The Role of Preoperative Inflammatory Markers in Pancreatectomy: a Norwegian Nationwide Cohort Study

Journal of Gastrointestinal Surgery (2023) 27:1650–1659 https://doi.org/10.1007/s11605-023-05726-5 ORIGINAL ARTICLE The Role of Preoperative Inflammatory Markers in Pancreatectomy: a Norwegian Nationwide Cohort Study Mushegh A. Sahakyan1,2,3 · Dyre Kleive4 · Rachel G. Dille‑Amdam5 · Trond Kjeseth4,6 · Kim Waardal7 · Bjørn Edwin1,2,4,8 · Linn S. Nymo9,10 · Kristoffer Lassen4,10 Received: 17 March 2023 / Accepted: 27 May 2023 / Published online: 15 June 2023 © The Author(s) 2023 Abstract Background and purpose Preoperative inflammatory markers, such as Glasgow prognostic score, modified Glasgow prognostic score and C-reactive protein to albumin ratio, were shown to be associated with prognosis in patients undergoing pancreatectomy for cancer. However, little is known about their predictive role in a Western population. Methods The Norwegian National Registry for Gastrointestinal Surgery (NORGAST) was used to capture all pancreatectomies performed within the study period (November 2015—April 2021). The association between the preoperative inflammatory markers and postoperative outcomes was studied. Their impact on survival was examined in patients operated for pancreatic ductal adenocarcinoma. Results A total of 1554 patients underwent pancreatectomy in this period. Glasgow prognostic score, modified Glasgow prognostic score and C-reactive protein to albumin ratio were associated with severe complications (Accordion grade ≥ III) in the univariable but not in the multivariable analysis. C-reactive protein to albumin ratio, but not Glasgow prognostic score and modified Glasgow prognostic score, was linked to survival following pancreatectomy for ductal adenocarcinoma. In the multivariable model, age, neoadjuvant chemotherapy, ECOG score, C-reactive protein to albumin ratio and total pancreatectomy correlated with survival. Also, preoperative C-reactive protein to albumin ratio was significantly associated with survival after pancreatoduodenectomy. Conclusions Preoperative Glasgow prognostic score, modified Glasgow prognostic score and C-reactive protein to albumin ratio have no role in predicting the complications after pancreatectomy. C-reactive protein to albumin ratio is a significant predictor for survival in ductal adenocarcinoma, yet its clinical relevance should be explored in conjunction with the pathology parameters and adjuvant therapy. Keywords Pancreatectomy · Inflammation · Morbidity · Cancer · Survival * Mushegh A. Sahakyan 1 The Intervention Center, Oslo University Hospital, Rikshospitalet, Oslo, Norway 2 Department of Research & Development, Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway 3 Department of Surgery N1, Yerevan State Medical University After M. Heratsi, Yerevan, Armenia 4 Department of HPB Surgery, Oslo University Hospital, Rikshospitalet, Oslo, Norway 5 Department of Gastrointestinal Surgery, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway 13 Vol:.(1234567890) 6 Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway 7 Department of Acute and Digestive Surgery, Haukeland University Hospital, Bergen, Norway 8 Institute of Clinical Medicine, Medical Faculty, University of Oslo, Oslo, Norway 9 Department of Gastrointestinal Surgery, University Hospital of North Norway, Tromsø, Norway 10 Institute of Clinical Medicine, UiT, the Arctic University of Norway, Tromsø, Norway Journal of Gastrointestinal Surgery (2023) 27:1650–1659 Introduction Cancer cells are known to activate systemic inflammatory pathways thereby providing favorable environment for cancer progression, immune evasion, and dissemination.1–3 In pancreatic cancer, inflammatory markers such as Glasgow prognostic score (GPS), platelet to lymphocyte ratio and neutrophil to lymphocyte ratio were shown to be associated with prognosis.4–6 GPS based on serum C-reactive protein and albumin levels was first introduced as a predictor for treatment outcome in primary unresectable pancreatic cancer.6 However, it soon became increasingly used also in patients undergoing pancreatectomy for cancer.7–9 Recently, other inflammatory markers derived from serum C-reactive protein and albumin levels, such as modified GPS (mGPS) and C-reactive protein to albumin ratio (CAR), have been reported in the literature.10,11 These were considered more sensitive than GPS in terms of predictive qualities, however published results are inconsistent and require further exploration.7,8,12,13 Notably, most of the studies comparing different inflammatory markers were conducted in Asia, while only a handful of reports have been published in the Western world. 4,14 Furthermore, most of the studies come from single centers and are affected by relatively small sample size. This study aims to examine the association between the preoperative inflammatory markers (GPS, mGPS, CAR), and postoperative outcomes of pancreatectomy in a complete national cohort, as well as their impact on survival in patients operated for pancreatic ductal adenocarcinoma (PDAC). Materials and methods Study design This is an observational nationwide cohort study using data collected in the Norwegian National Registry for Gastrointestinal Surgery (NORGAST). This registry covers all surgical (gastrointestinal, hepato-pancreato-biliary) procedures performed in Norway since 2015 including pancreatic resections.15 The Norwegian health care system is centralized to a degree where all patients referred for pancreatectomy are operated in one of the five hepatopancreato-biliary units located at the corresponding public university hospital. Each of these belongs to one of the four independent regional health authorities: South-Eastern, Western, Central and Northern. Data collection, procedure coding, as well as inclusion and exclusion criteria for NORGAST have been meticulously described elsewhere.16–18 1651 Information on patient demographics, baseline characteristics (including preoperative GPS, mGPS and CAR), surgical procedures, postoperative outcomes and survival are prospectively registered and updated. All patients who had undergone pancreatectomy for benign or malignant lesions in the pancreas and periampullary region were included in this study. Study period ranged from November 2015 to April 2021. The association between preoperative inflammatory markers (GPS, mGPS and CAR) and postoperative outcomes (severe complications, relaparotomy, single- and multiorgan failure, 90-day mortality) was examined. Patients without information on preoperative serum albumin, C-reactive protein or tumor histology were excluded from the analysis. The impact of GPS, mGPS and CAR on survival was studied in a subgroup containing only patients with PDAC. Hence, those diagnosed with other histological entities were excluded from the survival analysis. The last followup date was May 31st, 2021. The manuscript was completed in accordance with the Strengthening t (...truncated)