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Detection of digestive malignancies and post-gastrectomy complications via gastrointestinal fluid examination

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Abstract

To date, gastric carcinoma (GC) is one of the common and fatal digestive malignancies worldwide. The prognosis of GC is not always satisfactory because of late diagnosis. Scholars are keen on discovering novel accurate and economical biomarkers in body liquids for GC screening to detect and evaluate the lesion before the results of imaging techniques are obtained. While traditional serum assays have limited sensitivity and specificity, gastrointestinal juice may provide relevant specific biomarkers because of its close contact with the tumor. Herein, the current progress in the relationship between gastrointestinal fluid analyses and GC is systematically and comprehensively reviewed. The detection of gastric juice pH, fluorescence spectrum, cytology, Helicobacter pylori-associated markers, nitrosamines, conventional tumor markers, amino acids, proteomics, microRNAs, long noncoding RNAs, protein-coding genes, vitamin C, etc., and combination tests of different category markers could provide important diagnostic and prognostic clues for gastrointestinal diseases. Particularly, early GC may be efficiently screened using gastric juice. Gastrointestinal fluid examination could also predict the adverse effects of postgastrectomy, such as pancreatic leakage, fistula, and abscess. Gastric fluid markers should be further studied to reveal the early predicators of malignancy and complications. The methods for obtaining the samples of gastrointestinal juice with minimum incision should also be comprehensively investigated.

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References

  1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015; 65(2): 87–108

    Article  PubMed  Google Scholar 

  2. Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin 2016; 66(2): 115–132

    Article  PubMed  Google Scholar 

  3. Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, Safran H, dos Santos LV, Aprile G, Ferry DR, Melichar B, Tehfe M, Topuzov E, Zalcberg JR, Chau I, Campbell W, Sivanandan C, Pikiel J, Koshiji M, Hsu Y, Liepa AM, Gao L, Schwartz JD, Tabernero J; REGARD Trial Investigators. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 2014; 383(9911): 31–39

    Article  PubMed  CAS  Google Scholar 

  4. Xu AM, Huang L, Liu W, Gao S, Han WX, Wei ZJ. Neoadjuvant chemotherapy followed by surgery versus surgery alone for gastric carcinoma: systematic review and meta-analysis of randomized controlled trials. PLoS ONE 2014; 9(1): e86941

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Xu AM, Huang L, Zhu L, Wei ZJ. Significance of peripheral neutrophil-lymphocyte ratio among gastric cancer patients and construction of a treatment-predictive model: a study based on 1131 cases. Am J Cancer Res 2014; 4(2): 189–195

    PubMed  PubMed Central  Google Scholar 

  6. Jung JJ, Noh S, Jeung HC, Jung M, Kim TS, Noh SH, Roh JK, Chung HC, Rha SY. Chemokine growth-regulated oncogene 1 as a putative biomarker for gastric cancer progression. Cancer Sci 2010; 101(10): 2200–2206

    Article  PubMed  CAS  Google Scholar 

  7. Huang L, Xu AM, Li TJ, Han WX, Xu J. Should peri-gastrectomy gastric acidity be our focus among gastric cancer patients? World J Gastroenterol 2014; 20(22): 6981–6988

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Wu W, Chung MC. The gastric fluid proteome as a potential source of gastric cancer biomarkers. J Proteomics 2013; 90: 3–13

    Article  PubMed  CAS  Google Scholar 

  9. Lu PJ, Hsu PI, Chen CH, Hsiao M, Chang WC, Tseng HH, Lin KH, Chuah SK, Chen HC. Gastric juice acidity in upper gastrointestinal diseases. World J Gastroenterol 2010; 16(43): 5496–5501

    Article  PubMed  PubMed Central  Google Scholar 

  10. Shiotani A, Iishi H, Uedo N, Higashino K, Kumamoto M, Nakae Y, Tatsuta M. Hypoacidity combined with high gastric juice nitrite induced by Helicobacter pylori infection is associated with gastric cancer. Aliment Pharmacol Ther 2004; 20(Suppl 1):48–53

    Article  PubMed  CAS  Google Scholar 

  11. Sanduleanu S, Jonkers D, De Bruine A, Hameeteman W, Stockbrügger RW. Non-Helicobacter pylori bacterial flora during acidsuppressive therapy: differential findings in gastric juice and gastric mucosa. Aliment Pharmacol Ther 2001; 15(3): 379–388

    Article  PubMed  CAS  Google Scholar 

  12. Zhou LY, Lin SR, Li Y, Geng QM, Ding SG, Meng LM, Sun XN, Wang JT, Xu ZJ, Guo HL, Li CG, Cui RL. The intrinsic fluorescence spectrum of dilute gastric juice as a novel diagnostic tool for gastric cancer. J Dig Dis 2011; 12(4): 279–285

    Article  PubMed  Google Scholar 

  13. Deng K, Zhou LY, Lin SR, Li Y, Chen M, Geng QM, Li YW. A novel approach for the detection of early gastric cancer: fluorescence spectroscopy of gastric juice. J Dig Dis 2013; 14(6): 299–304

    Article  PubMed  CAS  Google Scholar 

  14. Levy MJ, Gleeson FC, Campion MB, Caudill JL, Clain JE, Halling K, Rajan E, Topazian MD, Wang KK, Wiersema MJ, Clayton A. Prospective cytological assessment of gastrointestinal luminal fluid acquired during EUS: a potential source of false-positive FNA and needle tract seeding. Am J Gastroenterol 2010; 105(6): 1311–1318

    Article  PubMed  Google Scholar 

  15. Kawamura O, Murakami M, Araki O, Yamada T, Tomizawa S, Shimoyama Y, Minashi K, Maeda M, Kusano M, Mori M. Relationship between gastric disease and deletion of cag pathogenicity island genes of Helicobacter pylori in gastric juice. Dig Dis Sci 2003; 48(1): 47–53

    Article  PubMed  CAS  Google Scholar 

  16. Tucci A, Bisceglia M, Rugge M, Tucci P, Marchegiani A, Papadopoli G, Spada A, Villani A, Pennelli G, Fusaroli P, Caravelli G, Catalano T, Cennamo V, Cianci M, De Fanis C, Fabbri C, Feliciangeli G, Gizzi G, Spadaccini A, Caletti G. Clinical usefulness of gastric-juice analysis in 2007: the stone that the builders rejected has become the cornerstone. Gastrointest Endosc 2007; 66(5): 881–890

    Article  PubMed  Google Scholar 

  17. Radziejewska I, Borzym-Kluczyk M, Kisiel DG, Namiot Z, Wosek J, Gindzienski A. The effect of Helicobacter pylori eradication treatment on the MUC 1 and Lewis antigens level in human gastric juice: a preliminary study. Dig Dis Sci 2008; 53(10): 2641–2645

    Article  PubMed  Google Scholar 

  18. Radziejewska I, Borzym-Kluczyk M, Kisiel DG, Namiot Z, Gindzienski A. The influence of Helicobacter pylori patients’ treatment on MUC 1 content in gastric juice. Hepatogastroenterology 2008; 55(86-87): 1887–1889

    PubMed  CAS  Google Scholar 

  19. Hayakawa T, Kaneko H, Konagaya T, Shinozaki K, Kasahara A, Funaki Y, Mori S, Yokoi T, Hirooka Y, Kusugami K, Kakumu S. Enhanced somatostatin secretion into the gastric juice with recovery of basal acid output after Helicobacter pylori eradication in gastric ulcers. J Gastroenterol Hepatol 2003; 18(5): 505–511

    Article  PubMed  CAS  Google Scholar 

  20. Nishibayashi H, Kanayama S, Kiyohara T, Yamamoto K, Miyazaki Y, Yasunaga Y, Shinomura Y, Takeshita T, Takeuchi T, Morimoto K, Matsuzawa Y. Helicobacter pylori-induced enlarged-fold gastritis is associated with increased mutagenicity of gastric juice, increased oxidative DNA damage, and an increased risk of gastric carcinoma. J Gastroenterol Hepatol 2003; 18(12): 1384–1391

