Li et al. BMC Cancer 2010, 10:535 http://www.biomedcentral.com/1471-2407/10/535 vascular invasion are classified as pT4 in the current 2002 TNM staging system. These published data strongly suggest HCC in advanced T stages are not clas- sified appropriately under the current TNM classification. In this study, we retrospectively analyzed the prospec- tively collected data of 298 patients with pT3-4N0M0 HCC who underwent partial hepatectomy to analyze the ability of the current TNM staging system to predict survival. Overall survival (OS) and cumulative recur- rence rate (CRR) of the four categories of locally advanced HCC patients were also compared. Methods Patients Between January 1993 and December 2000, 890 patients underwent hepatic resection for HCC with curative intent, which was defined as macroscopically complete tumor resection at Sun Yat-sen University Cancer Cen- ter. Three hundred and five (34.3%) patients were classi- fied as locally advanced stages (pT3-4N0M0) according to the 2002 version of American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) TNM staging system [8,9]. Seven patients who died within 30 days of operation were excluded, leaving 298 patients for the analyses. Preoperative liver functional reserve was assessed by blood biochemistry, Child-Pugh grading, and indocyanine green retention rate at 15 minutes (ICGR15). Only Child- Pugh A patients were offered major hepatic resection, which was defined as the resection of three or more Couinaud’s liver segments. In selected Child-Pugh B patients, minor hepatectomy, defined as resection of two or fewer liver segments, was carried out. MELD score was also calculated using pre-operative values of three laboratory tests: INR for prothrombin time, serum total bilirubin and serum creatinine [12]. In our daily practice, the “surgical margin” examination procedure is as fol- lows: the marginal liver tissues taken from the “tumor bed” in the residual liver were used for pathologic review to examine whether it is tumor-free. Both parenchymal involvement of the margin and vascular permeation at the margin were considered as “microscopic positive margin” (which means R1 resection). In the present study, all the tumors had been macroscopically comple- tely resected with a microscopically tumor-free margin proven by the pathologists (which means R0 resection). We define those with an obvious margin as “margin > 0 mm”, and the others whose tumor was resected along with the edge of the tumor without an obvious margin but microscopically also with a tumor-free margin as “margin = 0 mm”. Tumors with involvement of the ipsi- lateral branch of the portal or hepatic veins or invasion of adjacent organs were considered resectable provided Page 2 of 9 that en-bloc resection of the entire tumor could be per- formed with a tumor-free margin. Multiple tumors in more than one hemilivers were resected using extended right or left hepatectomy in patients with adequate hepa- tic functional reserve (Child-Pugh A and ICGR15 ≤ 10%); otherwise, separate minor hepatectomy of the tumors in the 2 hemilivers were performed. Histological diagnosis of HCC was reconfirmed by review of pathologic slides. Tumor grade was assessed using the nuclear grading scheme as outlined by Edmondson and Steiner. Tumor size was based on the largest diameter of the tumor in the resected specimen. The number of HCCs was defined by the total number of nodules, including intrahepatic metastasis. Major vas- cular invasion was defined as gross invasion of the trunk or the main branches of the portal or hepatic veins. Invasion of adjacent organs was defined as gross inva- sion of an adjacent organ other than the gallbladder which was resected en-bloc with the liver tumor. Per- foration into visceral peritoneum was based on gross and histological study of the visceral peritoneum. This study is a retrospective study of a prospectively collected database. All clinicopathological data were col- lected at the patient’s presentation and at follow-up vis- its until the patient died or lost to follow-up. We regularly updated the database especially for tumor recurrence and survival status. This study was approved by the Clinical Research Ethics Committee of Sun Yat- sen University Cancer Center and conformed to the ethical guidelines of the 1975 Declaration of Helsinki and the current ethical guidelines. Written informed consent for examination and treatment was obtained from each patient. Follow-up This study was censored on June 30, 2009. The median follow-up was 37 months, (range from 2 to 146 months). At each follow-up visit, we carried out a com- plete clinical examination of the patient. Serum alpha- fetoprotein (AFP), abdomen ultrasonography and chest x-ray were carried out once every 1-3 monthly in the first year, and once every 3-6 monthly thereafter. When tumor recurrence was suspected, computed tomography and/or magnetic resonance imaging and/or positron emission tomography were done. Whenever possible, salvage treatments were given to patients with recur- rence or metastases. The treatments included re-resec- tion, transarterial chemoembolization, radiofrequency ablation, percutaneous ethanol injection and systemic chemotherapy. Statistical Analysis Continuous data were expressed as either mean ± S.D. or medians (range), where appropriate. Chi-square or