Reference Citation Analysis: Find an Article, Find a Category, Find a Journal, Find a Scholar

For: Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, Schramm H, Fahlke J, Zuelke C, Burkart C, Gutberlet K, Kettner E, Schmalenberg H, Weigang-Koehler K, Bechstein WO, Niedergethmann M, Schmidt-Wolf I, Roll L, Doerken B, Riess H. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA 2007;297:267-77. [PMID: 17227978 DOI: 10.1001/jama.297.3.267] [Citation(s) in RCA: 1753] [Impact Index Per Article: 97.4] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]

For:	Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, Schramm H, Fahlke J, Zuelke C, Burkart C, Gutberlet K, Kettner E, Schmalenberg H, Weigang-Koehler K, Bechstein WO, Niedergethmann M, Schmidt-Wolf I, Roll L, Doerken B, Riess H. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA 2007;297:267-77. [PMID: 17227978 DOI: 10.1001/jama.297.3.267] [Citation(s) in RCA: 1753] [Impact Index Per Article: 97.4] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]

Number

Cited by Other Article(s)

Yong JP, Mu XY, Zhou CF, Zhang KK, Gao JQ, Guo ZZ, Zhou SF, Ma Z. Radiofrequency ablation of liver metastases in a patient with pancreatic cancer and long-term survival: A case report. World J Clin Cases 2025;13:100169. [DOI: 10.12998/wjcc.v13.i20.100169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Revised: 09/05/2024] [Accepted: 03/06/2025] [Indexed: 04/09/2025] Open

Abstract

BACKGROUND

According to the GLOBCAN2022 database, pancreatic cancer has become the 6th leading cause of cancer-related death worldwide. The latest statistics suggest that the incidence of pancreatic cancer is increasing at a rate of 0.5% to 1.0% per year, and it is expected to become the 2nd leading cause of tumor-related deaths in the United States by 2030. More than 50% of pancreatic cancer patients have already developed distant metastases at the time of diagnosis, with the liver being the most common site. Patients with pancreatic cancer with liver metastasis (PCLM) have a worse prognosis than those with locally progressed pancreatic cancer, with a median survival of less than six months. Therefore, the outcome of liver metastases is often a vital determinant of the prognosis of patients with PCLM. There are few successful cases of localized treatment for PCLM patients. Our department recently performed local radiofrequency ablation (RFA) treatment for a PCLM patient through an evidence-based medicine approach, with remarkable therapeutic effects.

CASE SUMMARY

The patient was admitted to the hospital on May 03, 2018, 3 weeks after pancreatic cancer surgery. In October 2017, the patient presented with lower back pain. No abnormalities were detected via computed tomography (CT), colonoscopy, or gastroscopy. However, on March 18, 2018, the patient was investigated in a foreign hospital via CT, which suggested occupational lesions in the descending part of the duodenum, and magnetic resonance imaging suggested pancreatic occupancy. He was considered to be suffering from pancreatic cancer. He underwent laparoscopic-assisted pancreatic + duodenum + superior mesenteric vein partial resection and reconstruction under general anesthesia on March 26, 2018 at The Affiliated Hospital of Xuzhou Medical University. The pancreas and duodenum were partially resected. Postoperative pathology showed adenocarcinoma of the pancreas (moderately differentiated), partly mucinous carcinoma, invading the mucosal layer of the duodenum; the tumor size was 4.5 cm × 4 cm × 4 cm. There was no apparent nerve or vascular invasion. There was no cancer or involvement of the pancreas section or expected hepatic duct margins. There was no cancer involvement in the gastric and duodenal sections. There was no cancer metastasis to the peripheral lymph nodes of the pancreas (0/9). No metastasis to the gastric lesser curvature or more significant curvature lymph nodes (0/1, 0/5) was detected, and the peri-intestinal lymph nodes showed no cancer metastasis (0/4). Although the gallbladder showed signs of chronic cholecystitis, there was no cancer involvement, and the lymph nodes in Groups 12 and 13 also showed no cancer metastasis (0/6, 0/1). His postoperative recovery was acceptable. CT was performed on May 2018 at our hospital and found the following: (1) Double lung bronchial vascular bundles slightly heavier than normal; (2) Postoperative changes in the pancreas and a retention tube shadow in front of the head of the pancreas; (3) Small cysts in the right lobe of the liver; (4) Abdominopelvic effusion; and (5) Para splenic enlargement. pTNM stage: PT3N0M0. The patient was in the second stage of postoperative pancreatic cancer, with a potential risk of recurrence considering the patient's postoperative body quality deviation. The patient was unable to tolerate the standard multidrug combination and underwent six cycles of single-agent gemcitabine chemotherapy from May 10, 2018 to August 31, 2018 (the specific drug dosage was 1.4 g/d1/d8 gemcitabine injection, which was repeated every 21 days). Efficacy was determined to be stable disease after 2, 4, and 6 cycles. The side effects during treatment were tolerable.

CONCLUSION

This case suggests that RFA can serve as a viable local treatment modality for selected patients with PCLM, offering a chance for long-term survival. Such localized interventions, when carefully tailored, may complement systemic therapies in controlling metastatic pancreatic cancer.

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Chuong MD, Ashman J, Jethwa K, Kharofa J, Kim H, Koay E, Ludmir E, Miller E, Nelson B, Reyngold M, Sanford N, Chang D. Moving From the Background Toward the Spotlight: A Critical Review of Radiation Therapy for Locally Advanced Pancreas Cancer. Int J Radiat Oncol Biol Phys 2025;122:294-312. [PMID: 40032056 DOI: 10.1016/j.ijrobp.2025.02.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 01/31/2025] [Accepted: 02/16/2025] [Indexed: 03/05/2025]

Zhang J, Kong X, Zhou B, Li R, Yu Z, Zhu J, Xi Q, Li Y, Zhao Z, Zhang R. Metabolic reprogramming of drug resistance in pancreatic cancer: mechanisms and effects. Mol Aspects Med 2025;103:101368. [PMID: 40398192 DOI: 10.1016/j.mam.2025.101368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2025] [Revised: 05/10/2025] [Accepted: 05/10/2025] [Indexed: 05/23/2025]

Affiliation(s)

Jinyi Zhang Guangdong Provincial Key Laboratory for Biotechnology Drug Candidates, Department of Biotechnology, Laboratory of Immunology and Inflammation, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou,The Second Clinical Medical School of Guangdong Pharmaceutical University, Guangzhou, China
Xueqing Kong Guangdong Provincial Key Laboratory for Biotechnology Drug Candidates, Department of Biotechnology, Laboratory of Immunology and Inflammation, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou,The Second Clinical Medical School of Guangdong Pharmaceutical University, Guangzhou, China
Boyan Zhou Guangdong Provincial Key Laboratory for Biotechnology Drug Candidates, Department of Biotechnology, Laboratory of Immunology and Inflammation, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou,The Second Clinical Medical School of Guangdong Pharmaceutical University, Guangzhou, China
Rui Li Guangdong Provincial Key Laboratory for Biotechnology Drug Candidates, Department of Biotechnology, Laboratory of Immunology and Inflammation, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou,The Second Clinical Medical School of Guangdong Pharmaceutical University, Guangzhou, China
Zhaoan Yu Guangdong Provincial Key Laboratory for Biotechnology Drug Candidates, Department of Biotechnology, Laboratory of Immunology and Inflammation, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou,The Second Clinical Medical School of Guangdong Pharmaceutical University, Guangzhou, China
Jinrong Zhu Guangdong Provincial Key Laboratory for Biotechnology Drug Candidates, Department of Biotechnology, Laboratory of Immunology and Inflammation, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou,The Second Clinical Medical School of Guangdong Pharmaceutical University, Guangzhou, China
Qing Xi Guangdong Provincial Key Laboratory for Biotechnology Drug Candidates, Department of Biotechnology, Laboratory of Immunology and Inflammation, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou,The Second Clinical Medical School of Guangdong Pharmaceutical University, Guangzhou, China
Yan Li Guangdong Provincial Key Laboratory for Biotechnology Drug Candidates, Department of Biotechnology, Laboratory of Immunology and Inflammation, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou,The Second Clinical Medical School of Guangdong Pharmaceutical University, Guangzhou, China
Zichao Zhao Department of Emergency Medicine, Shaodong People's Hospital, Shaodong City, Hunan Province, China.
Rongxin Zhang Guangdong Provincial Key Laboratory for Biotechnology Drug Candidates, Department of Biotechnology, Laboratory of Immunology and Inflammation, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou,The Second Clinical Medical School of Guangdong Pharmaceutical University, Guangzhou, China.

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Shukla A, Kalayarasan R, Sai Krishna P, Pottakkat B. Remnant pancreatic carcinoma: The current status. World J Clin Oncol 2025;16:107039. [DOI: 10.5306/wjco.v16.i5.107039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2025] [Revised: 03/31/2025] [Accepted: 04/11/2025] [Indexed: 05/19/2025] Open

Matsui Y, Hashimoto D, Nakagawa N, Yamaki S, Hayashi M, Takami H, Shibuya K, Yamada S, Satoi S, Fujii T. Long-term outcomes of prophylactic right-half dissection of the superior mesenteric artery nerve plexus in pancreatoduodenectomy for pancreatic ductal adenocarcinoma: five-year results from a randomized phase II trial. Surg Today 2025:10.1007/s00595-025-03062-6. [PMID: 40380996 DOI: 10.1007/s00595-025-03062-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2025] [Accepted: 04/23/2025] [Indexed: 05/19/2025]

Kobayashi K, Sawada Y, Sahara K, Kikuchi Y, Miyake K, Yabushita Y, Homma Y, Kumamoto T, Matsuyama R, Endo I. Clinical Relevance of High-Grade Pancreatic Intraepithelial Neoplasia at the Pancreatic Transection Margin in Patients with Pancreatic Ductal Adenocarcinoma. Ann Surg Oncol 2025:10.1245/s10434-025-17400-y. [PMID: 40360836 DOI: 10.1245/s10434-025-17400-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2025] [Accepted: 04/13/2025] [Indexed: 05/15/2025]

Azeez A, Noel C. Global status of research on quality of life in pancreatic cancer patients: A bibliometric and network analysis from 2005-2024. Clin Res Hepatol Gastroenterol 2025;49:102595. [PMID: 40210107 DOI: 10.1016/j.clinre.2025.102595] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2024] [Revised: 04/05/2025] [Accepted: 04/06/2025] [Indexed: 04/12/2025]

Abstract

BACKGROUND

Pancreatic cancer (PC) is a major global health challenge, with rising incidence and mortality rates, particularly in high-socio-demographic index regions. Given its high mortality and significant morbidity, research on patient quality of life (QoL) has gained momentum, addressing symptom burdens, psychological distress, and treatment-related outcomes. Bibliometric analysis provides a valuable approach to mapping research trends, identifying key contributors, and forecasting future directions.

OBJECTIVE

This study aimed to map global research on QoL in pancreatic cancer patients, highlighting key findings, challenges, and future directions through bibliometric analysis over the past two decades.

METHODS

Data for this study were collected from the Web of Science Core Collection (WoSCC) database, using specific search strategies to retrieve relevant documents on the quality of life in pancreatic cancer patients. The data were analysed using the Bibliometrix R package to create knowledge maps and visualize research trends, collaborations, and emerging hotspots in the field.

RESULTS

A total of 819 articles on pancreatic cancer and quality of life were identified, with an average citation count of 47.13 per article, highlighting moderate academic impact. The research revealed a growing trend in collaborative efforts, with an average of 9.42 co-authors per article and 16 % international collaborations. The United States emerged as the leading contributor, with 203 publications and the highest citation count, followed by France and the United Kingdom.

CONCLUSION

This bibliometric analysis highlights the growing volume of pancreatic cancer and quality of life research, with a steady annual growth rate of 6.9 % and increasing collaboration, especially from the United States. However, despite the rising number of publications, a decline in citation impact for recent studies suggests a need for continued innovation in therapeutic strategies to improve clinical outcomes.

