Resection For Small Hepatocellular Carcinoma Research Articles

Minor versus major hepatic resection for small hepatocellular carcinoma (HCC) in cirrhotic patients: A 20-year experience

The choice between minor versus major resection or anatomic versus nonantatomic resection for small (<5 cm) solitary hepatocellular carcinoma (HCC) in patients with cirrhosis is controversial. The aim of our study was to evaluate the long-term disease-free survival (DFS) and overall survival (OS) after minor or major hepatic resection for small solitary HCC in cirrhotic patients. Between January 1983 and December 2002, patients with solitary HCC of < or = 5 cm in size who had histologically proven liver cirrhosis and microscopically tumor-free margin were included. These selected patients underwent either minor (< or = 2 segments) or major (> or = 3 segments) hepatectomy. In 373 patients, 259 underwent minor and 114 underwent major hepatectomy. Patients in the minor resection group had more severe underlying liver disease (P = .005). Therefore, only 29.3% received anatomic resection in the minor resection group in comparison with 72.8% in the major hepatectomy group (P = .0001). No difference was found in postoperative morbidity (P = .105), mortality (P =.222), intrahepatic recurrence (P = .742), and 5-year DFS and OS (31.6% vs 31.8%, P = .932 and 50.7% vs 44.0%, P = .114) in both groups. The type of operative resection was not found to be a significant factor affecting survival in univariate analysis, but the preoperative liver function (alanine aminotransferase [AST] or alanine aminotransferase [ALT], serum albumin, or Child-Pugh status), tumor characteristics (alpha-feto protein, size, and presence of daughter nodules), and blood transfusion were found to be independent factors that affect the DFS and OS in a multivariate analysis. The severity of cirrhosis and tumor characteristics depicts long-term survival rather than the type of resection in HCC.

W1790 Percutaneous Radiofrequency Ablation Versus Surgical Resection for Small Hepatocellular Carcinoma: A Propensity-Score Matched Analysis

W1790 Percutaneous Radiofrequency Ablation Versus Surgical Resection for Small Hepatocellular Carcinoma: A Propensity-Score Matched Analysis

Predictive factors of advanced recurrence after curative resection of small hepatocellular carcinoma

The tumour recurrence rate after resection is still high even in patients with small hepatocellular carcinoma (HCC). The advanced patterns of recurrence occasionally occur after resection. In this study, we analysed the clinical and histological characteristics of small HCC and evaluated the predictive factors of advanced tumour recurrence. One hundred and sixty-five patients underwent resection of small HCC measuring 3 cm or less in greatest dimension. Patterns of tumour recurrences were classified into advanced recurrence and minor recurrence based on size, number, vascular invasion and extrahepatic metastasis of recurrent tumour. We created a simple index to closely evaluate the malignant potential of small HCC, named alpha-foetoprotein-size ratio index (ASRI). Overall tumour recurrence was significantly associated with tumour multiplicity (P<0.001) and ASRI (P=0.001). Tumour multiplicity, ASRI and tumour differentiation were independent and significant predictive factors of advanced recurrences. The overall survival rates were lower in the advanced recurrence group than the minor recurrence or the no recurrence group. Patients with advanced recurrences have a poor prognosis, although they have undergone curative resection of small HCC. On the other hand, patients with minor recurrences have a relatively good prognosis. ASRI was a useful index to predict advanced recurrence after curative resection of small HCC. The therapeutic management to prevent advanced recurrences is needed.

Risk factors and outcome of early recurrence after resection of small hepatocellular carcinomas

Background This study aimed to clarify risk factors for early recurrence and examine the subsequent outcome in patients undergoing potentially R0 resection of small hepatocellular carcinomas (HCCs) (≤2 cm in greatest dimension). Methods Eighty-nine patients were divided into 2 groups as follows: 26 patients suffering from recurrence within 2 years of surgery (early recurrence group) and 63 patients who were disease-free for at least 2 years (disease-free 2Y group). Results Only 7 of 63 patients (11%) from the group that was disease-free for at least 2 years died during the 5-year period after surgery, whereas 13 of 26 patients (50%) from the early recurrence group died. Multivariate analysis showed that the preoperative maximum removal rate of technetium-99m-diethylenetriamine pentaacetic acid-galactosyl human serum albumin and microscopic vascular invasion were independent predictors of the early recurrence of small HCC. Conclusions Early recurrence of small HCC is the leading cause of death within 5 years after R0 resection. The preoperative hepatic functional reserve influences early recurrence, even in patients with small tumors.

