Preoperative lymphocyte signature predicts pancreatic fistula after pancreatoduodenectomy

Preoperative lymphocyte signature predicts pancreatic fistula after pancreatoduodenectomy

  • Ma, L. W. et al. The cost of postoperative pancreatic fistula versus the cost of pasireotide: results from a prospective randomized trial. Ann. Surg. 265, 11–16 (2017).


    Google Scholar
     

  • Williamsson, C., Ansari, D., Andersson, R. & Tingstedt, B. Postoperative pancreatic fistula-impact on outcome, hospital cost and effects of centralization. HPB (Oxford) 19, 436–442 (2017).


    Google Scholar
     

  • Wellner, U. F. et al. A simple scoring system based on clinical factors related to pancreatic texture predicts postoperative pancreatic fistula preoperatively. HPB (Oxford) 12, 696–702 (2010).


    Google Scholar
     

  • Yamamoto, Y. et al. A preoperative predictive scoring system for postoperative pancreatic fistula after pancreaticoduodenectomy. World J. Surg. 35, 2747–2755 (2011).


    Google Scholar
     

  • Roberts, K. J. et al. Scoring system to predict pancreatic fistula after pancreaticoduodenectomy: a UK multicenter study. Ann. Surg. 261, 1191–1197 (2015).


    Google Scholar
     

  • Nishida, Y. et al. Preoperative sarcopenia strongly influences the risk of postoperative pancreatic fistula formation after pancreaticoduodenectomy. J. Gastrointest. Surg. 20, 1586–1594 (2016).


    Google Scholar
     

  • Schuh, F. et al. A Simple Classification of Pancreatic Duct Size and Texture Predicts postoperative Pancreatic Fistula: a classification of the International Study Group of Pancreatic Surgery (ISGPS). Ann. Surg. 277, e597–e608 (2023).


    Google Scholar
     

  • Callery, M. P., Pratt, W. B., Kent, T. S., Chaikof, E. L. & Vollmer, C. M. A prospectively validated clinical risk score accurately predicts pancreatic fistula after pancreatoduodenectomy. J. Am. Coll. Surg. 216, 1–14 (2013).


    Google Scholar
     

  • Nimptsch, U., Krautz, C., Weber, G. F., Mansky, T. & Grützmann, R. Nationwide in-hospital mortality following pancreatic surgery in Germany is higher than anticipated. Ann. Surg. 264, 1082–1090 (2016).


    Google Scholar
     

  • Farges, O. et al. The theory and practice of pancreatic surgery in France. Ann. Surg. 266, 797–804 (2017).


    Google Scholar
     

  • El Amrani, M. et al. Referring patients to expert centers after pancreatectomy is too late to improve outcome. Inter-hospital transfer analysis in nationwide study of 19,938 patients. Ann. Surg. 272, 723–730 (2020).


    Google Scholar
     

  • Mungroop, T. H. et al. Updated alternative fistula risk score (ua-FRS) to include minimally invasive pancreatoduodenectomy: pan-European validation. Ann. Surg. 273, 334–340 (2021).


    Google Scholar
     

  • Casciani, F., Bassi, C. & Vollmer, C. M. Decision points in pancreatoduodenectomy: insights from the contemporary experts on prevention, mitigation, and management of postoperative pancreatic fistula. Surgery 170, 889–909 (2021).


    Google Scholar
     

  • Fong, Z. V. et al. Early drain removal—the middle ground between the Drain versus No Drain debate in patients undergoing pancreaticoduodenectomy: a prospective validation study. Ann. Surg. 262, 378–383 (2015).


    Google Scholar
     

  • Van Hilst, J. et al. The inflammatory response after laparoscopic and open pancreatoduodenectomy and the association with complications in a multicenter randomized controlled trial. HPB 21, 1453–1461 (2019).


    Google Scholar
     

  • Garnier, J. et al. Establishment and external validation of neutrophil-to-lymphocyte ratio in excluding postoperative pancreatic fistula after pancreatoduodenectomy. BJS Open 7, zrac124 (2023).


    Google Scholar
     

  • Søreide, K., Healey, A. J., Mole, D. J. & Parks, R. W. Pre-, peri- and post-operative factors for the development of pancreatic fistula after pancreatic surgery. HPB 21, 1621–1631 (2019).


    Google Scholar
     

  • Verdonk, F. et al. Measuring the human immune response to surgery: multiomics for the prediction of postoperative outcomes. Curr. Opin. Crit. Care 27, 717–725 (2021).


    Google Scholar
     

  • Rumer, K. K. et al. Integrated single-cell and plasma proteomic modeling to predict surgical site complications: a prospective cohort study. Ann. Surg. 275, 582–590 (2022).


    Google Scholar
     

  • Fragiadakis, G. K. et al. Patient-specific immune states before surgery are strong correlates of surgical recovery. Anesthesiology 123, 1241–1255 (2015).


    Google Scholar
     

  • Verdonk, F. et al. An immune signature of postoperative cognitive decline: a prospective cohort study.Int. J. Surg. 110, 7749–7762 (2024).

  • Garnier, J. et al. Immediate variations in high-dimensional circulating immune cells following pancreatectomy. Clin. Transl. Immunol. 14, e70059 (2025).


    Google Scholar
     

  • Collins, G. S., Reitsma, J. B., Altman, D. G. & Moons, K. G. M. Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD Statement. BMC Med. 13, 1 https://doi.org/10.1186/s12916-014-0241-z (2015).

  • Bassi, C. et al. The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 years after. Surgery 161, 584–591 (2017).


    Google Scholar
     

  • Halloran, C. M. et al. A multicenter, randomized, double-blinded, clinical trial comparing Cattell-Warren and Blumgart anastomoses following partial pancreatoduodenectomy: PANasta trial. Ann. Surg. Open 3, e198 (2022).


    Google Scholar
     

  • Turrini, O. & Delpero, J. R. Omental flap for vessel coverage during pancreaticoduodenectomy. A Modified Technique. J. Chir. (Paris) 146, 545–548 (2009).


    Google Scholar
     

  • Pessaux, P. et al. External pancreatic duct stent decreases pancreatic fistula rate after pancreaticoduodenectomy: prospective multicenter randomized trial. Ann. Surg. 253, 879–885 (2011).


    Google Scholar
     

  • Ecker, B. L. et al. Characterization and optimal management of high-risk pancreatic anastomoses during pancreatoduodenectomy. Ann. Surg. 267, 608–616 (2018).


    Google Scholar
     

  • Van Unen, V. et al. Visual analysis of mass cytometry data by hierarchical stochastic neighbour embedding reveals rare cell types. Nat. Commun. 8, 1740 (2017).


    Google Scholar
     

  • Hédou, J. et al. Discovery of sparse, reliable omic biomarkers with Stabl. Nat. Biotechnol. 42, 1581–1593 (2024).


    Google Scholar
     

  • Ahmed, R. et al. CD57+ Memory T cells proliferate in vivo. Cell Rep 33, 108501 (2020).


    Google Scholar
     

  • Björkström, N. K. et al. Elevated numbers of FcγRIIIA+ (CD16+) effector CD8 T cells with NK cell-like function in chronic hepatitis C virus infection. J. Immunol. 181, 4219–4228 (2008).


    Google Scholar
     

  • Freuchet, A. et al. Identification of human exTreg cells as CD16+CD56+ cytotoxic CD4+ T cells. Nat. Immunol. 24, 1748–1761 (2023).


    Google Scholar
     

  • Hirono, S. et al. Risk factors for pancreatic fistula grade C after pancreatoduodenectomy: a large prospective, multicenter Japan-Taiwan collaboration study. J. Hepatobiliary Pancreat Sci. 27, 622–631 (2020).


    Google Scholar
     

  • Bassi, C. et al. Pancreatoduodenectomy at the Verona Pancreas Institute: the evolution of indications, surgical techniques, and outcomes: a retrospective analysis of 3000 consecutive cases. Ann. Surg. 276, 1029–1038 (2022).


    Google Scholar
     

  • McMillan, M. T. et al. The characterization and prediction of ISGPF Grade C fistulas following pancreatoduodenectomy. J. Gastrointest. Surg. 20, 262–276 (2016).


    Google Scholar
     

  • Hank, T. et al. Association between pancreatic fistula and long-term survival in the era of neoadjuvant chemotherapy. JAMA Surg. 154, 943 (2019).


    Google Scholar
     

  • Reinke, S. et al. Terminally differentiated CD8+ T cells negatively affect bone regeneration in humans. Sci. Transl. Med. 5, 177ra36 (2013).


    Google Scholar
     

  • Slade, M., Simmons, R., Yunis, E. & Greenberg, L. Immunodepression after major surgery in normal patients. Surgery 8, 363–372 (1975).


    Google Scholar
     

  • Cohen, J. T., Charpentier, K. P., Miner, T. J., Cioffi, W. G. & Beard, R. E. Lymphopenia following pancreaticoduodenectomy is associated with pancreatic fistula formation. Ann. Hepatobiliary Pancreat Surg. 25, 242–250 (2021).


    Google Scholar
     

  • Chretien, A. S. et al. Natural killer defective maturation is associated with adverse clinical outcome in patients with acute myeloid leukemia. Front. Immunol. 8, 573 (2017).


    Google Scholar
     

  • Conway Morris, A. et al. Cell-surface signatures of immune dysfunction risk-stratify critically ill patients: INFECT study. Intensive Care Med. 44, 627–635 (2018).


    Google Scholar
     

  • Sharma, P. & Allison, J. P. Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential. Cell 161, 205–214 (2015).


    Google Scholar
     

  • Werba, G. et al. Single-cell RNA sequencing reveals the effects of chemotherapy on human pancreatic adenocarcinoma and its tumor microenvironment. Nat. Commun. 14, 797 (2023).


    Google Scholar
     

  • Middelburg, J. et al. The MHC-E peptide ligands for checkpoint CD94/NKG2A are governed by inflammatory signals, whereas LILRB1/2 receptors are peptide indifferent. Cell Rep. 42, 113516 (2023).


