Department of Hepatobiliary and Pancreatic Oncology

Takuji Okusaka, Hideki Ueno, Chigusa Morizane, Susumu Hijioka, Shunsuke Kondo, Akihiro Ohba, Yoshikuni Nagashio, Yuta Maruki, Tomoyuki Satake, Kousuke Maehara, Kotaro Takeshita

Introduction

The Department of Hepatobiliary and Pancreatic Oncology treats tumors originating from the liver, biliary system or pancreas, which include hepatocellular carcinoma (HCC), biliary tract cancer and pancreatic cancer. As part of the multi-disciplinary care given at the National Cancer Center Hospital (NCCH), we work closely with surgeons and radiologists who have special expertise in these areas. We also conduct clinical and translational research on hepatobiliary and pancreatic tumors and seek to develop new and more effective diagnostic methods and treatments.

The Team and What We Do

The department consists of eight staff oncologists and several residents. We have used percutaneous ablation therapy for most patients with three or fewer HCC nodules, all of which are smaller than 3 cm in diameter. We also perform transcatheter arterial chemoembolization (TACE), mainly with patients with multiple HCC nodules. Systemic or intra-arterial chemotherapeutic regimens are indicated in advanced HCC patients for whom locoregional intervention and surgery are unsuitable or have been unsuccessful. In patients with unresectable pancreatic cancer or biliary tract cancer, chemotherapy is performed in clinical practice or as a clinical trial to develop new treatment. We have actively introduced endoscopic procedures for imaging diagnosis (endoscopic ultrasonography (EUS) and endoscopic retrograde cholangiopancreatography (ERCP)), tumor biopsy (EUS-guided fine needle aspiration (EUS-FNA)), and biliary drainage (including EUS-guided hepaticogastrostomy (EUS-HGS) and EUS-guided choledochoduodenostomy (EUS-CDS)) (Tables 1 & 2).

Table 1. Primary tumor 

Research activities

We published 17 papers as a first author in peer-reviewed journals in 2021.

We retrospectively reviewed the medical records of patients with Lynch syndrome-associated pancreatic or biliary tract malignant tumors at the National Cancer Center Hospital between March 1992 and October 2019. Fourteen patients were included. They had a history of multiple cancers and a family history of cancer. For the six patients with pancreatic malignant tumors, the median age was 63 years. The primary tumor site for five out of the six patients with pancreatic cancer was the body or tail. Only one patient had pancreatic head cancer. The median overall survival (OS) was 68 (range, 17-198) months. For the eight patients with biliary tract malignant tumors, the median age was 65.5 years. The primary tumor site for five out of the eight patients was the intrahepatic bile duct, whereas the primary site for two of them was the hilar bile duct. The median OS was 62 (range, 3-183) months. This study produced several observations on tumor location, late development, and favorable long-term outcomes. Additional studies are needed to identify the characteristics (J Hepatobiliary Pancreat Sci. 2022;29:377-384).

Endoscopic transpapillary re-intervention (ETP-RI) after multiple self-expandable metallic stent (SEMS) placement for unresectable malignant hilar biliary obstruction (MHBO) is challenging, but endoscopic ultrasound-guided biliary drainage (EUS-BD) could be an alternative following failed ETP-RI. We investigated appropriate re-intervention (RI) methods in MHBO after multiple SEMS placement and evaluated RI with EUS-BD (EUS-RI) benefits following ETP-RI failure. Patients requiring RI after multiple SEMS placement for MHBO between October 2017 and April 2021 were enrolled. Forty-nine patients underwent ETP-RI for MHBO. ETP-RI's technical success rate was 69.4%. Of 15 failed ETP-RI cases, all underwent EUS-RI, achieving technical and clinical success rates of 86.7% and 100%, respectively. Time to recurrent biliary obstruction (TRBO) after RI was significantly different between EUS-RI and ETP-RI (212 vs 84 days; P = .01). On multivariate analysis, EUS-RI was the only factor associated with TRBO (odds ratio: 4.48; 95% confidence interval: 1.01-19.91; P = .04). EUS-RI was effective and safe in difficult ETP-RI cases after multiple SEMS placement for MHBO (J Hepatobiliary Pancreat Sci. 2022;29:404-414).

