Breast Cancer Harboring HER2 Amplification and the L755S Mutation. Oncologist, 2021

6. Amemiya R, Miyoshi T, Aokage K, Suzuki J, Hoshino H, Udagawa H, Tane K, Sugano M, Kojima M, Fujii S, Kuwata T, Ochiai A, Goto K, Ikeda N, Tsuboi M, Ishii G. Prognostic impact of the tumor immune microenvironment in pulmonary pleomorphic carcinoma. Lung Cancer, 153:56-65, 2021

7. Suzuki J, Aokage K, Neri S, Sakai T, Hashimoto H, Su Y, Yamazaki S, Nakamura H, Tane K, Miyoshi T, Sugano M, Kojima M, Fujii S, Kuwata T, Ochiai A, Tsuboi M, Ishii G. Relationship between podoplanin-expressing cancer-associated fibroblasts and the immune microenvironment of early lung squamous cell carcinoma. Lung Cancer, 153:1-10, 2021

8. Sakai T, Udagawa H, Matsumoto S, Yoh K, Nosaki K, Ikeda T, Zenke Y, Kirita K, Niho S, Akimoto T, Goto K, Ishii G. Morphological, immune and genetic features in biopsy sample associated with the efficacy of pembrolizumab in patients with non-squamous non-small cell lung cancer. J Cancer Res Clin Oncol, 147:1227-1237, 2021

9. Sugita S, Kinoshita T, Kuwata T, Tokunaga M, Kaito A, Watanabe M, Tonouchi A, Sato R, Nagino M. Long-term oncological outcomes of laparoscopic versus open transhiatal resection for patients with Siewert type II adenocarcinoma of the esophagogastric junction. Surg Endosc, 35:340-348, 2021

10. Watanabe M, Kuwata T, Setsuda A, Tokunaga M, Kaito A, Sugita S, Tonouchi A, Kinoshita T, Nagino M. Molecular and pathological analyses of gastric stump cancer by next-generation sequencing and immunohistochemistry. Sci Rep, 11:4165, 2021

11. Shiraishi T, Ikeda K, Tsukada Y, Nishizawa Y, Sasaki T, Ito M, Kojima M, Ishii G, Tsumura R, Saijou S, Koga Y, Yasunaga M, Matsumura Y. High expression of TMEM180, a novel tumour marker, is associated with poor survival in stage III colorectal cancer. BMC Cancer, 21:302, 2021

12. Akagi K, Oki E, Taniguchi H, Nakatani K, Aoki D, Kuwata T, Yoshino T. Real-world data on microsatellite instability status in various unresectable or metastatic solid tumors. Cancer Sci, 112:1105-1113, 2021

13. Sunakawa H, Hori K, Kadota T, Shinmura K, Yoda Y, Ikematsu H, Tomioka T, Akimoto T, Hayashi R, Fujii S, Yano T. Relationship between the microvascular patterns observed by magnifying endoscopy with narrow-band imaging and the depth of invasion in superficial pharyngeal squamous cell carcinoma. Esophagus, 18:111-117, 2021

14. Ito R, Ikematsu H, Murano T, Shinmura K, Kojima M, Kumahara K, Furue Y, Sunakawa H, Minamide T, Sato D, Yamamoto Y, Takashima K, Yoda Y, Hori K, Yano T. Diagnostic ability of Japan Narrow-Band Imaging Expert Team classification for colorectal lesions by magnifying endoscopy with blue laser imaging versus narrow-band imaging. Endosc Int Open, 9:E271-E277, 2021

15. Mpekris F, Panagi M, Voutouri C, Martin JD, Samuel R, Takahashi S, Gotohda N, Suzuki T, Papageorgis P, Demetriou P, Pierides C, Koumas L, Costeas P, Kojima M, Ishii G, Constantinidou A, Kataoka K, Cabral H, Stylianopoulos T. Normalizing the Microenvironment Overcomes Vessel Compression and Resistance to Nano-immunotherapy in Breast Cancer Lung Metastasis. Adv Sci (Weinh), 8:2001917, 2021

16. Sekihara K, Aokage K, Hiyama T, Oiwa H, Miyoshi T, Tane K, Ishii G, Tsuboi M. Prognostic impact of home oxygen therapy on patients with resected non-small-cell lung cancer with interstitial lung disease. Surg Today, 51:1036-1043, 2021

