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10.1245/s10434-006-9318-z
Annals of Surgical Oncology 14:1356-1365 (2007)
© 2007 Society of Surgical Oncology
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Original Article

Anatomic Resection Independently Improves Long-Term Survival in Patients with T1–T2 Hepatocellular Carcinoma

Toshifumi Wakai, MD, PhD1, Yoshio Shirai, MD, PhD1, Jun Sakata, MD, PhD1, Kazuhiro Kaneko, MD1, Pauldion V. Cruz, MD, PhD1, Kouhei Akazawa, MD, PhD2 and Katsuyoshi Hatakeyama, MD, PhD, FACS1

1 Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Niigata City, 951-8510, Japan
2 Department of Medical Informatics, Niigata University Medical and Dental Hospital, 1-754 Asahimachi-dori, Niigata City, 951-8520, Japan

Correspondence: Address correspondence and reprint requests to: Yoshio Shirai, MD, PhD; E-mail: shiray{at}med.niigata-u.ac.jp


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: This study aimed to evaluate the effect of anatomic resection on long-term outcomes in patients with pathologic T1–T2 (pT1–T2) hepatocellular carcinoma.

Methods: A retrospective analysis of 158 consecutive patients who underwent either anatomic (n = 95) or nonanatomic (n = 63) resection for pT1–T2 hepatocellular carcinoma was conducted. Anatomic resection was defined as the complete removal of at least one Couinaud segment containing the tumor; nonanatomic resection was defined as removal of the tumor plus a rim of nonneoplastic liver parenchyma. The median follow-up time was 83 months.

Results: Patients who underwent anatomic resection were characterized by lower prevalence of cirrhosis (P = .015), more favorable hepatic function (P = .001), larger tumor size (P = .029), and higher prevalence of vascular invasion (P = .008) compared with patients who underwent nonanatomic resection. Anatomic resection provided better survival (median survival time, 122 months) than nonanatomic resection (median survival time, 76 months; P = .0358). Patients who underwent anatomic resection had better disease-free survival (P = .0121). Anatomic resection independently improved both survival (hazard ratio, .46; P = .003) and disease-free survival (hazard ratio, .55; P = .008). When stratified for pT classification, the effectiveness of anatomic resection remained only in patients with pT2 tumors in terms of survival (P = .0012) and disease-free survival (P = .0004).

Conclusions: Anatomic resection independently improves long-term survival in patients with T1–T2 hepatocellular carcinoma, probably because of the clearance of venous tumor thrombi within the resected domain.

Key Words: Liver neoplasms • Hepatocellular carcinoma • Anatomic resection • Nonanatomic resection • Multivariate analysis • Prognosis


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Hepatic resection is a widely accepted treatment modality for hepatocellular carcinoma (HCC).1–3 Because HCC spreads mainly by vascular invasion, anatomic resection has been advocated as the preferred treatment because it allows for the complete removal of the tumor-related domain, including possible venous tumor thrombi around the main tumor.4–9 The theoretical advantages of anatomic resection for the treatment of HCC include improved clearance of intrahepatic metastases via the portal vein,4–9 conservation of functional liver parenchyma,5,6 greater surgical margins,6,7 and improved survival outcomes.6–11 Although some authors have described the survival benefits of anatomic resection in selected patients with HCC,7–9 others have not been able to demonstrate these benefits.12–17 Thus, the effectiveness of anatomic resection for HCC remains controversial.

The current study compared the long-term outcomes of anatomic resection versus nonanatomic resection by univariate and multivariate analyses. The aim of the current study was to determine which hepatectomy procedure—anatomic resection or nonanatomic resection—is more beneficial for patients with pathologic T1–T2 (pT1–T2) HCC.18


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Patient Population
A total of 220 consecutive Japanese patients underwent a curative hepatic resection for HCC at the Division of Digestive and General Surgery, Niigata University Medical and Dental Hospital (Niigata, Japan), from January 1990 through December 2004. Curative hepatic resection was defined as a resection of all grossly visible hepatic tumors. Thirty-two patients who underwent a repeat hepatectomy for intrahepatic recurrences of HCC were excluded. Of the remaining 188 patients, 158 diagnosed with pT1–T2 HCC according to the tumor, node, metastasis (TNM) staging system18 formed the basis of this retrospective study. They included 114 men and 44 women with a median age of 65 years (range, 29–80 years). No patients had nodal involvement or distant metastases. Patients with advanced-stage tumors (pT3–T4) were excluded from the current study because these patients were treated mainly with anatomic resection.

