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Annual Report 2021

Department of Hepatobiliary and Pancreatic Surgery

Naoto Gotohda, Shin Kobayashi, Motokazu Sugimoto, Masashi Kudo, Ryo Morisue, Masaru Konishi, Masatake Taniguchi, Naoki Yagi, Ryuji Komine, Yusuke Abe, Tatsuki Ishikawa, Kimimasa Sasaki, Yu Shibahara, Kento Mishima, Yu Igata, Manabu Kujiraoka, Norikazu Une, Taiki Sunakawa

Introduction

 The Department of Hepatobiliary and Pancreatic Surgery consists of six staff surgeons, three chief residents and nine residents. Our department is responsible for the surgical treatment of patients with hepatic, biliary, and pancreatic cancer and duodenal cancer or low-grade malignant tumors. We conduct multidisciplinary treatment in cooperation with the Department of Hepatobiliary and Pancreatic Oncology, the Department of Diagnostic Radiology, and the Department of Radiation Oncology. In addition to conventional open surgery, we perform minimally invasive surgery: laparoscopic surgery for patients with liver and pancreatic tumors.

The Team and What We Do

 We work with outpatients five days a week and have approximately 20 inpatients. Staff meetings in which we discuss the treatment strategy or the key points of surgery for patients are held with all members of the department every morning. A Cancer Board is held in cooperation with radiologists and medical oncologists every Tuesday. A pathology conference is held monthly with pathologists. In 2021, 369 patients with hepatobiliary and pancreatic diseases underwent surgical treatment. The main diseases are shown in Table 1. Compared with the number of patients in 2020, the number of patients undergoing surgery in our department was similar (Table 2). We performed many laparoscopic surgeries for liver and pancreatic tumors in 2021. In 2020, we started performing laparoscopic pancreatoduodenectomy. The number of cases with laparoscopic pancreatoduodenectomy increased.

Table 1. Number of patients
Table 1. Number of patients

Table 1. Number of patients
Table 1. Number of patients

Table 2. Type of procedure
Table 2. Type of procedure

Table 2. Type of procedure
Table 2. Type of procedure

Research activities

1. Conversion surgery for pancreatic cancer

 Currently, the treatment outcomes of pancreatic cancer patients are improving remarkably with the chemotherapy regimen Gem+nab-PTX or FOLFIRINOX. We attempt conversion surgery for selected patients with borderline resectable or unresectable pancreatic cancer who received chemotherapy. We are currently evaluating good indications for conversion surgery.

2. Function-preserving surgery

 Pancreas-sparing duodenectomy (PSD) represents an alternative procedure to pancreaticoduodenectomy (PD) for patients with duodenal neoplasms. PSD is a less invasive procedure and has the advantage over PD of preservation of the pancreas. We are attempting to establish a safe procedure for PSD.

3. Evaluation of liver function

 Postoperative liver failure is one of the fatal complications after major hepatectomy. We usually evaluate liver function using the indocyanine green retention rate at 15 min (ICG15) test. We are developing an alternative evaluation of liver function employing liver-specific magnetic resonance imaging (MRI) with a gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) contrast agent instead of using the ICG15 test.

4. Cancer genome screening

 We conducted clinical studies for cancer genome screening. For patients with resectable HCC, analysis by blood screening (COSMOS-HCC-01) was started in 2020.

 “A multicenter proof of concept study for personalized perioperative therapy based on genetic alteration status for resectable oligometastases from colorectal cancer” (PRECISION study) (UMIN000042490): This is a multicenter prospective observational study to investigate the clinical utility of pre-treatment ctDNA analysis in patients undergoing surgery for colorectal oligometastases, conducted with a grant from AMED (20ck0106629h0001). The main eligibility criterion is patients with previously untreated resectable colorectal oligometastases, and the primary endpoint is the detection rate of pre-treatment ctDNA and the positive rate of BRAF V600E in tissue. The period of accrual and follow-up is two years each, and the study started in March 2021.

