Top

Published in:

01-03-2009 | Hepatobiliary and Pancreatic Tumors

Liver Cell Adenoma: A Multicenter Analysis of Risk Factors for Rupture and Malignancy

Authors: Jeremiah L. Deneve, DO, Timothy M. Pawlik, MD, MPH, Steve Cunningham, MD, Bryan Clary, MD, Srinevas Reddy, MD, Charles R. Scoggins, MD, MBA, Robert C. G. Martin, MD, Michael D’Angelica, MD, Charles A. Staley, MD, Michael A. Choti, MD, William R. Jarnagin, MD, Richard D. Schulick, MD, David A. Kooby, MD

Published in: Annals of Surgical Oncology | Issue 3/2009

Abstract

Background

Liver cell adenoma (LCA) is a benign hepatic tumor with poorly characterized risk for spontaneous rupture and malignant transformation.

Methods

Records from five tertiary hepatobiliary centers were reviewed for all patients treated for LCA from 1997 to 2006. Clinicopathological data were collected and analyzed, and factors that were associated with rupture and/or malignant transformation were assessed by using multivariable logistic regression.

Results

A total of 124 patients were analyzed, of which 8 (6.5%) were men; 119 patients underwent resection, and 5 patients had embolic therapy only. Mean patient age was 39 ± 11 years, and 55% had history of hormone use. Rupture occurred in 31 (25%) cases. Ruptured tumors were larger (10.5 ± 4.5 cm vs. 7.2 ± 4.8 cm; p = 0.001), and no tumor <5 cm ruptured. Patients with ruptured LCAs were more likely to require preoperative blood transfusion (32% vs. 9%, p = 0.006), preoperative embolization (16% vs. 1%, p = 0.021), and major (≥3 segments) hepatic resection (65% vs. 32%, p = 0.003). By multivariate analysis, increasing tumor size (odds ratio (OR), 7.8; 95% confidence interval (CI), 2.2-26.3; p < 0.01) and recent (within 6 months) hormone use (OR, 4.5; 95% CI, 1.5–13.3; p < 0.01) remained independently associated with risk of rupture. Five cases (4%) had evidence of underlying malignancy, but none had LCA <8 cm in diameter.

Conclusion

In this multicenter analysis of patients with LCAs, risk of rupture correlated with increasing tumor size and recent hormone use. Rupture is associated with greater need for preoperative blood transfusion and major hepatic resection. These data suggest that patients with asymptomatic LCAs approaching 4 cm and those requiring hormonal therapy should undergo surgical therapy.

Luka N. [On the clinical aspects and therapy of hepatocellular adenoma]. Helvetica Chirurgica Acta. 1964;31:470–92.PubMed

Puech A, Pages A, Dermenghem M, Seignalet J. [Multinodular adenoma of the liver]. Montpellier Med. 1964;65:114–9.PubMed

Littmann I, Berentey E, Magyar E, Balazs M. [Surgical treatment of liver adenoma caused by contraceptive agents]. Orvosi Hetilap. 1976;117:159–61.PubMed

Catalano PW, Martin EW Jr, Ellison C, Carey LC. Reasonable surgical treatment for tumors of the liver associated with the use of oral contraceptives. Surg Gynecol Obstet. 1979;148:759–63.PubMed

Sukharev VF, Medvedev VG, Tsvetkov EG, Masiutin VA. [Adenoma of the liver in a young woman]. Vestnik Khirurgii Imeni i - i - Grekova. 1998;157:90–1.PubMed

Shortell CK, Schwartz SI. Hepatic adenoma and focal nodular hyperplasia. Surg Gynecol Obstet. 1991;173:426–31.PubMed

Leese T, Farges O, Bismuth H. Liver cell adenomas. A 12-year surgical experience from a specialist hepato-biliary unit. Ann Surg. 1988;208:558–64.PubMedCrossRef

Ault GT, Wren SM, Ralls PW, et al. Selective management of hepatic adenomas. Am Surg. 1996;62:825–9.PubMed

Flowers BF, McBurney RP, Vera SR. Ruptured hepatic adenoma. A spectrum of presentation and treatment. Am Surg. 1990;56:380–3.PubMed

10.

Foster JH, Berman MM. The malignant transformation of liver cell adenomas. Arch Surg. 1994;129:712–7.PubMed

11.

Colonna JO 2nd, Olthoff KM, Seu P, Busuttil RW. Liver resection for primary neoplasms. Adv Surg. 1992;25:309–29.PubMed

12.

Van der Borght S, Libbrecht L, Katoonizadeh A, et al. Nuclear beta-catenin staining and absence of steatosis are indicators of hepatocellular adenomas with an increased risk of malignancy. Histopathology. 2007;51:855–6.PubMedCrossRef

13.

Colovic R, Grubor N, Micev M, Radak V. Hepatocellular adenoma with malignant alteration. Hepatogastroenterology. 2007;54:386–8.PubMed

14.

