Establishment and external validation of neutrophil-to-lymphocyte ratio in excluding postoperative pancreatic fistula after pancreatoduodenectomy

Jonathan Garnier, Marie-Sophie Alfano, Fabien Robin, Jacques Ewald, Abdallah Al Farai, Anais Palen, Amine Sebai, Djamel Mokart, Jean-Robert Delpero, Laurent Sulpice, Christophe Zemmour, Olivier Turrini, Jonathan Garnier, Marie-Sophie Alfano, Fabien Robin, Jacques Ewald, Abdallah Al Farai, Anais Palen, Amine Sebai, Djamel Mokart, Jean-Robert Delpero, Laurent Sulpice, Christophe Zemmour, Olivier Turrini

Abstract

Background: Factors excluding postoperative pancreatic fistula (POPF), facilitating early drain removal and hospital discharge represent a novel approach in patients undergoing enhanced recovery after pancreatic surgery. This study aimed to establish the relevance of neutrophil-to-lymphocyte ratio (NLR) in excluding POPF after pancreatoduodenectomy (PD).

Methods: A prospectively maintained database of patients who underwent PD at two high-volume centres was used. Patients were divided into three cohorts (training, internal, and external validation). The primary endpoints of this study were accuracy, optimal timing, and cutoff values of NLR for excluding POPF after PD.

Results: From 2012 to 2020, in a 2:1 ratio, 451 consecutive patients were randomly sampled as training (n = 301) and validation (n = 150) cohorts. Additionally, the external validation cohort included 197 patients between 2018 and 2020. POPF was diagnosed in 135 (20.8 per cent) patients. The 90-day mortality rate was 4.1 per cent. NLR less than 8.5 on postoperative day 3 (OR, 95 per cent c.i.) was significantly associated with the absence of POPF in the training (2.41, 1.19 to 4.88; P = 0.015), internal validation (5.59, 2.02 to 15.43; P = 0.001), and external validation (5.13, 1.67 to 15.76; P = 0.004) cohorts when adjusted for relevant clinical factors. Postoperative outcomes significantly differed using this threshold.

Conclusion: NLR less than 8.5 on postoperative day 3 may be a simple, independent, cost-effective, and easy-to-use criterion for excluding POPF.

© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd.

Figures

Fig. 1
Fig. 1
Flow diagram of the patient distribution in the enrolled cohorts of the study
Fig. 2
Fig. 2
Receiver operating characteristic (ROC) curve of neutrophil-to-lymphocyte ratio (NLR) on postoperative day 3 (POD3) in the external validation cohort (n = 197)

References

    1. Ma LW, Dominguez-Rosado I, Gennarelli RL, Bach PB, Gonen M, D’Angelica MIet al. . The cost of postoperative pancreatic fistula versus the cost of pasireotide: results from a prospective randomized trial. Ann Surg 2017;265:11–16
    1. Williamsson C, Ansari D, Andersson R, Tingstedt B. Postoperative pancreatic fistula-impact on outcome, hospital cost and effects of centralization. HPB (Oxford) 2017;19:436–442
    1. Bassi C, Marchegiani G, Dervenis C, Sarr M, Abu Hilal M, Adham Met al. . The 2016 update of the international study group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 years after. Surgery 2017;161:584–591
    1. Wellner UF, Kayser G, Lapshyn H, Sick O, Makowiec F, Höppner Jet al. . A simple scoring system based on clinical factors related to pancreatic texture predicts postoperative pancreatic fistula preoperatively. HPB (Oxford) 2010;12:696–702
    1. Yamamoto Y, Sakamoto Y, Nara S, Esaki M, Shimada K, Kosuge T. A preoperative predictive scoring system for postoperative pancreatic fistula after pancreaticoduodenectomy. World J Surg 2011;35:2747–2755
    1. Roberts KJ, Sutcliffe RP, Marudanayagam R, Hodson J, Isaac J, Muiesan Pet al. . Scoring system to predict pancreatic fistula after pancreaticoduodenectomy: a UK multicentre study. Ann Surg 2015;261:1191–1197
    1. Nishida Y, Kato Y, Kudo M, Aizawa H, Okubo S, Takahashi Det al. . Preoperative sarcopenia strongly influences the risk of postoperative pancreatic fistula formation after pancreaticoduodenectomy. J Gastrointest Surg 2016;20:1586–1594
    1. Pecorelli N, Capretti G, Sandini M, Damascelli A, Cristel G, De Cobelli Fet al. . Impact of sarcopenic obesity on failure to rescue from major complications following pancreaticoduodenectomy for cancer: results from a multicentre study. Ann Surg Oncol 2018;25:308–317
    1. Callery MP, Pratt WB, Kent TS, Chaikof EL, Vollmer CM. A prospectively validated clinical risk score accurately predicts pancreatic fistula after pancreatoduodenectomy. J Am Coll Surg 2013;216:1–14
    1. Miller BC, Christein JD, Behrman SW, Drebin JA, Pratt WB, Callery MPet al. . A multi-institutional external validation of the fistula risk score for pancreatoduodenectomy. J Gastrointest Surg 2014;18:172–179
    1. Shubert CR, Wagie AE, Farnell MB, Nagorney DM, Que FG, Reid Lombardo KMet al. . Clinical risk score to predict pancreatic fistula after pancreatoduodenectomy: independent external validation for open and laparoscopic approaches. J Am Coll Surg 2015;221:689–698
    1. Fong ZV V, Correa-Gallego C, Ferrone CR, Veillette GR, Warshaw AL, Lillemoe KDet al. . Early drain removal—the middle ground between the drain versus no drain debate in patients undergoing pancreaticoduodenectomy: a prospective validation study. Ann Surg 2015;262:378–383
    1. Bertens KA, Crown A, Clanton J, Alemi F, Alseidi AA, Biehl Tet al. . What is a better predictor of clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD): postoperative day one drain amylase (POD1DA) or the fistula risk score (FRS)? HPB (Oxford) 2017;19:75–81
    1. Partelli S, Pecorelli N, Muffatti F, Belfiori G, Crippa S, Piazzai Fet al. . Early postoperative prediction of clinically relevant pancreatic fistula after pancreaticoduodenectomy: usefulness of C-reactive protein. HPB (Oxford) 2017;19:580–586
    1. Van Hilst J, Brinkman DJ, de Rooij T, van Dieren S, Gerhards MF, de Hingh IHet al. . The inflammatory response after laparoscopic and open pancreatoduodenectomy and the association with complications in a multicentre randomized clinical trial. HPB (Oxford) 2019;21:1453–1461
    1. Tang F, Dai P, Wei Q, Gan K, Wang Z, Chen Het al. . The neutrophil-to-monocyte ratio and platelet-to-white blood cell ratio represent novel prognostic markers in patients with pancreatic cancer. Gastroenterol Res Pract 2021;2021:6693028.
    1. Al Lawati Y, Alkaaki A, Luis Ramírez García Luna J, Skothos E, Mueller C, Spicer Jet al. . The predictive value of inflammatory biomarkers in esophageal anastomotic leaks. Ann Thorac Surg 2021;112:1790–1796
    1. Paliogiannis P, Deidda S, Maslyankov S, Paycheva T, Farag A, Mashhour Aet al. . Blood cell count indexes as predictors of anastomotic leakage in elective colorectal surgery: a multicentre study on 1432 patients. World J Surg Oncol 2020;18:89.
    1. Hwang DW, Kim HJ, Lee JH, Song KB, Kim M, Lee SKet al. . Effect of enhanced recovery after surgery program on pancreaticoduodenectomy: a randomized clinical trial: jhbp.641. J Hepatobiliary Pancreat Sci 2019;26:360–369
    1. Collins GS, Reitsma JB, Altman DG, Moons K. Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD statement. BMC Med 2015;13:1.
    1. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004;240:205–213
    1. Mungroop TH, Klompmaker S, Wellner UF, Steyerberg EW, Coratti A, D’Hondt Met al. . Updated alternative fistula risk score (ua-FRS) to include minimally invasive pancreatoduodenectomy: pan-European validation. Ann Surg 2021;273:334–340
    1. Guilbaud T, Garnier J, Girard E, Ewald J, Risse O, Moutardier Vet 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;170:1508–1516
    1. Van Buren G, Bloomston M, Hughes SJ, Winter J, Behrman SW, Zyromski NJet al. . A randomized prospective multicentre trial of pancreaticoduodenectomy with and without routine intraperitoneal drainage. Ann Surg 2014;259:605–612
    1. Bassi C, Molinari E, Malleo G, Crippa S, Butturini G, Salvia Ret al. . Early versus late drain removal after standard pancreatic resections: results of a prospective randomized trial. Ann Surg 2010;252:207–214
    1. Salvia R, Marchegiani G, Andrianello S, Balduzzi A, Masini G, Casetti Let al. . Redefining the role of drain amylase value for a risk-based drain management after pancreaticoduodenectomy: early drain removal still is beneficial. J Gastrointest Surg 2021;25:1461–1470
    1. Trudeau MT, Maggino L, Chen B, McMillan MT, Lee MK, Roses Ret al. . Extended experience with a dynamic, data-driven selective drain management protocol in pancreaticoduodenectomy: progressive risk stratification for better practice. J Am Coll Surg 2020;230:809–818.e1
    1. Shin SH, Kang WH, Han IW, You Y, Lee H, Kim Het al. . National survey of Korean hepatobiliary-pancreatic surgeons on attitudes about the enhanced recovery after surgery protocol. Ann Hepatobiliary Pancreat Surg 2020;24:477–483
    1. Beane JD, House MG, Ceppa EP, Dolejs SC, Pitt HA. Variation in drain management after pancreatoduodenectomy: early versus delayed removal. Ann Surg 2019;269:718–724
    1. Xourafas D, Ejaz A, Tsung A, Dillhoff M, Pawlik TM, Cloyd JM. Validation of early drain removal after pancreatoduodenectomy based on modified fistula risk score stratification: a population-based assessment. HPB (Oxford) 2019;21:1303–1311
    1. Taniguchi K, Matsuyama R, Yabushita Y, Homma Y, Ota Y, Mori Ret al. . Prophylactic drain management after pancreaticoduodenectomy without focusing on the drain fluid amylase level: a prospective validation study regarding criteria for early drain removal that do not include the drain fluid amylase level. J Hepatobiliary Pancreat Sci 2020;27:950–961
    1. van Dongen JC, Smits FJ, van Santvoort HC, Molenaar IQ, Busch OR, Besselink MGet al. . C-reactive protein is superior to white blood cell count for early detection of complications after pancreatoduodenectomy: a retrospective multicentre cohort study. HPB (Oxford) 2020;22:1504–1512
    1. Connor S. Defining post-operative pancreatitis as a new pancreatic specific complication following pancreatic resection. HPB (Oxford) 2016;18:642–651
    1. Marchegiani G, Barreto SG, Bannone E, Sarr M, Vollmer CM, Connor Set al. . Postpancreatectomy acute pancreatitis (PPAP): definition and grading from the international study group for pancreatic surgery (ISGPS). Ann Surg 2022;275:663–672
    1. Cohen JT, Charpentier KP, Miner TJ, Cioffi WG, Beard RE. Lymphopenia following pancreaticoduodenectomy is associated with pancreatic fistula formation. Ann Hepatobiliary Pancreat Surg 2021;25:242–250
    1. Simpson RE, Fennerty ML, Colgate CL, Kilbane EM, Ceppa EP, House MGet al. . Post-pancreaticoduodenectomy outcomes and epidural analgesia: a 5-year single-institution experience. J Am Coll Surg 2019;228:453–462
    1. McMillan MT, Malleo G, Bassi C, Allegrini V, Casetti L, Drebin JAet al. . Multicentre, prospective trial of selective drain management for pancreatoduodenectomy using risk stratification. Ann Surg 2017;265:1209–1218

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren