Natural history of gallstone disease: Expectant management or active treatment? Results from a population-based cohort study
Corresponding Author
Davide Festi
Department of Clinical Medicine, University of Bologna, Bologna, Italy and
Professor Davide Festi, Dipartimento di Medicina Clinica, Policlinico S.Orsola-Malpighi, Via Massarenti 9, 40138 Bologna, Italy. Email: [email protected]Search for more papers by this authorMaria Letizia Bacchi Reggiani
Department of Cardiovascular Diseases, University of Bologna, Bologna, Italy,
Search for more papers by this authorAdolfo F. Attili
Department of Gastroenterology, University ‘La Sapienza’, Rome, Italy,
Search for more papers by this authorPaola Loria
Department of Internal Medicine, University of Modena, Modena, Italy,
Search for more papers by this authorPaolo Pazzi
Department of Internal Medicine, University of Ferrara, Ferrara, Italy,
Search for more papers by this authorEleonora Scaioli
Department of Clinical Medicine, University of Bologna, Bologna, Italy and
Search for more papers by this authorSimona Capodicasa
Department of Medicine and Aging, University of Chieti, Chieti, Italy
Search for more papers by this authorFerdinando Romano
Department of Medicine and Aging, University of Chieti, Chieti, Italy
Search for more papers by this authorEnrico Roda
Department of Clinical Medicine, University of Bologna, Bologna, Italy and
Search for more papers by this authorAntonio Colecchia
Department of Clinical Medicine, University of Bologna, Bologna, Italy and
Search for more papers by this authorCorresponding Author
Davide Festi
Department of Clinical Medicine, University of Bologna, Bologna, Italy and
Professor Davide Festi, Dipartimento di Medicina Clinica, Policlinico S.Orsola-Malpighi, Via Massarenti 9, 40138 Bologna, Italy. Email: [email protected]Search for more papers by this authorMaria Letizia Bacchi Reggiani
Department of Cardiovascular Diseases, University of Bologna, Bologna, Italy,
Search for more papers by this authorAdolfo F. Attili
Department of Gastroenterology, University ‘La Sapienza’, Rome, Italy,
Search for more papers by this authorPaola Loria
Department of Internal Medicine, University of Modena, Modena, Italy,
Search for more papers by this authorPaolo Pazzi
Department of Internal Medicine, University of Ferrara, Ferrara, Italy,
Search for more papers by this authorEleonora Scaioli
Department of Clinical Medicine, University of Bologna, Bologna, Italy and
Search for more papers by this authorSimona Capodicasa
Department of Medicine and Aging, University of Chieti, Chieti, Italy
Search for more papers by this authorFerdinando Romano
Department of Medicine and Aging, University of Chieti, Chieti, Italy
Search for more papers by this authorEnrico Roda
Department of Clinical Medicine, University of Bologna, Bologna, Italy and
Search for more papers by this authorAntonio Colecchia
Department of Clinical Medicine, University of Bologna, Bologna, Italy and
Search for more papers by this authorAbstract
Background and Aims: The knowledge of natural history is essential for disease management. We evaluated the natural history (e.g. frequency and characteristics of symptoms and clinical outcome) of gallstones (GS) in a population-based cohort study.
Methods: A total of 11 229 subjects (6610 men, 4619 women, age-range: 29–69 years, mean age: 48 years) were studied. At ultrasonography, GS were present in 856 subjects (338 men, 455 women) (7.1%). GS were followed by means of a questionnaire inquiring about the characteristics of specific biliary symptoms.
Results: At enrolment, 580 (73.1%) patients were asymptomatic, 94 (11.8%) had mild symptoms and 119 (15.1%) had severe symptoms. GS patients were followed up for a mean period of 8.7 years; 63 subjects (7.3%) were lost to follow up. At the end of the follow up, of the asymptomatic subjects, 453 (78.1%) remained asymptomatic; 61 (10.5%) developed mild symptoms and 66 (11.4%) developed severe symptoms. In subjects with mild symptoms, the symptoms disappeared in 55 (58.5%), became severe in 23 (24.5%), remained stable in 16 (17%); in subjects with severe symptoms, the symptoms disappeared in 62 (52.1%), became mild in 20 (16.8%) and remained stable in 37 (31.1%). A total of 189 cholecystectomies were performed: 41.3% on asymptomatic patients, 17.4% on patients with mild symptoms and 41.3% on patients with severe symptoms.
Conclusions: This study indicates that: (i) asymptomatic and symptomatic GS patients have a benign natural history; (ii) the majority of GS patients with severe or mild symptoms will no longer experience biliary pain; and (iii) a significant proportion of cholecystectomies are performed in asymptomatic patients. Expectant management still represents a valid therapeutic approach in the majority of patients.