17. Katsumata S, Aokage K, Ishii G, Hoshino H, Suzuki J, Miyoshi T, Tane K, Samejima J, Tsuboi M. Pathological features and prognostic implications of ground-glass opacity components on computed tomography for clinical stage I lung adenocarcinoma. Surg Today, 51:1188-1202, 2021

18. Morisue R, Kojima M, Suzuki T, Nakatsura T, Ojima H, Watanabe R, Sugimoto M, Kobayashi S, Takahashi S, Konishi M, Ishii G, Gotohda N, Fujiwara T, Ochiai A. Sarcomatoid hepatocellular carcinoma is distinct from ordinary hepatocellular carcinoma: Clinicopathologic, transcriptomic and immunologic analyses. Int J Cancer, 149:546-560, 2021

19. Su Y, Yamazaki S, Morisue R, Suzuki J, Yoshikawa T, Nakatsura T, Tsuboi M, Ochiai A, Ishii G. Tumor-Infiltrating T Cells Concurrently Overexpress CD200R with Immune Checkpoints PD-1, CTLA-4, and TIM-3 in Non-Small-Cell Lung Cancer. Pathobiology, 88:218-227, 2021

20. Matsumoto S, Nakanishi Y, Tanabe K, Yajima S, Watanabe R, Masuda H. A case of solid pseudopapillary neoplasm preoperatively diagnosed as left renal tumor. Urol Case Rep, 37:101630, 2021

21. Kobayashi S, Nakamura Y, Taniguchi H, Odegaard JI, Nomura S, Kojima M, Sugimoto M, Konishi M, Gotohda N, Takahashi S, Yoshino T. Impact of Preoperative Circulating Tumor DNA Status on Survival Outcomes After Hepatectomy for Resectable Colorectal Liver Metastases. Ann Surg Oncol, 2021

22. Yokohira M, Oshima M, Yamakawa K, Ye J, Nakano-Narusawa Y, Haba R, Fukumura Y, Hirabayashi K, Yamaguchi H, Kojima M, Okano K, Suzuki Y, Matsuda Y. Adequate tissue sampling for the assessment of pathological tumor regression in pancreatic cancer. Sci Rep, 11:6586, 2021

23. Inamori K, Togashi Y, Fukuoka S, Akagi K, Ogasawara K, Irie T, Motooka D, Kobayashi Y, Sugiyama D, Kojima M, Shiiya N, Nakamura S, Maruyama S, Suzuki Y, Ito M, Nishikawa H. Importance of lymph node immune responses in MSI-H/dMMR colorectal cancer. JCI Insight, 6:2021

24. Yagisawa M, Sawada K, Nakamura Y, Fujii S, Yuki S, Komatsu Y, Yoshino T, Sakamoto N, Taniguchi H. Prognostic Value and Molecular Landscape of HER2 Low-Expressing Metastatic Colorectal Cancer. Clin Colorectal Cancer, 20:113-120.e1, 2021

25. Tsuda H, Yoshida M, Akiyama F, Ohi Y, Kinowaki K, Kumaki N, Kondo Y, Saito A, Sasaki E, Nishimura R, Fujii S, Homma K, Horii R, Murata Y, Itami M, Kajita S, Kato H, Kurosumi M, Sakatani T, Shimizu S, Taniguchi K, Tamiya S, Nakamura H, Kanbayashi C, Shien T, Iwata H. Nuclear grade and comedo necrosis of ductal carcinoma in situ as histopathological eligible criteria for the Japan Clinical Oncology Group 1505 trial: an interobserver agreement study. Jpn J Clin Oncol, 51:434-443, 2021

26. Saito Y, Hayashi R, Iida Y, Mizumachi T, Fujii T, Matsumoto F, Beppu T, Yoshida M, Shinomiya H, Kamiyama R, Kitano M, Yokoshima K, Fujimoto Y, Hama T, Yamashita T, Okami K, Miura K, Fujisawa T, Sano D, Kato H, Minami S, Sugasawa M, Masuda M, Ota I, Iwae S, Kawata R, Monden N, Imai T, Asakage T, Okada M, Yoshikawa T, Tanioka K, Kitayama M, Doi M, Fujii S, Fujii M, Oridate N, Nakamizo M, Yoshimoto S, Homma A, Nibu KI, Yane K. Optimization of therapeutic strategy for p16-positive oropharyngeal squamous cell carcinoma: Multi-institutional observational study based on the national Head and Neck Cancer Registry of Japan. Cancer, 126:4177-4187, 2020