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Funamizu N, Sakamoto A, Mori S, Iwata M, Shine M, Ito C, Uraoka M, Ueno Y, Tamura K, Kamei Y, Takada Y, Aoki T, Umeda Y. Postoperative Geriatric Nutritional Risk Index as a Determinant of Tolerance to S-1 Adjuvant Chemotherapy After Curative Surgery for Pancreatic Ductal Adenocarcinoma: A Cohort Study with External Validation. Cancers (Basel) 2025;17:1448. [PMID: 40361375 PMCID: PMC12071064 DOI: 10.3390/cancers17091448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Revised: 04/23/2025] [Accepted: 04/24/2025] [Indexed: 05/15/2025] Open

Affiliation(s)

Naotake Funamizu Department of Hepato-Biliary Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon-City 791-0295, Japan; (A.S.); (M.I.); (M.S.); (C.I.); (M.U.); (Y.U.); (K.T.); (Y.K.); (Y.T.); (Y.U.)
Akimasa Sakamoto Department of Hepato-Biliary Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon-City 791-0295, Japan; (A.S.); (M.I.); (M.S.); (C.I.); (M.U.); (Y.U.); (K.T.); (Y.K.); (Y.T.); (Y.U.)
Shozo Mori Department of Hepato-Biliary Pancreatic Surgery, Dokkyo Medical University, Kitakobayashi 880, Mibu, Shimotsugagun 321-0293, Japan; (S.M.); (T.A.)
Miku Iwata Department of Hepato-Biliary Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon-City 791-0295, Japan; (A.S.); (M.I.); (M.S.); (C.I.); (M.U.); (Y.U.); (K.T.); (Y.K.); (Y.T.); (Y.U.)
Mikiya Shine Department of Hepato-Biliary Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon-City 791-0295, Japan; (A.S.); (M.I.); (M.S.); (C.I.); (M.U.); (Y.U.); (K.T.); (Y.K.); (Y.T.); (Y.U.)
Chihiro Ito Department of Hepato-Biliary Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon-City 791-0295, Japan; (A.S.); (M.I.); (M.S.); (C.I.); (M.U.); (Y.U.); (K.T.); (Y.K.); (Y.T.); (Y.U.)
Mio Uraoka Department of Hepato-Biliary Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon-City 791-0295, Japan; (A.S.); (M.I.); (M.S.); (C.I.); (M.U.); (Y.U.); (K.T.); (Y.K.); (Y.T.); (Y.U.)
Yoshitomo Ueno Department of Hepato-Biliary Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon-City 791-0295, Japan; (A.S.); (M.I.); (M.S.); (C.I.); (M.U.); (Y.U.); (K.T.); (Y.K.); (Y.T.); (Y.U.)
Kei Tamura Department of Hepato-Biliary Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon-City 791-0295, Japan; (A.S.); (M.I.); (M.S.); (C.I.); (M.U.); (Y.U.); (K.T.); (Y.K.); (Y.T.); (Y.U.)
Yoshiaki Kamei Department of Hepato-Biliary Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon-City 791-0295, Japan; (A.S.); (M.I.); (M.S.); (C.I.); (M.U.); (Y.U.); (K.T.); (Y.K.); (Y.T.); (Y.U.)
Yasutsugu Takada Department of Hepato-Biliary Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon-City 791-0295, Japan; (A.S.); (M.I.); (M.S.); (C.I.); (M.U.); (Y.U.); (K.T.); (Y.K.); (Y.T.); (Y.U.)
Taku Aoki Department of Hepato-Biliary Pancreatic Surgery, Dokkyo Medical University, Kitakobayashi 880, Mibu, Shimotsugagun 321-0293, Japan; (S.M.); (T.A.)
Yuzo Umeda Department of Hepato-Biliary Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon-City 791-0295, Japan; (A.S.); (M.I.); (M.S.); (C.I.); (M.U.); (Y.U.); (K.T.); (Y.K.); (Y.T.); (Y.U.)

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Yamane K, Morino K, Anazawa T, Nagai K, Sato A, Yoshimura M, Iwai T, Matsubara J, Fukuda A, Isoda H, Ogiso S, Uchida Y, Ito T, Ishii T, Hidaka Y, Ibi Y, Hatano E. Proposing oligo-recurrence criteria in pancreatic ductal adenocarcinoma: A stratified analysis of locoregional treatment benefits. Pancreatology 2025:S1424-3903(25)00077-8. [PMID: 40316466 DOI: 10.1016/j.pan.2025.04.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2025] [Revised: 04/17/2025] [Accepted: 04/20/2025] [Indexed: 05/04/2025]

Affiliation(s)

Kei Yamane Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Koshiro Morino Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Department of Gastroenterological Surgery, Tenri Hospital, Tenri, Japan
Takayuki Anazawa Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Kazuyuki Nagai Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Asahi Sato Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Michio Yoshimura Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Takahiro Iwai Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Junichi Matsubara Department of Medical Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Akihisa Fukuda Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Hiroyoshi Isoda Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Satoshi Ogiso Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Yoichiro Uchida Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Takashi Ito Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Takamichi Ishii Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Yu Hidaka Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Yumiko Ibi Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Etsuro Hatano Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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Manne A, Bao Y, Sheel A, Sara A, Manne U, Thanikachalam K, Esnakula A, Pawlik TM, Cloyd JM, Tsai S, Kasi A, Paluri RK, Sherpally D, Jeepalyam S, Yu L, Yang W. Prognostic significance of serum MUC5AC in resected pancreatic ductal adenocarcinoma: initial insights. Front Oncol 2025;15:1544928. [PMID: 40260290 PMCID: PMC12010103 DOI: 10.3389/fonc.2025.1544928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2024] [Accepted: 03/17/2025] [Indexed: 04/23/2025] Open

Abstract

Background

We investigated the association between serum MUC5AC (sMUC5AC) levels and patient outcomes in individuals who underwent resection for pancreatic ductal adenocarcinoma (PDA), including those treated with neoadjuvant therapy (NAT) and those who had upfront surgery (UpS) followed by adjuvant therapy.

Methods

Serum samples from the Ohio State University biorepository collected from January 2010 to June 2021 were utilized. The human MUC5AC kit (NBP2-76703) was used to perform enzyme-linked immunoassays to measure sMUC5AC levels. Logistic regression, Cox regression models (univariate and multivariate), recurrence prediction, analysis of variance (ANOVA), t-tests, and Wilcoxon tests were used for statistical analysis.

Results

In the NAT cohort (n = 23), elevated sMUC5AC levels were significantly (P < 0.05) associated with pathological treatment response, margin positivity, and residual disease. Among 21 patients who had an R0/R1 resection (R2 resection, n=2), higher sMUC5AC levels were associated with shorter progression-free survival (PFS) (HR: 1.64, P = 0.0006) and overall survival (OS) (HR: 1.6, P = 0.005) on univariate analysis. Multivariate models confirmed sMUC5AC as an independent predictor of PFS and OS alongside pathological differentiation and postoperative therapy. Patients with lower sMUC5AC levels had more favorable pathological characteristics, better treatment responses, and improved survival outcomes. These findings were consistent in the FOLFIRINOX subgroup (n = 17). In the UpS cohort (n = 17), post-resection sMUC5AC levels tend to be associated with PFS (P = 0.07) and OS (P = 0.05). Combining sMUC5AC with Carbohydrate antigen (CA) 19-9 enhanced sensitivity (79%) and specificity (67%) to predict recurrence. Higher sMUC5AC levels were associated with earlier recurrence and poor survival outcomes, highlighting its utility in post-surgery risk stratification. Among patients with pre-treatment data (n = 11), sMUC5AC levels were significantly higher among patients with poorly differentiated tumors.

Conclusion

This study provides compelling evidence for the clinical utility of sMUC5AC as a prognostic biomarker among patients with resected PDA. Future large-scale studies are needed to validate these findings and establish standard thresholds for sMUC5AC integration into clinical practice.

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Affiliation(s)

Ashish Manne Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center (OSUCCC), Columbus, OH, United States
Yonghua Bao Clinical & Translational Science Shared Resource, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States
Ankur Sheel Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center (OSUCCC), Columbus, OH, United States
Amir Sara Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center (OSUCCC), Columbus, OH, United States
Upender Manne Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, United States
Kannan Thanikachalam Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States
Ashwini Esnakula Department of Pathology, The Ohio State University Comprehensive Cancer Center (OSUCCC), Columbus, OH, United States
Timothy M. Pawlik Department of Surgery, Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center (OSUCCC), Columbus, OH, United States
Jordan M. Cloyd Department of Surgery, Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center (OSUCCC), Columbus, OH, United States
Susan Tsai Department of Surgery, Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center (OSUCCC), Columbus, OH, United States
Anup Kasi Division of Medical Oncology, University of Kansas Cancer Center, Westwood, KS, United States
Ravi Kumar Paluri Division of Hematology-Oncology, Department of Internal Medicine, Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC, United States
Deepak Sherpally Department of Internal Medicine, New York Medical College, Valhalla, NY, United States
Sravan Jeepalyam Department of Internal Medicine, Stormont Vail Health, Topeka, KS, United States
Lianbo Yu Center of Biostatistics and Bioinformatics, The Ohio State University, Columbus, OH, United States
Wancai Yang Clinical & Translational Science Shared Resource, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States

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Ke X, Yang M, Chen J, Hong R, Wang Z, Wang S, Zhang H, Lu J, Pan B, Gao Y, Liu X, Li X, Zhang Y, Su S, Wu H, Liang Z. Labor-Efficient Pathological Auxiliary Diagnostic Model for Primary and Metastatic Tumor Tissue Detection in Pancreatic Ductal Adenocarcinoma. Mod Pathol 2025;38:100764. [PMID: 40199428 DOI: 10.1016/j.modpat.2025.100764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Revised: 03/09/2025] [Accepted: 03/20/2025] [Indexed: 04/10/2025]

Abstract

Accurate histopathological evaluation of pancreatic ductal adenocarcinoma (PDAC), including primary tumor lesions and lymph node metastases, is critical for prognostic evaluation and personalized therapeutic strategies. Distinct from other solid tumors, PDAC presents unique diagnostic challenges owing to its extensive desmoplasia, unclear tumor boundary, and difficulty in differentiating from chronic pancreatitis. These characteristics not only complicate pathological diagnosis but also hinder the acquisition of pixel-level annotations required for training computational pathology models. In this study, we present PANseg, a multiscale weakly supervised deep learning framework for PDAC segmentation, trained and tested on 368 whole-slide images (WSIs) from 208 patients across 2 independent centers. Using only image-level labels (2048 × 2048 pixels), PANseg achieved comparable performance with fully supervised baseline (FSB) across the internal test set 1 (17 patients/58 WSIs; PANseg area under the receiver operating characteristic curve [AUROC]: 0.969 vs FSB AUROC: 0.968), internal test set 2 (40 patients/44 WSIs; PANseg AUROC: 0.991 vs FSB AUROC: 0.980), and external test set (20 patients/20 WSIs; PANseg AUROC: 0.950 vs FSB AUROC: 0.958). Moreover, the model demonstrated considerable generalizability with previously unseen sample types, attaining AUROCs of 0.878 on fresh-frozen specimens (20 patients/20 WSIs) and 0.821 on biopsy sections (20 patients/20 WSIs). In lymph node metastasis detection, PANseg augmented the diagnostic accuracy of 6 pathologists from 0.888 to 0.961, while reducing the average diagnostic time by 32.6% (72.0 vs 48.5 minutes). This study demonstrates that our weakly supervised model can achieve expert-level segmentation performance and substantially reduce annotation burden. The clinical implementation of PANseg holds great potential in enhancing diagnostic precision and workflow efficiency in the routine histopathological assessment of PDAC.

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Affiliation(s)

Xinyi Ke Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Moxuan Yang Thorough Lab, Thorough Future, Beijing, China; Department of Physics, Capital Normal University, Beijing, China
Jingci Chen Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Ruping Hong Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Zheng Wang Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Shuhao Wang Thorough Lab, Thorough Future, Beijing, China
Hui Zhang Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Junliang Lu Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Boju Pan Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Yike Gao Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Xiaoding Liu Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Xiaoyu Li Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Yang Zhang Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Si Su Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Huanwen Wu Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Zhiyong Liang Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

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Schwarz L, Bachet JB, Meurisse A, Bouché O, Assenat E, Piessen G, Hammel P, Regenet N, Taieb J, Turrini O, Paye F, Turpin A, Souche FR, Laurent C, Kianmanesh R, Michel P, Vernerey D, Mabrut JY, Turco C, Truant S, Sa Cunha A. Neoadjuvant FOLF(IRIN)OX Chemotherapy for Resectable Pancreatic Adenocarcinoma: A Multicenter Randomized Noncomparative Phase II Trial (PANACHE01 FRENCH08 PRODIGE48 study). J Clin Oncol 2025:JCO2401378. [PMID: 40184561 DOI: 10.1200/jco-24-01378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 01/10/2025] [Accepted: 02/12/2025] [Indexed: 04/06/2025] Open

Abstract

PURPOSE

Despite limited RCTs, neoadjuvant chemotherapy (NAC) shows promise for resectable pancreatic adenocarcinoma (rPAC). Few prospective results are available on completing the full therapeutic sequence and oncologic outcomes with NAC.

METHODS

The PANACHE01-PRODIGE48 phase II trial randomly assigned 153 patients with rPAC (2:2:1) to four cycles of NAC (modified leucovorin, fluorouracil, irinotecan, and oxaliplatin [mFOLFIRINOX], arm 1; leucovorin, fluorouracil, and oxaliplatin [FOLFOX], arm 2) or up-front surgery (control) across 28 French centers (February 2017-July 2020). The primary objective was to evaluate the feasibility and efficacy of these NAC regimens. Two binary primary end points included 1-year overall survival (OS) postrandomization and the rate of patients completing the full therapeutic sequence. Event-free survival (EFS) assessed time to failure, defined as progression before surgery, unresectable/metastatic disease at surgery, recurrence, or death.

RESULTS

The primary objective was achieved for arm 1. In the intention-to-treat population, 70.8% (90% CI, 60.8 to 79.6) and 68% (90% CI, 55.5 to 78.8) completed the therapeutic sequence in arm 1 and arm 2, respectively. Within 12 months postrandomization, 84.3% (90% CI, 75.3 to 90.9) and 71.4% (90% CI, 59.0 to 81.8) of the patients were alive in arm 1 and arm 2, respectively. Treatment was safe and well-tolerated in both NAC arms. Arm 2 was stopped after interim analysis for lack of efficacy (H0 rejection for 1-year OS). One-year EFS rates were 51.4% (95% CI, 41.0 to 64.3), 43.1% (95% CI, 31.3 to 59.5), and 38.7% (95% CI, 24.1 to 62.0) in arm 1, arm 2, and control arm, respectively.

CONCLUSION

The feasibility and efficacy of mFOLFIRINOX in the perioperative setting are confirmed concerning therapeutic sequence completion and oncologic outcomes, supporting ongoing trials (PREOPANC3, Alliance AO21806). Further research is needed to identify patients who benefit from NAC (ClinicalTrials.gov identifier: NCT02959879; EudraCT: 2015-001851-65).

