Gastric Cancer

, Volume 22, Issue 3, pp 632–639 | Cite as

The Cholegas trial: long-term results of prophylactic cholecystectomy during gastrectomy for cancer—a randomized-controlled trial

  • Lapo BenciniEmail author
  • Alberto Marchet
  • Sergio Alfieri
  • Fausto Rosa
  • Giuseppe Verlato
  • Daniele Marrelli
  • Franco Roviello
  • Fabio Pacelli
  • Luigi Cristadoro
  • Antonio Taddei
  • Marco Farsi
  • Italian Research Group for Gastric Cancer (GIRCG)
Original Article



The incidence of cholelithiasis has been shown to be higher for patients after gastrectomy than for the general population, due to vagal branch damage and gastrointestinal reconstruction. The aim of this trial was to evaluate the need for routine concomitant prophylactic cholecystectomy (PC) during gastrectomy for cancer.


A multicenter, randomized, controlled trial was conducted between November 2008 and March 2017. Of the total 130 included patients, 65 underwent PC and 65 underwent standard gastric surgery only for curable cancers. The primary endpoint was cholelithiasis-free survival after gastrectomy for gastric adenocarcinoma. Cholelithiasis was detected by ultrasound exam.


After a median follow-up of 62 months, eight patients (12.3%) in the control group developed biliary abnormalities (four cases of gallbladder calculi and four cases of biliary sludge), with only three (4.6%) being clinically relevant (two cholecystectomies needed, one acute pancreatitis). One patient in the PC group had asymptomatic biliary dilatation during sonography after surgery. The cholelithiasis-free survival did not show statistical significance between the two groups (P = 0.267). The number needed to treat with PC to avoid reoperation for cholelithiasis was 1:32.5.


Concomitant PC during gastric surgery for malignancies, although reducing the absolute number of biliary abnormalities, has no significant impact on the natural course of patients.


Prophylactic cholecystectomy Gastric surgery Gastric cancer 



Italian Research Group for Gastric Cancer (GIRCG): Other surgeons who participated in the study were Marco Bernini, MD, PhD (Surgical Oncology, Careggi University Hospital, Florence, Italy), Leonardo Gerard, MD (General Surgery, Ospedale Carlo Poma, Mantova, Italy), Renato Moretti (Surgical Oncology, Careggi University Hospital, Florence, Italy), Luca Cozzaglio, MD (Division of Surgical Oncology, Humanitas Hospital, Milan, Italy), Stefano Berardi, MD (Surgical Oncology Catholic University, Campobasso, Italy), and Paolo Bechi (General Surgery, Careggi University Hospital, Florence, Italy).


The native English-speaking translation was supported by the funds of the University of Florence, Italy.

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest to declare.

Ethical approval

A formal approval by the ethics committee of each participating center was obtained before the trial started recruitment.