Hepatectomy Procedures
In our department, hepatic resection is the standard treatment for HCC when tumors are considered resectable. Anatomic resection was performed in 95 patients and nonanatomic resection in 63. Intermittent clamping of the portal pedicle (15-minute clamping followed by 5-minute unclamping) was used during the hepatic resection. No patients underwent regional lymph node dissection in the hepatic hilum. Intraoperative ultrasonography was routinely used to evaluate the liver remnant for additional tumors. Anatomic resection was defined as the complete removal of at least one Couinaud segment19 containing the tumor. Nonanatomic resection was defined as the removal of the tumor plus a rim of nonneoplastic liver parenchyma. The three patients who underwent combined anatomic and nonanatomic resections were included in the anatomic resection group.

During the study period, anatomic resections were performed by means of the portal pedicle ligation technique via the posterior intrahepatic approach, which allowed early delineation of the segments to be removed before parenchymal transection.20–22 Anatomic resections in the current series included mono-segmentectomy (removal of one Couinaud segment) in 20 patients, bisegmentectomy (removal of two Couinaud segments) in 33 patients, central hepatectomy (removal of Couinaud segments IV, V, and VIII) in 1 patient, right hemihepatectomy (removal of Couinaud segments V–VIII) in 25 patients, left hemihepatectomy (removal of Couinaud segments II–IV) in 6 patients, and more extensive hepatectomy in 10 patients.

In this study, hepatic functional reserve estimations for individual patients were primarily made on the basis of the results of the indocyanine green clearance test.23,24 After the intravenous injection of indocyanine green (.5 mg/kg, Diagnogreen; Daiichi Pharmaceutical, Tokyo, Japan), the indocyanine green disappearance rate (KICG) was calculated by linear regression analysis of the plasma indocyanine green concentrations at 5, 10, and 15 minutes. For the current study, the median indocyanine green retention rate at 15 minutes was 15% (range, 3%–48%; reference range, 10% or less), whereas the median KICG was .134 (range, .046–.246).

In 1983, we established the following guidelines for determining the extent of hepatic resection: KICG ≥ .12 permits hemihepatectomy or a more extensive hepatectomy, .12 > KICG ≥.10 permits bisegmentectomy, .10 > KICG ≥ .08 permits monosegmentectomy, .08 > KICG ≥.06 permits nonanatomic resection including the enucleation of hepatic tumors, and KICG < .06 permits nonresectional treatment modalities including interventional radiological techniques.

In the current study, a hepatectomy procedure was selected for each patient, taking the primary tumor status (size, number, location), the hepatic functional reserve, and the patient’s general condition into account;25 there was a tendency toward a more extensive hepatectomy procedure selected among patients with larger tumors, more deeply located tumors, or better general conditions. The actual numbers of patients who underwent the different hepatectomy procedures in the current series are presented according to KICG values in Table 1Go. This table also demonstrates that the KICG-based guidelines were not followed for 13 patients, provided that the patient was fit enough for the procedure selected.


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  		TABLE 1. Hepatectomy procedures according to indocyanine green disappearance rate (KICG)
 
Laboratory Evaluation
The following laboratory tests were performed before resection: serum aspartate aminotransferase (AST) level, serum alanine aminotransferase (ALT) level, and serum alpha-fetoprotein (AFP) level, hepatitis B surface antigen (HBsAg), and antibody to hepatitis C virus (anti-HCV). Serum concentrations of AFP were determined by enzyme immunoassay (Luminomaster AFP; Sankyo Yell Yakuhin, Tokyo, Japan), with a reference range of <21 ng/mL. HBsAg and anti-HCV were detected in serum by radioimmunoassay (Lumipulse II HBsAg; Fujirebio, Tokyo, Japan) and a second-generation enzyme-linked immunosorbent assay (Lumipulse II Ortho HCV; Ortho-Clinical Diagnostics, Tokyo, Japan), respectively.

Pathologic Evaluation
Resected specimens were submitted to the Department of Surgical Pathology in our hospital. Each specimen was examined to determine the presence of cirrhosis, the number of hepatic tumors, the size of the largest hepatic tumor, the histologic grade, gross or microscopic vascular invasion, and hepatectomy margin status. A median of 12 microscopic slides of the resected liver from each patient was available (range, 2–36 slides). The pathologic findings were described according to the TNM staging system;18 the extent of the primary tumor was determined according to pT classification. Hepatectomy margin status was classified as either R0 (no residual tumor) or R1 (microscopic residual tumor),18 depending on the absence or presence of histologically verified tumor cells on the resection margin, respectively. Lymph node metastasis classification and distant metastasis classification were determined clinically (cN and cM, respectively) with preoperative imaging studies and surgical exploration.

A total of 236 hepatic tumors were resected in the current series. One hundred eighteen patients had a solitary tumor, and 40 had multiple tumors. The number of hepatic tumors was determined by gross examination of multiple slices from each resected specimen. This did not include satellite nodules, which we defined as additional tumors of less than half the diameter of the main tumor located no further from the main tumor than the diameter of the satellite. The definition followed that of Taylor et al.26 regarding colorectal carcinoma liver metastasis. In patients with multiple tumors, the largest tumor was chosen as a representative.

Cirrhosis in the adjacent (nontumorous) liver was diagnosed microscopically on the basis of the presence of regenerative nodules surrounded by fibrous septa. Histologic grade was determined according to the Edmondson-Steiner classification27 and was based on the areas of the tumor with the highest grade. Vascular invasion included both portal and hepatic venous invasion in the current study.

Patient Follow-up After Resection
Postoperative morbidity was defined as any postoperative complication that lengthened the hospital stay.25 Postoperative mortality was defined as any death occurring during the hospital stay for resection of HCC. Thirteen patients underwent adjuvant chemotherapy, which consisted of transarterial administration of 20 or 40 mg of doxorubicin combined with lipiodol. No patient received adjuvant radiotherapy.

Serum concentrations of AFP were measured, and abdominal ultrasonography and/or contrast-enhanced computed tomography were performed approximately 1 month after resection in all patients. Thereafter, patients were followed up every 3 months in outpatient clinics and monitored for disease recurrence by measuring AFP serum concentrations and/or imaging studies. When intrahepatic recurrences were detected, they were treated with either interventional radiological technique, repeat hepatectomy, or systemic chemotherapy when indicated. Patients with disseminated recurrences and those in a debilitated state were treated with supportive care. The median follow-up time after resection was 83 months (range, 8–190 months). At the time of disease status assessment, 58 patients had died of tumor recurrence. Ten patients had died of other causes with no evidence of disease. Thirty-eight patients were alive with recurrent disease, and the remaining 52 patients were alive with no evidence of disease.

The initial sites of recurrence after resection included the remnant liver alone in 89 patients, extra-hepatic organs alone in 5 patients, and the remnant liver plus extrahepatic organs in 2 patients. The pattern of intrahepatic recurrence was determined according to the classification proposed by Poon et al.28

Prognostic Factors
To determine factors influencing long-term outcomes after resection, 20 conventional variables18,29–31 were tested in all 158 patients: age (≤ 65 years vs. >65 years), sex, Child-Pugh classification (A vs. B + C), cirrhosis (absent vs. present), serum AST level (≤ 50 IU/L vs. >50 IU/L), serum ALT level (≤ 50 IU/L vs. >50 IU/L), serum AFP level (≤ 20 ng/mL vs. >20 ng/mL), HBsAg status (negative vs. positive), anti-HCV status (negative vs. positive), indocyanine green retention rate at 15 minutes (≤ 15% vs. >15%), number of hepatic tumors (solitary vs. multiple), size of the largest hepatic tumor (≤ 3 cm vs. >3 cm), Edmondson-Steiner grade (I–II vs. III–IV), vascular invasion (negative vs. positive), pT classification (pT1 vs. pT2), hepatectomy margin status (R0 vs. R1), operating time (≤ 300 minutes vs. > 300 minutes), estimated blood loss (≤ 700 mL vs. > 700 mL), adjuvant chemotherapy (absent vs. present), and type of hepatic resection (anatomic vs. nonanatomic resection).