Clinical trials

Thirty-two clinical studies are ongoing, including five phase I studies, 12 phase II studies, and six phase III studies, such as adjuvant chemotherapy after resection versus resection alone for patients with resectable tumors, and chemotherapy with a new regimen versus standard therapy for patients with advanced tumors, and several observation or registration trials. Our studies are supported by the National Cancer Center Research and Development Fund (2020-J-3), Project for Development of Innovative Research on Cancer Therapeutics (21ck0106632h0002, 21ck0106618h0002) from the Japan Agency for Medical Research and Development.

Education

Our staff members are working closely with residents to support their skill development and knowledge expansion in both clinical and research fields. We are conducting conferences daily for clinical practice and weekly for research development. The residents in our department published 12 papers as a first author in peer-reviewed journals in 2021, and are performing 30 planning-stage or ongoing studies as a leading researcher, with assistance from staff members.

Future prospects

Our department will continue to provide the best and latest diagnosis, treatment and supportive care, and develop more effective methods and techniques for all patients with hepatobiliary and pancreatic cancer in this country and all over the world. Among these, conducting clinical trials with novel promising agents for this disease is considered one of the most important tasks, and establishing cutting-edge endoscopic procedures in this field is the most significant mission for us.

List of papers published in 2018

Journal

1. Yamada I, Morizane C, Okusaka T, Mizusawa J, Kataoka T, Ueno M, Ikeda M, Okano N, Todaka A, Shimizu S, Mizuno N, Sekimoto M, Tobimatsu K, Yamaguchi H, Nishina T, Shirakawa H, Kojima Y, Oono T, Kawamoto Y, Furukawa M, Iwai T, Sudo K, Okamura K, Yamashita T, Kato N, Shioji K, Shimizu K, Nakagohri T, Kamata K, Ishii H, Furuse J. The clinical outcomes of combination chemotherapy in elderly patients with advanced biliary tract cancer: an exploratory analysis of JCOG1113. Scientific reports, 12:987, 2022

2. Kaku S, Horinouchi H, Watanabe H, Yonemori K, Okusaka T, Boku N, Yamazaki N, Kawai A, Ohe Y, Kusumoto M. Incidence and prognostic factors in severe drug-induced interstitial lung disease caused by antineoplastic drug therapy in the real world. Journal of cancer research and clinical oncology, 2022

3. Tsubokura M, Adegawa Y, Kojima M, Tanosaki R, Ohtake R, Kase Y, Iwashita N, Kasane M, Nakabayashi S, Takeuchi S, Kato K, Boku N, Kanemitsu Y, Okusaka T, Fujimoto H, Yonemori K, Ishiki H, Kawamura K, Satomi E, Matsushita H. Adverse effects of cell-free and concentrated ascites reinfusion therapy for malignant ascites: a single-institute experience. BMC cancer, 22:268, 2022

4. Shibayama T, Shimoi T, Mori T, Noguchi E, Honma Y, Hijioka S, Yoshida M, Ogawa C, Yonemori K, Yatabe Y, Yoshida A. Cytokeratin-positive Malignant Tumor in the Abdomen With EWSR1/FUS-CREB Fusion: A Clinicopathologic Study of 8 Cases. The American journal of surgical pathology, 46:134-146, 2022

5. Kitamura H, Hijioka S, Nagashio Y, Sugawara S, Nara S, Sone M, Esaki M, Arai Y, Okusaka T, Nakajima A. Use of endoscopic ultrasound-guided biliary drainage as a rescue of re-intervention after the placement of multiple metallic stents for malignant hilar biliary obstruction. Journal of hepato-biliary-pancreatic sciences, 29:404-414, 2022

6. Kitamura H, Hijioka S, Nagashio Y, Ban D, Esaki M, Okusaka T, Saito Y. A case of high grade pancreatic intraepithelial neoplasia diagnosed by endoscopic ultrasound-guided fine needle aspiration. Endoscopy, 2022