    Article  PubMed  Google Scholar 

  21. Akyuz M, Ata S and Dinc E.A chemometric optimization of method for determination of nitrosamines in gastric juices by GC-MS. J Pharm Biomed Anal 2016; 117: 26–36

  22. Duraker N, Naci Celik A, Gençler N. The prognostic significance of gastric juice CA 19-9 and CEA levels in gastric carcinoma patients. Eur J Surg Oncol 2002; 28(8): 844–849

    Article  PubMed  CAS  Google Scholar 

  23. Bazuro GE, Ferrario F, Dezi A, Ciaco A, Koch M, Capurso L. CEA in gastric juice and chronic atrophic gastritis: a prospective evaluation. J Clin Gastroenterol 1993; 16(2): 179–180

    Article  PubMed  CAS  Google Scholar 

  24. Muretto P, Graziano F, Staccioli MP, Barbanti I, Bartolucci A, Paolini G, Giordano D, Testa E, De Gaetano A. An endogastric capsule for measuring tumor markers in gastric juice: an evaluation of the safety and efficacy of a new diagnostic tool. Ann Oncol 2003; 14(1): 105–109

    Article  PubMed  CAS  Google Scholar 

  25. Xu AM, Huang L, Han WX, Wei ZJ. Monitoring of peri-distal gastrectomy carbohydrate antigen 19-9 level in gastric juice and its significance. Int J Clin Exp Med 2014; 7(1): 230–238

    PubMed  PubMed Central  Google Scholar 

  26. Huang L, Xu A, Li T, Han W, Wu S, Wang Y. Detection of perioperative cancer antigen 72-4 in gastric juice pre- and post-distal gastrectomy and its significances. Med Oncol 2013; 30(3): 651

    Article  PubMed  CAS  Google Scholar 

  27. Nagata Y, Sato T, Enomoto N, Ishii Y, Sasaki K, Yamada T. High concentrations of D-amino acids in human gastric juice. Amino Acids 2007; 32(1): 137–140

    Article  PubMed  CAS  Google Scholar 

  28. Deng K, Lin S, Zhou L, Li Y, Chen M, Wang Y, Li Y. High levels of aromatic amino acids in gastric juice during the early stages of gastric cancer progression. PLoS ONE 2012; 7(11): e49434

  29. Lian W, Ma DJ, Xu X, Chen Y, Wu YL. Rapid high-performance liquid chromatography method for determination of tryptophan in gastric juice. J Dig Dis 2012; 13(2): 100–106

    Article  PubMed  CAS  Google Scholar 

  30. Hsu PI, Chen CH, Hsieh CS, Chang WC, Lai KH, Lo GH, Hsu PN, Tsay FW, Chen YS, Hsiao M, Chen HC, Lu PJ. a1-Antitrypsin precursor in gastric juice is a novel biomarker for gastric cancer and ulcer. Clin Cancer Res 2007; 13(3): 876–883

    Article  PubMed  CAS  Google Scholar 

  31. Hsu PI, Chen CH, Hsiao M, Wu DC, Lin CY, Lai KH, Lu PJ. Diagnosis of gastric malignancy using gastric juice a1-antitrypsin. Cancer Epidemiol Biomarkers Prev 2010; 19(2): 405–411

    Article  PubMed  CAS  Google Scholar 

  32. Lee K, Kye M, Jang JS, Lee OJ, Kim T, Lim D. Proteomic analysis revealed a strong association of a high level of a1-antitrypsin in gastric juice with gastric cancer. Proteomics 2004; 4(11): 3343–3352

    Article  PubMed  CAS  Google Scholar 

  33. Kam SY, Hennessy T, Chua SC, Gan CS, Philp R, Hon KK, Lai L, Chan WH, Ong HS, Wong WK, Lim KH, Ling KL, Tan HS, Tan MM, Ho M, Kon OL. Characterization of the human gastric fluid proteome reveals distinct pH-dependent protein profiles: implications for biomarker studies. J Proteome Res 2011; 10(10): 4535–4546

    Article  PubMed  CAS  Google Scholar 

  34. Paulo JA, Lee LS, Wu B, Repas K, Banks PA, Conwell DL, Steen H. Proteomic analysis of endoscopically (endoscopic pancreatic function test) collected gastroduodenal fluid using in-gel tryptic digestion followed by LC-MS/MS. Proteomics Clin Appl 2010; 4(8-9): 715–725

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Kon OL, Yip TT, Ho MF, Chan WH, Wong WK, Tan SY, Ng WH, Kam SY, Eng A, Ho P, Viner R, Ong HS, Kumarasinghe MP. The distinctive gastric fluid proteome in gastric cancer reveals a multibiomarker diagnostic profile. BMC Med Genomics 2008; 1:54

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Chang WC, Hsu PI, Chen YY, Hsiao M, Lu PJ, Chen CH. Observation of peptide differences between cancer and control in gastric juice. Proteomics Clin Appl 2008; 2(1): 55–62

    Article  PubMed  CAS  Google Scholar 

  37. Cui L, Zhang X, Ye G, Zheng T, Song H, Deng H, Xiao B, Xia T, Yu X, Le Y, Guo J. Gastric juice microRNAs as potential biomarkers for the screening of gastric cancer. Cancer 2013; 119(9): 1618–1626

    Article  PubMed  CAS  Google Scholar 

  38. Yu X, Luo L, Wu Y, Yu X, Liu Y, Yu X, Zhao X, Zhang X, Cui L, Ye G, Le Y, Guo J. Gastric juice miR-129 as a potential biomarker for screening gastric cancer. Med Oncol 2013; 30(1): 365

    Article  PubMed  CAS  Google Scholar 

  39. Zhang X, Cui L, Ye G, Zheng T, Song H, Xia T, Yu X, Xiao B, Le Y, Guo J. Gastric juice microRNA-421 is a new biomarker for screening gastric cancer. Tumour Biol 2012; 33(6): 2349–2355

    Article  PubMed  CAS  Google Scholar 

  40. Shao Y, Ye M, Jiang X, Sun W, Ding X, Liu Z, Ye G, Zhang X, Xiao B, Guo J. Gastric juice long noncoding RNA used as a tumor marker for screening gastric cancer. Cancer 2014; 120(21): 3320–3328

    Article  PubMed  CAS  Google Scholar 

  41. Yang Y, Shao Y, Zhu M, Li Q, Yang F, Lu X, Xu C, Xiao B, Sun Y, Guo J. Using gastric juice lncRNA-ABHD11-AS1 as a novel type of biomarker in the screening of gastric cancer. Tumour Biol 2016; 37(1): 1183–1188

    Article  PubMed  CAS  Google Scholar 

  42. Dabrowska-Ufniarz E, Dzieniszewski J, Jarosz M, Wartanowicz M. Vitamin C concentration in gastric juice in patients with precancerous lesions of the stomach and gastric cancer. Med Sci Monit 2002; 8(2): CR96–CR103

    PubMed  CAS  Google Scholar 

  43. Kodama K, Sumii K, Kawano M, Kido T, Nojima K, Sumii M, Haruma K, Yoshihara M, Chayama K. Gastric juice nitrite and vitamin C in patients with gastric cancer and atrophic gastritis: is low acidity solely responsible for cancer risk? Eur J Gastroenterol Hepatol 2003; 15(9): 987–993

    Article  PubMed  CAS  Google Scholar 

  44. Wong SC, Yu H, So JB. Detection of telomerase activity in gastric lavage fluid: a novel method to detect gastric cancer. J Surg Res 2006; 131(2): 252–255