27. Kenmotsu H, Niho S, Tsuboi M, Wakabayashi M, Ishii G, Nakagawa K, Daga H, Tanaka H, Saito H, Aokage K, Takahashi T, Menju T, Kasai T, Yoshino I, Minato K, Okada M, Eba J, Asamura H, Ohe Y, Watanabe SI. Randomized Phase III Study of Irinotecan Plus Cisplatin Versus Etoposide Plus Cisplatin for Completely Resected High-Grade Neuroendocrine Carcinoma of the Lung: JCOG1205/1206. J Clin Oncol, 38:4292-4301, 2020

28. Kobayashi S, Takahashi S, Takahashi N, Masuishi T, Shoji H, Shinozaki E, Yamaguchi T, Kojima M, Gotohda N, Nomura S, Yoshino T, Taniguchi H. Survival Outcomes of Resected BRAF V600E Mutant Colorectal Liver Metastases: A Multicenter Retrospective Cohort Study in Japan. Ann Surg Oncol, 27:3307-3315, 2020

29. Sekine S, Yamashita S, Yamada M, Hashimoto T, Ogawa R, Yoshida H, Taniguchi H, Kojima M, Ushijima T, Saito Y. Clinicopathological and molecular correlations in traditional serrated adenoma. J Gastroenterol, 55:418-427, 2020

30. Kumagai S, Togashi Y, Kamada T, Sugiyama E, Nishinakamura H, Takeuchi Y, Vitaly K, Itahashi K, Maeda Y, Matsui S, Shibahara T, Yamashita Y, Irie T, Tsuge A, Fukuoka S, Kawazoe A, Udagawa H, Kirita K, Aokage K, Ishii G, Kuwata T, Nakama K, Kawazu M, Ueno T, Yamazaki N, Goto K, Tsuboi M, Mano H, Doi T, Shitara K, Nishikawa H. The PD-1 expression balance between effector and regulatory T cells predicts the clinical efficacy of PD-1 blockade therapies. Nat Immunol, 21:1346-1358, 2020

31. Kuwata T, Wakabayashi M, Hatanaka Y, Morii E, Oda Y, Taguchi K, Noguchi M, Ishikawa Y, Nakajima T, Sekine S, Nomura S, Okamoto W, Fujii S, Yoshino T. Impact of DNA integrity on the success rate of tissue-based next-generation sequencing: Lessons from nationwide cancer genome screening project SCRUM-Japan GI-SCREEN. Pathol Int, 70:932-942, 2020

32. Yamashita S, Hattori N, Fujii S, Yamaguchi T, Takahashi M, Hozumi Y, Kogawa T, El-Omar O, Liu YY, Arai N, Mori A, Higashimoto H, Ushijima T, Mukai H. Multi-omics analyses identify HSD17B4 methylation-silencing as a predictive and response marker of HER2-positive breast cancer to HER2-directed therapy. Sci Rep, 10:15530, 2020

33. Mukai H, Yamaguchi T, Takahashi M, Hozumi Y, Fujisawa T, Ohsumi S, Akabane H, Nishimura R, Takashima T, Park Y, Sagara Y, Toyama T, Imoto S, Mizuno T, Yamashita S, Fujii S, Uemura Y. Ki-67 response-guided preoperative chemotherapy for HER2-positive breast cancer: results of a randomised Phase 2 study. Br J Cancer, 122:1747-1753, 2020

34. Takehara K, Yamashita N, Watanabe R, Teramoto N, Tsuda H, Motohashi T, Harano K, Nakanishi T, Tokunaga H, Susumu N, Ueda Y, Yokoyama Y, Saito T. Clinical status and prognostic factors in Japanese patients with uterine leiomyosarcoma. Gynecol Oncol, 157:115-120, 2020

35. Yamazaki S, Su Y, Maruyama A, Makinoshima H, Suzuki J, Tsuboi M, Goto K, Ochiai A, Ishii G. Uptake of collagen type I via macropinocytosis cause mTOR activation and anti-cancer drug resistance. Biochem Biophys Res Commun, 526:191-198, 2020