Clinical trials

1. A phase III trial of S-1 versus observation in patients with resected biliary tract cancer (JCOG1202). Recruitment was completed in 2018, and the primary endpoint was analyzed in 2021. The three-year-survival rate is 67.6% in the surgery group, and 77.1% in the adjuvant chemotherapy group. There was a significant difference between the two groups. Based on these results, adjuvant chemotherapy with S-1 is regarded as the standard treatment in the field of biliary tract cancer.

2. A non-randomized controlled study comparing proton beam therapy and hepatectomy for resectable hepatocellular carcinoma (JCOG1315C). Recruitment started in 2016.

3. Japanese trial - A global study to evaluate the potential benefit of adjuvant chemotherapy for small bowel adenocarcinoma (JCOG1502C). Recruitment started in 2017.

4. A randomized phase II/III study of gemcitabine and nab-paclitaxel therapy versus S-1 and concurrent radiotherapy as neoadjuvant treatment for borderline resectable pancreatic cancer (GABARNANCE Trial). Recruitment started in 2017.

Education

 “Board-certified expert surgeons” have a high level of skill in the field of hepatobiliary-pancreatic surgery. To be qualified as one, surgeons are required to perform a prescribed number of operations under the guidance of a board-certified instructor. The residents of our department are being trained to receive the certification by the end of the chief resident course.

Future Prospects

 Our goal is the establishment of multidisciplinary treatment for patients with refractory hepatobiliary and pancreatic cancer and the establishment of minimally invasive surgery for patients with pancreatic cancer and liver cancer. We are conducting robotic surgery in our field.

List of papers published in 2021

Journal

1. Wakabayashi G, Cherqui D, Geller DA, Abu Hilal M, Berardi G, Ciria R, Abe Y, Aoki T, Asbun HJ, Chan ACY, Chanwat R, Chen KH, Chen Y, Cheung TT, Fuks D, Gotohda N, Han HS, Hasegawa K, Hatano E, Honda G, Itano O, Iwashita Y, Kaneko H, Kato Y, Kim JH, Liu R, López-Ben S, Morimoto M, Monden K, Rotellar F, Sakamoto Y, Sugioka A, Yoshiizumi T, Akahoshi K, Alconchel F, Ariizumi S, Benedetti Cacciaguerra A, Durán M, Garcia Vazquez A, Golse N, Miyasaka Y, Mori Y, Ogiso S, Shirata C, Tomassini F, Urade T, Wakabayashi T, Nishino H, Hibi T, Kokudo N, Ohtsuka M, Ban D, Nagakawa Y, Ohtsuka T, Tanabe M, Nakamura M, Tsuchida A, Yamamoto M . The Tokyo 2020 terminology of liver anatomy and resections: Updates of the Brisbane 2000 system. Journal of hepato-biliary-pancreatic sciences, 29:6-15, 2022

2. Morimoto M, Monden K, Wakabayashi T, Gotohda N, Abe Y, Honda G, Abu Hilal M, Aoki T, Asbun HJ, Berardi G, Chan ACY, Chanwat R, Chen KH, Chen Y, Cherqui D, Cheung TT, Ciria R, Fuks D, Geller DA, Han HS, Hasegawa K, Hatano E, Itano O, Iwashita Y, Kaneko H, Kato Y, Kim JH, Liu R, López-Ben S, Rotellar F, Sakamoto Y, Sugioka A, Yoshizumi T, Akahoshi K, Alconchel F, Ariizumi S, Benedetti Cacciaguerra A, Durán M, García Vázquez A, Golse N, Miyasaka Y, Mori Y, Ogiso S, Shirata C, Tomassini F, Urade T, Nishino H, Kunzler F, Kozono S, Osakabe H, Takishita C, Ban D, Hibi T, Kokudo N, Ohtsuka M, Nagakawa Y, Ohtsuka T, Tanabe M, Nakamura M, Yamamoto M, Tsuchida A, Wakabayashi G . Minimally invasive anatomic liver resection: Results of a survey of world experts. Journal of hepato-biliary-pancreatic sciences, 29:33-40, 2022