Statistical Analysis
Medical records and survival data were obtained for all patients. Categorical variables were compared by the Fisher exact test or the Pearson {chi}2 test; continuous variables were compared by the Mann-Whitney U-test. The causes of death were determined from the medical records. Deaths from other causes were treated as uncensored cases. The Kaplan-Meier method was used to estimate the cumulative incidences of events, and differences in these incidences were evaluated by the log rank test. The Cox proportional hazards regression model was performed to identify factors that were independently associated with survival and disease-free survival. In this model, a stepwise selection was used for variable selection with entry and removal limits of P < .1 and P > .15, respectively. The stability of each model was confirmed by a step-backward and step-forward fitting procedure, and variables identified as having an independent influence on survival and disease-free survival were identical in both procedures. The sample size of the current study (n = 158) provides 80% power at the .05 significance level. This is able to detect the significance of the hazard ratio .6 between levels of any dichotomous covariate entered into the Cox multivariate model, with an estimated event probability of 30%. All statistical evaluations were performed by SPSS 11.5J software (SPSS Japan, Tokyo, Japan). All tests were two-sided, and P values of < .05 were considered statistically significant.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
In the current study, the incidences of postoperative morbidity and mortality were 23.4% (37 of 158 patients) and 3.8% (6 of 158 patients), respectively. The overall cumulative survival rates after resection were 63% at 5 years and 42% at 10 years; the overall cumulative disease-free survival rates after resection were 35% at 5 years and 22% at 10 years. Vascular invasion was found in 38 (24%) of 158 patients and included gross involvement of vessels alone in 1 patient, microscopic involvement alone in 24 patients, and both gross and microscopic involvement in 13 patients.

Clinicopathologic Characteristics According to Type of Hepatic Resection
Patients who underwent anatomic resection had a lower prevalence of cirrhosis, a more favorable indocyanine green retention rate at 15 minutes, a larger tumor size, a higher prevalence of vascular invasion, a lower prevalence of tumor cells located on the hepatectomy margin (R1), a longer operating time, and a larger volume of estimated blood loss than patients who underwent nonanatomic resection (Table 2Go).


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  		TABLE 2. Clinicopathologic characteristics of 158 patients with hepatocellular carcinoma according to type of hepatic resection
 
Postoperative Morbidity and Mortality According to Type of Hepatic Resection
The incidence of postoperative morbidity was 22% (21 of 95 patients) after anatomic resection compared with 25% (16 of 63 patients) after nonanatomic resection (P = .702). The incidence of postoperative mortality was 2% (2 of 95 patients) after anatomic resection compared with 6% (4 of 63 patients) after nonanatomic resection (P = .217). Thus, the incidences of postoperative morbidity and mortality were comparable between patients undergoing anatomic resection and patients undergoing nonanatomic resection.

Factors Influencing Survival After Resection
Univariate analysis revealed that cirrhosis, serum AST level, serum AFP level, number of hepatic tumors, Edmondson-Steiner grade, pT classification, estimated blood loss, and type of hepatic resection were statistically significant prognostic factors for survival (Table 3Go). Variables that were significant in the univariate analyses were entered into multivariate analyses, which revealed that serum AST level ≤ 50 IU/L, serum AFP level ≤ 20 ng/mL, pT1 classification, estimated blood loss ≤ 700 mL, and anatomic resection were independent prognostic factors for favorable survival (Table 3Go).


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  		TABLE 3. Factors influencing survival after resection
 
Factors Influencing Disease-Free Survival After Resection
Univariate analyses revealed that cirrhosis, serum AST level, serum ALT level, serum AFP level, number of hepatic tumors, Edmondson-Steiner grade, pT classification, hepatectomy margin status, and type of hepatic resection were statistically significant prognostic factors for disease-free survival (Table 4Go). Variables that were significant in univariate analyses were entered into multivariate analyses, which revealed that serum AST level ≤ 50 IU/L, serum AFP level ≤ 20 ng/mL, Edmondson-Steiner grade I–II, pT1 classification, R0 hepatectomy margin status, and anatomic resection were independent prognostic factors for favorable disease-free survival (Table 4Go).