Micchelli S, Vivekanandan P, Boitnott J, et al. Malignant transformation of hepatic adenomas. Mod Pathol. 2008;21:491–7.PubMedCrossRef

15.

Fujita S, Kushihata F, Herrmann GE, et al. Combined hepatic resection and radiofrequency ablation for multiple hepatic adenomas. J Gastroenterol Hepatol. 2006;21:1351–4.PubMedCrossRef

16.

Terkivatan T, Hussain SM, De Man RA, Ijzermans JNM. Diagnosis and treatment of benign focal liver lesions. Scand J Gastroenterol Suppl. 2006;102–15.

17.

Leborgne J, Lehur PA, Horeau JM, et al. [Therapeutic problems caused by rupture of large hepatic adenoma with central location Apropos of 3 cases]. Chirurgie. 1990;116:454–60.PubMed

18.

Steinemann D, Skawran B, Becker T, et al. Assessment of differentiation and progression of hepatic tumors using array-based comparative genomic hybridization. Clin Gastroenterol Hepatol. 2006;4:1283–91.PubMedCrossRef

19.

Martin RCG 2nd, Brennan MF, Jaques DP. Quality of complication reporting in the surgical literature. Ann Surg. 2002;235:803–13.PubMedCrossRef

20.

Brooks AL, Benjamin SA, Jones RK, McClellan RO. Interaction of 144Ce and partial hepatectomy in the production of liver neoplasms in the Chinese hamster. Radiat Res. 1982;91:573–88.PubMedCrossRef

21.

Rooks JB, Ory HW, Ishak KG, et al. Epidemiology of hepatocellular adenoma. The role of oral contraceptive use. JAMA. 1979;242:644–8.PubMedCrossRef

22.

Stoot JHMB, van der Linden E, Terpstra OT, Schaapherder AFM. Life-saving therapy for haemorrhaging liver adenomas using selective arterial embolization. Br J Surg. 2007;94:1249–53.PubMedCrossRef

23.

Steinbrecher UP, Lisbona R, Huang SN, Mishkin S. Complete regression of hepatocellular adenoma after withdrawal of oral contraceptives. Dig Dis Sci. 1981;26:1045–50.PubMedCrossRef

24.

Terkivatan T, de Wilt JH, de Man RA, et al. Treatment of ruptured hepatocellular adenoma. Br J Surg. 2001;88:207–9.PubMedCrossRef

25.

Erdogan D, Busch ORC, van Delden OM, et al. Management of spontaneous haemorrhage and rupture of hepatocellular adenomas. A single centre experience. Liver Int. 2006;26:433–8.PubMedCrossRef

26.

Toso C, Majno P, Andres A, et al. Management of hepatocellular adenoma: solitary-uncomplicated, multiple and ruptured tumors. World J Gastroenterol. 2005;11:5691–5.PubMed

27.

Cho SW, Marsh JW, Steel J, et al. Surgical management of hepatocellular adenoma: take it or leave it? Ann Surg Oncol. 2008;15:2795–803.PubMedCrossRef

28.

Baum JK, Bookstein JJ, Holtz F, Klein EW. Possible association between benign hepatomas and oral contraceptives. Lancet. 1973;2:926–9.PubMedCrossRef

29.

Edmondson HA, Henderson B, Benton B. Liver-cell adenomas associated with use of oral contraceptives. N Engl J Med. 1976;294:470–2.PubMed

30.

Psatha EA, Semelka RC, Armao D, et al. Hepatocellular adenomas in men: MRI findings in four patients. J Magnetic Reson Imag. 2005;22:258–64.CrossRef

31.

Ramakrishna B, Sitaram V, Khanduri P. Large encapsulated hepatocellular adenoma in a male. Liver. 1996;16:235–6.PubMed

32.

Deodhar KK, Desouza LJ, Jagannath P, Krishnamurthy S. Spontaneously occurring liver cell adenoma in an adult male. Indian J Gastroenterol. 1996;15:28–9.PubMed

33.

Aseni P, Sansalone CV, Sammartino C, et al. Rapid disappearance of hepatic adenoma after contraceptive withdrawal. J Clin Gastroenterol. 2001;33:234–6.PubMedCrossRef

34.

Ramseur WL, Cooper MR. Asymptomatic liver cell adenomas. Another case of resolution after discontinuation of oral contraceptive use. JAMA. 1978;239:1647–8.PubMedCrossRef

35.

Edmondson HA, Reynolds TB, Henderson B, Benton B. Regression of liver cell adenomas associated with oral contraceptives. Ann Intern Med. 1977;86:180–2.PubMed

36.

Iwatsuki S, Todo S, Starzl TE. Excisional therapy for benign hepatic lesions. Surg Gynecol Obstet. 1990;171:240–6.PubMed

37.

Brenner DJ, Hall EJ. Computed tomography: an increasing source of radiation exposure. N Engl J Med. 2007;357:2277–84.PubMedCrossRef

38.