    Article  PubMed  CAS  Google Scholar 

  45. Muretto P, Ruzzo A, Pizzagalli F, Graziano F, Maltese P, Zingaretti C, Berselli E, Donnarumma N, Magnani M. Endogastric capsule for E-cadherin gene (CDH1) promoter hypermethylation assessment in DNA from gastric juice of diffuse gastric cancer patients. Ann Oncol 2008; 19(3): 516–519

    Article  PubMed  CAS  Google Scholar 

  46. Chae HD, Kim IH, Lee GH, Shin IH, Suh HS, Jeon CH. Gastric cancer detection using gastric juice pepsinogen and melanomaassociated gene RNA. Am J Clin Pathol 2013; 140(2): 209–214

    Article  PubMed  Google Scholar 

  47. Ruan HL, Hong RT, Xie HJ, Hu NZ, Xu JM, Zhang W. Significance of elevated levels of collagen type IV and hyaluronic acid in gastric juice and serum in gastric cancer and precancerous lesion. Dig Dis Sci 2011; 56(7): 2001–2008

    Article  PubMed  CAS  Google Scholar 

  48. Dias A, Garcia C, Majewski M, Wallner G, McCallum RW, Poplawski C, Sarosiek J. Gastric juice prostaglandins and peptide growth factors as potential markers of chronic atrophic gastritis, intestinal metaplasia and gastric cancer: their potential clinical implications based on this pilot study. Dig Dis Sci 2011; 56(11): 3220–3225

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Mehmet N, Refik M, Harputluoglu M, Ersoy Y, Aydin NE, Yildirim B. Serum and gastric fluid levels of cytokines and nitrates in gastric diseases infected with Helicobacter pylori. New Microbiol 2004; 27(2): 139–148

    PubMed  CAS  Google Scholar 

  50. Seo KW, Yoon KY, Lee SH, Shin YM, Choi KH, Hwang HY. Amylase, lipase, and volume of drainage fluid in gastrectomy for the early detection of complications caused by pancreatic leakage. J Korean Surg Soc 2011; 81(6): 402–407

    Article  PubMed  PubMed Central  Google Scholar 

  51. De Sol A, Cirocchi R, Di Patrizi MS, Boccolini A, Barillaro I, Cacurri A, Grassi V, Corsi A, Renzi C, Giuliani D, Coccetta M, Avenia N. The measurement of amylase in drain fluid for the detection of pancreatic fistula after gastric cancer surgery: an interim analysis. World J Surg Oncol 2015; 13:65

    Article  PubMed  PubMed Central  Google Scholar 

  52. Tomimaru Y, Miyashiro I, Kishi K, Motoori M, Yano M, Shingai T, Noura S, Ohue M, Ohigashi H, Ishikawa O. Is routine measurement of amylase concentration in drainage fluid necessary after total gastrectomy for gastric cancer? J Surg Oncol 2011; 104(3): 274–277

    Article  PubMed  CAS  Google Scholar 

  53. Iwata N, Kodera Y, Eguchi T, Ohashi N, Nakayama G, Koike M, Fujiwara M, Nakao A. Amylase concentration of the drainage fluid as a risk factor for intra-abdominal abscess following gastrectomy for gastric cancer. World J Surg 2010; 34(7): 1534–1539

    Article  PubMed  Google Scholar 

  54. Migita K, Takayama T, Matsumoto S, Wakatsuki K, Tanaka T, Ito M, Nakajima Y. Impact of bacterial culture positivity of the drainage fluid during the early postoperative period on the development of intra-abdominal abscesses after gastrectomy. Surg Today 2014; 44(11): 2138–2145

    Article  PubMed  Google Scholar 

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Acknowledgements

We sincerely want to thank the reviewers for the constructive comments and suggestions. This paper is supported by the National Natural Science Foundation of China (No. 81572350). The funder did not take part in the design, data collection, and analysis of the study and the preparation and publication of the manuscript.

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Correspondence to Lei Huang.

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Huang, L., Xu, A. Detection of digestive malignancies and post-gastrectomy complications via gastrointestinal fluid examination. Front. Med. 11, 20–31 (2017). https://doi.org/10.1007/s11684-016-0493-4

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