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Affiliation(s)

Lilian Schwarz Department of Digestive Surgery, Rouen University Hospital, Rouen, France Department of Genomic and Personalized Medicine in Cancer and Neurological Disorders, UNIROUEN, UMR 1245 INSERM, Rouen University Hospital, Normandie University, Rouen, France
Jean-Baptiste Bachet Department of Hepato-Gastroenterology, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France
Aurelia Meurisse Methodology and Quality of Life in Oncology Unit, Besançon University Hospital, Besançon, France EFS, INSERM, UMR RIGHT, Université de Franche-Comté, Besançon, France
Olivier Bouché Digestive Oncology Department, Centre Hospitalier Universitaire Robert Debré, Reims, France
Eric Assenat Medical Oncology Department, Centre Hospitalier Universitaire de Saint-Eloi, Montpellier, France
Guillaume Piessen Department of Digestive and Oncological Surgery, Claude Huriez University Hospital, Chu Lille, France
Pascal Hammel Digestive and Medical Oncology Department, Hôpital Paul Brousse and University Paris-Saclay, Villejuif, France
Nicolas Regenet Department of Digestive Surgery, Centre Hospitalier Universitaire de Nantes, Nantes, France
Julien Taieb Department of Hepato-Gastroenterology, Georges Pompidou European Hospital, Carpem, Sorbonne Paris City, Paris Descartes University, Paris, France
Olivier Turrini Department of Surgical Oncology, Institut Paoli-Calmettes, CRCM, Aix-Marseille University, Marseille, France
Francois Paye Department of Surgery, Saint Antoine Hospital, Paris, France Bd de l'Hôpital, Sorbonne Université, Paris, France
Anthony Turpin Department of Medical Oncology, Claude Huriez University Hospital, Chu Lille, France
Francois-Regis Souche Department of Digestive Surgical Oncology, University Hospital of Montpellier, Montpellier, France
Christophe Laurent Department of Hepato-Bilio-Pancreatic Surgery and Liver Transplantation, Haut Lévêque Hospital, CHU de Bordeaux, Pessac, France
Reza Kianmanesh Digestive Surgery Department, Centre Hospitalier Universitaire Robert Debré, Reims, France
Pierre Michel Department of Genomic and Personalized Medicine in Cancer and Neurological Disorders, UNIROUEN, UMR 1245 INSERM, Rouen University Hospital, Normandie University, Rouen, France Department of Digestive Oncology, Rouen University Hospital, Rouen, France
Dewi Vernerey Methodology and Quality of Life in Oncology Unit, Besançon University Hospital, Besançon, France EFS, INSERM, UMR RIGHT, Université de Franche-Comté, Besançon, France
Jean-Yves Mabrut Digestive Surgery and Liver Transplantation Department, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France INSERM, CRCL UMR1052, Université de Lyon, Université Lyon 1, Lyon, France
Celia Turco Digestive Surgery Department, University Hospital of Besançon, Besançon, France
Stephanie Truant Department of Digestive Surgery and Liver Transplantation Department, CHRU Lille, CANTHER Laboratory Inserm UMR-S1277, University of Lille, Lille, France
Antonio Sa Cunha Centre Hépato-Biliaire, Hôpital Universitaire Paul Brousse, Université Paris-Saclay, Villejuif, France

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Takematsu T, Hayashi H, Ogawa D, Nakao Y, Yamao T, Kitano Y, Nakagawa S, Mima K, Baba Y, Baba H. Molecular Alterations Influencing the Prognostic Outcome in Small Pancreatic Cancer (≤2 cm). Pancreas 2025;54:e295-e302. [PMID: 40262101 DOI: 10.1097/mpa.0000000000002430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2024] [Accepted: 11/01/2024] [Indexed: 04/24/2025]

Steen TV, Espinoza I, Duran C, Casadevall G, Serrano-Hervás E, Cuyàs E, Verdura S, Kemble G, Kaufmann SH, McWilliams R, Osuna S, Billadeau DD, Menendez JA, Lupu R. Fatty acid synthase (FASN) inhibition cooperates with BH3 mimetic drugs to overcome resistance to mitochondrial apoptosis in pancreatic cancer. Neoplasia 2025;62:101143. [PMID: 39999714 PMCID: PMC11908614 DOI: 10.1016/j.neo.2025.101143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Accepted: 02/17/2025] [Indexed: 02/27/2025]

Abstract

Resistance to mitochondrial apoptosis is a major driver of chemoresistance in pancreatic ductal adenocarcinoma (PDAC). However, pharmacological manipulation of the mitochondrial apoptosis threshold in PDAC cells remains an unmet therapeutic goal. We hypothesized that fatty acid synthase inhibitors (FASNis), a family of targeted metabolic therapeutics recently entering the clinic, could lower the apoptotic threshold in chemoresistant PDAC cells and be synergistic with BH3 mimetics that neutralize anti-apoptotic proteins. Computational studies with TVB-3166 and TVB-3664, two analogues of the clinical-grade FASNi TVB-2640 (denifanstat), confirmed their uncompetitive behavior towards NADPH when bound to the FASN ketoacyl reductase domain. The extent of NADPH accumulation, a consequence of FASN inhibition, paralleled the sensitivity of PDAC cells to the apoptotic effects of TVB FASNis in conventional PDAC cell lines that naturally express varying levels of FASN. FASN inhibition dramatically increased the sensitivity of "FASN-high" expressing PDAC cells to the BCL2/BCL-XL/BCL-W inhibitor ABT-263/navitoclax and the BCL2-selective inhibitor ABT-199/venetoclax, both in vitro and in in vivo xenografted tumors. The ability of TVB FASNis to shift the balance of pro- and anti-apoptotic proteins and thereby push PDAC cells closer to the apoptotic threshold was also observed in cell lines developed from patient-derived xenografts (PDXs) representative of the classical (pancreatic) transcriptomic subtype of PDAC. Experiments in PDAC PDXs in vivo confirmed the synergistic antitumor activity of TVB-3664 with navitoclax and venetoclax, independent of the nature of the replication stress signature of patient-derived PDAC cells. The discovery that targeted inhibition of FASN is a metabolic perturbation that sensitizes PDAC cells to BH3 mimetics warrants further investigation to overcome resistance to mitochondrial apoptosis in PDAC patients.

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Affiliation(s)

Travis Vander Steen Division of Experimental Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA
Ingrid Espinoza National Institute of Health, National Heart Lung and Blood Institute (NHLBI), Bethesda, MD 20817, USA; Lung Development and Pediatric Branch (HNH36), Bethesda, MD 20817, USA
Cristina Duran Institut de Química Computacional i Catàlisi and Departament de Química, Universitat de Girona, Girona 17003, Spain
Guillem Casadevall Institut de Química Computacional i Catàlisi and Departament de Química, Universitat de Girona, Girona 17003, Spain
Eila Serrano-Hervás Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology, Girona 17007, Spain; Metabolism and Cancer Group,Girona Biomedical Research Institute (IDIBGI), Salt 17190, Girona, Spain
Elisabet Cuyàs Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology, Girona 17007, Spain; Metabolism and Cancer Group,Girona Biomedical Research Institute (IDIBGI), Salt 17190, Girona, Spain
Sara Verdura Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology, Girona 17007, Spain; Metabolism and Cancer Group,Girona Biomedical Research Institute (IDIBGI), Salt 17190, Girona, Spain
George Kemble Sagimet Biosciences Inc., San Mateo, CA 94402, USA
Scott H Kaufmann Mayo Clinic Cancer Center, Rochester, MN 55905, USA; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, 55905, USA; Division of Oncology Research, Mayo Clinic, Rochester, MN, 55905, USA
Robert McWilliams Mayo Clinic Cancer Center, Rochester, MN 55905, USA; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, 55905, USA
Sílvia Osuna Institut de Química Computacional i Catàlisi and Departament de Química, Universitat de Girona, Girona 17003, Spain; ICREA, Barcelona 08010, Spain
Daniel D Billadeau Mayo Clinic Cancer Center, Rochester, MN 55905, USA; Division of Oncology Research, Mayo Clinic, Rochester, MN, 55905, USA; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA; Department of Immunology College of Medicine, Mayo Clinic, Rochester, MN 55905, USA
Javier A Menendez Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology, Girona 17007, Spain; Metabolism and Cancer Group,Girona Biomedical Research Institute (IDIBGI), Salt 17190, Girona, Spain.
Ruth Lupu Division of Experimental Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA; Mayo Clinic Cancer Center, Rochester, MN 55905, USA; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA.

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Palmer DH, Jackson R, Springfeld C, Ghaneh P, Rawcliffe C, Halloran CM, Faluyi O, Cunningham D, Wadsley J, Darby S, Meyer T, Gillmore R, Lind P, Glimelius B, Falk S, Ma YT, Middleton GW, Cummins S, Ross PJ, Wasan H, McDonald A, Crosby T, Hammel P, Borg D, Sothi S, Valle JW, Mehrabi A, Bailey P, Tjaden C, Michalski C, Hackert T, Büchler MW, Neoptolemos JP. Pancreatic Adenocarcinoma: Long-Term Outcomes of Adjuvant Therapy in the ESPAC4 Phase III Trial. J Clin Oncol 2025;43:1240-1253. [PMID: 39637340 PMCID: PMC11949205 DOI: 10.1200/jco.24.01118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Revised: 09/08/2024] [Accepted: 10/03/2024] [Indexed: 12/07/2024] Open

Abstract

PURPOSE

The ESPAC4 trial showed that adjuvant chemotherapy with gemcitabine plus capecitabine (GemCap) produced longer overall survival (OS) than gemcitabine monotherapy. Subsequently, the PRODIGE24-CCTG PA.6 trial showed even longer survival for modified fluorouracil, folinic acid, irinotecan, and oxaliplatin (mFOLFIRINOX) than gemcitabine but had more restrictive eligibility criteria. Our aim was to analyze the ESPAC4 survival on long-term follow-up.

METHODS

The OS of 732 ESPAC4 patients comparing 367 randomly assigned to gemcitabine and 365 to GemCap was previously reported after a median follow-up time of 43.2 months (95% CI, 39.7 to 45.5) and 458 deaths. Analysis was now carried out after a median follow-up of 104 months (101-108) and 566 deaths.

RESULTS

The median OS was 29.5 months (27.5-32.1) for all patients, 28.4 months (25.2-32.0) in the gemcitabine group and 31.6 months (26.5-38.0) in the GemCap group (hazard ratio [HR], 0.83 [0.71 to 0.98]; P = .031). R0 patients given gemcitabine had a median survival of 32.2 months (27.9-41.6) compared with 49.9 months (39.0-82.3) for those given GemCap (HR, 0.63 [0.47 to 0.84]; P = .002). Lymph node-negative patients had significantly higher 5 year OS rates on GemCap (59% [49%-71%]) than gemcitabine (53% [42%-66%]; HR, 0.63 [0.41 to 0.98]; P = .04) but not those with positive lymph nodes (P = .225). The OS advantage for GemCap was retained in the PRODIGE24 subgroup of 193 (26.4%) ESPAC4 patients not eligible for PRODIGE24 with a median survival of 20.7 (16.2-27.3) months in patients allocated to gemcitabine compared with 25.9 (22.3-30.2) months for ineligible patients allocated to GemCap (HR, 0.71 [95% CI, 0.52 to 0.98]; χ2log-rank-1df = 4.31; P = .038).

CONCLUSION

GemCap is a standard option for patients not eligible for mFOLFIRINOX. Exploratory evidence suggests that GemCap may be particularly efficacious in R0 patients and also in lymph node-negative patients.

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Affiliation(s)

Daniel H. Palmer University of Liverpool, Liverpool, United Kingdom
Richard Jackson University of Liverpool, Liverpool, United Kingdom
Christoph Springfeld Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany Champalimaud Foundation, Lisbon, Portugal
Paula Ghaneh University of Liverpool, Liverpool, United Kingdom
Charlotte Rawcliffe University of Liverpool, Liverpool, United Kingdom
Christopher M. Halloran University of Liverpool, Liverpool, United Kingdom
Olusola Faluyi The Clatterbridge Cancer Centre NHS Foundation Trust, Liverpool, United Kingdom
David Cunningham Royal Marsden Hospital, London, United Kingdom
Jonathan Wadsley Weston Park Cancer Centre, Sheffield, United Kingdom
Suzanne Darby Weston Park Hospital, Sheffield, United Kingdom
Tim Meyer Department of Oncology, Royal Free Hospital and UCL Cancer Institute, University College London, London, United Kingdom
Roopinder Gillmore Royal Free Hospital, London, United Kingdom
Pehr Lind Department of Oncology, Stockholm Söder Hospital, Stockholm, Sweden Karolinska Institute, Stockholm, Sweden
Bengt Glimelius Department of Immunology, Genetics and Pathology, University of Uppsala, Uppsala, Sweden
Stephen Falk Bristol Cancer Institute, Bristol, United Kingdom
Yuk Ting Ma University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom
Gary William Middleton University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom
Sebastian Cummins Royal Surrey County Hospital, Guildford, United Kingdom
Paul J. Ross Guy's & St Thomas' and King's College Hospitals, London, United Kingdom
Harpreet Wasan Hammersmith Hospital, London, United Kingdom
Alec McDonald The Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom
Tom Crosby Velindre Cancer Centre, Cardiff, United Kingdom
Pascal Hammel Hôpital Paul Brousse (APHP), Paris-Saclay University, Villejuif, France
David Borg Skåne University Hospital, Lund, Sweden Department of Clinical Sciences Lund, Oncology and Therapeutic Pathology, Lund University, Lund, Sweden
Sharmila Sothi University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
Juan W. Valle Cholangiocarcinoma Foundation, Herriman, UT
Arianeb Mehrabi Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
Peter Bailey Champalimaud Foundation, Lisbon, Portugal Division of Applied Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany
Christine Tjaden MRI TUM, Klinikum rechts der Isar of the Technical University of Munich, Munich, Germany
Christoph Michalski Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
Thilo Hackert Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany
Markus W. Büchler Champalimaud Foundation, Lisbon, Portugal Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
John P. Neoptolemos Champalimaud Foundation, Lisbon, Portugal Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany

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Huang J, Zhang Q, Ge Y, Zheng R, Yang M, Sun Y, Go VLW, Zhang Z, Fang H, Liu J, Guo J, Xiao GG. Serum microRNA-24-based nomogram predicts prognosis for patients with resected pancreatic cancer. Sci Rep 2025;15:8159. [PMID: 40059103 PMCID: PMC11891307 DOI: 10.1038/s41598-024-82369-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2024] [Accepted: 12/04/2024] [Indexed: 05/13/2025] Open

Affiliation(s)

Jing Huang National Key Laboratory of Fine Chemical Engineering and Department of Pharmacology in School of Chemical Engineering, Dalian University of Technology, Dalian, 116024, China
Qian Zhang School of Basic Medical Sciences, Xiangnan University, Chenzhou, 423000, China
Yang Ge Department of Food Safety and Toxicology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200240, China
Ren Zheng National Key Laboratory of Fine Chemical Engineering and Department of Pharmacology in School of Chemical Engineering, Dalian University of Technology, Dalian, 116024, China
Minwei Yang Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China
Yongwei Sun Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China
Vay Liang W Go David Geffen School of Medicine at UCLA, The UCLA Agi Hirshberg Center for Pancreatic Diseases, Los Angeles, CA, 90095, USA
Zhigang Zhang State Key Laboratory of Oncogenes and Related Genes, School of Medicine, Ren Ji Hospital, Shanghai Cancer Institute, Shanghai Jiao Tong University, Shanghai, 200025, China
Huilong Fang School of Basic Medical Sciences, Xiangnan University, Chenzhou, 423000, China
Jianzhou Liu Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
Junchao Guo Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
Gary Guishan Xiao National Key Laboratory of Fine Chemical Engineering and Department of Pharmacology in School of Chemical Engineering, Dalian University of Technology, Dalian, 116024, China. Functional Genomics and Proteomics Laboratories, Osteoporosis Research Center, Creighton University Medical Center, Omaha, NE, 68124, USA. National Key Laboratory of Fine Chemical Engineering, and Center for Molecular Pharmacology and Department of Pharmacology in School of Chemical Engineering at, Dalian University of Technology, Dalian, China.

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Biesma NC, Graus MUJE, Cirkel GA, Besselink MG, de Groot JWB, Koerkamp BG, Herbschleb KH, Los M, Verdonk RC, Wilmink JW, Cervantes A, Valle JW, Valkenburg-van Iersel LBJ, Froeling FEM, Molenaar IQ, Daamen LA, de Vos-Geelen J, van Santvoort HC. Perspectives of the medical oncologist regarding adjuvant chemotherapy for pancreatic cancer: An international expert survey and case vignette study. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025;51:109544. [PMID: 39689462 DOI: 10.1016/j.ejso.2024.109544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 11/19/2024] [Accepted: 12/10/2024] [Indexed: 12/19/2024]

Affiliation(s)

N C Biesma University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Regional Academic Cancer Center Utrecht, Department of Surgery, the Netherlands.
M U J E Graus Maastricht University Medical Center, Department of Internal Medicine, Division of Medical Oncology, GROW, Research Institute for Oncology & Reproduction, Maastricht, the Netherlands
G A Cirkel University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein & Meander Medical Center Amersfoort, Regional Academic Cancer Center Utrecht, Department of Medical Oncology, the Netherlands
M G Besselink Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, the Netherlands; Cancer Center Amsterdam, the Netherlands
J W B de Groot Isala Oncology Center, Department of Medical Oncology, Zwolle, the Netherlands
B Groot Koerkamp Erasmus Medical Center, Department of Surgery, Rotterdam, the Netherlands
K H Herbschleb University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Regional Academic Cancer Center Utrecht, Department of Medical Oncology, the Netherlands
M Los University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Regional Academic Cancer Center Utrecht, Department of Medical Oncology, the Netherlands
R C Verdonk University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Regional Academic Cancer Center Utrecht, Department of Gastroenterology and Hepatology, the Netherlands
J W Wilmink Cancer Center Amsterdam, the Netherlands; Amsterdam UMC, Location University of Amsterdam, Department of Medical Oncology, Amsterdam, the Netherlands
A Cervantes Department of Medical Oncology, Biomedical Research Institute INCLIVA, University of Valencia, Spain
J W Valle Cholangiocarcinoma Foundation, Herriman, Utah, USA; Division of Cancer Sciences, The University of Manchester, Manchester, United Kingdom
L B J Valkenburg-van Iersel Maastricht University Medical Center, Department of Internal Medicine, Division of Medical Oncology, GROW, Research Institute for Oncology & Reproduction, Maastricht, the Netherlands
F E M Froeling Dept. of Medical Oncology, Clinical Senior Lecturer and Honorary Consultant Medical Oncologist, University of Glasgow and Beatson West of Scotland Cancer Centre, United Kingdom
I Q Molenaar University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Regional Academic Cancer Center Utrecht, Department of Surgery, the Netherlands
L A Daamen University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Regional Academic Cancer Center Utrecht, Department of Surgery, the Netherlands; University Medical Center Utrecht Cancer Center, Division of Imaging & Oncology, Utrecht, the Netherlands
J de Vos-Geelen Maastricht University Medical Center, Department of Internal Medicine, Division of Medical Oncology, GROW, Research Institute for Oncology & Reproduction, Maastricht, the Netherlands
H C van Santvoort University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Regional Academic Cancer Center Utrecht, Department of Surgery, the Netherlands.

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Kersch CN, Grossberg AJ. Perioperative Radiation for Patients with Resectable Pancreatic Cancer: an Updated Review After the Initial RTOG 0848 Results. J Gastrointest Cancer 2025;56:70. [PMID: 39987276 DOI: 10.1007/s12029-025-01185-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/27/2025] [Indexed: 02/24/2025]

Abstract

PURPOSE

Pancreatic cancer remains one of the most lethal malignancies, with limited long-term survival despite advances in treatment strategies. While surgical resection offers the best chance for cure in localized disease, high rates of recurrence underscore the need for effective adjuvant therapies. Over four decades, the role of adjuvant chemoradiation (CRT) has been the subject of significant debate, with numerous trials yielding mixed outcomes regarding its impact on survival. Improvements in chemotherapy regimens and radiotherapy techniques have prompted renewed efforts to define the value of CRT, particularly in comparison to chemotherapy alone. The recent initial results of RTOG 0848 mark a critical milestone in this ongoing discussion, providing contemporary evidence that challenges established assumptions and refines patient selection criteria. By identifying specific subgroups-such as lymph node-negative patients-which may benefit from CRT, the trial offers clarity while highlighting the limitations of CRT in other populations.

METHODS

Herein, we review prior prospective and retrospective trials that investigated the role of perioperative CRT, in particular radiation therapy, for resectable pancreatic cancer.

RESULTS

This review examines the trajectory of research on CRT in pancreatic cancer, assesses the implications of RTOG 0848 for current clinical practice, and underscores the importance of further studies to optimize the integration of multimodal therapy in the management of this aggressive disease.

CONCLUSION

The combination of results from RTOG 0848 in conjunction with the results of prior prospective and retrospective trials lend support for the use of adjuvant RT for patients with both lymph node-negative and lymph node-positive disease. However, several open questions remain about the role of this therapy in select patient cohorts, and whether neoadjuvant versus advent radiation is optimal.

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Zhang J, Cai H, Zhang M, Cai Y, Peng B. Perioperative risk factors for overall survival of patients with pancreatic ductal adenocarcinoma underwent laparoscopic pancreaticoduodenectomy. Updates Surg 2025:10.1007/s13304-025-02081-9. [PMID: 39833516 DOI: 10.1007/s13304-025-02081-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Accepted: 01/07/2025] [Indexed: 01/22/2025]

Zhan T, Betge J, Schulte N, Dreikhausen L, Hirth M, Li M, Weidner P, Leipertz A, Teufel A, Ebert MP. Digestive cancers: mechanisms, therapeutics and management. Signal Transduct Target Ther 2025;10:24. [PMID: 39809756 PMCID: PMC11733248 DOI: 10.1038/s41392-024-02097-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Revised: 10/20/2024] [Accepted: 11/29/2024] [Indexed: 01/16/2025] Open

Affiliation(s)

Tianzuo Zhan Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany DKFZ Hector Cancer Institute at University Medical Center Mannheim, Mannheim, Germany Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, Heidelberg, Germany
Johannes Betge Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany DKFZ Hector Cancer Institute at University Medical Center Mannheim, Mannheim, Germany Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany Junior Clinical Cooperation Unit Translational Gastrointestinal Oncology and Preclinical Models, German Cancer Research Center (DKFZ), Heidelberg, Germany
Nadine Schulte Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Lena Dreikhausen Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, Heidelberg, Germany
Michael Hirth Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Moying Li Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Philip Weidner Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Antonia Leipertz Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Andreas Teufel Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Matthias P Ebert Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. DKFZ Hector Cancer Institute at University Medical Center Mannheim, Mannheim, Germany. Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, Heidelberg, Germany.

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Wehrle CJ, Chang J, Gross A, Perlmutter B, Naples R, Stackhouse K, Augustin T, Joyce D, Simon R, Schlegel A, Walsh RM, Naffouje SA, Parente A. Sequence of Chemotherapy May Not Impact Survival After Resection of Pancreatic Tail Adenocarcinoma. J Surg Oncol 2025. [DOI: 10.1002/jso.28086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Accepted: 01/01/2025] [Indexed: 02/03/2025]

Janczewski LM, Visenio MR, Joung RHS, Yang AD, Odell DD, Danielson EC, Posner MC, Skolarus TA, Bentrem DJ, Bilimoria KY, Merkow RP. Assessment of intermediate-term mortality following pancreatectomy for cancer. J Natl Cancer Inst 2025;117:49-57. [PMID: 39212612 PMCID: PMC11717425 DOI: 10.1093/jnci/djae215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 08/08/2024] [Accepted: 08/27/2024] [Indexed: 09/04/2024] Open

Abstract

BACKGROUND

Pancreatic cancer remains highly lethal, and resection represents the only chance for cure. Although patients are counseled regarding short-term (0-3 months) mortality, little is known about mortality 3-6 months (intermediate-term) following surgery. We assessed predictors of intermediate-term mortality, evaluated hospital-level variation, and developed a nomogram to predict intermediate-term mortality risk.

METHODS

Patients undergoing pancreatic cancer resection were identified from the National Cancer Database (2010-2020). Multivariable logistic regression identified predictors of intermediate-term mortality and assessed differences between short-term and intermediate-term mortality. Multinomial regression grouped by intermediate-term mortality quartiles evaluated hospital-level variation. A neural network model was constructed to predict intermediate-term mortality risk. All statistical tests were 2-sided.

RESULTS

Of 45 297 patients, 3974 (8.9%) died within 6 months of surgery of which 2216 (5.1%) were intermediate-term. Intermediate-term mortality was associated with increasing T category, positive nodes, lack of systemic therapy, and positive margins (all P < .05) compared with survival beyond 6 months. Compared with short-term mortality, intermediate-term mortality was associated with treatment at high-volume hospitals, positive nodes, neoadjuvant systemic therapy, adjuvant radiotherapy, and positive margins (all P < .05). Median intermediate-term mortality rate per hospital was 4.5% (interquartile range [IQR] = 2.6-6.5). Highest quartile hospitals had decreased odds of treatment with neoadjuvant systemic therapy, neoadjuvant radiotherapy, and adjuvant radiotherapy (all P < .05). The neural network nomogram was highly accurate (accuracy = 0.9499; area under the receiver operating characteristics curve = 0.7531) in predicting individualized intermediate-term mortality risk.

CONCLUSION

Nearly 10% of patients undergoing pancreatectomy for cancer died within 6 months, of which one-half occurred in the intermediate term. These data have real-world implications to improve shared decision making when discussing curative-intent pancreatectomy.

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Birrer M, Saad B, Drews S, Pradella C, Flaifel M, Charitakis E, Ortlieb N, Haberstroh A, Ochs V, Taha-Mehlitz S, Burri E, Heigl A, Frey DM, Cattin PC, Honaker MD, Taha A, Rosenberg R. Radiofrequency ablation (RFA) in unresectable pancreatic adenocarcinoma: meta-analysis & systematic review. Surg Endosc 2025;39:141-152. [PMID: 39658672 PMCID: PMC11666652 DOI: 10.1007/s00464-024-11450-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2024] [Accepted: 11/23/2024] [Indexed: 12/12/2024]

Affiliation(s)

Mathias Birrer Department of Visceral Surgery, Cantonal Hospital Baselland, Liestal, Switzerland Faculty of Medicine, University of Basel, Basel, Switzerland
Baraa Saad School of Medicine, St George's University of London, London, UK
Susanne Drews Department of Visceral Surgery, Cantonal Hospital Baselland, Liestal, Switzerland
Charlotte Pradella Department of Visceral Surgery, Cantonal Hospital Baselland, Liestal, Switzerland
Mariana Flaifel School of Medicine, St George's University of London, London, UK
Emmanouil Charitakis Medoc Swiss, Science and Statistics, Basel, Switzerland
Niklas Ortlieb Medoc Swiss, Science and Statistics, Basel, Switzerland
Amanda Haberstroh Laupus Health Sciences Library, East Carolina University, Greenville, NC, USA
Vincent Ochs Department of Biomedical Engineering, Faculty of Medicine, University of Basel, Allschwil, Switzerland
Stephanie Taha-Mehlitz Clarunis, Department of Visceral Surgery, University Center for Gastrointestinal and Liver Diseases, St. Clara Hospital and University Hospital Basel, Basel, Switzerland
Emanuel Burri Department of Gastroenterology and Hepatology, Medical University Clinic, Cantonal Hospital Baselland, Liestal, Switzerland
Andres Heigl Department of Visceral Surgery, Cantonal Hospital Baselland, Liestal, Switzerland
Daniel M Frey Faculty of Medicine, University of Basel, Basel, Switzerland Department of Surgery, Klinik-Impuls, Zurich, Switzerland
Philippe C Cattin Department of Biomedical Engineering, Faculty of Medicine, University of Basel, Allschwil, Switzerland
Michael D Honaker Department of Surgery, Brody School of Medicine, East Carolina University, Greenville, NC, USA
Anas Taha Department of Visceral Surgery, Cantonal Hospital Baselland, Liestal, Switzerland. Department of Biomedical Engineering, Faculty of Medicine, University of Basel, Allschwil, Switzerland. Department of Surgery, Brody School of Medicine, East Carolina University, Greenville, NC, USA.
Robert Rosenberg Department of Visceral Surgery, Cantonal Hospital Baselland, Liestal, Switzerland

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Mizutani S, Taniai N, Sukegawa M, Haruna T, Furuki H, Takata H, Ueda J, Yoshioka M, Aimoto T, Sakamoto S, Suzuki K, Nakamura Y, Yoshida H. Pancreatectomy with Celiac Axis Resection and Reconstruction for Locally Advanced Pancreatic Cancer. Cancers (Basel) 2024;16:4115. [PMID: 39682301 DOI: 10.3390/cancers16234115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 12/02/2024] [Accepted: 12/06/2024] [Indexed: 12/18/2024] Open

Abstract

BACKGROUND

With the advent of effective chemotherapy, conversion surgery (CS) has been performed in patients who have responded to pretreatment, even for pancreatic cancer diagnosed as unresectable (UR) at the time of initial diagnosis. In CS, major arterial resection and reconstruction are necessary for complete radical resection.

METHODS

We discuss the key points for safely performing pancreatectomy with celiac axis (CA) resection combined with reconstruction, divided into resection and arterial reconstruction. The possibility of safe pancreatectomy concurrent with CA resection and reconstruction depends on the ability to create a "golden view" that provides an unimpaired view of the Abdominal Aorta, CA, Superior Mesenteric Artery, Inferior Vena Cava, and left renal vein from the ventral side. Pancreatectomy concurrent with CA resection requires arterial reconstruction. Postoperatively, arterial blood flow must be maintained. To achieve this, tension-free and short bypass should be observed.

RESULTS

From 2014 to 2024, sixteen URLA patients underwent CS, requiring major artery en bloc resection after pretreatment. We performed DP-CAR in eight patients, gastrectomy-distal pancreatectomy-splenectomy (Appleby procedure) procedure in one patient, PD-CHAR in two patients, PD-CAR in two patients, TP-CAR(spleen preserving) in one patient, and TP-CAR+TG in two patients. In total, five patients required surgery with CA reconstruction. Histopathologically, four of the five patients had T4 pancreatic cancer. The R0 surgical rate was 80%. Complication of Clavien-Dindo IIIa or higher was observed in one patient. There were no deaths.

CONCLUSIONS

Parallel to the determination of pretreatment, surgeons must be prepared to safely and reliably perform pancreatectomies that require concurrent major arterial resection and reconstruction.

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Affiliation(s)

Satoshi Mizutani Digestive Surgery, Nippon Medical School Musashikosugi Hospital, 1-383 Kosugimachi, Nakahara, Kawasaki 211-8533, Kanagawa, Japan
Nobuhiko Taniai Digestive Surgery, Nippon Medical School Musashikosugi Hospital, 1-383 Kosugimachi, Nakahara, Kawasaki 211-8533, Kanagawa, Japan
Makoto Sukegawa Digestive Surgery, Nippon Medical School Musashikosugi Hospital, 1-383 Kosugimachi, Nakahara, Kawasaki 211-8533, Kanagawa, Japan
Takahiro Haruna Digestive Surgery, Nippon Medical School Musashikosugi Hospital, 1-383 Kosugimachi, Nakahara, Kawasaki 211-8533, Kanagawa, Japan
Hiroyasu Furuki Digestive Surgery, Nippon Medical School Musashikosugi Hospital, 1-383 Kosugimachi, Nakahara, Kawasaki 211-8533, Kanagawa, Japan
Hideyuki Takata Digestive Surgery, Nippon Medical School Musashikosugi Hospital, 1-383 Kosugimachi, Nakahara, Kawasaki 211-8533, Kanagawa, Japan
Junji Ueda Digestive Surgery, Nippon Medical School Musashikosugi Hospital, 1-383 Kosugimachi, Nakahara, Kawasaki 211-8533, Kanagawa, Japan
Masato Yoshioka Digestive Surgery, Nippon Medical School Musashikosugi Hospital, 1-383 Kosugimachi, Nakahara, Kawasaki 211-8533, Kanagawa, Japan
Takayuki Aimoto Digestive Surgery, Nippon Medical School Musashikosugi Hospital, 1-383 Kosugimachi, Nakahara, Kawasaki 211-8533, Kanagawa, Japan
Shunichiro Sakamoto Department of Cardiovascular Surgery, Nippon Medical School Musashikosugi Hospital, 1-383 Kosugimachi, Nakahara, Kawasaki 211-8533, Kanagawa, Japan
Kenji Suzuki Department of Cardiovascular Surgery, Nippon Medical School Musashikosugi Hospital, 1-383 Kosugimachi, Nakahara, Kawasaki 211-8533, Kanagawa, Japan
Yoshiharu Nakamura Department of Surgery, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamakari, Inzai 270-1694, Chiba, Japan
Hiroshi Yoshida Department of Surgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo, Tokyo 113-8603, Japan

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Robinson RM, Reyes L, Christopher BN, Duncan RM, Burge RA, Siegel J, Nasarre P, Wang P, O'Bryan JP, Hobbs GA, Klauber-DeMore N, Dolloff NG. A High-Affinity Monoclonal Antibody Against the Pancreatic Ductal Adenocarcinoma Target, Anterior Gradient-2 (AGR2/PDIA17). Antibodies (Basel) 2024;13:101. [PMID: 39727484 DOI: 10.3390/antib13040101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 11/07/2024] [Accepted: 11/22/2024] [Indexed: 12/28/2024] Open

Truntzer C, Ouahbi D, Huppé T, Rageot D, Ilie A, Molimard C, Beltjens F, Bergeron A, Vienot A, Borg C, Monnien F, Bibeau F, Derangère V, Ghiringhelli F. Deep Multiple Instance Learning Model to Predict Outcome of Pancreatic Cancer Following Surgery. Biomedicines 2024;12:2754. [PMID: 39767661 PMCID: PMC11673784 DOI: 10.3390/biomedicines12122754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 11/25/2024] [Accepted: 11/29/2024] [Indexed: 01/11/2025] Open

Affiliation(s)

Caroline Truntzer Cancer Biology Transfer Platform, Georges-François Leclerc Cancer Centre—Unicancer, F-21000 Dijon, France INSERM, LNC-UMR1231 Research Center, F-21000 Dijon, France
Dina Ouahbi Cancer Biology Transfer Platform, Georges-François Leclerc Cancer Centre—Unicancer, F-21000 Dijon, France
Titouan Huppé Cancer Biology Transfer Platform, Georges-François Leclerc Cancer Centre—Unicancer, F-21000 Dijon, France
David Rageot Cancer Biology Transfer Platform, Georges-François Leclerc Cancer Centre—Unicancer, F-21000 Dijon, France INSERM, LNC-UMR1231 Research Center, F-21000 Dijon, France
Alis Ilie Cancer Biology Transfer Platform, Georges-François Leclerc Cancer Centre—Unicancer, F-21000 Dijon, France
Chloe Molimard Department of Pathology, CHU Besançon, F-25000 Besançon, France
Françoise Beltjens Department of Pathology, Georges-François Leclerc Cancer Centre—Unicancer, F-21000 Dijon, France
Anthony Bergeron Department of Pathology, Georges-François Leclerc Cancer Centre—Unicancer, F-21000 Dijon, France
Angelique Vienot Department of Medical Oncology, CHU Besançon, F-25000 Besançon, France
Christophe Borg Department of Medical Oncology, CHU Besançon, F-25000 Besançon, France
Franck Monnien Department of Pathology, CHU Besançon, F-25000 Besançon, France
Frédéric Bibeau Department of Pathology, CHU Besançon, F-25000 Besançon, France
Valentin Derangère Cancer Biology Transfer Platform, Georges-François Leclerc Cancer Centre—Unicancer, F-21000 Dijon, France INSERM, LNC-UMR1231 Research Center, F-21000 Dijon, France
François Ghiringhelli Cancer Biology Transfer Platform, Georges-François Leclerc Cancer Centre—Unicancer, F-21000 Dijon, France INSERM, LNC-UMR1231 Research Center, F-21000 Dijon, France Department of Medical Oncology, Centre Georges-François Leclerc, F-21000 Dijon, France

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Yamaguchi N, Wu YG, Ravetch E, Takahashi M, Khan AG, Hayashi A, Mei W, Hsu D, Umeda S, de Stanchina E, Lorenz IC, Iacobuzio-Donahue CA, Tavazoie SF. A Targetable Secreted Neural Protein Drives Pancreatic Cancer Metastatic Colonization and HIF1α Nuclear Retention. Cancer Discov 2024;14:2489-2508. [PMID: 39028915 PMCID: PMC11611693 DOI: 10.1158/2159-8290.cd-23-1323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 05/29/2024] [Accepted: 07/18/2024] [Indexed: 07/21/2024]

Yamada D, Takeda Y, Takahashi H, Sasaki K, Iwagami Y, Tomimaru Y, Noda T, Kobayashi S, Asaoka T, Shimizu J, Doki Y, Eguchi H. Preoperative nutritional status is a useful predictor of the feasibility of postoperative treatment in octogenarian-plus pancreatic ductal adenocarcinoma patients. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024;50:108650. [PMID: 39244977 DOI: 10.1016/j.ejso.2024.108650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 08/28/2024] [Accepted: 08/31/2024] [Indexed: 09/10/2024]

Abstract

BACKGROUND

The suitability of radical surgery for very elderly pancreatic cancer (PC) patients remains controversial due to concerns about postoperative functional reserve. Inflammatory-nutritional status may help identify elderly patients at risk of compromised postoperative treatment tolerance.

METHODS

This retrospective analysis included 121 patients over eighty who were diagnosed with PC in 2010-2019, 40 of whom underwent radical surgery. Surgical outcomes were compared with those of 205 younger patients (under 80 years-old) who underwent radical surgery. K-means cluster analysis was conducted with four inflammatory-nutritional indices (NLR, PLR, PNI, and mGPS) to define, and the indices using ordinal logistic analysis were evaluated in each cluster to create a formula named 'nutritional index (NTI)', which was then used to redefine the clusters. The predictive ability of the NTI was validated in other octogenarians who underwent pancreatectomy for PC between 2020 and 2023.

RESULTS

Patients older than eighty exhibited comparable overall survival to younger patients (median survival time, 30.7/37.1 months, p = 0.20). However, octogenarian-plus patients had lower rates of adjuvant chemotherapy (AC) initiation (45/80 %) and treatment upon recurrence (52/84 %), resulting in shorter survival after recurrence (7.4/11.1 months, p = 0.06). Inflammatory-nutritional status was significantly associated with overall survival, with poor nutritional status being linked to lower rates of AC initiation and/or treatment upon recurrence. NTI effectively predicted AC feasibility.

CONCLUSIONS

Radical surgery for octogenarian-plus PC patients meeting the current criteria was safe, but lower rates of postoperative treatment initiation may lead to poorer outcomes after recurrence. Inflammatory-nutritional status assessment could enhance surgical eligibility in octogenarian-plus PC patients.

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Affiliation(s)

Daisaku Yamada Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2-E2, Suita, Osaka, 565-0871, Japan
Yu Takeda Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2-E2, Suita, Osaka, 565-0871, Japan
Hidenori Takahashi Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2-E2, Suita, Osaka, 565-0871, Japan.
Kazuki Sasaki Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2-E2, Suita, Osaka, 565-0871, Japan
Yoshifumi Iwagami Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2-E2, Suita, Osaka, 565-0871, Japan
Yoshito Tomimaru Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2-E2, Suita, Osaka, 565-0871, Japan
Takehiro Noda Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2-E2, Suita, Osaka, 565-0871, Japan
Shogo Kobayashi Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2-E2, Suita, Osaka, 565-0871, Japan
Tadafumi Asaoka Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2-E2, Suita, Osaka, 565-0871, Japan; Department of Surgery, Osaka Police Hospital, Osaka, Japan
Junzo Shimizu Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2-E2, Suita, Osaka, 565-0871, Japan; Department of Gastroenterological Surgery, Toyonaka Municipal Hospital, Osaka, Japan
Yuichiro Doki Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2-E2, Suita, Osaka, 565-0871, Japan
Hidetoshi Eguchi Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2-E2, Suita, Osaka, 565-0871, Japan

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Chao T, Wang ZX, Bowne WB, Yudkoff CJ, Torjani A, Swaminathan V, Kavanagh TR, Roadarmel A, Sholevar CJ, Cannaday S, Krampitz G, Zhan T, Gorgov E, Nevler A, Lavu H, Yeo CJ, Peiper SC, Jiang W. Association of Mutant KRAS Alleles With Morphology and Clinical Outcomes in Pancreatic Ductal Adenocarcinoma. Arch Pathol Lab Med 2024;148:1299-1309. [PMID: 38452805 DOI: 10.5858/arpa.2023-0005-oa] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/21/2023] [Indexed: 03/09/2024]

Abstract

CONTEXT.—

Mutant KRAS is the main oncogenic driver in pancreatic ductal adenocarcinomas (PDACs). However, the clinical and phenotypic implications of harboring different mutant KRAS alleles remain poorly understood.

OBJECTIVE.—

To characterize the potential morphologic and clinical outcome differences in PDACs harboring distinct mutant KRAS alleles.

DESIGN.—

Cohort 1 consisted of 127 primary conventional PDACs with no neoadjuvant therapy, excluding colloid/mucinous, adenosquamous, undifferentiated, and intraductal papillary mucinous neoplasm-associated carcinomas, for which an in-house 42-gene mutational panel had been performed. A morphologic classification system was devised wherein each tumor was assigned as conventional, papillary/large duct (P+LD, defined as neoplastic glands with papillary structure and/or with length ≥0.5 mm), or poorly differentiated (when the aforementioned component was 60% or more of the tumor). Cohort 2 was a cohort of 88 PDACs in The Cancer Genome Atlas, which were similarly analyzed.

RESULTS.—

In both cohorts, there was significant enrichment of P+LD morphology in PDACs with KRAS G12V and G12R compared with G12D. In the entire combined cohort, Kaplan-Meier analyses showed longer overall survival (OS) with KRAS G12R as compared with G12D (median OS of 1255 versus 682 days, P = .03) and in patients whose PDACs displayed P+LD morphology as compared with conventional morphology (median OS of 1175 versus 684 days, P = .04). In the adjuvant-only subset, KRAS G12R had the longest OS compared with G12D, G12V, and other alleles (median OS unreached/undefined versus 1009, 1129, and 1222 days, respectively).

CONCLUSIONS.—

PDACs with different mutant KRAS alleles are associated with distinct morphologies and clinical outcomes, with KRAS G12R allele associated with P+LD morphology and longer OS when compared with G12D using Kaplan-Meier studies.

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Affiliation(s)

Timothy Chao From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania
Zi-Xuan Wang From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania
Wilbur B Bowne From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania the Pancreatic, Biliary and Related Cancer Center, Sidney Kimmel Cancer Center, Jefferson Health, Philadelphia, Pennsylvania (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo, Jiang)
Clifford J Yudkoff From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania
Ava Torjani From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania
Vishal Swaminathan From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania
Taylor R Kavanagh From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania
Austin Roadarmel From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania
Cyrus J Sholevar From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania
Shawnna Cannaday From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania the Pancreatic, Biliary and Related Cancer Center, Sidney Kimmel Cancer Center, Jefferson Health, Philadelphia, Pennsylvania (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo, Jiang)
Geoffrey Krampitz From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania the Pancreatic, Biliary and Related Cancer Center, Sidney Kimmel Cancer Center, Jefferson Health, Philadelphia, Pennsylvania (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo, Jiang)
Tingting Zhan From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania
Eliyahu Gorgov From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania the Pancreatic, Biliary and Related Cancer Center, Sidney Kimmel Cancer Center, Jefferson Health, Philadelphia, Pennsylvania (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo, Jiang)
Avinoam Nevler From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania the Pancreatic, Biliary and Related Cancer Center, Sidney Kimmel Cancer Center, Jefferson Health, Philadelphia, Pennsylvania (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo, Jiang)
Harish Lavu From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania the Pancreatic, Biliary and Related Cancer Center, Sidney Kimmel Cancer Center, Jefferson Health, Philadelphia, Pennsylvania (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo, Jiang)
Charles J Yeo From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania the Pancreatic, Biliary and Related Cancer Center, Sidney Kimmel Cancer Center, Jefferson Health, Philadelphia, Pennsylvania (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo, Jiang)
Stephen C Peiper From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania
Wei Jiang From the Department of Pathology and Genomic Medicine (Chao, Wang, Peiper, Jiang), the Department of Surgery (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo), Sidney Kimmel Medical College (Yudkoff, Torjani, Swaminathan, Kavanagh, Roadarmel, Sholevar), and the Division of Biostatistics in the Department of Pharmacology & Experimental Therapeutics (Zhan), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania the Pancreatic, Biliary and Related Cancer Center, Sidney Kimmel Cancer Center, Jefferson Health, Philadelphia, Pennsylvania (Bowne, Cannaday, Krampitz, Gorgov, Nevler, Lavu, Yeo, Jiang)

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Tushoski-Alemán GW, Crespin AJ, Oguejiofor CJ, Szymkiewicz DD, Herremans KM, Han S, Hughes SJ. Variability of quality-of-life measurements and reporting in randomised controlled trials of pancreatic cancer: a systematic review. BMJ Open 2024;14:e083696. [PMID: 39551595 PMCID: PMC11574412 DOI: 10.1136/bmjopen-2023-083696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Accepted: 10/11/2024] [Indexed: 11/19/2024] Open

Abstract

OBJECTIVES

This systematic review aims to evaluate the methodology used in pancreatic cancer (PC) randomised controlled trials (RCTs) measuring quality of life (QOL) and focuses on the type, frequency, survey compliance and duration of these assessments.

DESIGN

Systematic review of PC RCTs measuring QOL.

DATA SOURCES

A search of PubMed.gov and ClinicalTrials.gov was conducted for PC RCTs measuring QOL from inception to 21 March 2023. Only phase III RCTs were included. Studies were excluded if QOL was not measured, the study was phase I/II, in the second-line setting or unavailable in English. Data were independently extracted by two reviewers in a standardised fashion.

PRIMARY AND SECONDARY OUTCOME MEASURES

Primary outcomes included the type of QOL instrument used, the timing and frequency of assessments, methods of analysis and survey completion rates (SCRs) over time. Secondary outcomes included patient demographics, significant QOL improvements and the frequency of trials measuring QOL.

RESULTS

Out of 269 studies screened, 54 RCTs were identified, and 24 measured QOL (involving 11 229 patients). Instruments used included the EORTC QLQ-C30 (n=15), FACT-HEP (n=3), Spitzer-QOL-Index (n=2), EQ-5D (n=2), LASA (n=1) and FACT-PA (n=1). Most trials assessed QOL until disease progression or death (10/24), with 4-week intervals being the most common (7/24). SCRs were reported in 15/24 trials, with disease stage influencing SCRs over time. In trials with metastatic, locally advanced/metastatic, and resectable disease, the median times to reach a 50% response rate-defined as the point where the number of surveys completed was half of the enrolled participants-were 12.41 weeks (n=2), 14.14 weeks (n=10), and 54.2 weeks (n=3), respectively." Only 2/24 trials reported significant QOL improvements between treatment arms. Patient age was reported in all trials, while race/ethnicity was only reported in 4/24 trials.

CONCLUSIONS

Significant variability exists in the timing, methods and reporting of QOL assessments in PC trials. There is a need for further research to assess the implications of missing data and consider the temporality of QOL assessment in patients with advanced cancers and poor prognosis.

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Maehira H, Mori H, Nitta N, Maekawa T, Nishina Y, Ishikawa H, Takebayashi K, Kaida S, Miyake T, Tani M. Clinical impact of the prognostic nutritional index and skeletal muscle index for the incompletion of adjuvant chemotherapy for pancreatic cancer. Asian J Surg 2024:S1015-9584(24)02484-9. [PMID: 39537486 DOI: 10.1016/j.asjsur.2024.10.151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 09/26/2024] [Accepted: 10/10/2024] [Indexed: 11/16/2024] Open

Topkan E, Kucuk A, Ozturk D, Ozkan EE, Kılıç Durankuş N, Şenyürek Ş, Selek U, Pehlivan B. High Systemic Immune-Inflammation Index Values Before Treatment Predict Poor Pancreatic Cancer Outcomes After Definitive Chemoradiotherapy. Clin Med Insights Oncol 2024;18:11795549241298552. [PMID: 39525980 PMCID: PMC11544671 DOI: 10.1177/11795549241298552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Accepted: 10/22/2024] [Indexed: 11/16/2024] Open

Abstract

Background

The systemic immune-inflammation index (SII) is an effective tool for predicting the prognosis of patients with cancer. However, its value in patients with locally advanced pancreatic ductal adenocarcinoma (LA-PDAC) undergoing definitive chemoradiotherapy has yet to be addressed. Therefore, we aimed to retrospectively investigate the prognostic significance of the pretreatment SII on the survival outcomes of patients with unresectable LA-PDAC treated with concurrent chemoradiotherapy (C-CRT).

Methods

The study included 163 patients with LA-PDAC who had received C-CRT. Using receiver operating characteristic (ROC) curve analysis, the utility of a pre-C-CRT cutoff that could stratify survival results was investigated. The primary and secondary endpoints were the correlations between SII levels and overall survival (OS) and progression-free survival (PFS).

Results

At a median follow-up period of 15 months (range: 3.2-94.5), the median OS and PFS rates for the entire group were 15.7 months (95% confidence interval [CI]: 13.4-17.9), and 7.8 months (95% CI: 6.1-9.4), respectively. We divided the patients into 2 SII cohorts based on the ROC curve analysis (area under the curve [AUC]: 71.9%; sensitivity: 68.9%; specificity: 66.7%): SII < 538 (N = 70) and SII ⩾ 538 (N = 93). Comparative survival analysis showed significantly inferior median OS (13.0 vs 25.4 months; P < .001) and PFS (7.0 vs 15.2 months; P = .003) in patients with SII ⩾ 538 compared with those with SII < 538 before treatment. In multivariate analyses, the Eastern Cooperative Oncology Group (ECOG) performance of 2, N1-2 lymph node, CA 19-9 > 90 U/mL, and SII ⩾ 538 status emerged as independent prognosticators of inferior OS and PFS.

Conclusions

Present results indicate that patients with unresectable LA-PDAC who underwent C-CRT and had a pretreatment SII ⩾ 538 had significantly worse OS and PFS outcomes compared with those with lower SII values.

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van Goor IWJM, Andel PCM, Buijs FS, Besselink MG, Bonsing BA, Bosscha K, Busch OR, Cirkel GA, van Dam RM, Festen S, Koerkamp BG, van der Harst E, de Hingh IHJT, Kazemier G, Liem MSL, Meijer G, de Meijer VE, Nieuwenhuijs VB, Roos D, Schreinemakers JMJ, Stommel MWJ, Wit F, Verdonk RC, van Santvoort HC, Molenaar IQ, Intven MPW, Daamen LA. Prediction of Isolated Local Recurrence After Resection of Pancreatic Ductal Adenocarcinoma: A Nationwide Study. Ann Surg Oncol 2024;31:8264-8275. [PMID: 38937412 PMCID: PMC11467030 DOI: 10.1245/s10434-024-15664-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Accepted: 06/10/2024] [Indexed: 06/29/2024]

Abstract

BACKGROUND

Distinguishing postoperative fibrosis from isolated local recurrence (ILR) after resection of pancreatic ductal adenocarcinoma (PDAC) is challenging. A prognostic model that helps to identify patients at risk of ILR can assist clinicians when evaluating patients' postoperative imaging. This nationwide study aimed to develop a clinically applicable prognostic model for ILR after PDAC resection.

PATIENTS AND METHODS

An observational cohort study was performed, including all patients who underwent PDAC resection in the Netherlands (2014-2019; NCT04605237). On the basis of recurrence location (ILR, systemic, or both), multivariable cause-specific Cox-proportional hazard analysis was conducted to identify predictors for ILR and presented as hazard ratios (HRs) with 95% confidence intervals (CIs). A predictive model was developed using Akaike's Information Criterion, and bootstrapped discrimination and calibration indices were assessed.

RESULTS

Among 1194/1693 patients (71%) with recurrence, 252 patients (21%) developed ILR. Independent predictors for ILR were resectability status (borderline versus resectable, HR 1.42; 95% CI 1.03-1.96; P = 0.03, and locally advanced versus resectable, HR 1.11; 95% CI 0.68-1.82; P = 0.66), tumor location (head versus body/tail, HR 1.50; 95% CI 1.00-2.25; P = 0.05), vascular resection (HR 1.86; 95% CI 1.41-2.45; P < 0.001), perineural invasion (HR 1.47; 95% CI 1.01-2.13; P = 0.02), number of positive lymph nodes (HR 1.04; 95% CI 1.01-1.08; P = 0.02), and resection margin status (R1 < 1 mm versus R0 ≥ 1 mm, HR 1.64; 95% CI 1.25-2.14; P < 0.001). Moderate performance (concordance index 0.66) with adequate calibration (slope 0.99) was achieved.

CONCLUSIONS

This nationwide study identified factors predictive of ILR after PDAC resection. Our prognostic model, available through www.pancreascalculator.com , can be utilized to identify patients with a higher a priori risk of developing ILR, providing important information in patient evaluation and prognostication.

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Affiliation(s)

I W J M van Goor Department of Surgery, Regional Academic Cancer Center Utrecht, Utrecht University, University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands. Department of Radiation Oncology, Regional Academic Cancer Center Utrecht, Utrecht University, University Medical Center Utrecht Cancer Center, Utrecht, The Netherlands.
P C M Andel Department of Surgery, Regional Academic Cancer Center Utrecht, Utrecht University, University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands
F S Buijs Department of Surgery, Regional Academic Cancer Center Utrecht, Utrecht University, University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands
M G Besselink Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands Cancer Center Amsterdam, Amsterdam, The Netherlands
B A Bonsing Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
K Bosscha Department of Surgery, Jeroen Bosch Hospital, Den Bosch, The Netherlands
O R Busch Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands Cancer Center Amsterdam, Amsterdam, The Netherlands
G A Cirkel Department of Medical Oncology, University Medical Center Utrecht Cancer Center & Meander Medical Center Amersfoort, Regional Academic Cancer Center Utrecht, Utrecht University, Utrecht, The Netherlands
R M van Dam Department of Surgery, Maastricht University Medical Center+, Maastricht, The Netherlands
S Festen Department of Surgery, OLVG, Amsterdam, The Netherlands
B Groot Koerkamp Department of Surgery, Erasmus Medical Center Cancer Institute, Rotterdam, The Netherlands
E van der Harst Department of Surgery, Maasstad Hospital, Rotterdam, The Netherlands
I H J T de Hingh Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
G Kazemier Cancer Center Amsterdam, Amsterdam, The Netherlands Department of Surgery, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, The Netherlands
M S L Liem Department of Surgery, Medisch Spectrum Twente, Enschede, The Netherlands
G Meijer Department of Radiation Oncology, Regional Academic Cancer Center Utrecht, Utrecht University, University Medical Center Utrecht Cancer Center, Utrecht, The Netherlands
V E de Meijer Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
V B Nieuwenhuijs Department of Surgery, Isala, Zwolle, The Netherlands
D Roos Department of Surgery, Renier de Graaf Gasthuis, Delft, The Netherlands
J M J Schreinemakers Department of Surgery, Amphia Hospital, Breda, The Netherlands
M W J Stommel Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
F Wit Department of Surgery, Tjongerschans Hospital, Heerenveen, The Netherlands
R C Verdonk Department of Gastroenterology, Regional Academic Cancer Center Utrecht, Utrecht, The Netherlands
H C van Santvoort Department of Surgery, Regional Academic Cancer Center Utrecht, Utrecht University, University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands
I Q Molenaar Department of Surgery, Regional Academic Cancer Center Utrecht, Utrecht University, University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands
M P W Intven Department of Radiation Oncology, Regional Academic Cancer Center Utrecht, Utrecht University, University Medical Center Utrecht Cancer Center, Utrecht, The Netherlands
L A Daamen Department of Surgery, Regional Academic Cancer Center Utrecht, Utrecht University, University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands. Imaging Division, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.

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Wang J, Yang J, Narang A, He J, Wolfgang C, Li K, Zheng L. Consensus, debate, and prospective on pancreatic cancer treatments. J Hematol Oncol 2024;17:92. [PMID: 39390609 PMCID: PMC11468220 DOI: 10.1186/s13045-024-01613-x] [Citation(s) in RCA: 21] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Accepted: 09/25/2024] [Indexed: 10/12/2024] Open

Affiliation(s)

Junke Wang Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China Department of Oncology and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans St, Baltimore, MD, 21287, USA The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
Jie Yang Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, 37 Guoxue Alley, Chengdu, 610041, Sichuan, China Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
Amol Narang Department of Oncology and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans St, Baltimore, MD, 21287, USA The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
Jin He Department of Oncology and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans St, Baltimore, MD, 21287, USA The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA The Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
Christopher Wolfgang Department of Surgery, New York University School of Medicine and NYU-Langone Medical Center, New York, NY, USA
Keyu Li Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, 37 Guoxue Alley, Chengdu, 610041, Sichuan, China. Department of Oncology and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans St, Baltimore, MD, 21287, USA. The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Lei Zheng Department of Oncology and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans St, Baltimore, MD, 21287, USA. The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. The Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. The Multidisciplinary Gastrointestinal Cancer Laboratories Program, the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.

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Kumar S, Sarma M. Dissociative electron attachment to halogenated nucleotides: a quest for better radiosensitizers. Phys Chem Chem Phys 2024;26:25524-25532. [PMID: 39328041 DOI: 10.1039/d4cp02258k] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/28/2024]

Seufferlein T, Mayerle J, Boeck S, Brunner T, Ettrich TJ, Grenacher L, Gress TM, Hackert T, Heinemann V, Kestler A, Sinn M, Tannapfel A, Wedding U, Uhl W. S3-Leitlinie Exokrines Pankreaskarzinom – Version 3.1. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024;62:1724-1785. [PMID: 39389105 DOI: 10.1055/a-2338-3716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/12/2024]

Funamizu N, Mori S, Sakamoto A, Iwata M, Shine M, Ito C, Uraoka M, Ueno Y, Tamura K, Umeda Y, Aoki T, Takada Y. C-Reactive Protein-to-Albumin Ratio as a Predictive Indicator for Evaluating Tolerability in S-1 Adjuvant Chemotherapy after Curative Surgery for Pancreatic Cancer: An External Validation Cohort Study. Cancers (Basel) 2024;16:3372. [PMID: 39409992 PMCID: PMC11475895 DOI: 10.3390/cancers16193372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Revised: 09/26/2024] [Accepted: 09/30/2024] [Indexed: 10/20/2024] Open

Affiliation(s)

Naotake Funamizu Department of Hepato-Biliary Pancreatic and Transplantation Surgery, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon 791-0295, Ehime, Japan; (A.S.); (M.I.); (M.S.); (C.I.); (M.U.); (Y.U.); (K.T.); (Y.U.); (Y.T.)
Shozo Mori Department of Hepato-Biliary Pancreatic Surgery, Dokkyo Medical University, Kitakobayashi 880, Mibu, Shimotsugagun 321-0293, Tochigi, Japan; (S.M.); (T.A.)
Akimasa Sakamoto Department of Hepato-Biliary Pancreatic and Transplantation Surgery, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon 791-0295, Ehime, Japan; (A.S.); (M.I.); (M.S.); (C.I.); (M.U.); (Y.U.); (K.T.); (Y.U.); (Y.T.)
Miku Iwata Department of Hepato-Biliary Pancreatic and Transplantation Surgery, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon 791-0295, Ehime, Japan; (A.S.); (M.I.); (M.S.); (C.I.); (M.U.); (Y.U.); (K.T.); (Y.U.); (Y.T.)
Mikiya Shine Department of Hepato-Biliary Pancreatic and Transplantation Surgery, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon 791-0295, Ehime, Japan; (A.S.); (M.I.); (M.S.); (C.I.); (M.U.); (Y.U.); (K.T.); (Y.U.); (Y.T.)
Chihiro Ito Department of Hepato-Biliary Pancreatic and Transplantation Surgery, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon 791-0295, Ehime, Japan; (A.S.); (M.I.); (M.S.); (C.I.); (M.U.); (Y.U.); (K.T.); (Y.U.); (Y.T.)
Mio Uraoka Department of Hepato-Biliary Pancreatic and Transplantation Surgery, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon 791-0295, Ehime, Japan; (A.S.); (M.I.); (M.S.); (C.I.); (M.U.); (Y.U.); (K.T.); (Y.U.); (Y.T.)
Yoshitomo Ueno Department of Hepato-Biliary Pancreatic and Transplantation Surgery, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon 791-0295, Ehime, Japan; (A.S.); (M.I.); (M.S.); (C.I.); (M.U.); (Y.U.); (K.T.); (Y.U.); (Y.T.)
Kei Tamura Department of Hepato-Biliary Pancreatic and Transplantation Surgery, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon 791-0295, Ehime, Japan; (A.S.); (M.I.); (M.S.); (C.I.); (M.U.); (Y.U.); (K.T.); (Y.U.); (Y.T.)
Yuzo Umeda Department of Hepato-Biliary Pancreatic and Transplantation Surgery, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon 791-0295, Ehime, Japan; (A.S.); (M.I.); (M.S.); (C.I.); (M.U.); (Y.U.); (K.T.); (Y.U.); (Y.T.)
Taku Aoki Department of Hepato-Biliary Pancreatic Surgery, Dokkyo Medical University, Kitakobayashi 880, Mibu, Shimotsugagun 321-0293, Tochigi, Japan; (S.M.); (T.A.)
Yasutsugu Takada Department of Hepato-Biliary Pancreatic and Transplantation Surgery, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon 791-0295, Ehime, Japan; (A.S.); (M.I.); (M.S.); (C.I.); (M.U.); (Y.U.); (K.T.); (Y.U.); (Y.T.)

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Seufferlein T, Mayerle J, Boeck S, Brunner T, Ettrich TJ, Grenacher L, Gress TM, Hackert T, Heinemann V, Kestler A, Sinn M, Tannapfel A, Wedding U, Uhl W. S3-Leitlinie Exokrines Pankreaskarzinom – Version 3.1. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024;62:874-995. [PMID: 39389103 DOI: 10.1055/a-2338-3533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/12/2024]

Tazuma S, Sudo T, Ishikawa A, Yamaguchi A, Shibata Y, Ishida Y, Kuraoka K, Uemura K, Takahashi S, Tashiro H. Effects of transmembrane serine protease 4 on the survival in patients with pancreatic ductal adenocarcinoma undergoing surgery followed by adjuvant chemotherapy. Surg Today 2024;54:1208-1219. [PMID: 38637344 DOI: 10.1007/s00595-024-02824-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Accepted: 02/25/2024] [Indexed: 04/20/2024]

Khalid A, Pasha SA, Demyan L, Standring O, Newman E, King DA, DePeralta D, Gholami S, Weiss MJ, Melis M. Modified 5-Item Frailty Index (mFI-5) may predict postoperative outcomes after pancreatoduodenectomy for pancreatic Cancer. Langenbecks Arch Surg 2024;409:286. [PMID: 39305322 DOI: 10.1007/s00423-024-03483-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2024] [Accepted: 09/17/2024] [Indexed: 09/25/2024]

Abstract

BACKGROUND

Pancreatic Ductal Adenocarcinoma (PDAC) primarily affects older individuals with diminished physiological reserves. The Modified 5-Item Frailty Index (mFI-5) is a novel risk stratification tool proposed to predict postoperative morbidity and mortality. This study aimed to validate the mFI-5 for predicting surgical outcomes in patients undergoing pancreatoduodenectomy (PD) for PDAC.

METHODS

Our retrospective PDAC database included patients who underwent PD between 2014 and 2023. Patients were stratified by mFI-5 scores (0 best - 5 worst), which assess preoperative CHF, diabetes mellitus, history of COPD or pneumonia, functional health status, and hypertension requiring medication. Associations between mFI-5 scores and outcomes, including postoperative complications and mortality, were analyzed using logistic regression, Cox proportional hazards models, and Kaplan-Meier survival analysis.

RESULTS

Among 250 PDAC patients undergoing PD, 142 (56.8%) had mFI-5 scores ≤ 1, and 25 (10%) had scores ≥ 3. No patients had scores > 4. Higher mFI-5 scores correlated with older age (p < 0.001) and tobacco use (p = 0.036). Multivariate analysis identified age (RR 1.02, p = 0.038), ASA class (ASA III; RR 2.61, p < 0.001; ASA IV; RR 2.63, p = 0.026), and moderate alcohol consumption (RR 0.56, p = 0.038) as frailty predictors. An mFI-5 score > 2 independently associated with higher mortality (HR 2.08, p = 0.026). Median overall survival was significantly lower for patients with mFI-5 scores > 2 than for those with scores ≤ 2 (21.3 vs. 42.1 months, p = 0.022).

CONCLUSIONS

The mFI-5 is a valuable tool for predicting postoperative morbidity and mortality in PDAC patients undergoing PD. Integrating frailty assessment into preoperative evaluations can enhance patient selection and surgical outcomes. Future research should focus on incorporating frailty assessments into surgical planning and patient management to improve outcomes in this vulnerable population.

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Amhis N, Carignan J, Tai LH. Transforming pancreaticobiliary cancer treatment: Exploring the frontiers of adoptive cell therapy and cancer vaccines. MOLECULAR THERAPY. ONCOLOGY 2024;32:200825. [PMID: 39006944 PMCID: PMC11246060 DOI: 10.1016/j.omton.2024.200825] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 07/16/2024]

Zhou L, Zhang L. Effect of postsurgical adjuvant chemotherapy timing on outcomes in patients with pancreatic cancer - a systematic review and meta-analysis. J Chemother 2024:1-11. [PMID: 39289876 DOI: 10.1080/1120009x.2024.2402175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Revised: 08/12/2024] [Accepted: 09/03/2024] [Indexed: 09/19/2024]

Takeda Y, Yamada D, Kobayashi S, Sasaki K, Iwagami Y, Tomimaru Y, Noda T, Takahashi H, Asaoka T, Shimizu J, Doki Y, Eguchi H. MicroRNA-26a-5p is a reliable biomarker in the adjuvant setting for pancreatic ductal adenocarcinoma. PLoS One 2024;19:e0310328. [PMID: 39288140 PMCID: PMC11407630 DOI: 10.1371/journal.pone.0310328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Accepted: 08/28/2024] [Indexed: 09/19/2024] Open

Brugiapaglia S, Spagnolo F, Intonti S, Novelli F, Curcio C. Fighting Pancreatic Cancer with a Vaccine-Based Winning Combination: Hope or Reality? Cells 2024;13:1558. [PMID: 39329742 PMCID: PMC11430323 DOI: 10.3390/cells13181558] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 09/06/2024] [Accepted: 09/15/2024] [Indexed: 09/28/2024] Open

Castanet F, Dembinski J, Cabarrou B, Garnier J, Laurent C, Regenet N, Sa Cunha A, Maulat C, Chiche L, Pittau G, Carrère N, Regimbeau JM, Turrini O, Sauvanet A, Muscari F. Influence of pancreatic fistula on survival after upfront pancreatoduodenectomy for pancreatic ductal adenocarcinoma: multicentre retrospective study. BJS Open 2024;8:zrae125. [PMID: 39453763 PMCID: PMC11505446 DOI: 10.1093/bjsopen/zrae125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Revised: 08/06/2024] [Accepted: 09/07/2024] [Indexed: 10/27/2024] Open

Abstract

BACKGROUND

The effects of postoperative pancreatic fistula on survival rates remain controversial. The aim of the present study was to evaluate the influence of postoperative pancreatic fistula on overall survival and recurrence-free survival after upfront pancreatoduodenectomy for pancreatic ductal adenocarcinoma.

