Evaluation of the impact of spontaneous tumor rupture on the outcome of patients with resectable hepatocellular carcinoma

Abstract

Introduction: Spontaneous tumor rupture is a life-threatening complication of hepatocellular carcinoma (HCC) with a high mortality rate (1). Our previous study showed that 20% of patients with tumor rupture were successfully managed by a two-stage approach that consisted of initial haemostasis by hepatic artery embolization followed by interval hepatic resection (2). With this approach, long-term survival was attainable but the level of prognostic impact of tumor rupture on these patients remains unclear. The aim of our study was to elucidate the prognostic implication of tumor rupture on the survival outcomes in patients with resectable HCC in comparison with those who had resectable non-ruptured HCC. Methods: From January 2001-December 2010, a total of 838 patients received hepatic resections for HCC in our center. Among them, 39 patients had ruptured HCC prior to resection (Group I). Their demographics, operative details and tumor characteristics were reviewed and compared with the remaining 799 patients with non-ruptured HCC (Group II). Survival analysis was conducted by Kaplan Meier methods and was stratified according to the 7th AJCC/TNM staging classification. P-value < 0.05 was considered to be significant. Results: There was no significant difference in age, hepatitis B positivity, indocyanine green clearance rate and liver function between the two groups. As expected, patients in Group I had a significantly larger tumor size than Group II (10cm vs. 5cm, p<0.001). However, there was no difference in tumor multiplicity, frequency of microvascular (Group I vs. II: 64.1% vs. 48.8%, p=0.062) and major vascular invasion (Group I vs. II: 15.4% vs. 9.1%, p=0.306) between the two groups. The 3- and 5-year disease-free survival (DFS) rates for Group I were 25.1% and 20.9%, and the corresponding survival rates for Group II were 42.7% and 35.8% respectively (p=0.034). When stratified according to the TNM classification, after excluding tumor rupture from the staging, the 3- and 5-year DFS rates for T1 were both 80% in Group I (n=7); 66.6% and 55.2% in Group II (p=0.401); for T2 were 16.7% in Group I, and 34.0% and 28.6% in Group II (p=0.055); for T3 were both 15.8% in Group I, and 16.9% and 14.9% in Group II (P=0.532). When the overall survival was stratified according to the median tumor size i.e. 10cm as cutoff value, only patients in Group I had significantly worse survival than Group II when tumor size ≤ 10cm (p=0.011). There was no significant difference in survival between Group I and II when tumor size > 10cm. Conclusion: Spontaneous tumor rupture appeared to have an adverse prognostic impact on patients with T2 tumors or tumor size ≤ 10cm. However, its influence on T3 tumors and tumor size > 10cm was otherwise not significant. Due to our insufficient sample size, further studies are warranted to evaluate the impact of tumor rupture on T1 tumors. Re-defining the significance of tumor rupture in future AJCC/TNM staging for patients with resectable disease may be indicated.