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  		TABLE 4. Factors influencing disease-free survival after resection
 
Impact of Anatomic Resection on Long-Term Outcomes
Both survival (P = .0358; Table 3Go) and disease-free survival (P = .0121; Table 4Go) were significantly better in patients undergoing anatomic resection than in patients undergoing nonanatomic resection (Fig. 1Go). When all 158 patients were divided according to pT classification, further significant differences were observed. Of the 90 patients with pT1 tumors, the differences in long-term outcomes between the anatomic and nonanatomic resection groups were not significant, although there were slightly better outcomes for the patients undergoing anatomic resection (Fig. 2Go). Of the 68 patients with pT2 tumors, both survival (P = .0012) and disease-free survival (P = .0004) were markedly better for the patients undergoing anatomic resection (Fig. 3Go). Even in the subgroup of patients with cirrhosis (n = 86), anatomic resection favorably affected both survival (P = .0448) and disease-free survival (P = .0227).


Figure 1
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  		FIG. 1. Kaplan-Meier survival estimates according to type of hepatic resection in 158 patients. (A) Postresectional survival was better in patients undergoing anatomic resection (median survival time, 122 months; cumulative 10-year survival rate, 51%) than in patients undergoing nonanatomic resection (median survival time, 76 months; cumulative 10-year survival rate, 29%; P = .0358). (B) Disease-free survival was better in patients undergoing anatomic resection (median disease-free survival time, 47 months; cumulative 2-year disease-free survival rate, 61%) than in patients undergoing nonanatomic resection (median disease-free survival time, 20 months; cumulative 2-year disease-free survival rate, 42%; P = .0121).

 

Figure 2
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  		FIG. 2. Kaplan-Meier survival estimates according to type of hepatic resection in 90 patients with pathologic T1 tumors. (A) Pos-tresectional survival was better in patients undergoing anatomic resection (median survival time, 122 months) than in patients undergoing nonanatomic resection (median survival time, 112 months), although the difference was not significant (P = .4301). (B) Disease-free survival was better in patients undergoing anatomic resection (median disease-free survival time, 58 months) than in patients undergoing nonanatomic resection (median disease-free survival time, 29 months), although the difference was not signifi-cant (P = .2340).

 

Figure 3
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  		FIG. 3. Kaplan-Meier survival estimates according to type of hepatic resection in 68 patients with pathologic T2 tumors. (A) Pos-tresectional survival was better in patients undergoing anatomic resection (median survival time, 111 months; cumulative 10-year survival rate, 47%) than in patients undergoing nonanatomic resection (median survival time, 33 months; cumulative 10-year survival rate, 0%; P = .0012). (B) Disease-free survival was better in patients undergoing anatomic resection (median disease-free survival time, 42 months; cumulative 2-year disease-free survival rate, 51%) than in patients undergoing nonanatomic resection (median disease-free survival time, 10 months; cumulative 2-year disease-free survival rate, 17%; P = .0004).

 
Pattern of Intrahepatic Recurrence After Resection
There was a significant difference in the pattern of intrahepatic recurrence between patients undergoing anatomic resection and patients undergoing nonanatomic resection (P = .011; Table 5Go). Intrahepatic recurrence after anatomic resection was characterized by fewer marginal recurrences and more recurrences in distal segments.


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  		TABLE 5. Pattern of intrahepatic recurrence after resection
 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Although earlier authors have implied that anatomic resection is oncologically superior to nonanatomic resection, there is a paucity of evidence supporting the benefits of anatomic resection in terms of long-term survival.7–9 This prompted us to conduct the current study, which demonstrated that anatomic resection led to improved survival in patients with pT1–T2 HCC. The better hepatic functional reserve observed in patients who underwent anatomic resection may partly explain this. In the current study, however, multivariate analyses revealed that anatomic resection is a favorable independent prognostic factor, suggesting that anatomic resection is an oncologically more effective treatment modality for pT1–T2 HCCs than nonanatomic resection.