Kooby DA, Stockman J, Ben-Porat L, et al. Influence of transfusions on perioperative and long-term outcome in patients following hepatic resection for colorectal metastases. Ann Surg. 2003;237:860–70.PubMedCrossRef

39.

Klatskin G. Hepatic tumors: possible relationship to use of oral contraceptives. Gastroenterology. 1977;73:386–94.PubMed

40.

Bianco A, D’Ambra L, Bonfante P, et al. [Surgical timing in bleeding liver adenoma: case report]. Giornale di Chir. 2007;28:390–3.

41.

Jabbour N, Brenner M, Gagandeep S, et al. Major hepatobiliary surgery during pregnancy: safety and timing. Am Surg 2005;71:354–8.PubMed

42.

Zucman-Rossi J, Jeannot E, Nhieu JTV, et al. Genotype-phenotype correlation in hepatocellular adenoma: new classification and relationship with HCC. Hepatology. 2006;43:515–24.PubMedCrossRef

43.

Korula J, Yellin A, Kanel G, et al. Hepatocellular carcinoma coexisting with hepatic adenoma. Incidental discovery after long-term oral contraceptive use. West J Med. 1991;155:416–8.PubMed

44.

Perret AG, Mosnier JF, Porcheron J, et al. Role of oral contraceptives in the growth of a multilobular adenoma associated with a hepatocellular carcinoma in a young woman. J Hepatol. 1996;25:976–9.PubMedCrossRef

45.

Ferrell LD. Hepatocellular carcinoma arising in a focus of multilobular adenoma. A case report. Am J Surg Pathol. 1993;17:525–9.PubMedCrossRef

46.

Tesluk H, Lawrie J. Hepatocellular adenoma. Its transformation to carcinoma in a user of oral contraceptives. Arch Pathol Lab Med. 1981;105:296–9.PubMed

47.

Herman P, Machado MA, Volpe P, et al. [Transformation of hepatic adenoma into hepatocellular carcinoma in patients with prolonged use of oral contraceptives]. Rev Hosp Clin Fac Med Sao Paulo 1994;49:30–3.PubMed

48.

Gordon SC, Reddy KR, Livingstone AS, et al. Resolution of a contraceptive-steroid-induced hepatic adenoma with subsequent evolution into hepatocellular carcinoma. Ann Intern Med. 1986;105:547–9.PubMed

49.

Gyorffy EJ, Bredfeldt JE, Black WC. Transformation of hepatic cell adenoma to hepatocellular carcinoma due to oral contraceptive use. Ann Intern Med. 1989;110:489–90.PubMed

50.

Closset J, Veys I, Peny MO, et al. Retrospective analysis of 29 patients surgically treated for hepatocellular adenoma or focal nodular hyperplasia. Hepatogastroenterology. 2000;47:1382–4.PubMed

51.

Ito M, Sasaki M, Wen CY, et al. Liver cell adenoma with malignant transformation: a case report. World J Gastroenterol. 2003;9:2379–81.PubMed

52.

Wagner WH, Lundell CJ, Donovan AJ. Percutaneous angiographic embolization for hepatic arterial hemorrhage. Arch Surg. 1985;120:1241–9.PubMed

53.

Stoot JHMB, van Roosmalen J, Terpstra OT, Schaapherder AFM. Life-threatening hemorrhage from adenomas in the liver during pregnancy. Dig Surg. 2006;23:155.PubMedCrossRef

Title: Liver Cell Adenoma: A Multicenter Analysis of Risk Factors for Rupture and Malignancy
Authors: Jeremiah L. Deneve, DO
Timothy M. Pawlik, MD, MPH
Steve Cunningham, MD
Bryan Clary, MD
Srinevas Reddy, MD
Charles R. Scoggins, MD, MBA
Robert C. G. Martin, MD
Michael D’Angelica, MD
Charles A. Staley, MD
Michael A. Choti, MD
William R. Jarnagin, MD
Richard D. Schulick, MD
David A. Kooby, MD
Publication date: 01-03-2009
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue 3/2009
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-008-0275-6

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Liver Cell Adenoma: A Multicenter Analysis of Risk Factors for Rupture and Malignancy

Abstract

Background

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 3/2009

Solitary Dermal Melanoma: Beginning or End of the Metastatic Process?

Port-A-Cath Implantation Using Percutaneous Puncture Without Guidance

Variations in Axillary Staging: Much Ado About Nothing?

Meta-Analysis of the Clamp-Crushing Technique for Transection of the Parenchyma in Elective Hepatic Resection: Back to Where We Started?

Automated Microscopy to Evaluate Surgical Specimens Via Touch Prep in Breast Cancer

Evaluation of 47 Soft Tissue Sarcoma Resection Specimens after Isolated Limb Perfusion with TNF-α and Melphalan: Histologically Characterized Improved Margins Correlate with Absence of Recurrences