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Incidence and Impact of Non-alcoholic Fatty Liver Disease (NAFLD) in Patients with Adenocarcinoma of the Esophagus Treated with Curative Intent

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Abstract

Background and Aims

Esophageal adenocarcinoma (EAC) is associated with visceral obesity (VO). Non-alcoholic fatty liver disease (NAFLD) is common within this phenotype; however, its incidence and clinical significance in EAC have not been studied.

Study design

A total of 559 patients with hepatic stetatosis (HS) defined by unenhanced CT were enrolled. In a sub-study, in 140 consecutive patients a liver biopsy was taken intraoperatively to study HS and non-alcoholic steatohepatitis (NASH). Postoperative complications were defined as per the Esophageal Complications Consensus Group (ECCG). Liver biochemistry was measured peri-operatively, with an ALT > 5 defined as acute liver injury (ALI). Mann–Whitney U test or Fisher’s exact test was utilized and the Kaplan–Meier method for survival.

Results

42% (n = 234/559) of patients had CT-defined HS. HS was associated with VO in 56% of cases, metabolic syndrome (Met S) in 37% and type 2 diabetes in 25%, compared with 44, 21, and 15% in non-HS patients (p < 0.01). Pathologic HS was present in 32% (45/140) and graded as mild, moderate, and severe in 73, 24, and 3%, respectively, with NASH reported in 16% and indefinite/borderline NASH in 42% of HS cases. Postoperative ALI was similar (p = 0.88) in both HS (10%) and non-HS cohorts (11%). Operative complication severity was similar in both cohorts. 5-yr survival was 53% (HS) vs 50% (p = 0.890).

Conclusion

This study establishes for the first time the incidence and clinical impact of NAFLD in EAC patients undergoing surgery and highlights no major impact on oncologic outcomes, nor in the severity of complications.

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References

  1. Coleman HG, Xie SH, Lagergren J (2018) The epidemiology of esophageal adenocarcinoma. Gastroenterology 154(2):390–405

    Article  Google Scholar 

  2. Kyrgiou M, Kalliala I, Markozannes G et al (2017) Adiposity and cancer at major anatomical sites: umbrella review of the literature. BMJ. 356:j477

    Article  Google Scholar 

  3. Lauby-Secretan B, Scoccianti C, Loomis D et al (2016) Body Fatness and Cancer-Viewpoint of the IARC Working Group. N Engl J Med 375(8):794–798

    Article  Google Scholar 

  4. Renehan AG, Tyson M, Egger M et al (2008) Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 371(9612):569–578

    Article  Google Scholar 

  5. Himbert C, Delphan M, Scherer D et al (2017) Signals from the adipose microenvironment and the obesity-cancer link-A systematic review. Cancer Prev Res (Phila) 10(9):494–506

    Article  CAS  Google Scholar 

  6. O’Sullivan J, Lysaght J, Donohoe CL et al (2018) Obesity and gastrointestinal cancer: the interrelationship of adipose and tumour microenvironments. Nat Rev Gastroenterol Hepatol 15(11):699–714

    Article  Google Scholar 

  7. Sheka AC, Adeyi O, Thompson J, Crawford PA, Ikramuddin S (2020) Nonalcohololic steatohepatitis. A review. JAMA 323:1175–1183

    Article  CAS  Google Scholar 

  8. Zm Younossi, Koenig AB, Abdelatif D, Fazel Y, Wymer M (2016) Global epidemiology of non-alcoholic fatty liver disease- metas-analytic assessment of prevalence, incidence and outcomes. Hepatology 64:73–84

    Google Scholar 

  9. Younossi A, Anstree QM, Marietti M et al (2018) Global burden of NAFLD and NASH; trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol 15:11–20

    Article  Google Scholar 

  10. Younossi ZM, Golabi P, de Avila L, Minhui Pail K et al (2019) The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: a systematic review and meta-analysis. J Hepatol 71:793–801