In the current study, the long-term survival outcomes after anatomic resection were far better than those after nonanatomic resection, despite the larger tumor size and the higher prevalence of vascular invasion in patients undergoing anatomic resection. HCC primarily spreads through intrahepatic portal venous branches or hepatic venous tributaries.18,32,33 Intrahepatic recurrences after curative resection may be attributed mainly to venous tumor thrombi in the remnant liver tissue, whereas some of the intrahepatic recurrences may be due to multicentric carcinogenesis associated with the injured liver.34 It is apparent that anatomic resection eradicates venous tumor thrombi present within the anatomically resected domain. As the survival benefits of anatomic resection may be partly due to better clearance of venous tumor thrombi within the adjacent liver, we have intended to perform anatomic resection for HCC, provided that the patient is robust and that the hepatic functional reserve of the patient is at a level permitted for anatomic resection.35

Several methods for anatomic resection of the liver have been proposed.6,36–39 The "classical" controlled method is to isolate and ligate the main branches of the portal vein and hepatic artery extrahepatically and then to transect the liver parenchyma along the ischemic demarcation line.40,41 This method, however, is only applicable to hemihepatectomy or more extended hepatectomy. Another method is to first transect the liver parenchyma along the estimated location of a portal scissura, then to isolate and ligate the portal pedicle(s) of the tumor-related domain (anterior intrahepatic approach), and finally to transect the parenchyma along the demarcation line.42,43 The third is to first trace the border of the segment or segments on the surface of the liver under ultrasonic guidance, then to transect the parenchyma, and finally to isolate and ligate the portal pedicle of the segment.44 The disadvantage of the latter two methods is that both the portal scissurae and the border of segment may be difficult to locate before portal pedicle ligation. Another method involves ultrasonically guided subsegmentectomy that used dye injection mapping. This method, however, may be difficult for large tumors because they often receive two or more afferent portal pedicles. Finally, anatomic resection after intrahepatic portal pedicle ligation at the hepatic hilum (posterior intrahepatic approach) has been proposed20–22 and has been widely accepted over the past decade. Considering the disadvantages of other methods, we prefer this method and currently perform most anatomic resections via the posterior intrahepatic approach.

Hasegawa et al.7 reported that anatomic resection for solitary HCC (pT1 or pT2) provides more favorable outcomes than nonanatomic resection. As a solitary HCC may be categorized as pT1 or pT2 according to the presence or absence of vascular invasion in the TNM staging system,18 one third of their patients had a pT2 tumor. The results of the current study also showed that anatomic resection was effective for pT1–T2 HCC (Fig. 1Go). As the status of vascular invasion cannot be evaluated accurately before resection, anatomic resection should be considered for all clinical T1–T2 tumors when feasible. In addition, new results from the current study found that after stratification according to pT classification, anatomic resection was only effective in patients with pT2 tumors (Fig. 3Go), whereas the outcome after anatomic resection was slightly better than that after nonanatomic resection in patients with pT1 tumors (Fig. 2Go). Thus, patients with pT2 tumors seem to be good candidates for anatomic resection.

Intrahepatic recurrences after resection of HCC occur as either intrahepatic metastases from the primary tumor or multicentric new lesions.34 Previous reports including ours34,45–47 have suggested that early (within approximately 2 years after resection) recurrences include both intrahepatic metastases from the primary and multicentric lesions, whereas late (more than approximately 2 years after resection) recurrences are predominantly of multicentric origin. In the current study, disease-free survival was better after anatomic resection, with the beneficial effect obvious within approximately 2 years after resection (Fig. 1BGo). Assuming that the incidence of multicentric lesions is constant with time and is not affected by the type hepatic resection, this observation implies that anatomic resection reduces the incidence of intrahepatic metastases from the primary tumor.

Serum AFP levels independently affected the outcome after resection in the current study. Experimental studies have suggested that AFP may enhance the proliferation of human HCC cell lines, probably through its specific membrane receptors.48 Earlier surgical investigations have suggested that high serum AFP levels are closely associated with both the high prevalence of vascular invasion and unfavorable outcomes after resection in patients with HCC.33,49,50 We previously reported similar results.35,51 Taken together, the above findings suggest that high serum AFP levels indicate unfavorable outcomes after resection, probably because of the enhanced proliferation of tumor cells and the possible presence of vascular invasion, which may lead to intrahepatic recurrences.

There are two main limitations to the current study. First, it was a retrospective analysis of a small number of patients. Second, the median follow-up time was short in some patients. However, we believe that these limitations do not greatly influence the outcome of the study, because the differences between groups were too marked to have resulted from these biases.

In conclusion, anatomic resection independently improves long-term survival in patients with T1–T2 HCC, probably because of the clearance of venous tumor thrombi within the resected domain.

Received for publication March 16, 2006. Accepted for publication November 22, 2006.


   REFERENCES
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 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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