Three Molecular Developmental Pathways of Remnant Pancreatic Cancer After Resection: A Nationwide Project Study of Japan Pancreas Society

Shuji Suzuki¹, Yuko Omori^{2

3}, Yusuke Ono^{3

4}, Katsuya Hirose², Taito Itoh², Hidenori Karasaki⁵, Mitsugi Shimoda¹, Yuichi Nagakawa⁶, Ryota Higuchi⁷, Itaru Endo⁸, Toshiki Rikiyama⁹, Michiaki Unno¹⁰, Tsutomu Fujii¹¹, Yuki Sunagawa¹², Hidetoshi Eguchi¹³, Hideki Sasanuma¹⁴, Takahiro Akahori¹⁵, Keiichi Okano¹⁶, Masaji Tani¹⁷, Satoshi Hirano¹⁸, Yasuhiro Shimizu¹⁹, Minoru Kitago²⁰, Shugo Mizuno²¹, Tomohisa Yamamoto²², Masayuki Furukawa²³, Masayuki Ohtsuka²⁴, Motokazu Sugimoto²⁵, Akira Matsushita²⁶, Kenichi Hakamada²⁷, Hisato Igarashi²⁸, Tamotsu Kuroki²⁹, Satoshi Tanno³⁰, Yoshihisa Tsuji³¹, Atsushi Masamune³², Kazuhiro Mizumoto³³, Yoshiki Hirooka³⁴, Hiroki Yamaue³⁵, Kazuichi Okazaki³⁶, Sohei Satoi²², Yoshifumi Takeyama³⁷, Yusuke Mizukami^{3

4}, Toru Furukawa²

Affiliations

¹ Department of Gastroenterological Surgery, Ibaraki Medical Center, Tokyo Medical University, Ami, Japan.
² Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
³ Institute of Biomedical Research, Sapporo Higashi Tokushukai Hospital, Sapporo, Japan.
⁴ Department of Medicine, Division of Gastroenterology, Asahikawa Medical University, Asahikawa, Japan.
⁵ Department of Surgery, Engaru Kosei Hospital, Monbetsu, Japan.
⁶ Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan.
⁷ Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.
⁸ Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan.
⁹ Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
¹⁰ Department of Surgery, Tohoku University Graduate School of Medicine. Sendai, Japan.
¹¹ Department of Surgery and Science, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan.
¹² Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
¹³ Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
¹⁴ Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Japan.
¹⁵ Department of Surgery, Nara Medical University, Kashihara, Japan.
¹⁶ Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Miki, Japan.
¹⁷ Department of Surgery, Shiga University of Medical Science, Ohtsu, Japan.
¹⁸ Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Japan.
¹⁹ Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.
²⁰ Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
²¹ Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Hospital, Tsu, Japan.
²² Department of Surgery, Kansai Medical University, Hirakata, Japan.
²³ Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
²⁴ Department of General Surgery, Chiba University, Chiba, Japan.
²⁵ Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Kashiwa, Japan.
²⁶ Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan.
²⁷ Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
²⁸ Igarashi Medical Clinic, Shimonoseki, Japan.
²⁹ Department of Surgery, NHO Nagasaki Medical Center, Omura, Japan.
³⁰ Department of Gastroenterology, IMS Sapporo Digestive Disease Center General Hospital, Sapporo, Japan.
³¹ Department of General Medicine, Sapporo Medical University, Sapporo, Japan.
³² Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
³³ International University of Health and Welfare, Tokyo, Japan.
³⁴ Department of Gastroenterology and Hepatology, Fujita Health University School of Medicine, Toyoake, Japan.
³⁵ Second Department of Surgery, Wakayama Medical University, Wakayama, Japan.
³⁶ Department of Gastroenterology and Hepatology, Kansai Medical University, Hirakata, Japan.
³⁷ Department of Surgery, Kindai University School of Medicine, Osakasayama, Japan.

PMID: 39016004
DOI: 10.1097/SLA.0000000000006444

Multicenter Study

Three Molecular Developmental Pathways of Remnant Pancreatic Cancer After Resection: A Nationwide Project Study of Japan Pancreas Society

Shuji Suzuki et al. Ann Surg. 2025.

. 2025 Jun 1;281(6):1015-1025.

doi: 10.1097/SLA.0000000000006444. Epub 2024 Jul 17.