  1. 1.
    Kobayashi T, Hisanaga M, Kanehiro H, et al. Analysis of risks factors for the development of gallstones after gastrectomy. Br J Surg. 2005;92:1399–403.CrossRefPubMedGoogle Scholar
  2. 2.
    Sakorafas GH, Milingos D, Peros G. Asymptomatic cholelithiasis: is cholecystectomy really needed? Dig Dis Sci. 2007;52:1313–25.CrossRefPubMedGoogle Scholar
  3. 3.
    Fukagawa T, Katai H, Saka M, et al. Gallstone formation after gastric cancer surgery. J Gastrointest Surg. 2009;13:886–9.CrossRefGoogle Scholar
  4. 4.
    Li VKM, Pulido N, Martinez-Suartez P, et al. Symptomatic gallstones after sleeve gastrectomy. Surg Endosc. 2009;23:2488–92.CrossRefPubMedGoogle Scholar
  5. 5.
    Liang TJ, Liu SI, Chen YC, et al. Analysis of gallstone disease after gastric cancer surgery. Gastric Cancer. 2017;20:895–903.CrossRefPubMedGoogle Scholar
  6. 6.
    Inoue K, Fuchigami A, Higashide S, et al. Gallbladder sludge and stone formation in relation to contractile function after gastrectomy. Ann Surg. 1992;215:19–26.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Qvist N. Review article: gall-bladder motility after intestinal surgery. Aliment Pharmacol Ther. 2000;14(s2):35–8.CrossRefPubMedGoogle Scholar
  8. 8.
    Wu CC, Chen CY, Wu TC, et al. Cholelithiasis and cholecystitis after gastrectomy for gastric carcinoma: a comparison of lymphadenectomy of varying extent. Hepatogastroenterology. 1995;42:867–72.PubMedGoogle Scholar
  9. 9.
    Tomita R, Tanjoh K, Fujisaki S. Total gastrectomy reconstructed by interposition of a jejunal J pouch with preservation of hepatic vagus branch and lower esophageal sphincter for T2 gastric cancer without lymph node metastasis. Hepatogastroenterology. 2004;51:1233–40.PubMedGoogle Scholar
  10. 10.
    Akatsu T, Yoshida M, Kubota T, et al. Gallstone disease after extended (D2) lymph node dissection for gastric cancer. World J Surg. 2005;29:182–6.CrossRefPubMedGoogle Scholar
  11. 11.
    Paik KH, Lee JC, Kim HW, et al. Risk factors for gallstone formation in resected gastric cancer patients. Medicine (Baltimore). 2016;95:e3157.CrossRefGoogle Scholar
  12. 12.
    Tyrväinen T, Nordback I, Toikka J, et al. Impaired gallbladder function in patients after total gastrectomy. Scand J Gastroenterol. 2017;52:334–7.CrossRefPubMedGoogle Scholar
  13. 13.
    Oh SJ, Choi WB, Song J, et al. Complications requiring reoperation after gastrectomy for gastric cancer: 17 years experience in a single institute. J Gastrointest Surg. 2009;13:239–45.CrossRefGoogle Scholar
  14. 14.
    Gillen S, Michalski CW, Schuster T, et al. Simultaneous/Incidental cholecystectomy during gastric/esophageal resection: systematic analysis of risks and benefits. World J Surg. 2010;34:1008–14.CrossRefPubMedGoogle Scholar
  15. 15.
    Liu XS, Zhang Q, Zhong J, et al. Acute cholecystitis immediately after radical gastrectomy: a report of three cases. World J Gastroenterol. 2010;16:2702–2074.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Oida T, Kano H, Mimatsu K, et al. Cholecystitis or cholestasis after total gastrectomy and esophagectomy. Hepatogastroenterology. 2012;59:1455–7.PubMedGoogle Scholar
  17. 17.
    Jayakrishnan TT, Groeschl RT, George B, et al. Review of the impact of antineoplastic therapies on the risk for cholelithiasis and acute cholecystitis. Ann Surg Oncol. 2014;21:240–7.CrossRefPubMedGoogle Scholar
  18. 18.
    Sasaki A, Nakajima J, Nitta H, et al. Laparoscopic cholecystectomy in patients with a history of gastrectomy. Surg Today. 2008;38:790–4.CrossRefPubMedGoogle Scholar
  19. 19.
    Fraser SA, Sigman H. Conversion in laparoscopic cholecystectomy after gastric resection: a 15-year review. Can J Surg. 2009;52:463–6.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Miftode SV, Troja A, El-Sourani N, et al. Simultaneous cholecystectomy during gastric and oesophageal resection: a retrospective analysis and critical review of literature. Int J Surg. 2014;12:1357–9.CrossRefPubMedGoogle Scholar
  21. 21.
    Juhasz EZ, Wolff BG, Meagher AP, et al. Incidental cholecystectomy during colorectal surgery. Ann Surg. 1994;219:467–74.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Wolff BG. Current status of incidental surgery. Dis Colon Rect. 1995;38:435–41.CrossRefGoogle Scholar
  23. 23.
    Watemberg S, Landau O, Avrahami R, et al. Incidental cholecystectomy in the over-70 age group. A 19-year retrospective, comparative study. Int Surg. 1997;82:102–4.PubMedGoogle Scholar
  24. 24.