7. Takamizawa S, Morizane C, Tanabe N, Maruki Y, Kondo S, Hijioka S, Ueno H, Sugano K, Hiraoka N, Okusaka T. Clinical characteristics of pancreatic and biliary tract cancers associated with Lynch syndrome. Journal of hepato-biliary-pancreatic sciences, 29:377-384, 2022

8. Ohashi Y, Ikeda M, Kunitoh H, Sasako M, Okusaka T, Mukai H, Fujiwara K, Nakamura M, Oba MS, Kimura T, Ibusuki K, Takita A, Sakon M. One-year incidence of venous thromboembolism, bleeding, and death in patients with solid tumors newly initiating cancer treatment: Results from the Cancer-VTE Registry. Thrombosis research, 213:203-213, 2022

9. Yoshinari M, Hijioka S, Okusaka T, Saito Y. Endoscopic ultrasonography-guided hepaticogastrostomy with parenchymal metal stent placement. Endoscopy, 2022

10. Satake T, Maruki Y, Kubo Y, Takahashi M, Ohba A, Nagashio Y, Kondo S, Hijioka S, Morizane C, Ueno H, Okusaka T. Atezolizumab-induced Encephalitis in a Patient with Hepatocellular Carcinoma: A Case Report and Literature Review. Internal medicine (Tokyo, Japan), 2022

11. . Koga T, Hijioka S, Nagashio Y, Ohba A, Maruki Y, Yoshinari M, Hisada Y, Harai S, Kitamura H, Maehara K, Murashima Y, Kawasaki Y, Kawahara S, Takeshita K, Yamada N, Satake T, Kondo S, Morizane C, Ueno H, Okusaka T, Saito Y. Endoscopic ultrasound-guided choledochoduodenostomy without fistula dilation using a stent with a 5.9-Fr delivery system: Comparison to a conventional procedure with fistula dilation. DEN open, 2:e56, 2022

12. Sato A, Fujimori M, Shirai Y, Umezawa S, Mori M, Jinno S, Umehashi M, Okamura M, Okusaka T, Majima Y, Miyake S, Uchitomi Y. Assessing the need for a question prompt list that encourages end-of-life discussions between patients with advanced cancer and their physicians: A focus group interview study - ERRATUM. Palliative & supportive care, 1-3, 2022

13.  Masui T, Ito T, Komoto I, Kojima S, Kasai Y, Tanabe M, Hara K, Hirano S, Okusaka T, Ichikawa Y, Kinugasa Y, Kokudo N, Kudo A, Sakurai A, Sugihara K, Date H, Haruma K, Hijioka S, Hirata K, Yamano H, Sakamine M, Kikuchi T, Fukushima M, Imamura M, Uemoto S. Nationwide registry for patients with neuroendocrine neoplasm of pancreas, gastrointestinal tract, lungs, bronchi, or thymus in Japan. International journal of clinical oncology, 27:840-849, 2022

14. Azemoto N, Ueno M, Yanagimoto H, Mizuno N, Kawamoto Y, Maruki Y, Watanabe K, Suzuki R, Kaneko J, Hisada Y, Sato H, Kobayashi S, Miyata H, Furukawa M, Mizukami T, Miwa H, Ohno Y, Tsuji K, Tsujimoto A, Nagano H, Okuyama H, Asagi A, Okano N, Ishii H, Morizane C, Ikeda M, Furuse J. Endoscopic duodenal stent placement versus gastrojejunostomy for unresectable pancreatic cancer patients with duodenal stenosis before introduction of initial chemotherapy (GASPACHO study): a multicenter retrospective study. Japanese journal of clinical oncology, 52:134-142, 2022

15.  Motzer RJ, Taylor MH, Evans TRJ, Okusaka T, Glen H, Lubiniecki GM, Dutcus C, Smith AD, Okpara CE, Hussein Z, Hayato S, Tamai T, Makker V. Lenvatinib dose, efficacy, and safety in the treatment of multiple malignancies. Expert review of anticancer therapy, 22:383-400, 2022