    Article  Google Scholar 

  11. Jarvis H, Craig S, Barker R, Spiers G et al (2020) Metabolic risk factors and incident advanced liver disease in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of population-based observational studies. PLoS Med 17:e10003100

    Article  Google Scholar 

  12. Chalasani N, Younossi Z, Lavine KE et al (2018) The diagnosis and management of non-alcoholic fatty liver disease: practice guidance from the American association for the study of liver diseases. Hepatology 67:328–357

    Article  Google Scholar 

  13. Lee DH (2017) Imaging evaluation of non-alcoholic fatty liver disease. Clin Mol Hepatol 23:290–301

    Article  Google Scholar 

  14. Byun J, Lee SS, Dung YTS, Shin Y et al (2019) CT indices for the diagnosis of hepatic steatosis using non-enhanced CT images: development and validation of diagnostic cut off values in a large cohort with pathologic reference standard. Eur Radiol 29:4427–4435

    Article  Google Scholar 

  15. Low DE, Kuppusamy MK, Alderson S, Cecconello I et al (2019) Benchmarking complications associated with esophagectomy. Ann SUrg 269:291–298

    Article  Google Scholar 

  16. Lenz A, Franklin GA, Cheadle WC (2007) Systemic inflammation after trauma. Injury 38:1336–1345

    Article  Google Scholar 

  17. Ssentongo P, Sssentongo AE, Dykes T, Pauli EM, Soybel DI (2018) Nonalcoholic fatty liver disease as a high-value predictor of postoperative hyperglycemic and its associated complication in major abdominal surgery. J Am Coll Surg 227:419–429

    Article  Google Scholar 

  18. Vincent JL, de Mendonca A, Cantraine F et al (1998) Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicentre, prospective study. working groups on “sepsis related problems” of the European society of intensive care medicine. Crit Care Med 26:1793–800

    Article  CAS  Google Scholar 

  19. van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP et al (2012) Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 366(22):2074–2084

    Article  Google Scholar 

  20. Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M et al (2006) Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 355(1):11–20

    Article  CAS  Google Scholar 

  21. Mourtzakis M, Prado CM, Lieffers JR, Reiman T, McCargar LJ, Baracos VE (2008) A practical and precise approach to quantification of body composition in cancer patients using computed tomography images acquired during routine care. Appl Physiol Nutr Metab 33(5):997–1006. https://doi.org/10.1139/H08-075

    Article  Google Scholar 

  22. Doyle SL, Bennett AM, Donohoe CL et al (2013) Establishing computed tomography-defined visceral fat area thresholds for use in obesity-related cancer research. Nutr Res 33(3):171–179

    Article  CAS  Google Scholar 

  23. Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, Yeh M, McCullough AJ, Sanyal AJ (2005) Nonalcoholic Steatohepatitis Clinical Research Network. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 1:1313–21. https://doi.org/10.1002/hep.20701 (PMID: 15915461)

    Article  Google Scholar 

  24. Juluri R, Vuppalanchi R, Olson J et al (2011) Generalizability of the nonalcoholic steatohepatitis Clinical Research Network histologic scoring system for nonalcoholic fatty liver disease. J Clin Gastroenterol 45(1):55–58. https://doi.org/10.1097/MCG.0b013e3181dd1348

    Article  Google Scholar 

  25. Low DE, Alderson D, Cecconello I et al (2015) International consensus on standardization of data collection for complications associated with esophagectomy: esophagectomy complications consensus group (ECCG). Ann Surg 262(2):286–294

    Article  Google Scholar 

  26. Dindo D, Demartines N, Clavien PA (2004) Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240(2):205–213

    Article  Google Scholar 

  27. Slankamenac K, Graf R, Barkun J et al (2013) The comprehensive complication index: a novel continuous scale to measure surgical morbidity. Ann Surg 258(1):1–7

    Article  Google Scholar 

  28. Grundy SM, Cleeman JI, Daniels SR et al. (2005) Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement [published correction appears in Circulation. 2005 Oct 25;112(17):e297] [published correction appears in Circulation. 2005 Oct 25;112(17):e298]. Circulation. 2005;112(17):2735–2752.