3. Gotohda N, Cherqui D, Geller DA, Abu Hilal M, Berardi G, Ciria R, Abe Y, Aoki T, Asbun HJ, Chan ACY, Chanwat R, Chen KH, Chen Y, Cheung TT, Fuks D, Han HS, Hasegawa K, Hatano E, Honda G, Itano O, Iwashita Y, Kaneko H, Kato Y, Kim JH, Liu R, López-Ben S, Morimoto M, Monden K, Rotellar F, Sakamoto Y, Sugioka A, Yoshiizumi T, Akahoshi K, Alconchel F, Ariizumi S, Benedetti Cacciaguerra A, Durán M, Garcia Vazquez A, Golse N, Miyasaka Y, Mori Y, Ogiso S, Shirata C, Tomassini F, Urade T, Wakabayashi T, Nishino H, Hibi T, Kokudo N, Ohtsuka M, Ban D, Nagakawa Y, Ohtsuka T, Tanabe M, Nakamura M, Yamamoto M, Tsuchida A, Wakabayashi G . Expert Consensus Guidelines: How to safely perform minimally invasive anatomic liver resection. Journal of hepato-biliary-pancreatic sciences, 29:16-32, 2022

4. Monden K, Alconchel F, Berardi G, Ciria R, Akahoshi K, Miyasaka Y, Urade T, García Vázquez A, Hasegawa K, Honda G, Kaneko H, Hoon Kim J, Tanabe M, Yamamoto M, Wakabayashi G . Landmarks and techniques to perform minimally invasive liver surgery: A systematic review with a focus on hepatic outflow. Journal of hepato-biliary-pancreatic sciences, 29:66-81 , 2022

5. Morimoto M, Tomassini F, Berardi G, Mori Y, Shirata C, Abu Hilal M, Asbun HJ, Cherqui D, Gotohda N, Han HS, Kato Y, Rotellar F, Sugioka A, Yamamoto M, Wakabayashi G. Glissonean approach for hepatic inflow control in minimally invasive anatomic liver resection: A systematic review . Journal of hepato-biliary-pancreatic sciences, 29:51-65 , 2022

6. Ciria R, Berardi G, Nishino H, Chan ACY, Chanwat R, Chen KH, Chen Y, Cheung TT, Fuks D, Geller DA, Iwashita Y, Liu R, López-Ben S, Yamamoto M, Wakabayashi G. A snapshot of the 2020 conception of anatomic liver resections and their applicability on minimally invasive liver surgery. A preparatory survey for the Expert Consensus Meeting on Precision Anatomy for Minimally Invasive HBP Surgery . Journal of hepato-biliary-pancreatic sciences, 29:41-50 , 2022

7. Todaka A, Nara S, Motoi F, Morinaga S, Toshiyama R, Higuchi R, Konishi M, Shirakawa H, Tsumura H, Okuyama H, Nagano H, Shioji K, Sugimachi K, Asagi A, Mizuno N, Furuse J. Postoperative Treatment of Resectable Pancreatic Cancer With Positive Peritoneal Lavage Cytology: A Multicentre Retrospective Study . Anticancer research, 42:893-902 , 2022

8. Ishizu K, Hashimoto T, Naka T, Yatabe Y, Kojima M, Kuwata T, Nonaka S, Oda I, Esaki M, Kudo M, Gotohda N, Yoshida T, Yoshikawa T, Sekine S. APC mutations are common in adenomas but infrequent in adenocarcinomas of the non-ampullary duodenum. Journal of gastroenterology, 56:988-998, 2021

9. Sasaki K, Kobayashi S, Kudo M, Sugimoto M, Takahashi S, Nakamura Y, Kawazoe A, Shitara K, Kinoshita T, Gotohda N. Hypothyroidism and hypopituitarism as immune-related adverse events due to lenvatinib plus pembrolizumab therapy in the immediate postoperative period after laparoscopic hepatectomy for liver metastases from gastric cancer: a case report. Surgical case reports, 7:267, 2021

