1. Hepatic Adenoma – Can we do more? Joint Hospital Grand Round 2011-02-19

2. TWO CASES PRESENTATION Professional Challenge You May Face of…

3. April, 2007 F/25 History of Acute Leukemia with Bone Marrow Transplant in 1994 On Hormonal Replacement Therapy

4. Presented sudden onset of upper abdominal pain with guarding Clinically suggested peritonitis

5. Emergency Laparoscopy Performed Intra-operative Findings – Haemoperitoneum with 1L old blood and clots – Large subcapsular haematoma occupying most inferior surface of right lobe of liver – Small capsular tear with slow oozing – Stomach, Gallbladder, small bowel and ovary normal Oozing stopped with Surgicel packing

6. Computer Tomography – Enhancing lesion with haemorrhage in segment VI/VII, suggestive hepatic adenoma with haemorrhage

7. November, 2010 F/19 Good Past Health, No history of use of oral contraceptive pills Presented sudden onset of right upper quadrant pain and tachycardia

8. Computer Tomography – Circumscribed 10cm intrahepatic mass in right lobe of liver with contrast leakage right anterior and posterior aspect of lesion suggestive haemorrage in hepatic adenoma

9. Uncommon but You May Want to Know More HEPATIC ADENOMA

10. Hepatic Adenoma Reported incidence 3-4 per 100,000 per year (1), (2) Increased case reported since 1970s as introduction of OCP in 1960s – Real incidence maybe underestimated as many patients are asymptomatic Most common in women in their third and fourth decades (3) Female/Male Ratio 11:1 (3) (1) Rooks JB et al, JAMA 242(1979):644-648 (2) Leese T et al, Ann Surg 208(1988):558-564 (3)Joseph F et al, Surg Clin N Am 90(2010):719-315

11. Risk Factors Oral Contraception – 10 times higher incidence when used for more than 2 years (1), but these estimations were performed in 1970s – Lower risk was suggested in 2 nd and 3 rd generation OCP with lower dose of estrogen (4) – Cessation of OCP was reported to cause regression of hepatic adenoma (5-10) (1) Rooks JB et al, JAMA 242(1979):644-648 (4)Edmondson HA et al. N Engl J Med. 1976;294(9):470-2 (5) Anderson PH et al, Arch Surg 1976; 111:898–900. (6) Aseni P et al. J Clin Gastroenterol 2001; 33:234–6. (7) Steinbrecher UP et al, Dig Dis Sci 1981; 26:1045–50. (8). Buhler H et al, Gastroenterology 1982; 82:775–82. (9) Edmondson HA et al, Ann Intern Med 1977; 86:180–2. (10) Ramseur WL et al, JAMA 1978; 239:1647–8.

12. Risk Factors Use of anabolic steroids Glycogen Storage Disease

13. Presentation Asymptomatic – Incidental findings in imaging Right Upper Quadrant Pain or mass in 25-50% (3) Complications – Spontaneous Rupture – Malignant Transformation (3) Joseph F et al, Surg Clin N Am 90(2010)

14. Imaging Computer Tomography – Typically as a discrete, hypodense lesion that shows arterial-phase enhancement and may become iso-dense on delayed images (3) – Sometime differentiating hepatic adenoma from HCC is difficult – With the evidence of portal hypertension, cirrhosis and elevated AFP, the diagnosis of HCC is favored. (3) Joseph F et al, Surg Clin N Am 90(2010)

15. Imaging Magnetic Resonance Imaging – Isointense or hyperintense on T1 weighted images – Variable hyperintensity in T2 weighted images – Most HCC are characteristically hypointense on T1 W and hyperintense on T2 W images

16. COMPLICATIONS 1/ Spontaneous Rupture 2/ Malignant Transformation to Hepatocellular Carcinoma

21. Incidence of haemorrhage was reported upto 30% Risk Factors for rupture – Size >7cm – Contraceptive use

22. Malignant Transformation to Hepatocellular Carcinoma

23. Overall frequency of malignant transformation rate was 4.2%. Risk Factors – Risk analysis of size was difficult because studies report only mean size – 3 cases size less than 5cm – Contraceptive use, anerobic steriod and glycogen storage disease were high risk group.

24. CAN WE DO MORE TO PREVENT COMPLICATIONS? With advance in hepatectomy and new interventions to liver tumors…

25. Surgery - Hepatectomy Classically hepatic adenoma was treated conservatively if size less then 5cm. Because there were only scanty reports of rupture and malignant transformation in this size.

27. The median diameter was 9 cm (range, 1–18 cm).

29. Other Modalities – TAE and RFA

32. TWO CASES PRESENTATION Professional Challenge You May Face of…

33. Outcomes of The Two Young Ladies Both of them were treated conservatively initially. Elective hepatectomy were done with no complication. Follow up well with no recurrence. Right HepatectomySegment 5/6 Bisegmentectomy

34. Conclusion Hepatic Adenoma may present in complications as rupture or malignant transformation. The most common risk factor is use of oral contraceptive pills. With advance in surgical techniques, open and laparoscopic hepatectomy, indication of surgery for hepatic adenoma may be extended. Other modalities such as TAE and RFA may be future alternative treatments.

35. References (1) Rooks JB et al, Epidemiolog of hepatic adenoma. The role of oral contraceptive use. JAMA 242(1979):644-648 (2) Leese T et al, Liver cell adenomas. A 12-year surgical experience from a specialist hepato-biliary unit. Ann Surg 208(1988):558-564 (3) Joseph F et al, Management of Benign Hepatic Tumors Surg Clin N Am 90(2010):719-315 (4) Edmondson HA et al, Liver-cell adenomas associated with use of oral contraceptives. N Engl J Med. Feb 26 1976;294(9):470-2 (5) Anderson PH et al, Hepatic adenoma–observation after estrogen withdrawal. Arch Surg 1976; 111:898–900. (6) Aseni P et al, Rapid disappearanceof hepatic adenoma after contraceptive withdrawal. J Clin Gastroenterol 2001; 33:234–6. (7) Steinbrecher UP et al, Complete regression of hepatocellular adenoma after withdrawal of oral contraceptives. Dig Dis Sci 1981; 26:1045–50. (8). Buhler H et al, Regression of liver cell adenoma. A follow-up study of three consecutive patients after discontinuation of oral contraceptive use. Gastroenterology 1982; 82:775–82. (9) Edmondson HA et al. Regression of liver cell adenomas associated with oral contraceptives. Ann Intern Med 1977; 86:180–2. (10) Ramseur WL et al. Asymptomatic liver cell adenomas. another case of resolution after discontinuation of oral contraceptive use. JAMA 1978; 239:1647–8.

36. Role of FNAC of Liver 1.Safety – Hepatic Adenoma is vascular and puncture may provoke bleeding and rupture. 2.Sampling – False Negative from FNAC – Harboring of Liver Cell Dysplasia and small HCC inside adenoma 3.Pathology Diagnosis – Differentiating hepatic adenoma and well differentiated HCC is a pathological challenge.