    Murata A, Okamoto K, Muramatsu K, et al. Effects of additional laparoscopic cholecystectomy on outcomes of laparoscopic gastrectomy in patients with gastric cancer based on a national administrative database. J Surg Res. 2014;186:157–63.CrossRefPubMedGoogle Scholar
  25. 25.
    Kwon AH, Inui H, Imamura A, et al. Laparoscopic cholecystectomy and choledocholithotomy in patients with a previous gastrectomy. J Am Coll Surg. 2001;193:614–9.CrossRefPubMedGoogle Scholar
  26. 26.
    Joohyun K, Jeong NC, Sun HJ, et al. Multivariable analysis of cholecystectomy after gastrectomy: laparoscopy is a feasible initial approach even in the presence of common bile duct stones or acute cholecystitis. World J Surg. 2012;36:638–44.CrossRefGoogle Scholar
  27. 27.
    Lepage C, Sant M, Verdecchia A, et al. EUROCARE working group. Operative mortality after gastric cancer resection and long-term survival differences across Europe. Br J Surg. 2010;97:235–9.CrossRefPubMedGoogle Scholar
  28. 28.
    Marrelli D, Pedrazzani C, Morgagni P, et al. on behalf of the Italian Research Group for Gastric Cancer (GIRCG). Changing clinical and pathological features of gastric cancer over time. Br J Surg. 2011;98:1273–83.CrossRefPubMedGoogle Scholar
  29. 29.
    Farsi M, Bernini M, Bencini L, et al. GIRCG (Gruppo Italiano di Ricerca sul Cancro Gastrico). The CHOLEGAS study: multicentric randomized, blinded, controlled trial of gastrectomy plus prophylactic cholecystectomy versus gastrectomy only, in adults submitted to gastric cancer surgery with curative intent. Trials. 2009;15:10–32.Google Scholar
  30. 30.
    Bernini M, Bencini L, Sacchetti R, et al. Italian Research Group for Gastric Cancer (IRGGC). The Cholegas Study: safety of prophylactic cholecystectomy during gastrectomy for cancer: preliminary results of a multicentric randomized clinical trial. Gastric Cancer. 2013;16:370–6.CrossRefPubMedGoogle Scholar
  31. 31.
    Enzinger PC, Benedetti JK, Meyerhardt JA, et al. Impact of hospital volume on recurrence and survival after surgery for gastric cancer. Ann Surg. 2007;245:426–34.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Hartgrink HH, Jansen EP, van Grieken NC, et al. Gastric cancer. Lancet. 2009;374:477–90.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Kodera E, Fujiwara M, Ito Y, et al. Radical surgery for gastric carcinoma: it is not an issue of whether to perform D1 or D2. Dissect as many lymph nodes as possible and you will be rewarded. Acta Chir Belg. 2009;109:27–35.CrossRefPubMedGoogle Scholar
  34. 34.
    Shi Y, Zhou Y. The role of surgery in the treatment of gastric cancer. J Surg Oncol. 2010;101:687–92.CrossRefPubMedGoogle Scholar
  35. 35.
    Saka M, Morita S, Fukagawa T, et al. Present and future status of gastric cancer surgery. Jpn J Clin Oncol. 2011;41:307–13.CrossRefPubMedGoogle Scholar
  36. 36.
    Kimura J, Kunisaki C, Takagawa R, et al. Is routine prophylactic cholecystectomy necessary during gastrectomy for gastric cancer? World J Surg. 2017;41:1047–53.CrossRefPubMedGoogle Scholar
  37. 37.
    Verlato G, Marrelli D, Accordini S, et al. Short-term and long-term risk factors in gastric cancer. World J Gastroenterol. 2015;21:6434–43.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Abraham S, Rivero HG, Erlikh IV, et al. Surgical and nonsurgical management of gallstones. Am Fam Physician. 2014;89:795–802.PubMedGoogle Scholar
  39. 39.
    Karanicolas PJ, Graham D, Gönen M, et al. Quality of life after gastrectomy for adenocarcinoma: a prospective cohort study. Ann Surg. 2013;257:1039–46.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2018

Authors and Affiliations

  • Lapo Bencini
    • 1
    Email author
  • Alberto Marchet
    • 2
  • Sergio Alfieri
    • 3
  • Fausto Rosa
    • 3
  • Giuseppe Verlato
    • 4
  • Daniele Marrelli
    • 5
  • Franco Roviello
    • 5
  • Fabio Pacelli
    • 6
  • Luigi Cristadoro
    • 7
  • Antonio Taddei
    • 8
  • Marco Farsi
    • 1
  • Italian Research Group for Gastric Cancer (GIRCG)
  1. 1.Division of Oncologic Surgery and Robotics, Department of OncologyCareggi University HospitalFlorenceItaly
  2. 2.Department of SurgeryUniversity HospitalPaduaItaly
  3. 3.Digestive Surgery of University Hospital “A. Gemelli”RomeItaly
  4. 4.Unit of Epidemiology and Medical StatisticsUniversity of VeronaVeronaItaly
  5. 5.Department of SurgeryUniversity of SienaSienaItaly
  6. 6.Surgical Oncology Catholic UniversityCampobassoItaly
  7. 7.General Surgery“C. Poma” HospitalPieve di CorianoItaly
  8. 8.General SurgeryCareggi University HospitalFlorenceItaly

Personalised recommendations