16. Yachida S, Totoki Y, Noë M, Nakatani Y, Horie M, Kawasaki K, Nakamura H, Saito-Adachi M, Suzuki M, Takai E, Hama N, Higuchi R, Hirono S, Shiba S, Kato M, Furukawa E, Arai Y, Rokutan H, Hashimoto T, Mitsunaga S, Kanda M, Tanaka H, Takata S, Shimomura A, Oshima M, Hackeng WM, Okumura T, Okano K, Yamamoto M, Yamaue H, Morizane C, Arihiro K, Furukawa T, Sato T, Kiyono T, Brosens LAA, Wood LD, Hruban RH, Shibata T . Comprehensive Genomic Profiling of Neuroendocrine Carcinomas of the Gastrointestinal System. Cancer discovery, 12:692-711, 2022

17. Watanabe H, Fujishima F, Komoto I, Imamura M, Hijioka S, Hara K, Yatabe Y, Kudo A, Masui T, Tsuchikawa T, Sakamoto K, Shiga H, Nakamura T, Nakaya N, Motoi F, Unno M, Sasano H. Somatostatin Receptor 2 Expression Profiles and Their Correlation with the Efficacy of Somatostatin Analogues in Gastrointestinal Neuroendocrine Tumors. Cancers, 14:2022

18. Inaba Y, Hijioka S, Iwama I, Asai T, Miyamura H, Chatani S, Hasegawa T, Murata S, Kato M, Sato Y, Yamaura H, Onaya H, Shimizu J, Hara K. Clinical usefulness of Somatostatin Receptor Scintigraphy in the Diagnosis of Neuroendocrine Neoplasms. Asia Oceania journal of nuclear medicine & biology, 10:1-13, 2022

19. Ueno M, Morizane C, Okusaka T, Mizusawa J, Kataoka T, Ikeda M, Ozaka M, Okano N, Sugimori K, Todaka A, Shimizu S, Mizuno N, Yamamoto T, Sano K, Tobimatsu K, Katanuma A, Miyamoto A, Yamaguchi H, Nishina T, Shirakawa H, Kojima Y, Oono T, Kawamoto Y, Furukawa M, Iwai T, Sudo K, Miyakawa H, Yamashita T, Yasuda I, Takahashi H, Kato N, Shioji K, Shimizu K, Nakagohri T, Kamata K, Ishii H, Furuse J. Comparison of gemcitabine-based chemotherapies for advanced biliary tract cancers by renal function: an exploratory analysis of JCOG1113. Scientific reports, 11:12885, 2021

20. Kobayashi S, Ueno M, Ogawa G, Fukutomi A, Ikeda M, Okusaka T, Sato T, Ito Y, Kadota T, Ioka T, Sugimori K, Sata N, Nakamori S, Shimizu K, Mizuno N, Ishii H, Furuse J. Impact of Renal Function on S-1 + Radiotherapy for Locally Advanced Pancreatic Cancer: An Integrated Analysis of Data From 2 Clinical Trials. Pancreas, 50:965-971, 2021

21. Mizuno T, Yoshida T, Sunami K, Koyama T, Okita N, Kubo T, Sudo K, Shimoi T, Ueno H, Saito E, Katanoda K, Shibata T, Yonemori K, Okusaka T, Boku N, Ohe Y, Hiroshima Y, Ueno M, Kuboki Y, Doi T, Nakamura K, Kohno T, Yatabe Y, Yamamoto N. Study protocol for NCCH1908 (UPFRONT-trial): a prospective clinical trial to evaluate the feasibility and utility of comprehensive genomic profiling prior to the initial systemic treatment in advanced solid tumour patients. Japanese journal of clinical oncology, 51:1757-1760, 2021

22. Yazaki S, Yoshida T, Kojima Y, Yagishita S, Nakahama H, Okinaka K, Matsushita H, Shiotsuka M, Kobayashi O, Iwata S, Narita Y, Ohba A, Takahashi M, Iwasa S, Kobayashi K, Ohe Y, Yoshida T, Hamada A, Doi T, Yamamoto N. Difference in SARS-CoV-2 Antibody Status Between Patients With Cancer and Health Care Workers During the COVID-19 Pandemic in Japan. JAMA oncology, 7:1141-1148, 2021

23. Okusaka T, Ikeda K, Kudo M, Finn R, Qin S, Han KH, Cheng AL, Piscaglia F, Kobayashi M, Sung M, Chen M, Wyrwicz L, Yoon JH, Ren Z, Mody K, Dutcus C, Tamai T, Ren M, Hayato S, Kumada H. Safety and efficacy of lenvatinib by starting dose based on body weight in patients with unresectable hepatocellular carcinoma in REFLECT. Journal of gastroenterology, 56:570-580, 2021

24. Okusaka T. Cholangiocarcinoma: is it time for a revolution? Expert review of gastroenterology & hepatology, 15:467-470, 2021

25. Hijioka S, Morizane C, Ikeda M, Ishii H, Okusaka T, Furuse J. Current status of medical treatment for gastroenteropancreatic neuroendocrine neoplasms and future perspectives. Japanese journal of clinical oncology, 51:1185-1196, 2021

26. Hijioka S, Nagashio Y, Ohba A, Maruki Y, Okusaka T. The Role of EUS and EUS-FNA in Differentiating Benign and Malignant Gallbladder Lesions. Diagnostics (Basel, Switzerland), 11:2021

27. Hijioka S, Okusaka T. Enormous Potential of Endoscopic Ultrasound-guided Liver Biopsies. Internal medicine (Tokyo, Japan), 60:1655-1656, 20213 randomised self-controlled study. BMJ Open, 10:e038276, 2020

28. Harai S, Hijioka S, Maruki Y, Ohba A, Nagashio Y, Okusaka T, Saito Y. Endoscopic ultrasound-guided hepaticoduodenostomy with anterograde stenting for recurrent hepatic hilar obstruction. Endoscopy, 2021

29. Aoki T, Kubota K, Kiritani S, Arita J, Morizane C, Masui T, Kudo A, Komoto I, Hatano E, Ito T, Osamura RY, Unno M, Uemoto S, Kokudo N. Survey of surgical resections for neuroendocrine liver metastases: A project study of the Japan Neuroendocrine Tumor Society (JNETS). Journal of hepato-biliary-pancreatic sciences, 28:489-497, 2021

30. Kelley RK, Sangro B, Harris W, Ikeda M, Okusaka T, Kang YK, Qin S, Tai DW, Lim HY, Yau T, Yong WP, Cheng AL, Gasbarrini A, Damian S, Bruix J, Borad M, Bendell J, Kim TY, Standifer N, He P, Makowsky M, Negro A, Kudo M, Abou-Alfa GK. Safety, Efficacy, and Pharmacodynamics of Tremelimumab Plus Durvalumab for Patients With Unresectable Hepatocellular Carcinoma: Randomized Expansion of a Phase I/II Study. Journal of clinical oncology: official journal of the American Society of Clinical Oncology, 39:2991-3001, 2021

31. Sasaki M, Ueno H, Mitsunaga S, Ohba A, Hosoi H, Kobayashi S, Ueno M, Terazawa T, Goto M, Inoue D, Namiki S, Sakamoto Y, Kondo S, Morizane C, Ikeda M, Okusaka T. A phase II study of FOLFIRINOX with primary prophylactic pegfilgrastim for chemotherapy-naïve Japanese patients with metastatic pancreatic cancer. International journal of clinical oncology, 26:2065-2072, 2021

32.  Ito T, Masui T, Komoto I, Doi R, Osamura RY, Sakurai A, Ikeda M, Takano K, Igarashi H, Shimatsu A, Nakamura K, Nakamoto Y, Hijioka S, Morita K, Ishikawa Y, Ohike N, Kasajima A, Kushima R, Kojima M, Sasano H, Hirano S, Mizuno N, Aoki T, Aoki T, Ohtsuka T, Okumura T, Kimura Y, Kudo A, Konishi T, Matsumoto I, Kobayashi N, Fujimori N, Honma Y, Morizane C, Uchino S, Horiuchi K, Yamasaki M, Matsubayashi J, Sato Y, Sekiguchi M, Abe S, Okusaka T, Kida M, Kimura W, Tanaka M, Majima Y, Jensen RT, Hirata K, Imamura M, Uemoto S. JNETS clinical practice guidelines for gastroenteropancreatic neuroendocrine neoplasms: diagnosis, treatment, and follow-up: a synopsis. Journal of gastroenterology, 56:1033-1044, 2021