36. Oki T, Aokage K, Nomura S, Tane K, Miyoshi T, Shiiya N, Funai K, Tsuboi M, Ishii G. Optimal method for measuring invasive size that predicts survival in invasive mucinous adenocarcinoma of the lung. J Cancer Res Clin Oncol, 146:1291-1298, 2020

37. Sato K, Mimaki S, Yamashita R, Togashi Y, Naito T, Udagawa H, Katsumata S, Nakasone S, Miyoshi T, Tane K, Aokage K, Sugano M, Kojima M, Fujii S, Kuwata T, Ochiai A, Goto K, Tsuboi M, Tsuchihara K, Ishii G. Association between the mutational smoking signature and the immune microenvironment in lung adenocarcinoma. Lung Cancer, 147:12-20, 2020

38. Koike Y, Aokage K, Ikeda K, Nakai T, Tane K, Miyoshi T, Sugano M, Kojima M, Fujii S, Kuwata T, Ochiai A, Tanaka T, Suzuki K, Tsuboi M, Ishii G. Machine learning-based histological classification that predicts recurrence of peripheral lung squamous cell carcinoma. Lung Cancer, 147:252-258, 2020

39. Sekihara K, Aokage K, Miyoshi T, Tane K, Ishii G, Tsuboi M. Perioperative pirfenidone treatment as prophylaxis against acute exacerbation of idiopathic pulmonary fibrosis: a single-center analysis. Surg Today, 50:905-911, 2020

40. Udagawa H, Kirita K, Naito T, Nomura S, Ishibashi M, Matsuzawa R, Hisakane K, Usui Y, Matsumoto S, Yoh K, Niho S, Ishii G, Goto K. Feasibility and utility of transbronchial cryobiopsy in precision medicine for lung cancer: Prospective single-arm study. Cancer Sci, 111:2488-2498, 2020

41. Sugita S, Kinoshita T, Kuwata T, Tokunaga M, Kaito A, Watanabe M, Tonouchi A, Sato R, Nagino M. Intramucosal-lymphatic invasion has a slight impact on lymph node metastasis in patients with early gastric cancer. Surg Today, 50:484-489, 2020

42. Kumagai S, Togashi Y, Sakai C, Kawazoe A, Kawazu M, Ueno T, Sato E, Kuwata T, Kinoshita T, Yamamoto M, Nomura S, Tsukamoto T, Mano H, Shitara K, Nishikawa H. An Oncogenic Alteration Creates a Microenvironment that Promotes Tumor Progression by Conferring a Metabolic Advantage to Regulatory T Cells. Immunity, 53:187-203.e8, 2020

43. Sugita S, Kuwata T, Tokunaga M, Kaito A, Watanabe M, Tonouchi A, Kinoshita T, Nagino M. Clinical significance of lymphatic invasion in the esophageal region in patients with adenocarcinoma of the esophagogastric junction. J Surg Oncol, 122:433-441, 2020

44. Sato D, Takamatsu T, Umezawa M, Kitagawa Y, Maeda K, Hosokawa N, Okubo K, Kamimura M, Kadota T, Akimoto T, Kinoshita T, Yano T, Kuwata T, Ikematsu H, Takemura H, Yokota H, Soga K. Distinction of surgically resected gastrointestinal stromal tumor by near-infrared hyperspectral imaging. Sci Rep, 10:21852, 2020

45. Fukuoka S, Hara H, Takahashi N, Kojima T, Kawazoe A, Asayama M, Yoshii T, Kotani D, Tamura H, Mikamoto Y, Hirano N, Wakabayashi M, Nomura S, Sato A, Kuwata T, Togashi Y, Nishikawa H, Shitara K. Regorafenib Plus Nivolumab in Patients With Advanced Gastric or Colorectal Cancer: An Open-Label, Dose-Escalation, and Dose-Expansion Phase Ib Trial (REGONIVO, EPOC1603). J Clin Oncol, 38:2053-2061, 2020