10. Kobayashi S, Takahashi S, Nomura S, Kojima M, Kudo M, Sugimoto M, Konishi M, Gotohda N, Taniguchi H, Yoshino T. BRAF V600E potentially determines “Oncological Resectability” for “Technically Resectable” colorectal liver metastases. Cancer medicine, 10:6998-7011, 2021

11. Komine R, Kojima M, Ishi G, Kudo M, Sugimoto M, Kobayashi S, Takahashi S, Konishi M, Kobayashi T, Akimoto T, Murakami A, Sasaki M, Tanaka M, Matsuzaki A, Ohike N, Uchida K, Sugiyama T, Hirabayashi K, Tajiri T, Ishida K, Kai K, Omori Y, Notohara K, Yamaguchi H, Matsuda Y, Naito Y, Fukumura Y, Hamada Y, Mihara Y, Masugi Y, Gotohda N, Harada K, Fukushima N, Furukawa T. Recognition and pathological features of periampullary region adenocarcinoma with an indeterminable origin. Cancer medicine, 10:3499-3510, 2021

12. Okubo S, Suzuki T, Hioki M, Shimizu Y, Toyama H, Morinaga S, Gotohda N, Uesaka K, Ishii G, Takahashi S, Kojima M. The immunological impact of preoperative chemoradiotherapy on the tumor microenvironment of pancreatic cancer. Cancer science, 112:2895-2904, 2021

13. Kudo M, Kobayashi S, Kojima M, Kobayashi T, Sugimoto M, Takahashi S, Konishi M, Ishii G, Gotohda N. Impact of previous history of choledochojejunostomy on the incidence of organ/space surgical site infection after hepatectomy. Asian journal of surgery, 44:1520-1528, 2021

14. Miyama A, Morise Z, Aldrighetti L, Belli G, Ratti F, Cheung TT, Lo CM, Tanaka S, Kubo S, Okamura Y, Uesaka K, Monden K, Sadamori H, Hashida K, Kawamoto K, Gotohda N, Chen KH, Kanazawa A, Takeda Y, Ohmura Y, Ueno M, Ogura T, Suh KS, Kato Y, Sugioka A, Belli A, Nitta H, Yasunaga M, Cherqui D, Halim NA, Laurent A, Kaneko H, Otsuka Y, Kim KH, Cho HD, Lin CCW, Ome Y, Seyama Y, Troisi RI, Berardi G, Rotellar F, Wilson GC, Geller DA, Soubrane O, Yoh T, Kaizu T, Kumamoto Y, Han HS, Ekmekcigil E, Dagher I, Fuks D, Gayet B, Buell JF, Ciria R, Briceno J, O'Rourke N, Lewin J, Edwin B, Shinoda M, Abe Y, Hilal MA, Alzoubi M, Tanabe M, Wakabayashi G. Multicenter Propensity Score-Based Study of Laparoscopic Repeat Liver Resection for Hepatocellular Carcinoma: A Subgroup Analysis of Cases with Tumors Far from Major Vessels . Cancers, 13:2021

15. Gotohda N, Kato Y, Takahashi S, Konishi M. Proposal of Perihilar Surrounding Area in Relation to Regional Lymphadenectomy in Selected Patients With Intrahepatic Cholangiocarcinoma. International Surgery, 105:92-98, 2021

16. 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. International journal of cancer, 149:546-560, 2021

17. 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. Annals of surgical oncology, 28:4744-4755, 2021

18. Edeline J , Hirano S, Bertaut A, Konishi M, Benabdelghani M, Uesaka K, Watelet J, Ohtsuka M, Hammel P, Kaneoka Y, Joly J P, Yamamoto M, Monard L, Ambo Y, Louvet C, Ando M, Malka D, Nagino M, Phelip J M, Ebata T. Individual patient data meta-analysis of adjuvant gemcitabine-based chemotherapy for biliary tract cancer: combined analysis of the BCAT and PRODIGE-12 studies. Eur J Cancer, 164:80-87, 2022