Authors

Affiliations

¹ Department of Gastroenterological Surgery, Ibaraki Medical Center, Tokyo Medical University, Ami, Japan.
² Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
³ Institute of Biomedical Research, Sapporo Higashi Tokushukai Hospital, Sapporo, Japan.
⁴ Department of Medicine, Division of Gastroenterology, Asahikawa Medical University, Asahikawa, Japan.
⁵ Department of Surgery, Engaru Kosei Hospital, Monbetsu, Japan.
⁶ Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan.
⁷ Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.
⁸ Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan.
⁹ Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
¹⁰ Department of Surgery, Tohoku University Graduate School of Medicine. Sendai, Japan.
¹¹ Department of Surgery and Science, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan.
¹² Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
¹³ Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
¹⁴ Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Japan.
¹⁵ Department of Surgery, Nara Medical University, Kashihara, Japan.
¹⁶ Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Miki, Japan.
¹⁷ Department of Surgery, Shiga University of Medical Science, Ohtsu, Japan.
¹⁸ Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Japan.
¹⁹ Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.
²⁰ Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
²¹ Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Hospital, Tsu, Japan.
²² Department of Surgery, Kansai Medical University, Hirakata, Japan.
²³ Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
²⁴ Department of General Surgery, Chiba University, Chiba, Japan.
²⁵ Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Kashiwa, Japan.
²⁶ Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan.
²⁷ Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
²⁸ Igarashi Medical Clinic, Shimonoseki, Japan.
²⁹ Department of Surgery, NHO Nagasaki Medical Center, Omura, Japan.
³⁰ Department of Gastroenterology, IMS Sapporo Digestive Disease Center General Hospital, Sapporo, Japan.
³¹ Department of General Medicine, Sapporo Medical University, Sapporo, Japan.
³² Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
³³ International University of Health and Welfare, Tokyo, Japan.
³⁴ Department of Gastroenterology and Hepatology, Fujita Health University School of Medicine, Toyoake, Japan.
³⁵ Second Department of Surgery, Wakayama Medical University, Wakayama, Japan.
³⁶ Department of Gastroenterology and Hepatology, Kansai Medical University, Hirakata, Japan.
³⁷ Department of Surgery, Kindai University School of Medicine, Osakasayama, Japan.

PMID: 39016004
DOI: 10.1097/SLA.0000000000006444

Abstract

Objective: To clarify the molecular mechanism of remnant pancreatic cancer (PC) development after primary PC resection.

Background: Molecular mechanisms of the development of remnant PCs after primary PC resection are largely unknown.

Methods: Forty-three patients undergoing remnant PC resection after primary PC resection between 2001 and 2017 at 26 institutes were retrospectively analyzed. Clinicopathologic features and molecular alterations detected by targeted amplicon sequencing of 36 PC-associated genes were evaluated.

Results: These patients showed significantly lower body mass indices and higher hemoglobin A1c values at remnant PC resection than at primary PC resection. A comparison of the molecular features between primary and remnant PCs indicated that remnant PCs were likely to develop through 3 different molecular pathways: successional, showing identical and accumulated alterations (n = 14); phylogenic, showing identical and distinct alterations (n = 26); and distinct, showing independent distinctive alterations (n = 3). The similarity of gene alterations was associated with time to the remnant PC development ( r = 0.384, P = 0.0173). Phylogenic pathways were significantly associated with the intraductal spread of carcinoma ( P = 0.007). Patient survival did not differ significantly depending on these molecular pathways.

Conclusions: Molecular profiling uncovered 3 pathways for the development of remnant PCs, namely, successional, phylogenic, and distinct pathways. The vast majority of remnant PCs are likely to be molecularly associated with primary PCs either in the successional or phylogenic way. This information could impact the design of a strategy for monitoring and treating remnant PCs.

Keywords: initial pancreatic cancer; molecular developmental pathway; remnant pancreatic cancer.

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Conflict of interest statement

The authors report no conflicts of interest.

References

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1. Crippa S, Tamburrino D, Partelli S, et al. Total pancreatectomy: indications, different timing, and perioperative and long-term outcomes. Surgery. 2011;149:79–86.
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1. Suzuki S, Furukawa T, Oshima N, et al. Original scientific reports: clinicopathological findings of remnant pancreatic cancers in survivors following curative resections of pancreatic cancers. World J Surg. 2016;40:974–981.

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Three Molecular Developmental Pathways of Remnant Pancreatic Cancer After Resection: A Nationwide Project Study of Japan Pancreas Society

Affiliations

Three Molecular Developmental Pathways of Remnant Pancreatic Cancer After Resection: A Nationwide Project Study of Japan Pancreas Society

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources