Endoscopy 2021; 53(08): 774-781
DOI: 10.1055/a-1292-8747
Original article

Neutrophil to lymphocyte ratio and risk of neoplastic progression in patients with Barrett’s esophagus

Noam Peleg*
1   Division of Gastroenterology, Rabin Medical Center, Petah-Tikva, Israel
2   Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
,
Hemda Schmilovitz-Weiss*
1   Division of Gastroenterology, Rabin Medical Center, Petah-Tikva, Israel
2   Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
,
Steven Shamah
1   Division of Gastroenterology, Rabin Medical Center, Petah-Tikva, Israel
2   Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
,
Ariel Schwartz
3   Department of Pathology, Rabin Medical Center, Petah-Tikva, Israel
,
Iris Dotan
1   Division of Gastroenterology, Rabin Medical Center, Petah-Tikva, Israel
2   Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
,
Boris Sapoznikov
1   Division of Gastroenterology, Rabin Medical Center, Petah-Tikva, Israel
2   Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
› Author Affiliations

Abstract

Background Patient’s with Barrett’s esophagus (BE) are at risk of progression to esophageal adenocarcinoma (EAC). Neutrophil to lymphocyte ratio (NLR) was found to be a predictor of poor prognosis in patients with EAC; however, its performance in premalignant esophageal lesions is vague. We aimed to evaluate the utility of NLR as a predictor of histologic progression in patients with BE.

Methods A prospective cohort of patients with proven BE in a tertiary referral center was retrospectively analyzed. All biopsies were reviewed by an expert gastrointestinal pathologist. The discriminatory capacity of NLR was evaluated by area under the receiver operating characteristic (AUC) curve analysis and Cox regression analysis.

Results 324 patients (mean age 62.3 years, 241 [74.4 %] males) were included in the final analysis. Overall, 13 patients demonstrated histologic progression to neoplasia over a mean follow-up of 3.7 years (progression risk 1.0 % per year). The AUC of NLR for progression to high grade dysplasia (HGD) or EAC was 0.88 (95 % confidence interval [CI] 0.83 – 0.96), and baseline NLR was associated with a 3-fold increase of progression to HGD and EAC during follow-up (hazard ratio [HR] 3.2, 95 %CI 1.5 – 5.8; P < 0.001). Notably, in a subgroup analysis of patients with nondysplastic BE (NDBE) at presentation, NLR was also a risk factor for histologic progression (HR 2.4, 95 %CI 1.7 – 3.4; P < 0.001).

Conclusion NLR predicted histologic progression in patients with BE. Patients with NDBE and NLR above 2.4 can be considered for specific surveillance programs with shorter intervals between sessions.

* These authors contributed equally to the study.


