Predictive value of inflammatory markers in clinically relevant postoperative pancreatic fistula of pancreatectomy_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WANG Haodong , WU Jiahao , GUO Wenyi ,  WANG Lei

Department of Pancreatic Surgery, Qilu Hospital of Shandong University, Jinan 250012, P. R. China;

Corresponding author：

WANG Lei, Email: qlwanglei1102@163.com

Keywords：

clinically relevant postoperative pancreatic fistula; inflammatory marker; early prediction

DOI：

10.7507/1007-9424.202502084

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective This study summarizes the latest research on the use of inflammatory markers to predict clinically relevant postoperative pancreatic fistula (CR-POPF), and explores the impact of perioperative inflammatory regulation on CR-POPF, providing references for early warning and individualized intervention for CR-POPF. Methods A systematic review and summary of relevant literature from the past decade on the early prediction and diagnosis of CR-POPF using inflammatory biomarkers. Results The inflammatory cascade triggered by pancreatic surgery plays a significant role in the development and progression of pancreatic fistulas. Numerous studies have confirmed that following pancreaticoduodenectomy and distal pancreatectomy, inflammatory markers such as interleukin-6 (IL-6), C-reactive protein (CRP), procalcitonin (PCT), inflammatory cells, and other inflammatory markers have significant predictive and diagnostic value for early CR-POPF. Additionally, studies have shown that dynamic monitoring of the trends and magnitude of changes in these inflammatory markers, as well as the establishment of predictive models incorporating inflammatory indicators, can enhance the accuracy of predicting CR-POPF. Furthermore, appropriate anti-inflammatory therapy during the perioperative period plays a positive role in the prevention and treatment of CR-POPF. Conclusions Early prediction of CR-POPF is crucial for improving postoperative clinical outcomes and short-term prognosis in patients. Traditional inflammatory markers such as IL-6, CRP and PCT have unique value in the early prediction and diagnosis of CR-POPF. Dynamic monitoring can reflect changes in disease status, thereby influencing clinical management. Future research should further clarify and standardize the predictive timepoints and threshold criteria for inflammatory markers, and explore novel inflammatory markers to provide more accurate and comprehensive guidance for early risk stratification and personalized management of pancreatic fistula in clinical practice.

1.	Yuan F, Essaji Y, Belley-Cote EP, et al. Postoperative complications in elderly patients following pancreaticoduodenectomy lead to increased postoperative mortality and costs. A retrospective cohort study. Int J Surg, 2018, 60: 204-209.
2.	Bootsma BT, Plat VD, van de Brug T, et al. Somatostatin analogues for the prevention of pancreatic fistula after open pancreatoduodenectomy: a nationwide analysis. Pancreatology, 2022, 22(3): 421-426.
3.	Sakamoto K, Ogawa K, Tamura K, et al. Postoperative elevation of C-reactive protein levels and high drain fluid amylase output are strong predictors of pancreatic fistulas after distal pancreatectomy. J Hepatobiliary Pancreat Sci, 2021, 28(10): 874-882.
4.	Kim HS, Kim H, Kwon W, et al. Perioperative and oncologic outcome of robot-assisted minimally invasive (hybrid laparoscopic and robotic) pancreatoduodenectomy: based on pancreatic fistula risk score and cancer/staging matched comparison with open pancreatoduodenectomy. Surg Endosc, 2021, 35(4): 1675-1681.
5.	Smits FJ, Molenaar IQ, Besselink MG, et al. Early recognition of clinically relevant postoperative pancreatic fistula: a systematic review. HPB (Oxford), 2020, 22(1): 1-11.
6.	Bassi C, Marchegiani G, Dervenis C, et al. The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 years after. Surgery, 2017, 161(3): 584-591.
7.	Rykina-Tameeva N, MacCulloch D, Hipperson L, et al. Drain fluid biomarkers for the diagnosis of clinically relevant postoperative pancreatic fistula: a diagnostic accuracy systematic review and meta-analysis. Int J Surg, 2023, 109(8): 2486-2499.
8.	Kanda M, Fujii T, Takami H, et al. Novel diagnostics for aggravating pancreatic fistulas at the acute phase after pancreatectomy. World J Gastroenterol, 2014, 20(26): 8535-8544.
9.	Margraf A, Ludwig N, Zarbock A, et al. Systemic Inflammatory Response Syndrome After Surgery: Mechanisms and Protection. Anesth Analg, 2020, 131(6): 1693-1707.
10.	李嘉泰, 张玉婷, 拜重阳, 等. 全身免疫炎症指数联合中性粒细胞与单核细胞比值对老年结肠癌患者术后吻合口漏的预测价值. 中国普外基础与临床杂志, 2024, 31(12): 1491-1498.
11.	康志勇, 姜昌镐. 结直肠癌术后吻合口漏的相关因素及预防研究进展. 中国普外基础与临床杂志, 2020, 27(11): 1450-1456.
12.	Bona D, Danelli P, Sozzi A, et al. C-reactive protein and procalcitonin levels to predict anastomotic leak after colorectal surgery: systematic review and meta-analysis. J Gastrointest Surg, 2023, 27(1): 166-179.
13.	Ausania F, Gonzalez-Abós C, Martinez-Perez A, et al. Postoperative day one systemic inflammatory response syndrome is a powerful early biomarker of clinically relevant pancreatic fistula. HPB (Oxford), 2023, 25(1): 73-80.
14.	Mintziras I, Maurer E, Kanngiesser V, et al. C-reactive protein and drain amylase accurately predict clinically relevant pancreatic fistula after partial pancreaticoduodenectomy. Int J Surg, 2020, 76: 53-58.
15.	Jawa RS, Anillo S, Huntoon K, et al. Analytic review: interleukin-6 in surgery, trauma, and critical care: part I: basic science. J Intensive Care Med, 2011, 26(1): 3-12.
16.	Rettig TC, Verwijmeren L, Dijkstra IM, et al. Postoperative interleukin-6 level and early detection of complications after elective major abdominal surgery. Ann Surg, 2016, 263(6): 1207-1212.
17.	Deng S, Luo J, Ouyang Y, et al. Application analysis of omental flap isolation and modified pancreaticojejunostomy in pancreaticoduodenectomy (175 cases). BMC Surg, 2022, 22(1): 127. doi: 10.1186/s12893-022-01552-9.
18.	Gasteiger S, Primavesi F, Göbel G, et al. Early Post-operative pancreatitis and systemic inflammatory response assessed by serum lipase and IL-6 predict pancreatic fistula. World J Surg, 2020, 44(12): 4236-4244.
19.	Sasaki K, Asaoka T, Eguchi H, et al. Plasma ghrelin suppression as an early predictor for postoperative complications after pancreatoduodenectomy. Pancreatology, 2018, 18(1): 73-78.
20.	Marchegiani G, Perri G, Giovinazzo F, et al. High values of drain fluid epidermal growth factor and transforming growth factor-beta are associated with the development of pancreatic fistula after pancreatoduodenectomy. Dig Surg, 2022, 39(2-3): 125-132.
21.	Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest, 2003, 111(12): 1805-1812.
22.	Vasavada B, Patel H. Postoperative serum procalcitonin versus C-reactive protein as a marker of postoperative infectious complications in pancreatic surgery: a meta-analysis. ANZ J Surg, 2021, 91(5): E260-E270.
23.	Guilbaud T, Garnier J, Girard E, et al. Postoperative day 1 combination of serum C-reactive protein and drain amylase values predicts risks of clinically relevant pancreatic fistula. The “90-1000” score. Surgery, 2021, 170(5): 1508-1516.
24.	Raza SS, Nutu A, Powell-Brett S, et al. Early postoperative risk stratification in patients with pancreatic fistula after pancreaticoduodenectomy. Surgery, 2023, 173(2): 492-500.
25.	Li B, Pu N, Chen Q, et al. Comprehensive diagnostic nomogram for predicting clinically relevant postoperative pancreatic fistula after pancreatoduodenectomy. Front Oncol, 2021, 11: 717087. doi: 10.3389/fonc.2021.717087.
26.	Pecorelli N, Guarneri G, Palucci M, et al. Early biochemical predictors of clinically relevant pancreatic fistula after distal pancreatectomy: a role for serum amylase and C-reactive protein. Surg Endosc, 2022, 36(7): 5431-5441.
27.	Sakamoto K, Ogawa K, Tamura K, et al. Postoperative elevation of C-reactive protein levels and high drain fluid amylase output are strong predictors of pancreatic fistulas after distal pancreatectomy. J Hepatobiliary Pancreat Sci, 2021, 28(10): 874-882.
28.	Funamizu N, Utsunomiya T, Honjo M, et al. Preoperative C-reactive protein-to-albumin ratio predicts postoperative pancreatic fistula following pancreatoduodenectomy: a single-center, retrospective study. Curr Oncol, 2022, 29(12): 9867-9874.
29.	Sakamoto T, Yagyu Y, Uchinaka EI, et al. Predictive significance of C-reactive protein-to-albumin ratio for postoperative pancreatic fistula after pancreaticoduodenectomy. Anticancer Res, 2019, 39(11): 6283-6290.
30.	Liu R, Cai Y, Cai H, et al. Dynamic prediction for clinically relevant pancreatic fistula: a novel prediction model for laparoscopic pancreaticoduodenectomy. BMC Surg, 2021, 21(1): 7. doi: 10.1186/s12893-020-00968-5.
31.	Hata T, Mizuma M, Motoi F, et al. Serum procalcitonin as an early diagnostic marker of severe postoperative complications after elective pancreaticoduodenectomy. J Hepatobiliary Pancreat Sci, 2020, 27(10): 767-775.
32.	Ma J, Jiang P, Ji B, et al. Post-operative procalcitonin and C-reactive protein predict pancreatic fistula after laparoscopic pancreatoduodenectomy. BMC Surg, 2021, 21(1): 171. doi: 10.1186/s12893-021-01177-4.
33.	Coppola A, La Vaccara V, Angeletti S, et al. Postoperative procalcitonin is a biomarker for excluding the onset of clinically relevant pancreatic fistula after pancreaticoduodenectomy. J Gastrointest Oncol, 2023, 14(2): 1077-1086.
34.	van Dongen JC, Smits FJ, van Santvoort HC, et al. C-reactive protein is superior to white blood cell count for early detection of complications after pancreatoduodenectomy: a retrospective multicenter cohort study. HPB (Oxford), 2020, 22(10): 1504-1512.
35.	Ma M, Li G, Zhou B, et al. Comprehensive analysis of the association between inflammation indexes and complications in patients undergoing pancreaticoduodenectomy. Front Immunol, 2023, 14: 1303283. doi: 10.3389/fimmu.2023.1303283.
36.	Huang H, Wang C, Ji F, et al. Nomogram based on albumin and neutrophil-to-lymphocyte ratio for predicting postoperative complications after pancreaticoduodenectomy. Gland Surg, 2021, 10(3): 877-891.
37.	Garnier J, Alfano MS, Robin F, et al. Establishment and external validation of neutrophil-to-lymphocyte ratio in excluding postoperative pancreatic fistula after pancreatoduodenectomy. BJS Open, 2023, 7(1): zrac124. doi: 10.1093/bjsopen/zrac124.
38.	Caputo D, Coppola A, Cascone C, et al. Preoperative systemic inflammatory biomarkers and postoperative day 1 drain amylase value predict grade C pancreatic fistula after pancreaticoduodenectomy. Ann Med Surg (Lond), 2020, 57: 56-61.
39.	Cohen JT, Charpentier KP, Miner TJ, et al. Lymphopenia following pancreaticoduodenectomy is associated with pancreatic fistula formation. Ann Hepatobiliary Pancreat Surg, 2021, 25(2): 242-250.
40.	李浩, 王飞通, 王聪, 等. 预后营养指数对远端胰腺切除术后临床相关胰瘘的影响及其相关因素分析. 中国普外基础与临床杂志, 2022, 29(2): 211-217.
41.	Aronen A, Aittoniemi J, Huttunen R, et al. P-suPAR may reflect the inflammatory response after pancreatic surgery. Pancreatology, 2024, 24(1): 146-151.
42.	Wüster C, Shi H, Kühlbrey CM, et al. Pancreatic inflammation and proenzyme activation are associated with clinically relevant postoperative pancreatic fistulas after pancreas resection. Ann Surg, 2020, 272(5): 863-870.
43.	Yang Y, Huang Q, Luo C, et al. MicroRNAs in acute pancreatitis: From pathogenesis to novel diagnosis and therapy. J Cell Physiol, 2020, 235(3): 1948-1961.
44.	Li L, Liu Q, Le C, et al. Toll-like receptor 2 deficiency alleviates acute pancreatitis by inactivating the NF-κB/NLRP3 pathway. Int Immunopharmacol, 2023 Aug: 121: 110547. doi: 10.1016/j.intimp.2023.110547.
45.	Arriaga-Pizano L, Boscó-Gárate I, Martínez-Ordaz JL, et al. High serum levels of high-mobility group box 1 (HMGB1) and low levels of heat shock protein 70 (Hsp70) are associated with poor prognosis in patients with acute pancreatitis. Arch Med Res, 2018, 49(7): 504-511.
46.	Greer PJ, Lee PJ, Paragomi P, et al. Severe acute pancreatitis exhibits distinct cytokine signatures and trajectories in humans: a prospective observational study. Am J Physiol Gastrointest Liver Physiol, 2022, 323(5): G428-G438.
47.	Dai S, Peng Y, Wang G, et al. Risk factors of delayed gastric emptying in patients after pancreaticoduodenectomy: a comprehensive systematic review and meta-analysis. Int J Surg, 2023, 109(7): 2096-2119.
48.	Camilleri M, Chedid V, Ford AC, et al. Gastroparesis. Nat Rev Dis Primers, 2018, 4(1): 41. doi: 10.1038/s41572-018-0038-z.
49.	Rykina-Tameeva N, Samra JS, Sahni S, et al. Non-surgical interventions for the prevention of clinically relevant postoperative pancreatic fistula-a narrative review. Cancers (Basel), 2023, 15(24): 5865. doi: 10.3390/cancers15245865.
50.	Sandini M, Ruscic KJ, Ferrone CR, et al. Intraoperative dexamethasone decreases infectious complications after pancreaticoduodenectomy and is associated with long-term survival in pancreatic Cancer. Ann Surg Oncol, 2018, 25(13): 4020-4026.
51.	Antila A, Siiki A, Sand J, et al. Perioperative hydrocortisone treatment reduces postoperative pancreatic fistula rate after open distal pancreatectomy. A randomized placebo-controlled trial. Pancreatology, 2019, 19(5): 786-792.
52.	Tarvainen T, Sirén J, Kokkola A, et al. Effect of hydrocortisone vs. pasireotide on pancreatic surgery complications in patients with high risk of pancreatic fistula: a randomized clinical trial. JAMA Surg, 2020, 155(4): 291-298.
53.	Sueda S, Adkins A, Dehal A, et al. Effects of ketorolac on complications and postoperative pancreatic fistula in patients undergoing pancreatectomy. HPB (Oxford), 2023, 25(6): 636-643.
54.	Kunstman JW, Brandt WS, Azar SA, et al. Comprehensive analysis of the effect of ketorolac administration after pancreaticoduodenectomy. J Am Coll Surg, 2020, 230(6): 935-942.
55.	PARANOIA Study Group: ; Writing group: ; Halle-Smith JM, Pande R, Hall L, et al. Perioperative interventions to reduce pancreatic fistula following pancreatoduodenectomy: meta-analysis. Br J Surg, 2022, 109(9): 812-821.

1. Yuan F, Essaji Y, Belley-Cote EP, et al. Postoperative complications in elderly patients following pancreaticoduodenectomy lead to increased postoperative mortality and costs. A retrospective cohort study. Int J Surg, 2018, 60: 204-209.
2. Bootsma BT, Plat VD, van de Brug T, et al. Somatostatin analogues for the prevention of pancreatic fistula after open pancreatoduodenectomy: a nationwide analysis. Pancreatology, 2022, 22(3): 421-426.
3. Sakamoto K, Ogawa K, Tamura K, et al. Postoperative elevation of C-reactive protein levels and high drain fluid amylase output are strong predictors of pancreatic fistulas after distal pancreatectomy. J Hepatobiliary Pancreat Sci, 2021, 28(10): 874-882.
4. Kim HS, Kim H, Kwon W, et al. Perioperative and oncologic outcome of robot-assisted minimally invasive (hybrid laparoscopic and robotic) pancreatoduodenectomy: based on pancreatic fistula risk score and cancer/staging matched comparison with open pancreatoduodenectomy. Surg Endosc, 2021, 35(4): 1675-1681.
5. Smits FJ, Molenaar IQ, Besselink MG, et al. Early recognition of clinically relevant postoperative pancreatic fistula: a systematic review. HPB (Oxford), 2020, 22(1): 1-11.
6. Bassi C, Marchegiani G, Dervenis C, et al. The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 years after. Surgery, 2017, 161(3): 584-591.
7. Rykina-Tameeva N, MacCulloch D, Hipperson L, et al. Drain fluid biomarkers for the diagnosis of clinically relevant postoperative pancreatic fistula: a diagnostic accuracy systematic review and meta-analysis. Int J Surg, 2023, 109(8): 2486-2499.
8. Kanda M, Fujii T, Takami H, et al. Novel diagnostics for aggravating pancreatic fistulas at the acute phase after pancreatectomy. World J Gastroenterol, 2014, 20(26): 8535-8544.
9. Margraf A, Ludwig N, Zarbock A, et al. Systemic Inflammatory Response Syndrome After Surgery: Mechanisms and Protection. Anesth Analg, 2020, 131(6): 1693-1707.
10. 李嘉泰, 张玉婷, 拜重阳, 等. 全身免疫炎症指数联合中性粒细胞与单核细胞比值对老年结肠癌患者术后吻合口漏的预测价值. 中国普外基础与临床杂志, 2024, 31(12): 1491-1498.
11. 康志勇, 姜昌镐. 结直肠癌术后吻合口漏的相关因素及预防研究进展. 中国普外基础与临床杂志, 2020, 27(11): 1450-1456.
12. Bona D, Danelli P, Sozzi A, et al. C-reactive protein and procalcitonin levels to predict anastomotic leak after colorectal surgery: systematic review and meta-analysis. J Gastrointest Surg, 2023, 27(1): 166-179.
13. Ausania F, Gonzalez-Abós C, Martinez-Perez A, et al. Postoperative day one systemic inflammatory response syndrome is a powerful early biomarker of clinically relevant pancreatic fistula. HPB (Oxford), 2023, 25(1): 73-80.
14. Mintziras I, Maurer E, Kanngiesser V, et al. C-reactive protein and drain amylase accurately predict clinically relevant pancreatic fistula after partial pancreaticoduodenectomy. Int J Surg, 2020, 76: 53-58.
15. Jawa RS, Anillo S, Huntoon K, et al. Analytic review: interleukin-6 in surgery, trauma, and critical care: part I: basic science. J Intensive Care Med, 2011, 26(1): 3-12.
16. Rettig TC, Verwijmeren L, Dijkstra IM, et al. Postoperative interleukin-6 level and early detection of complications after elective major abdominal surgery. Ann Surg, 2016, 263(6): 1207-1212.
17. Deng S, Luo J, Ouyang Y, et al. Application analysis of omental flap isolation and modified pancreaticojejunostomy in pancreaticoduodenectomy (175 cases). BMC Surg, 2022, 22(1): 127. doi: 10.1186/s12893-022-01552-9.
18. Gasteiger S, Primavesi F, Göbel G, et al. Early Post-operative pancreatitis and systemic inflammatory response assessed by serum lipase and IL-6 predict pancreatic fistula. World J Surg, 2020, 44(12): 4236-4244.
19. Sasaki K, Asaoka T, Eguchi H, et al. Plasma ghrelin suppression as an early predictor for postoperative complications after pancreatoduodenectomy. Pancreatology, 2018, 18(1): 73-78.
20. Marchegiani G, Perri G, Giovinazzo F, et al. High values of drain fluid epidermal growth factor and transforming growth factor-beta are associated with the development of pancreatic fistula after pancreatoduodenectomy. Dig Surg, 2022, 39(2-3): 125-132.
21. Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest, 2003, 111(12): 1805-1812.
22. Vasavada B, Patel H. Postoperative serum procalcitonin versus C-reactive protein as a marker of postoperative infectious complications in pancreatic surgery: a meta-analysis. ANZ J Surg, 2021, 91(5): E260-E270.
23. Guilbaud T, Garnier J, Girard E, et al. Postoperative day 1 combination of serum C-reactive protein and drain amylase values predicts risks of clinically relevant pancreatic fistula. The “90-1000” score. Surgery, 2021, 170(5): 1508-1516.
24. Raza SS, Nutu A, Powell-Brett S, et al. Early postoperative risk stratification in patients with pancreatic fistula after pancreaticoduodenectomy. Surgery, 2023, 173(2): 492-500.
25. Li B, Pu N, Chen Q, et al. Comprehensive diagnostic nomogram for predicting clinically relevant postoperative pancreatic fistula after pancreatoduodenectomy. Front Oncol, 2021, 11: 717087. doi: 10.3389/fonc.2021.717087.
26. Pecorelli N, Guarneri G, Palucci M, et al. Early biochemical predictors of clinically relevant pancreatic fistula after distal pancreatectomy: a role for serum amylase and C-reactive protein. Surg Endosc, 2022, 36(7): 5431-5441.
27. Sakamoto K, Ogawa K, Tamura K, et al. Postoperative elevation of C-reactive protein levels and high drain fluid amylase output are strong predictors of pancreatic fistulas after distal pancreatectomy. J Hepatobiliary Pancreat Sci, 2021, 28(10): 874-882.
28. Funamizu N, Utsunomiya T, Honjo M, et al. Preoperative C-reactive protein-to-albumin ratio predicts postoperative pancreatic fistula following pancreatoduodenectomy: a single-center, retrospective study. Curr Oncol, 2022, 29(12): 9867-9874.
29. Sakamoto T, Yagyu Y, Uchinaka EI, et al. Predictive significance of C-reactive protein-to-albumin ratio for postoperative pancreatic fistula after pancreaticoduodenectomy. Anticancer Res, 2019, 39(11): 6283-6290.
30. Liu R, Cai Y, Cai H, et al. Dynamic prediction for clinically relevant pancreatic fistula: a novel prediction model for laparoscopic pancreaticoduodenectomy. BMC Surg, 2021, 21(1): 7. doi: 10.1186/s12893-020-00968-5.
31. Hata T, Mizuma M, Motoi F, et al. Serum procalcitonin as an early diagnostic marker of severe postoperative complications after elective pancreaticoduodenectomy. J Hepatobiliary Pancreat Sci, 2020, 27(10): 767-775.
32. Ma J, Jiang P, Ji B, et al. Post-operative procalcitonin and C-reactive protein predict pancreatic fistula after laparoscopic pancreatoduodenectomy. BMC Surg, 2021, 21(1): 171. doi: 10.1186/s12893-021-01177-4.
33. Coppola A, La Vaccara V, Angeletti S, et al. Postoperative procalcitonin is a biomarker for excluding the onset of clinically relevant pancreatic fistula after pancreaticoduodenectomy. J Gastrointest Oncol, 2023, 14(2): 1077-1086.
34. van Dongen JC, Smits FJ, van Santvoort HC, et al. C-reactive protein is superior to white blood cell count for early detection of complications after pancreatoduodenectomy: a retrospective multicenter cohort study. HPB (Oxford), 2020, 22(10): 1504-1512.
35. Ma M, Li G, Zhou B, et al. Comprehensive analysis of the association between inflammation indexes and complications in patients undergoing pancreaticoduodenectomy. Front Immunol, 2023, 14: 1303283. doi: 10.3389/fimmu.2023.1303283.
36. Huang H, Wang C, Ji F, et al. Nomogram based on albumin and neutrophil-to-lymphocyte ratio for predicting postoperative complications after pancreaticoduodenectomy. Gland Surg, 2021, 10(3): 877-891.
37. Garnier J, Alfano MS, Robin F, et al. Establishment and external validation of neutrophil-to-lymphocyte ratio in excluding postoperative pancreatic fistula after pancreatoduodenectomy. BJS Open, 2023, 7(1): zrac124. doi: 10.1093/bjsopen/zrac124.
38. Caputo D, Coppola A, Cascone C, et al. Preoperative systemic inflammatory biomarkers and postoperative day 1 drain amylase value predict grade C pancreatic fistula after pancreaticoduodenectomy. Ann Med Surg (Lond), 2020, 57: 56-61.
39. Cohen JT, Charpentier KP, Miner TJ, et al. Lymphopenia following pancreaticoduodenectomy is associated with pancreatic fistula formation. Ann Hepatobiliary Pancreat Surg, 2021, 25(2): 242-250.
40. 李浩, 王飞通, 王聪, 等. 预后营养指数对远端胰腺切除术后临床相关胰瘘的影响及其相关因素分析. 中国普外基础与临床杂志, 2022, 29(2): 211-217.
41. Aronen A, Aittoniemi J, Huttunen R, et al. P-suPAR may reflect the inflammatory response after pancreatic surgery. Pancreatology, 2024, 24(1): 146-151.
42. Wüster C, Shi H, Kühlbrey CM, et al. Pancreatic inflammation and proenzyme activation are associated with clinically relevant postoperative pancreatic fistulas after pancreas resection. Ann Surg, 2020, 272(5): 863-870.
43. Yang Y, Huang Q, Luo C, et al. MicroRNAs in acute pancreatitis: From pathogenesis to novel diagnosis and therapy. J Cell Physiol, 2020, 235(3): 1948-1961.
44. Li L, Liu Q, Le C, et al. Toll-like receptor 2 deficiency alleviates acute pancreatitis by inactivating the NF-κB/NLRP3 pathway. Int Immunopharmacol, 2023 Aug: 121: 110547. doi: 10.1016/j.intimp.2023.110547.
45. Arriaga-Pizano L, Boscó-Gárate I, Martínez-Ordaz JL, et al. High serum levels of high-mobility group box 1 (HMGB1) and low levels of heat shock protein 70 (Hsp70) are associated with poor prognosis in patients with acute pancreatitis. Arch Med Res, 2018, 49(7): 504-511.
46. Greer PJ, Lee PJ, Paragomi P, et al. Severe acute pancreatitis exhibits distinct cytokine signatures and trajectories in humans: a prospective observational study. Am J Physiol Gastrointest Liver Physiol, 2022, 323(5): G428-G438.
47. Dai S, Peng Y, Wang G, et al. Risk factors of delayed gastric emptying in patients after pancreaticoduodenectomy: a comprehensive systematic review and meta-analysis. Int J Surg, 2023, 109(7): 2096-2119.
48. Camilleri M, Chedid V, Ford AC, et al. Gastroparesis. Nat Rev Dis Primers, 2018, 4(1): 41. doi: 10.1038/s41572-018-0038-z.
49. Rykina-Tameeva N, Samra JS, Sahni S, et al. Non-surgical interventions for the prevention of clinically relevant postoperative pancreatic fistula-a narrative review. Cancers (Basel), 2023, 15(24): 5865. doi: 10.3390/cancers15245865.
50. Sandini M, Ruscic KJ, Ferrone CR, et al. Intraoperative dexamethasone decreases infectious complications after pancreaticoduodenectomy and is associated with long-term survival in pancreatic Cancer. Ann Surg Oncol, 2018, 25(13): 4020-4026.
51. Antila A, Siiki A, Sand J, et al. Perioperative hydrocortisone treatment reduces postoperative pancreatic fistula rate after open distal pancreatectomy. A randomized placebo-controlled trial. Pancreatology, 2019, 19(5): 786-792.
52. Tarvainen T, Sirén J, Kokkola A, et al. Effect of hydrocortisone vs. pasireotide on pancreatic surgery complications in patients with high risk of pancreatic fistula: a randomized clinical trial. JAMA Surg, 2020, 155(4): 291-298.
53. Sueda S, Adkins A, Dehal A, et al. Effects of ketorolac on complications and postoperative pancreatic fistula in patients undergoing pancreatectomy. HPB (Oxford), 2023, 25(6): 636-643.
54. Kunstman JW, Brandt WS, Azar SA, et al. Comprehensive analysis of the effect of ketorolac administration after pancreaticoduodenectomy. J Am Coll Surg, 2020, 230(6): 935-942.
55. PARANOIA Study Group: ; Writing group: ; Halle-Smith JM, Pande R, Hall L, et al. Perioperative interventions to reduce pancreatic fistula following pancreatoduodenectomy: meta-analysis. Br J Surg, 2022, 109(9): 812-821.

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