33. Yanai Y, Makihara RA, Matsunaga N, Shimizu R, Tominaga S, Hoshino S, Nishibuchi Y, Maruki Y, Ohba A, Shimizu K, Okusaka T. A feasibility study of a peer discussion group intervention for patients with pancreatobiliary cancer and their caregivers. Palliative & supportive care, 1-8, 2021

34. Tsujie M, Iwai T, Kubo S, Ura T, Hatano E, Sakai D, Takeda Y, Kaibori M, Kobayashi T, Katanuma A, Katayose Y, Fukase K, Sakurai N, Ito Y, Sato F, Maeda A, Asada M, Morizane C. Erratum to: Fibroblast growth factor receptor 2 (FGFR2) fusions in Japanese patients with intrahepatic cholangiocarcinoma. Japanese journal of clinical oncology, 51:1694, 2021

35. Okuma HS, Yonemori K, Kojima Y, Tanioka M, Sudo K, Noguchi E, Hijioka S, Wakakuwa K, Kato K, Hirakawa A, Kuchiba A, Kubo T, Ichikawa H, Yoshida A, Yatabe Y, Nakamura K, Mano H, Yamamoto N, Fujiwara Y. Clinical Utility of Circulating Tumor DNA in Advanced Rare Cancers. Frontiers in oncology, 11:732525, 2021

36. Shibayama T, Makise N, Motoi T, Mori T, Hiraoka N, Yonemori K, Watanabe SI, Esaki M, Morizane C, Okuma T, Kawai A, Ushiku T, Yatabe Y, Yoshida A. Clinicopathologic Characterization of Epithelioid Hemangioendothelioma in a Series of 62 Cases: A Proposal of Risk Stratification and Identification of a Synaptophysin-positive Aggressive Subset. The American journal of surgical pathology, 45:616-626, 2021

37. Ito T, Fujimori N, Honma Y, Kudo A, Hijioka S, Katsushima S, Kimura Y, Fukutomi A, Hisamatsu S, Nakajima A, Shimatsu A. Long-term safety and efficacy of lanreotide autogel in Japanese patients with neuroendocrine tumors: Final results of a phase II open-label extension study. Asia-Pacific journal of clinical oncology, 17:e153-e161, 2021

38. Kitamura H, Hijioka S, Maruki Y, Ohba A, Nagashio Y, Okusaka T, Saito Y. Novel double endoscopic ultrasound-guided hepaticogastrostomy for two-hole benign anastomotic stenosis with difficult gastrointestinal approach. Endoscopy, 53:E140-E142, 2021

39. Koga T, Hijioka S, Ishikawa Y, Ito K, Harai S, Okusaka T, Saito Y. Duckbill-type antireflux self-expandable metal stent placement for post-choledochojejunostomy reflux cholangitis. Endoscopy, 53:E174-E176, 2021

40. Koga T, Hijioka S, Hisada Y, Maruki Y, Nagashio Y, Okusaka T, Saito Y. Endoscopic ultrasound-guided choledochoduodenostomy without fistula dilation using a novel fully covered metallic stent with a 5.9-Fr ultra-thin delivery system. Endoscopy, 53:E223-E225, 2021

41. Maehara K, Hijioka S, Sakamoto T, Maruki Y, Tamada K, Okusaka T, Saito Y. Novel biliary drainage of a choledochojejunal anastomotic stenosis using a double-balloon endoscope and forward-viewing endoscopic ultrasound. Endoscopy, 53:E242-E244, 2021

42. Hisada Y, Hijioka S, Ohba A, Nagashio Y, Kanai Y, Okusaka T, Saito Y. Novel endoscopic ultrasound-guided hepaticoduodenostomy using a forward-viewing echoendoscope for altered anatomy. Endoscopy, 53:E340-E342, 2021

43.  Ikeda M, Okusaka T, Ohno I, Mitsunaga S, Kondo S, Ueno H, Morizane C, Gemmoto K, Suna H, Ushida Y, Furuse J. Phase I studies of peptide vaccine cocktails derived from GPC3, WDRPUH and NEIL3 for advanced hepatocellular carcinoma. Immunotherapy, 13:371-385, 2021