Figs. 1s, 2s, Table 1s



Publication History

Received: 17 March 2020

Accepted: 19 October 2020

Accepted Manuscript online:
19 October 2020

Article published online:
16 December 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Shaheen NJ, Falk GW, Iyer PG. et al. ACG Clinical Guideline: Diagnosis and management of Barrett’s esophagus. Am J Gastroenterol 2016; 111: 30-50
  • 2 Fitzgerald RC, di Pietro M, Ragunath K. et al. British Society of Gastroenterology guidelines on the diagnosis and management of Barrett’s oesophagus. Gut 2014; 63: 7-42
  • 3 Desai TK, Krishnan K, Samala N. et al. The incidence of oesophageal adenocarcinoma in non-dysplastic Barrett’s oesophagus: a meta-analysis. Gut 2012; 61: 970-976
  • 4 Whiteman DC, Appleyard M, Bahin FF. et al. Australian clinical practice guidelines for the diagnosis and management of Barrett’s esophagus and early esophageal adenocarcinoma. J Gastroenterol Hepatol 2015; 30: 804-820
  • 5 Codipilly DC, Chandar AK, Singh S. et al. The effect of endoscopic surveillance in patients with Barrett’s esophagus: a systematic review and meta-analysis. Gastroenterology 2018; 154: 2068-2086
  • 6 Thota PN, Lee H-J, Goldblum JR. et al. Risk stratification of patients with Barrett’s esophagus and low-grade dysplasia or indefinite for dysplasia. Clin Gastroenterol Hepatol 2015; 13: 459-465
  • 7 Parasa S, Vennalaganti S, Gaddam S. et al. Development and validation of a model to determine risk of progression of Barrett’s esophagus to neoplasia. Gastroenterology 2018; 154: 1282-1289
  • 8 Fels Elliott DR, Fitzgerald RC. Molecular markers for Barrett’s esophagus and its progression to cancer. Curr Opin Gastroenterol 2013; 29: 437-445
  • 9 Weaver JMJ, Ross-Innes CS, Shannon N. et al. Ordering of mutations in preinvasive disease stages of esophageal carcinogenesis. Nat Genet 2014; 46: 837-843
  • 10 Ljungström L, Pernestig A-K, Jacobsson G. et al. Diagnostic accuracy of procalcitonin, neutrophil-lymphocyte count ratio, C-reactive protein, and lactate in patients with suspected bacterial sepsis. PLoS One 2017; 12: e0181704
  • 11 de Jager CPC, van Wijk PTL, Mathoera RB. et al. Lymphocytopenia and neutrophil-lymphocyte count ratio predict bacteremia better than conventional infection markers in an emergency care unit. Crit Care 2010; 14: R192
  • 12 Mierke CT. The fundamental role of mechanical properties in the progression of cancer disease and inflammation. Rep Prog Phys 2014; 77: 076602
  • 13 Kidane D, Chae WJ, Czochor J. et al. Interplay between DNA repair and inflammation, and the link to cancer. Crit Rev Biochem Mol Biol 2014; 49: 116-139
  • 14 Grenader T, Waddell T, Peckitt C. et al. Prognostic value of neutrophil-to-lymphocyte ratio in advanced oesophago-gastric cancer: exploratory analysis of the REAL-2 trial. Ann Oncol 2016; 27: 687-692
  • 15 Pine JK, Morris E, Hutchins GG. et al. Systemic neutrophil-to-lymphocyte ratio in colorectal cancer: the relationship to patient survival, tumour biology and local lymphocytic response to tumour. Br J Cancer 2015; 113: 204-211
  • 16 Zhang X, Jiang Y, Wang Y. et al. Prognostic role of neutrophil-lymphocyte ratio in esophageal cancer: a systematic review and meta-analysis. Medicine (Baltimore) 2018; 97: e13585
  • 17 Huang Y, Sun Y, Peng P. et al. Prognostic and clinicopathologic significance of neutrophil-to-lymphocyte ratio in esophageal squamous cell carcinoma: evidence from a meta-analysis. Onco Targets Ther 2017; 10: 1165-1172
  • 18 Lavery DL, Martinez P, Gay LJ. et al. Evolution of oesophageal adenocarcinoma from metaplastic columnar epithelium without goblet cells in Barrett’s oesophagus. Gut 2016; 65: 907-913
  • 19 Montgomery E, Bronner MP, Goldblum JR. et al. Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation. Hum Pathol 2001; 32: 368-378
  • 20 Alvarez Herrero L, Curvers WL, van Vilsteren FGI. et al. Validation of the Prague C&M classification of Barrett’s esophagus in clinical practice. Endoscopy 2013; 45: 876-882
  • 21 Levine DS, Blount PL, Rudolph RE. et al. Safety of a systematic endoscopic biopsy protocol in patients with Barrett’s esophagus. Am J Gastroenterol 2000; 95: 1152-1157
  • 22 Qiao Y, Hyder A, Bae SJ. et al. Surveillance in patients with Barrett’s esophagus for early detection of esophageal adenocarcinoma: a systematic review and meta-analysis. Clin Transl Gastroenterol 2015; 6: e131
  • 23 Roberts KJ, Harper E, Alderson D. et al. Long-term survival and cost analysis of an annual Barrett’s surveillance programme. Eur J Gastroenterol Hepatol 2010; 22: 399-403
  • 24 Kuipers EJ, Spaander MC. Natural history of Barrett’s esophagus. Dig Dis Sci 2018; 63: 1997-2004
  • 25 Quante M, Graham TA, Jansen M. Insights into the pathophysiology of esophageal adenocarcinoma. Gastroenterology 2018; 154: 406-420
  • 26 Pirozzolo G, Gisbertz SS, Castoro C. et al. Neutrophil-to-lymphocyte ratio as prognostic marker in esophageal cancer: a systematic review and meta-analysis. J Thorac Dis 2019; 11: 3136-3145
  • 27 Nakamura K, Yoshida N, Baba Y. et al. Elevated preoperative neutrophil-to-lymphocytes ratio predicts poor prognosis after esophagectomy in T1 esophageal cancer. Int J Clin Oncol 2017; 22: 469-475
  • 28 Campos VJ, Mazzini GS, Juchem JF. et al. Neutrophil-lymphocyte ratio as a marker of progression from non-dysplastic Barrett’s esophagus to esophageal adenocarcinoma: a cross-sectional retrospective study. J Gastrointest Surg 2020; 24: 8-18