46. Kawazoe A, Fukuoka S, Nakamura Y, Kuboki Y, Wakabayashi M, Nomura S, Mikamoto Y, Shima H, Fujishiro N, Higuchi T, Sato A, Kuwata T, Shitara K. Lenvatinib plus pembrolizumab in patients with advanced gastric cancer in the first-line or second-line setting (EPOC1706): an open-label, single-arm, phase 2 trial. Lancet Oncol, 21:1057-1065, 2020

47. Kubota Y, Kawazoe A, Sasaki A, Mishima S, Sawada K, Nakamura Y, Kotani D, Kuboki Y, Taniguchi H, Kojima T, Doi T, Yoshino T, Ishii G, Kuwata T, Shitara K. The Impact of Molecular Subtype on Efficacy of Chemotherapy and Checkpoint Inhibition in Advanced Gastric Cancer. Clin Cancer Res, 26:3784-3790, 2020

48. Ishii T, Kawazoe A, Sasaki A, Mishima S, Kentaro S, Nakamura Y, Kotani D, Kuboki Y, Taniguchi H, Kojima T, Doi T, Yoshino T, Kuwata T, Ishii G, Shitara K. Clinical and molecular factors for selection of nivolumab or irinotecan as third-line treatment for advanced gastric cancer. Ther Adv Med Oncol, 12:1758835920942377, 2020

49. Kawazoe A, Kuboki Y, Shinozaki E, Hara H, Nishina T, Komatsu Y, Yuki S, Wakabayashi M, Nomura S, Sato A, Kuwata T, Kawazu M, Mano H, Togashi Y, Nishikawa H, Yoshino T. Multicenter Phase I/II Trial of Napabucasin and Pembrolizumab in Patients with Metastatic Colorectal Cancer (EPOC1503/SCOOP Trial). Clin Cancer Res, 26:5887-5894, 2020

50. Tsumura R, Koga Y, Hamada A, Kuwata T, Sasaki H, Doi T, Aikawa K, Ohashi A, Katano I, Ikarashi Y, Ito M, Ochiai A. Report of the use of patient-derived xenograft models in the development of anticancer drugs in Japan. Cancer Sci, 111:3386-3394, 2020

51. Nomura H, Tsuji D, Demachi K, Mochizuki N, Matsuzawa H, Yano T, Daiko H, Fujii S, Kojima T, Itoh K, Kawasaki T. ABCB1 and ABCC2 genetic polymorphism as risk factors for neutropenia in esophageal cancer patients treated with docetaxel, cisplatin, and 5-fluorouracil chemotherapy. Cancer Chemother Pharmacol, 86:315-324, 2020

52. Inaba A, Hori K, Yoda Y, Ikematsu H, Takano H, Matsuzaki H, Watanabe Y, Takeshita N, Tomioka T, Ishii G, Fujii S, Hayashi R, Yano T. Artificial intelligence system for detecting superficial laryngopharyngeal cancer with high efficiency of deep learning. Head Neck, 42:2581-2592, 2020

53. Yamamoto Y, Kadota T, Yoda Y, Hori K, Hatogai K, Kojima T, Fujii S, Akimoto T, Yano T. Review of early endoscopic findings in patients with local recurrence after definitive chemoradiotherapy for esophageal squamous cell carcinoma. Esophagus, 17:433-439, 2020

54. Umemoto K, Togashi Y, Arai Y, Nakamura H, Takahashi S, Tanegashima T, Kato M, Nishikawa T, Sugiyama D, Kojima M, Gotohda N, Kuwata T, Ikeda M, Shibata T, Nishikawa H. The potential application of PD-1 blockade therapy for early-stage biliary tract cancer. Int Immunol, 32:273-281, 2020

55. Kojima M, Yamauchi C, Oyamada S, Hojo T, Iwase S, Naito A, Yamano K, Takahashi S, Ochiai A. Assessment of Upper Limb Physiological Features in Patients with Lymphedema After Breast Surgery Using Multiple Instruments. Lymphat Res Biol, 18:239-246, 2020

56. Takahashi D, Kojima M, Morisue R, Sugimoto M, Kobayashi S, Takahashi S, Konishi M, Gotohda N, Ikeda M, Ochiai A. Comparison of morphological features in lymph node metastasis between pancreatic neuroendocrine neoplasms and pancreatic ductal adenocarcinomas. Pancreatology, 20:936-943, 2020

57. Kudo M, Kobayashi T, Gotohda N, Konishi M, Takahashi S, Kobayashi S, Sugimoto M, Okubo S, Martin J, Cabral H, Ishii G, Kojima M. Clinical Utility of Histological and Radiological Evaluations of Tumor Necrosis for Predicting Prognosis in Pancreatic Cancer. Pancreas, 49:634-641, 2020

58. Nishida Y, Nagatsuma AK, Kojima M, Gotohda N, Ochiai A. Novel stromal biomarker screening in pancreatic cancer patients using the in vitro cancer-stromal interaction model. BMC Gastroenterol, 20:411, 2020

59. Yasuta S, Kobayashi T, Aizawa H, Takahashi S, Ikeda M, Konishi M, Kojima M, Kuno H, Uesaka K, Morinaga S, Miyamoto A, Toyama H, Takakura N, Sugimachi K, Takayama W. Relationship between surgical R0 resectability and findings of peripancreatic vascular invasion on CT imaging after neoadjuvant S-1 and concurrent radiotherapy in patients with borderline resectable pancreatic cancer. BMC Cancer, 20:1184, 2020

60. Okuyama H, Ikeda M, Okusaka T, Furukawa M, Ohkawa S, Hosokawa A, Kojima Y, Hara H, Murohisa G, Shioji K, Asagi A, Mizuno N, Kojima M, Yamanaka T, Furuse J. A Phase II Trial of Everolimus in Patients with Advanced Pancreatic Neuroendocrine Carcinoma Refractory or Intolerant to Platinum-Containing Chemotherapy (NECTOR Trial). Neuroendocrinology, 110:988-993, 2020

61. Watanabe K, Mitsunaga S, Kojima M, Suzuki H, Irisawa A, Takahashi H, Sasaki M, Hashimoto Y, Imaoka H, Ohno I, Ikeda M, Akimoto T, Ochiai A. The "histological replacement growth pattern" represents aggressive invasive behavior in liver metastasis from pancreatic cancer. Cancer Med, 9:3130-3141, 2020

62. Ishii G, Ishii T. Review of cancer-associated fibroblasts and their microenvironment in post-chemotherapy recurrence. Hum Cell, 33:938-945, 2020

63. Miyashita T, Neri S, Hashimoto H, Akutsu A, Sugano M, Fujii S, Ochiai A, Ishii G. Fibroblasts-dependent invasion of podoplanin-positive cancer stem cells in squamous cell carcinoma. J Cell Physiol, 235:7251-7260, 2020

64. Nobusawa S, Nakata S, Nakano Y, Kawamura A, Yoshida M, Tamura A, Hasegawa D, Kosaka Y, Ito I, Watanabe R, Oishi T, Hayashi N, Ishikawa E, Sakamoto N, Okura N, Murakami C, Ichimura K, Hirato J, Yokoo H. CNS Low-grade Diffusely Infiltrative Tumors With INI1 Deficiency, Possessing a High Propensity to Progress to Secondary INI1-deficient Rhabdoid Tumors. Am J Surg Pathol, 44:1459-1468, 2020

65. Notohara K, Kamisawa T, Fukushima N, Furukawa T, Tajiri T, Yamaguchi H, Aishima S, Fukumura Y, Hirabayashi K, Iwasaki E, Kanno A, Kasashima S, Kawashima A, Kojima M, Kubota K, Kuraishi Y, Mitsuhashi T, Naito Y, Naitoh I, Nakase H, Nishino T, Ohike N, Sakagami J, Shimizu K, Shiokawa M, Uehara T, Ikeura T, Kawa S, Okazaki K. Guidance for diagnosing autoimmune pancreatitis with biopsy tissues. Pathol Int, 70:699-711, 2020

66. Takahashi S, Ohno I, Ikeda M, Konishi M, Kobayashi T, Akimoto T, Kojima M, Morinaga S, Toyama H, Shimizu Y, Miyamoto A, Tomikawa M, Takakura N, Takayama W, Hirano S, Otsubo T, Nagino M, Kimura W, Sugimachi K, Uesaka K. Neoadjuvant S-1 With Concurrent Radiotherapy Followed by Surgery for Borderline Resectable Pancreatic Cancer: A Phase II Open-Label Multicenter Prospective Trial (JASPAC05). Ann Surg, 2020

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