  29. Mengardo V, Pucetti F, Mc Cormack O, Chaudry A, Allum WH (2018) The impact of obesity on esophagectomy: a meta-analysis. Dis Esophagus. https://doi.org/10.1093/dote/dox149

    Article  Google Scholar 

  30. Elliott JA, Donlon NE, Beddy P, Donohoe CL et al (2022) Visceral obesity with an without metabolic syndrome: incidnce and clinical impact in esophageal adenocarcinoma treated with curative intent. Dis Esophagus. https://doi.org/10.1093/dote/doab094

    Article  Google Scholar 

  31. Dutta S, Fullarton GM, Forshaw MJ, Horgan PG et al (2011) Peristent elevation of C-reactive protein following esophagogastric cancer resection as a predictor of postoperative surgical site infections complications. World J Surg 35:1017–1025

    Article  Google Scholar 

  32. Labgaa I, Mantziari S, Genety M, Elliott JA et al (2020) Early postoperative decrease of albumin is an independent predictor of major complications after oncological esophagectomy: a multicenter study. J Surg Oncol. https://doi.org/10.1002/jso.26317

    Article  Google Scholar 

  33. Lopez-Delgado JC, Ballus J, Esteve F, Beatncur-Zambrano NL et al (2016) Outcomes of abdominal surgery in liver cirrhosis. World J Gastroenterol 22:2657–2667

    Article  CAS  Google Scholar 

  34. Asti E, Sozzi M, Bonitta G, Bernardi D, Bonavina L (2018) Esophagectomy in patients with liver cirrhosis: a systematic review and Bayesian meta-analysis. J Visceral Surg. https://doi.org/10.1016/j.vissrug.2018.03.014

    Article  Google Scholar 

  35. Kaffarnik M, Stoeger G, Liebich J et al (2018) Liver function, quantified by limax, after major abdominal surgery. comparison between open and laparoscopic approach. World J Surg 42:557–66

    Article  Google Scholar 

  36. Jeong GA, Cho GS, Shin EJ et al (2011) Liver function alterations after laparoscopy-assisted gastrectomy for gastric cancer and its clinical significance. World J Gastroenterol 17:372–378

    Article  Google Scholar 

  37. European Association for the Study of the Liver; European Association for the Study of Diabetes; European Association for the Study of Obesity. EASL-EASD-EASO clinical practice guidelines for the management of non-alcoholic fatty liver disease. Obesity Facts 2016; 9:65–90

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Authors and Affiliations

  1. Department of Surgery, Trinity College Dublin, and the Trinity St. James’s Cancer Institute Dublin, Dublin, Ireland

    John V. Reynolds, Noel E. Donlon, Jessie A. Elliott, Brendan Moran, Hugo Temperley, Tim S. Nugent, Maria Davern, Sinead King, Melissa Conroy, Joanne Lysaght, Narayanasamy Ravi & Clare L. Donohoe

  2. Department of Pathology, St. James’s Hospital and Trinity College Dublin, Dublin, Ireland

    Carmel Ryan & Stephen Finn

  3. Hepatology Department, Department of Medicine, St. James’s Hospital and Trinity College Dublin, Dublin, Ireland

    Suzanne Norris

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  1. John V. Reynolds
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Correspondence to John V. Reynolds.

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Reynolds, J.V., Donlon, N.E., Elliott, J.A. et al. Incidence and Impact of Non-alcoholic Fatty Liver Disease (NAFLD) in Patients with Adenocarcinoma of the Esophagus Treated with Curative Intent. World J Surg 47, 227–235 (2023). https://doi.org/10.1007/s00268-022-06781-w

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