    Google Scholar
     

  • Hyung, J. et al. Tumor immune-gene expression profiles and peripheral immune phenotypes associated with clinical outcomes of locally advanced pancreatic cancer following FOLFIRINOX. ESMO Open 7, 100484 (2022).


    Google Scholar
     

  • Shinde, R. S. et al. External validation and comparison of the original, alternative and updated-alternative fistula risk scores for the prediction of postoperative pancreatic fistula after pancreatoduodenectomy. Pancreatology 20, 751–756 (2020).


    Google Scholar
     

  • Gu, Z. et al. Development and validation of a novel nomogram to predict postoperative pancreatic fistula after pancreatoduodenectomy using lasso-logistic regression: an international multi-institutional observational study. Int. J. Surg. 109, 4027–4040 (2023).


    Google Scholar
     

  • Ashraf Ganjouei, A. et al. A machine learning approach to predict postoperative pancreatic fistula after pancreaticoduodenectomy using only preoperatively known data. Ann. Surg. Oncol. 30, 7738–7747 (2023).


    Google Scholar
     

  • Verma, A. et al. Machine learning-based prediction of postoperative pancreatic fistula following pancreaticoduodenectomy. Ann. Surg. 280, 325–331 (2024).


    Google Scholar
     

  • Ingwersen, E. W. et al. Radiomics preoperative-Fistula risk score (RAD-FRS) for pancreatoduodenectomy: development and external validation. BJS Open 7, zrad100 (2023).


    Google Scholar
     

  • Mišić, V. V., Gabel, E., Hofer, I., Rajaram, K. & Mahajan, A. Machine learning prediction of postoperative emergency department hospital readmission. Anesthesiology 132, 968–980 (2020).


    Google Scholar
     

  • Durand, X. et al. Predicthor: AI-powered predictive risk model for 30-day mortality and 30-day complications in patients undergoing thoracic surgery for lung cancer. Ann. Surg. Open 6, e578 (2025).


    Google Scholar
     

  • Tarvainen, T., Sirén, J., Kokkola, A. & Sallinen, V. Effect of hydrocortisone vs pasireotide on pancreatic surgery complications in patients with high risk of pancreatic fistula: a randomized clinical trial. JAMA Surg 155, 291–298 (2020).


    Google Scholar
     

  • Palen, A., Garnier, J., Delpero, J. R., Turrini, O. & Ewald, J. Protective peritoneal patch for arteries during pancreatoduodenectomy: good value for money. Langenbecks Arch Surg 407, 377–382 (2022).


    Google Scholar
     

  • Smits, F. J. et al. Algorithm-based care versus usual care for the early recognition and management of complications after pancreatic resection in the Netherlands: an open-label, nationwide, stepped-wedge cluster-randomised trial. Lancet 399, 1867–1875 (2022).


    Google Scholar
     

  • De Luca, R. et al. Immunonutrition and prehabilitation in pancreatic cancer surgery: A new concept in the era of ERAS® and neoadjuvant treatment. Eur. J. Surg. Oncol. 49, 542–549 (2023).


    Google Scholar
     

  • Barberan-Garcia, A. et al. Personalised prehabilitation in high-risk patients undergoing elective major abdominal surgery: a randomized blinded controlled trial. Ann. Surg. 267, 50–56 (2018).


    Google Scholar
     

  • Cambriel, A. et al. Immune modulation by personalized vs standard prehabilitation before major surgery: a randomized clinical trial. JAMA Surg. 161, 20–30 (2026).

  • Balzano, G. et al. Total pancreatectomy with islet autotransplantation as an alternative to high-risk pancreatojejunostomy after pancreaticoduodenectomy: a prospective randomized trial. Ann. Surg. 277, 894–903 (2023).


    Google Scholar
     

  • Stoop, T. F. et al. Systematic review and meta-analysis of the role of total pancreatectomy as an alternative to pancreatoduodenectomy in patients at high risk for postoperative pancreatic Fistula: is it a justifiable indication? Ann Surg. 278, e702–e711 (2023).


    Google Scholar
     

  • Davern, M. et al. PD-1 blockade attenuates surgery-mediated immunosuppression and boosts Th1 immunity perioperatively in oesophagogastric junctional adenocarcinoma. Front. Immunol. 14, 1150754 (2023).


    Google Scholar
     

  • Hotchkiss, R. S. et al. Immune checkpoint inhibition in sepsis: a Phase 1b randomized, placebo-controlled, single ascending dose study of antiprogrammed cell death-ligand 1 antibody (BMS-936559). Crit. Care Med. 47, 632–642 (2019).


    Google Scholar
     

  • Becht, E. et al. Reverse-engineering flow-cytometry gating strategies for phenotypic labelling and high-performance cell sorting. Bioinformatics 35, 301–308 (2019).


    Google Scholar
     

  • De Graaf, N. et al. Minimally invasive versus open pancreatoduodenectomy for resectable neoplasms. NEJM Evid. 4, EVIDoa2500045 (2025).


    Google Scholar
     

  • Maslove, D. M. et al. Redefining critical illness. Nat. Med. 28, 1141–1148 (2022).


    Google Scholar