METHODS

Patients operated on between January 2007 and December 2017 at seven tertiary pancreatic centres for pancreatic ductal adenocarcinoma were included in the study. Postoperative pancreatic fistula was defined using the 2016 International Study Group on Pancreatic Surgery grading system. The impact of postoperative pancreatic fistula on overall survival, recurrence-free survival (excluding 90-day postoperative deaths) and corresponding risk factors were investigated by univariable and multivariable analyses. Comparisons between groups were made using the chi-squared or Fisher's exact test for categorical variables and the Mann-Whitney U test for continuous variables. Odds ratios were estimated with their 95% confidence intervals. Survival rates were calculated using the Kaplan-Meier method with their 95% confidence intervals.

RESULTS

A total of 819 patients were included between 2007 and 2017. Postoperative pancreatic fistula occurred in 14.4% (n = 118) of patients; of those, 7.8% (n = 64) and 6.6% (n = 54) accounted for grade B and grade C postoperative pancreatic fistula respectively. The 5-year overall survival was 37.0% in the non-postoperative pancreatic fistula group and 45.3% in the postoperative pancreatic fistula cohort (P = 0.127). Grade C postoperative pancreatic fistula (excluding 90-day postoperative deaths) was not a prognostic factor for overall survival. The 5-year recurrence-free survival was 26.0% for patients without postoperative pancreatic fistula and 43.7% for patients with postoperative pancreatic fistula (P = 0.003). Eight independent prognostic factors for recurrence-free survival were identified: age over 70 years, diabetes, moderate or poor tumour differentiation, T3/T4 tumour stage, lymph node positive status, resection margins R1, vascular emboli and perineural invasion.

CONCLUSION

This high-volume cohort showed that grade C postoperative pancreatic fistula, based on the 2016 International Study Group on Pancreatic Surgery grading system, does not impact overall or recurrence-free survival (excluding 90-day postoperative deaths).

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Heervä E, Väliaho V, Nurmi H, Lietzen E, Ålgars A, Kauhanen S. Outcomes After Multimodality Treatment of Pancreatic Cancer in an Unselected Single-Center Cohort. Cancer Manag Res 2024;16:1065-1076. [PMID: 39220815 PMCID: PMC11363961 DOI: 10.2147/cmar.s465512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Accepted: 08/02/2024] [Indexed: 09/04/2024] Open

Ohya H, Miyake K, Fukuoka H, Oshi M, Ishibe A, Narita K, Kasahara K, Endo I. SLC7A11 and the glutathione pathway as novel prognostic markers in resectable pancreatic ductal adenocarcinoma: A metabolomics study of clinical specimens. Pancreatology 2024;24:779-786. [PMID: 38866682 DOI: 10.1016/j.pan.2024.05.530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 05/06/2024] [Accepted: 05/31/2024] [Indexed: 06/14/2024]

Suzuki S, Nagakawa Y, Miyamoto R, Osakabe H, Kiya Y, Yamaguchi H, Nagao T, Einama T, Ao T, Shimoda M. Prognostic factors based on histological categorization of desmoplastic reactions in pancreatic cancer. World J Surg 2024;48:1973-1980. [PMID: 38943046 DOI: 10.1002/wjs.12269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Accepted: 06/16/2024] [Indexed: 06/30/2024]

Cecchini M, Salem RR, Robert M, Czerniak S, Blaha O, Zelterman D, Rajaei M, Townsend JP, Cai G, Chowdhury S, Yugawa D, Tseng R, Mejia Arbelaez C, Jiao J, Shroyer K, Thumar J, Kortmansky J, Zaheer W, Fischbach N, Persico J, Stein S, Khan SA, Cha C, Billingsley KG, Kunstman JW, Johung KL, Wiess C, Muzumdar MD, Spickard E, Aushev VN, Laliotis G, Jurdi A, Liu MC, Escobar-Hoyos L, Lacy J. Perioperative Modified FOLFIRINOX for Resectable Pancreatic Cancer: A Nonrandomized Controlled Trial. JAMA Oncol 2024;10:1027-1035. [PMID: 38900452 PMCID: PMC11190830 DOI: 10.1001/jamaoncol.2024.1575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 01/09/2024] [Indexed: 06/21/2024]

Abstract

Importance

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignant tumor, and durable disease control is rare with the current standard of care, even for patients who undergo surgical resection.

Objective

To assess whether neoadjuvant modified 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (mFOLFIRINOX) leads to early control of micrometastasis and improves survival.

Design, Setting, and Participants

This open-label, single-arm, phase 2 nonrandomized controlled trial for resectable PDAC was conducted at the Yale Smilow Cancer Hospital from April 3, 2014, to August 16, 2021. Pancreatic protocol computed tomography was performed at diagnosis to assess surgical candidacy. Data were analyzed from January to July 2023.

Interventions

Patients received 6 cycles of neoadjuvant mFOLFIRINOX before surgery and 6 cycles of adjuvant mFOLFIRINOX. Whole blood was collected and processed to stored plasma for analysis of circulating tumor DNA (ctDNA) levels. Tumors were evaluated for treatment response and keratin 17 (K17) expression.

Main Outcomes and Measures

The primary end point was 12-month progression-free survival (PFS) rate. Additional end points included overall survival (OS), ctDNA level, tumor molecular features, and K17 tumor levels. Survival curves were summarized using Kaplan-Meier estimator.

Results

Of 46 patients who received mFOLFIRINOX, 31 (67%) were male, and the median (range) age was 65 (46-80) years. A total of 37 (80%) completed 6 preoperative cycles and 33 (72%) underwent surgery. A total of 27 patients (59%) underwent resection per protocol (25 with R0 disease and 2 with R1 disease); metastatic or unresectable disease was identified in 6 patients during exploration. Ten patients underwent surgery off protocol. The 12-month PFS was 67% (90% CI, 56.9-100); the median PFS and OS were 16.6 months (95% CI, 13.3-40.6) and 37.2 months (95% CI, 17.5-not reached), respectively. Baseline ctDNA levels were detected in 16 of 22 patients (73%) and in 3 of 17 (18%) after 6 cycles of mFOLFIRINOX. Those with detectable ctDNA levels 4 weeks postresection had worse PFS (hazard ratio [HR], 34.0; 95% CI, 2.6-4758.6; P = .006) and OS (HR, 11.7; 95% CI, 1.5-129.9; P = .02) compared with those with undetectable levels. Patients with high K17 expression had nonsignificantly worse PFS (HR, 2.7; 95% CI, 0.7-10.9; P = .09) and OS (HR, 3.2; 95% CI, 0.8-13.6; P = .07).

Conclusions and Relevance

This nonrandomized controlled trial met its primary end point, and perioperative mFOLFIRINOX warrants further evaluation in randomized clinical trials. Postoperative ctDNA positivity was strongly associated with recurrence. K17 and ctDNA are promising biomarkers that require additional validation in future prospective studies.

Trial Registration

ClinicalTrials.gov Identifier: NCT02047474.

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Affiliation(s)

Michael Cecchini Department of Internal Medicine (Medical Oncology), Yale University School of Medicine, New Haven, Connecticut
Ronald R. Salem Department of Surgery, Yale University School of Medicine, New Haven, Connecticut
Marie Robert Department of Pathology, Yale University School of Medicine, New Haven, Connecticut
Suzanne Czerniak Department of Radiology, Yale University School of Medicine, New Haven, Connecticut
Ondrej Blaha Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut
Daniel Zelterman Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut
Moein Rajaei Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut
Jeffrey P. Townsend Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut
Guoping Cai Department of Pathology, Yale University School of Medicine, New Haven, Connecticut
Sumedha Chowdhury Department of Therapeutic Radiology, Yale School of Public Health, New Haven, Connecticut
Deanne Yugawa Department of Pathology, Yale University School of Medicine, New Haven, Connecticut Department of Therapeutic Radiology, Yale School of Public Health, New Haven, Connecticut
Robert Tseng Department of Therapeutic Radiology, Yale School of Public Health, New Haven, Connecticut
Carlos Mejia Arbelaez Department of Pathology, Yale University School of Medicine, New Haven, Connecticut Department of Therapeutic Radiology, Yale School of Public Health, New Haven, Connecticut
Jingjing Jiao Department of Pathology, Yale University School of Medicine, New Haven, Connecticut
Kenneth Shroyer Department of Pathology, Renaissance School of Medicine, Stony Brook University, Stony Brook, New York
Jaykumar Thumar Department of Internal Medicine (Medical Oncology), Yale University School of Medicine, New Haven, Connecticut
Jeremy Kortmansky Department of Internal Medicine (Medical Oncology), Yale University School of Medicine, New Haven, Connecticut
Wajih Zaheer Department of Internal Medicine (Medical Oncology), Yale University School of Medicine, New Haven, Connecticut
Neal Fischbach Department of Internal Medicine (Medical Oncology), Yale University School of Medicine, New Haven, Connecticut
Justin Persico Department of Internal Medicine (Medical Oncology), Yale University School of Medicine, New Haven, Connecticut
Stacey Stein Department of Internal Medicine (Medical Oncology), Yale University School of Medicine, New Haven, Connecticut
Sajid A. Khan Department of Surgery, Yale University School of Medicine, New Haven, Connecticut
Charles Cha Department of Surgery, Yale University School of Medicine, New Haven, Connecticut
Kevin G. Billingsley Department of Surgery, Yale University School of Medicine, New Haven, Connecticut
John W. Kunstman Department of Surgery, Yale University School of Medicine, New Haven, Connecticut
Kimberly L. Johung Department of Therapeutic Radiology, Yale School of Public Health, New Haven, Connecticut
Christina Wiess Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut
Mandar D. Muzumdar Department of Internal Medicine (Medical Oncology), Yale University School of Medicine, New Haven, Connecticut
Erik Spickard Natera Inc, Austin, Texas
Vasily N. Aushev Natera Inc, Austin, Texas
George Laliotis Natera Inc, Austin, Texas
Adham Jurdi Natera Inc, Austin, Texas
Minetta C. Liu Natera Inc, Austin, Texas
Luisa Escobar-Hoyos Department of Therapeutic Radiology, Yale School of Public Health, New Haven, Connecticut Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut
Jill Lacy Department of Internal Medicine (Medical Oncology), Yale University School of Medicine, New Haven, Connecticut

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Buchholz M, Majchrzak-Stiller B, Peters I, Hahn S, Skrzypczyk L, Beule L, Uhl W, Braumann C, Strotmann J, Höhn P. Maintenance Therapy for Pancreatic Cancer, a New Approach Based on the Synergy between the Novel Agent GP-2250 (Misetionamide) and Gemcitabine. Cancers (Basel) 2024;16:2612. [PMID: 39061250 PMCID: PMC11275110 DOI: 10.3390/cancers16142612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Accepted: 07/18/2024] [Indexed: 07/28/2024] Open

Affiliation(s)

Marie Buchholz Department of General and Visceral Surgery, Division of Molecular and Clinical Research, St. Josef-Hospital, Ruhr-University Bochum, 44791 Bochum, Germany; (B.M.-S.); (I.P.); (L.S.); (L.B.); (W.U.); (C.B.); (J.S.); (P.H.)
Britta Majchrzak-Stiller Department of General and Visceral Surgery, Division of Molecular and Clinical Research, St. Josef-Hospital, Ruhr-University Bochum, 44791 Bochum, Germany; (B.M.-S.); (I.P.); (L.S.); (L.B.); (W.U.); (C.B.); (J.S.); (P.H.)
Ilka Peters Department of General and Visceral Surgery, Division of Molecular and Clinical Research, St. Josef-Hospital, Ruhr-University Bochum, 44791 Bochum, Germany; (B.M.-S.); (I.P.); (L.S.); (L.B.); (W.U.); (C.B.); (J.S.); (P.H.)
Stephan Hahn Department of Molecular Gastrointestinal Oncology, Ruhr-University Bochum, 44780 Bochum, Germany;
Lea Skrzypczyk Department of General and Visceral Surgery, Division of Molecular and Clinical Research, St. Josef-Hospital, Ruhr-University Bochum, 44791 Bochum, Germany; (B.M.-S.); (I.P.); (L.S.); (L.B.); (W.U.); (C.B.); (J.S.); (P.H.)
Lena Beule Department of General and Visceral Surgery, Division of Molecular and Clinical Research, St. Josef-Hospital, Ruhr-University Bochum, 44791 Bochum, Germany; (B.M.-S.); (I.P.); (L.S.); (L.B.); (W.U.); (C.B.); (J.S.); (P.H.)
Waldemar Uhl Department of General and Visceral Surgery, Division of Molecular and Clinical Research, St. Josef-Hospital, Ruhr-University Bochum, 44791 Bochum, Germany; (B.M.-S.); (I.P.); (L.S.); (L.B.); (W.U.); (C.B.); (J.S.); (P.H.)
Chris Braumann Department of General and Visceral Surgery, Division of Molecular and Clinical Research, St. Josef-Hospital, Ruhr-University Bochum, 44791 Bochum, Germany; (B.M.-S.); (I.P.); (L.S.); (L.B.); (W.U.); (C.B.); (J.S.); (P.H.) Department of General, Visceral and Vascular Surgery, Evangelische Kliniken Gelsenkirchen, Akademisches Lehrkrankenhaus der Universität Duisburg-Essen, 45878 Gelsenkirchen, Germany
Johanna Strotmann Department of General and Visceral Surgery, Division of Molecular and Clinical Research, St. Josef-Hospital, Ruhr-University Bochum, 44791 Bochum, Germany; (B.M.-S.); (I.P.); (L.S.); (L.B.); (W.U.); (C.B.); (J.S.); (P.H.)
Philipp Höhn Department of General and Visceral Surgery, Division of Molecular and Clinical Research, St. Josef-Hospital, Ruhr-University Bochum, 44791 Bochum, Germany; (B.M.-S.); (I.P.); (L.S.); (L.B.); (W.U.); (C.B.); (J.S.); (P.H.)

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