References
- 1 Shaffer EA. Gallstone disease: epidemiology of gallbladder stone disease. Best. Pract. Res. Clin. Gastroenterol. 2006; 20: 981–96.
- 2 Portincasa P, Moschetta A, Palasciano G. Cholesterol gallstone disease. Lancet 2006; 368: 230–9.
- 3 Sandler RS, Everhart JE, Donowitz M et al. The burden of selected digestive diseases in the United States. Gastroenterology 2002; 122: 1500–11.
- 4 Aerts R, Penninckz F. The burden of gallstone disease in Europe. Aliment. Pharmacol. Ther. 2003; 18 (Suppl. 3): 49–53.
- 5 Kim WR, Brown RS, Terrault NA, El-Serag H. Burden of liver disease in the United States: summary of a workshop. Hepatology 2002; 36: 227–42.
- 6 Kang JY, Ellis C, Majeed A et al. Gallstones- an increasing problem: a study of hospital admissions in England between 1989/1990 and 1999/2000. Aliment. Pharmacol. Ther. 2003; 17: 561–9.
- 7 American College of Physicians. Guidelines for the treatment of gallstones. Ann. Intern. Med. 1993; 119: 620–2.
- 8 Roda E, Festi D, Lezoche E, Leuschner U, Paugartner G, Sauerbruch T. Strategies in the treatment of biliary stones. Gastroenterol. Int. 2000; 13: 7–15.
- 9 National Institutes of Health Consensus Development Conference Statement on gallstones and laparoscopic cholecystectomy. Am. J. Surg. 1993; 165: 390–8.
- 10 Keus F, De Jong JA, Gooszen HG, Van Laarhoven CJ. Laparoscopic versus open cholecystectomy for patients with symptomatic cholecystolithiasis. Cochrane Database Syst. Rev. 2006; (4): CD006231.
- 11 Legorreta AP, Silber JH, Costantino GN, Kobylinski RW, Zatz SL. Increased cholecystectomy rate after the introduction of laparoscopic cholecystectomy. JAMA 1993; 270: 1429–32.
- 12 Lam CM, Murray FE, Cuschieri A. Increased cholecystectomy rate after the introduction of laparoscopic cholecystectomy in Scotland. Gut 1996; 38: 282–4.
- 13 Wagh MS, Thompson CC. Surgery insight: natural orifice transluminal endoscopic surgery: an analysis of work to date. Nat. Clin. Pract. Gastroenterol. Hepatol. 2007; 4: 386–92.
- 14 Sondenaa K, Nesvik I, Solhaug JH, Soreide O. Randomization to surgery or observation in patients with symptomatic gallbladder stone disease. The problem of evidence-based medicine in clinical practice. Scand. J. Gastroenterol. 1997; 32: 611–16.
- 15 Friedman GD. Natural history of asymptomatic and symptomatic gallstones. Am. J. Surg. 1993; 165: 399–404.
- 16 Brugge WR. The silent gallstone. In: NH Afdhal, ed. Gallbladder and Biliary Tract Diseases. New York: Marcel Dekker, Inc, 2000; 447–54.
- 17
Attili AF,
Carulli N,
Roda E et al.
Epidemiology of gallstone disease in Italy: prevalence data of the Multicenter Italian Study on Cholelithiasis (MICOL).
Am. J. Epidemiol.
1995; 15: 158–65.
10.1093/oxfordjournals.aje.a117403 Google Scholar
- 18 Festi D, Dormi A, Capodicasa S et al. Incidence of gallstone disease in Italy: results from a multicenter, population-based Italian study (the MICOL project). World. J. Gastroenterol. 2008; 14: 5282–9.
- 19 Festi D, Sottili S, Colecchia A et al. Clinical manifestations of gallstone disease: evidence from the Multicenter Italian Study on Cholelithiasis (MICOL). Hepatology 1999; 30: 839–46.
- 20 Leopold GR, Amberg J, Gosink BB, Mittelstaedt C. Gray scale ultrasonic cholecystography: a comparison with conventional radiographic techniques. Radiology 1976; 121: 445–8.
- 21 Cucchiaro G, Rossitch JC, Bowie J et al. Clinical significance of ultrasonographically detected coincidental gallstones. Dig. Dis. Sci. 1990; 35: 417–21.
- 22 Keulemans YC, Venneman NG, Gouma DJ, Van Berge Henegouwen GP. New strategies for the treatment of gallstone disease. Scand. J. Gastroenterol. 2002; 236 (Suppl.): 87–90.
- 23 Lammert F, Miguel JF. Gallstone disease: from genes to evidence-based therapy. J. Hepatol. 2008; 48 (Suppl.): S124–35.
- 24 Mouret P. Celioscopic surgery. Evolution or revolution? Chirurgie 1990; 116: 829–32. (In French.)
- 25 Berggren U, Gordh T, Grama D, Haglund U, Rastad J, Arvidsson D. Laparoscopic versus open cholecystectomy: hospitalization, sick leave, analgesia, and trauma responses. Br. J. Surg. 1994; 81: 1362–5.
- 26 Gurusamy KS, Samraj K. Cholecystectomy versus no cholecystectomy in patients with silent gallstones. Cochrane Database Syst. Rev. 2007; (1): CD006230.
- 27 Schwesinger WH, Diehl AK. Changing indications for laparoscopic cholecystectomy. Surg. Clin. North Am. 1996; 76: 493–504.
- 28
Yano H,
Kinuta M,
Iwazana T et al.
Laparoscopic cholecystectomy for asymptomatic cholelithiasis.
Dig. Endosc.
2003; 15: 190–5.
10.1046/j.1443-1661.2003.00243.x Google Scholar
- 29 Portincasa P, Moschetta A, Petruzzelli M, Palasciano G, Di Ciaula H, Pezzolla A. Symptoms and diagnosis of gallbladder stones. Best. Pract. Res. Clin. Gastroenterol. 2006; 20: 1017–29.
- 30 Attili AF, De Santis A, Capri R et al. The natural history of gallstones: the GREPCO experience. Hepatology 1995; 21: 655–60.
- 31 Angelico F, Del Ben M, Barbato A, Conti R, Urbinati G. Ten-year incidence and natural history of gallstone disease in a rural population of women in central Italy. The Rome Group for the Epidemiology and Prevention of Cholelithiasis (GREPCO). Ital. J. Gastroenterol. Hepatol. 1997; 29: 249–54.
- 32 Barbara L, Sama C, Morselli-Labate AM et al. The natural history of gallstones: the Sirmione Study. Ital. J. Gastroenterol. 1993; 25 (Suppl. 1): 9. Abstract.
- 33 Sakorafas GH, Milingos D, Peros G. Asymptomatic cholelithiasis: is cholecystectomy really needed? A critical reappraisal 15 years after the introduction of laparoscopic cholecystectomy. Dig. Dis. Sci. 2007; 52: 1313–25.
- 34 Ransohoff DF, Gracie WA. Management of patients with symptomatic gallstones: a quantitative analysis. Am. J. Med. 1990; 88: 154–60.
- 35 Ransohoff DF, Gracie WA. Treatment of gallstones. Ann. Intern. Med. 1993; 119: 606–19.
- 36 Vetrhus M, Soreide O, Solhaug JH, Nesvik I, Sondenaa K. Symptomatic, non complicated gallbladder stone disease. Operation or observation? A randomized clinical study. Scand. J. Gastroenterol. 2002; 37: 834–9.
- 37 Vetrhus M, Soreide O, Eide GE, Solhaug JH, Nesvik I, Sondenaa K. Pain and quality of life in patients with symptomatic, non-complicated gallbladder stones: results of a randomized controlled trial. Scand. J. Gastroenterol. 2004; 39: 270–6.
- 38 Friedman GD, Raviola CA, Fireman B. Prognosis of gallstones with mild or no symptoms: 25 years of follow up in a health maintenance organization. J. Clin. Epidemiol. 1989; 42: 127–36.
- 39 Colecchia A, Sandri L, Bacchi-Reggiani ML et al. Is it possible to predict the clinical course of gallstone disease? Usefulness of gallbladder motility evaluation in a clinical setting. Am. J. Gastroenterol. 2006; 101: 2576–81.
- 40 Venneman NG, Renooij W, Rehfeld JF et al. Small gallstones, preserved gallbladder motility, and fast crystallization are associated with pancreatitis. Hepatology 2005; 41: 738–46.
- 41 Attili AF, Natali L, Cincis M et al. Incidence and indications for cholecystectomy in a public health district of a small town in central Italy. J. Clin. Gastroenterol. 1991; 13: 580–2.
- 42 Halldestam I, Kullman E, Borch K. Defined indications for elective cholecystectomy for gallstone disease. Br. J. Surg. 2008; 9: 620–6.
- 43 Maringhini A, Moreau JA, Melton LJ, Hench VS, Zinsmeister AR, DiMagno EP. Gallstones, gallbladder cancer, and other gastrointestinal malignancies. An epidemiologic study in Rochester, Minnesota. Ann. Intern. Med. 1987; 107: 30–5.
- 44 Shao T, Yang YX. Cholecystectomy and the risk of colorectal cancer. Am. J. Gastroenterol. 2005; 100: 1813–20.
- 45 Goldacre MJ, Abisgold JD, Seagroatt V, Yeates D. Cancer after cholecystectomy: record-linkage cohort study. Br. J. Cancer. 2005; 92: 1307–9.