Prognostic Factors and Clinicopathologic Features after Resection of Small Hepatocellular Carcinoma (≤2 cm)

Purpose: Hepatectomy has been regarded as the first treatment of choice for small hepatocellular carcinoma. However, hepatectomy for treatment of small hepatocellular carcinoma remains a critical issue. This study evaluates the role of treatment regarding the survival rate and clinicopathological features after resection of small hepatocellular carcinoma (≤2 cm) Methods: This retrospective study was based on the medical records of 48 small hepatocellular carcinoma (≤2 cm) patients who received surgical hepatectomy from 1990 to 2005. Patients who revealed on postoperative pathologic reports were enrolled. The survival rate was analyzed according to clinicopathologic and therapeutic factors and we analyzed the pathologic features of the recurrence group. Results: The presence of liver cirrhosis, ICGR15 (Indocyanine green retension-15) was statistically significant in the univariate analysis. The vascular invasion rate and capsule formation rate was 90, 80% in the recurrence group. Conclusion: In the small hepatocellular carcinoma (≤2 cm), the presence of liver cirrhosis, ICGR15 (Indocyanine green retension-15) should be checked to predict prognosis. The small hepatocellular carcinoma (≤2 cm) is similar to advanced hepatocellular carcinoma so hepatectomy may play an important role in the small hepatocellular carcinoma (≤2 cm). (J Korean Surg Soc 2009;76:94-99)

Efficacy of anatomic resection vs nonanatomic resection for small nodular hepatocellular carcinoma based on gross classification

It has been reported that anatomic resection may be preferable to nonanatomic resection for small hepatocellular carcinomas (HCCs), by reducing so-called "micrometastases" (portal venous tumor extension and intrahepatic metastases). Nonanatomic resection or ablation has also been used as therapy for small HCCs. We studied the effectiveness of anatomic resection for small nodular HCCs, especially from the viewpoints of tumor size and gross classification. A retrospective cohort study was performed in 116 consecutive patients who underwent curative hepatic resection for HCCs 3 cm or smaller and with three or fewer nodules. The outcome of anatomic resection (including segmentectomy, sectoriectomy, and hemihepatectomy) was compared to that of nonanatomic partial hepatectomy. The group that underwent anatomic resection (n = 52) had relatively better overall survival and significantly better recurrence-free survival than those with nonanatomic resection (n = 64). On Cox multivariate analysis, however, liver function was more closely associated with survival. The effect of anatomic resection was more prominent in the subgroup with the nonboundary type nodules (single nodular type with extranodular growth, confluent multinodular type, and invasive type) than in the subgroup with the boundary type (vaguely nodular and single nodular type). Micrometastases in the nonboundary type were found further from the main tumor (9.5 +/- 6.2 mm) than those in the boundary type (within 3.1 +-1.4 mm). In patients with HCC nodules equal to or less than 3 cm and with the nonboundary type, anatomic resection should be employed to the extent that liver function allows, because this procedure would be more favorable than nonanatomic resection in eradicating micrometastases that have extended away from the tumor's margin.

Percutaneous tumor ablation or surgical resection for small hepatocellular carcinoma?

Percutaneous tumor ablation or surgical resection for small hepatocellular carcinoma?

Surgical treatment with microwave coagulo-necrotic therapy (MCN) and/or hepatic resection for small hepatocellular carcinoma

In our institute, hepatic resection and/or MCN have been used for HCC. This study assesses the efficacy of these treatments, especially for small HCC measuring 2 cm or less in greatest diameter.From July 1994 to March 2004, 60 patients with small HCC underwent hepatic resection (Hr) and/or MCN (Hr, 3; MCN, 55; Hr + MCN, 2).The cumulative 1-, 3-, and 5-year survival rates in MCN group were 100, 97.0, 91.6%, in Hr group were 100, 100, 100%, and in Hr + MCN group were 100, 100, - %. The cumulative 1-, 3-, and 5-year survival rates of Liver damage (LD)-A group were 100, 100, 100%, of LD-B group were 100, 100, 92.3%, and of LD-C group were 100, 0% (p < 0.0001).In conclusion, both Hr and MCN, especially MCN are the effective local treatment for small HCC with LD A or B.

Hepatitis C virus infection is a risk factor for tumor recurrence after resection of small hepatocellular carcinomas.

Hepatocellular carcinoma (HCC) is closely associated with chronic hepatitis B or C virus (HBV, HCV) infection. Tumor recurrence frequently occurs after surgical resection and may adversely affect the outcome. This study aimed to investigate the effect of viral hepatitis in association with HCC recurrence after resection. A total of 248 patients [HBV in 165, HCV in 44, dual HBV+HCV in 15, and non-B non-C (NBNC) in 24] who underwent curative resection for HCC were included. The cumulative recurrence rate was compared according to the etiology of the underlying hepatitis and was stratified by tumor size and other clinicopathologic parameters. Altogether, 116 patients (47%) had a tumor recurrence within 17 +/- 11 months after resection. No significant difference in recurrence was noted among the four groups of patients (HBV, HCV, HBV+HCV, NBNC) ( p = 0.248). Persistent hepatitis was more common in the HCV group ( p < 0.001) after resection. Among the 157 patients with a small (= 5 cm) tumor, the recurrence rate was significantly higher in the HCV group than in the HBV, HBV+HCV, and NBNC groups ( p = 0.036). Cox multivariate analysis showed that HCV infection [relative risk (RR) 4.4, 95% confidence interval (CI) 1.3-14.8, p = 0.018] and vascular invasion (RR 3.2, 95% CI 1.2-8.9, p = 0.044) were independent predictors of tumor recurrence. Stratified analysis in other parameters did not show significant differences in terms of tumor recurrence among the four virologic groups ( p > 0.1 for all parameters). In conclusion, patients with small HCCs and concurrent HCV infection are at a high risk of tumor recurrence after resection.

Appropriate surgical management of small hepatocellular carcinomas in patients infected with hepatitis C virus.

We investigated the incidence of recurrence after resection of small hepatocellular carcinomas (HCC) in patients infected with hepatitis C virus (HCV) to determine the appropriate surgical management of these patients. Sixty-one patients with anti-HCV antibody who underwent curative liver resection for small HCC (<or= 2.0 cm in greatest diameter) were categorized into two groups. Group 1 consisted of 27 patients with serum concentrations of type IV collagen 7S domain (7S collagen), a marker for hepatic fibrosis, < 8 ng/ml. Group 2 consisted of 34 patients with serum concentrations of 7S collagen >or= 8 ng/ml. Serum concentration of 7S collagen correlated with the severity of active hepatitis and the degree of fibrosis in the noncancerous hepatic tissue, both of which are related to risk potential of hepatocarcinogenesis. Serum concentration of total bilirubin, aspartate aminotransferase activity, indocyanine green retention rate at 15 minutes, the proportion of patients who were Child-Pugh class B, and the proportion of patients with severe active hepatitis or cirrhosis (determined by histologic examination) were significantly higher in group 2 than in group 1. Platelet count was significantly lower in group 2. Tumor-free survival rates were not different between the groups. In group 1, nonanatomic resection was a risk factor for recurrence by univariate and multivariate analyses (odds ratio = 3.45, p = 0.040). In group 2, nonanatomic resection was not a risk factor for recurrence. In patients with small HCV-related HCC, anatomic resection is recommended when the serum concentration of 7S collagen is low (< 8 ng/ml) because the potential of hepatocarcinogenesis may be low even after the operation.

Thirty years’ studies on surgery and related basic research of hepatocellular carcinoma

To emphasize the role of clinical innovation and basic research on the advances of hepatocellular carcinoma (HCC) surgery, related papers published by the author's institution in the last three decades and recent data were analysed. In the 1970s−1980s, diagnosis using alpha fetoprotein assay and innovation of limited resection instead of lobectomy have resulted in early diagnosis and resection of small HCC. These have led to a marked increase of long‐term survivors of HCC. In the 1980s−1990s, research works including establishment of human HCC nude mice model, experimental multimodality therapy and studies on targeting therapy have been conducted. These have made resection possible in some patients after downstaging of initially unresectable HCC. The 5‐year survival of unresectable HCC was improved. Since the early 1990s, research works have been carried out on metastatic recurrence of HCC, including the establishment of metastatic human HCC model, the molecular basis of HCC metastasis, angiogenesis and experimental intervention. These provide clues for prediction and prevention of metastatic recurrence of HCC. Translation from bench to bedside has resulted in improved disease free survival after curative HCC resection in a randomized control trial using interferon alpha. It is concluded, clinical innovation and basic research are essential for progress of HCC surgery.

Clinicopathologic features and factors related to survival of patients with small hepatocellular carcinoma after hepatic resection.

Hepatic resection for small hepatocellular carcinomas (HCCs) offers patients a chance of cure but is associated with a significant tumor recurrence rate. We characterized 145 resected small HCCs and defined patients who would most benefit from hepatic resection. A retrospective study was conducted of 485 HCC patients who had undergone curative resection. The clinical features and survival rates of patients with HCCs </= 3 cm (group 1, n = 145) were compared with those of patients with HCCs > 3 cm (group 2, n = 340). Compared with group 2 patients, group 1 had worse liver function, a higher frequency of hepatitis C infection, and a lower alpha-fetoprotein level. The 1-, 3-, and 5-year disease-free survival rates of group 1 were better than those of group 2 (82%, 59%, and 42% vs. 56%, 39%, and 31%, respectively) ( p < 0.001). From the sixth postoperative year onward, the proportions of disease-free survivors were not significantly different between the two groups (32% vs. 31%). By multivariate analysis, factors influencing small-HCC patients' outcomes were tumor centrally located ( p = 0.003), indocyanine green retention rate > 10% ( p = 0.017), and albumin level < 3.7 g/dl ( p = 0.004). A clinical risk scoring system incorporating these factors correlated closely with the patients' outcomes and it may be used to select patients who would most benefit from hepatic resection.

Preoperative predictors of survival after resection of small hepatocellular carcinomas.

To determine preoperative predictors of survival that can guide the choice of treatment for patients with small hepatocellular cancers (HCCs). The treatment of patients with small (</=5 cm in diameter) HCCs is controversial. A cohort of 249 patients (69 women, 180 men; median age 62 years) who underwent resection with curative intent for small HCC was identified from a multiinstitutional database. For each patient, the clinical data and pathology slides were reviewed. Six clinical factors (age, gender, preoperative alpha-fetoprotein level, hepatitis serology, number of tumors [single vs. multiple], and Child-Pugh score) and three pathologic factors (hepatitis activity score, fibrosis score, and Edmondson-Steiner tumor grade) that can be determined before surgery were correlated with survival. Log-rank tests and Cox proportional hazards modeling were used to determine factors influencing survival. The median overall survival for the entire cohort was 4.2 years. The estimated overall 5- and 8-year survival rates were 41.1% and 19.8%, respectively. Multivariate Cox analysis indicated that fibrosis score, Edmondson-Steiner grade, and Child-Pugh score were simultaneously significant predictors of survival after resection. A prognostic scoring system based on these covariates was derived and applied to the entire cohort. Patients lacking all three risk factors were assigned a score of 1, patients with one risk factor were assigned a score of 2, and patients with two or three risk factors were assigned a score of 3. Pairwise log-rank tests indicated significant differences in survival between scores 1 and 2, scores 2 and 3, and scores 1 and 3. This scoring system retained its prognostic significance when a subset of 98 patients with positive hepatitis C serology was analyzed separately. Patients with small HCCs who will derive the least benefit from resection can be identified before surgery using a score based on tumor grade and the severity of underlying liver disease. In these patients, transplantation and/or ablation should be considered as possible alternative therapies.

Long-term survival and pattern of recurrence after resection of small hepatocellular carcinoma in patients with preserved liver function: implications for a strategy of salvage transplantation.

To evaluate the survival results and pattern of recurrence after resection of potentially transplantable small hepatocellular carcinomas (HCC) in patients with preserved liver function, with special reference to the implications for a strategy of salvage transplantation. Primary resection followed by transplantation for recurrence or deterioration of liver function has been recently suggested as a rational strategy for patients with HCC 5 cm or smaller and preserved liver function. However, there are no published data on transplantability after HCC recurrence or long-term deterioration of liver function after resection of small HCC in Child-Pugh class A patients. Such data are critical in determining the feasibility of salvage transplantation. From a prospective database of 473 patients with resection of HCC between 1989 and 1999, 135 patients age 65 years or younger had Child-Pugh class A chronic liver disease (chronic hepatitis or cirrhosis) and transplantable small HCC (solitary < or =5 cm or two or three tumors < or = 3 cm). Survival results were analyzed and the pattern of recurrence was examined for eligibility for salvage transplantation based on the same criteria as those of primary transplantation for HCC. Overall survival rates at 1, 3, 5, and 10 years were 90%, 76%, 70%, and 35%, respectively, and the corresponding disease-free survival rates were 74%, 50%, 36%, and 22%. Cirrhosis and oligonodular tumors were predictive of worse disease-free survival. Patients with concomitant oligonodular tumors and cirrhosis had a 5-year overall survival rate of 48% and a disease-free survival rate of 0%, which were significantly worse compared with other subgroups. At a median follow-up of 48 months, 67 patients had recurrence and 53 (79%) of them were considered eligible for salvage transplantation. Decompensation from Child-Pugh class A to B or C without recurrence occurred in only six patients. For Child-Pugh class A patients with small HCC, hepatic resection is a reasonable first-line treatment associated with a favorable 5-year overall survival rate. A considerable proportion of patients may survive without recurrence for 5 or even 10 years; among those with recurrence, the majority may be eligible for salvage transplantation. These data suggest that primary resection and salvage transplantation may be a feasible and rational strategy for patients with small HCC and preserved liver function. Primary transplantation may be a preferable option for the subset of patients with oligonodular tumors in cirrhotic liver in view of the poor survival results after resection.

Is surgery for large hepatocellular carcinoma justified?

Background/Aims: Most hepatocellular carcinomas are still discovered at an advanced stage and are left untreated as large hepatocellular carcinomas are contraindications to liver transplantation and percutaneous ethanol injection and are usually considered as poor indications for liver resection. The aim of this study was to reassess the results of surgery in these patients. Methods: Between 1984 and 1996, 256 patients underwent resection of biopsy-proven, non-fibrolamellar hepatocellular carcinoma. Of these, 121 had a tumour diameter of less than 5 cm (small hepatocellular carcinomas) and 94 a tumour diameter of more than 8 cm (large hepatocellular carcinomas). The short- and long-term outcome of patients with small and large hepatocellular carcinomas were compared. Results: The in-hospital mortality rate following resection of small and large hepatocellular carcinomas was comparable (11.5 vs. 10.6%), even after stratifying for the presence and severity of an underlying liver disease. In patients with a chronic liver disease, large hepatocellular carcinomas were associated with a greater risk of death and recurrence during the first 2 operative years. In the long term, however (3–5 years), survival and disease-free survival following resection of small and large hepatocellular carcinomas were comparable (34 vs. 31% and 25 vs. 21% at 5 years). Similarly, treatment of and survival after the onset of recurrence were not influenced by the size of the initial tumour. Conclusions: Patients with large hepatocellular carcinomas should not be abandoned and should be considered for liver resection as this treatment may be associated with an in-hospital mortality rate and a long-term survival comparable to that observed after resection of small hepatocellular carcinomas.

Evaluation of surgical resection for small hepatocellular carcinomas

The surgical results for small hepatocellular carcinomas (HCCs) are not necessarily satisfactory. The resectional therapy for small HCC was evaluated to elucidate its benefits and limitations. Data were analyzed concerning 52 patients having small HCC of <3 cm in diameter and <3 nodules, who underwent hepatic resections from 1978 to 1989. Cumulative and disease-free survival at 5 years after resection were 57% and 37%, respectively. Histologic features, such as differentiation of HCCs, pseudocapsular invasion, and ploidy pattern of nuclear DNA, appeared to be good prognostic indicators. The survival rate of the large-resection group (number of resected segments greater than number of tumor-occupying segments) was significantly better than that in the small-resection group (84% versus 48% at 5 years, P<0.05). Surgical resection of small HCCs is a safe and effective therapy. A large resection appears to provide better patient survival and tumor-free survival compared to a small resection.

Surgical resection for small hepatocellular carcinoma

Surgical resection for hepatocellular carcinoma (HCC) can be curative in selected patients, particularly in those with a solitary small HCC (s-sHCC; 2 cm or less in diameter). However, even these patients often have a risk of tumor recurrence or death from underlying liver dysfunction. Therefore it is important to determine which clinicopathologic features are related to the long-term prognosis after resection of s-sHCC. Fifty patients with s-sHCC underwent partial hepatectomy at our department between 1977 and 1992. Six (12%) died of liver failure in hospital after operation. Eight clinicopathologic features were examined in the remaining 44 patients with regard to their long-term prognosis by use of univariate and multivariate analyses. The 1-, 3-, and 5-year survival rates were 90%, 75%, and 53%, respectively. The corresponding disease-free survival rates were 80%, 53%, and 30%, respectively. None of the following parameters was significantly related to survival rate or disease-free survival rate: presence of vascular invasion or capsular formation, the distance of free surgical margin (1 cm or more or not), serum alpha-fetoprotein level, positive hepatitis B surface antigen, and preoperative transarterial embolization. Complicated liver function was the only significant factor related to survival rate and disease-free survival rate. A good hepatic reserve is an important factor in treating patients with s-sHCC by surgical resection, even for a long-term prognosis. Liver transplantation should be considered for patients with severe cirrhosis and s-sHCC, even though a curative resection might be possible.

Secondary prevention of hepatocellular carcinoma.

Two decades have gone by since the earlier trials of alpha-fetoprotein (AFP) screening for hepatocellular carcinoma (HCC) were conducted in Africa and China. It is accepted that early detection, diagnosis and treatment of HCC remains an important target to be achieved before a breakthrough appears on the primary prevention of HCC. In the present study, screening investigations were performed in a high risk population of HCC, defined as persons who had hepatitis, blood transfusions, a family history of HCC, and were hepatitis B virus carriers. Ultrasonography combined with AFP serosurvey was accepted as an effective screening procedure to detect small HCC. Early diagnosis of HCC was not difficult if tumour markers and medical imaging were combined. Early resection has been proven to prolong survival of patients with small HCC. Repeated intralesional ethanol injection is an alternative treatment to surgery, while transcatheter arterial embolization is a less effective alternative. Re-resection of subclinical recurrence after curative resection has proven of merit in prolonging survival even further. Resection of small HCC remains an important approach in getting long-term HCC survival and to improving 5-year survival rates. It is more effective than treatment of large HCC. Studies on the secondary prevention of HCC have stimulated research into tumour markers, the natural history and cellular origin of HCC and oncogenes. However, the issue of 'cost-effectiveness' remains to be evaluated.

Nm23-H1 Expression and disease recurrence after surgical resection of small hepatocellular carcinoma

Background/Aims: The nm23-H1 gene is thought to act as a metastasis-suppressor gene. This study investigates the relationship between nm23-H1 messenger RNA (mRNA) expression and intrahepatic tumor recurrence after surgical resection of small hepatocellular carcinoma. Methods: Seventeen cirrhotic patients with solitary hepatocellular carcinoma <5 cm underwent surgical resection. In 7 patients, the neoplasm recurred after a 12-month median follow-up, whereas the other 10 patients were free of disease after a 30-month median follow-up. Both groups were similar according to age, sex, etiology, status of the underlying liver, tumor size, and other pathological characteristics of the neoplasm. nm23-H1 mRNA levels were assessed in matched tumor and surrounding cirrhotic liver samples by Northern blot hybridization using a 900-base pair probe, which is a BamHI fragment of pnm23-H1 recombinant complementary DNA clone encoding the nm23-H1 human gene. Results: Eight of the 10 patients without disease recurrence during follow-up showed nm23-H1 overexpression with an increase ranging between three- and 45-fold when compared with the nontumoral surrounding liver. Only 1 of the 7 patients with tumor recurrence showed higher nm23-H1 mRNA levels in the tumor than in the nonneoplastic sample (P = 0.013). Conclusions: nm23 mRNA overexpression in small solitary hepatocellular carcinoma is associated with a lower recurrence rate after surgical resection, suggesting that this gene may participate in the metastatic dissemination of this neoplasm.

Hepatic resection for small hepatocellular carcinoma: the Queen Mary Hospital experience.

The clinico-pathological features and long-term results of 39 patients with resected small hepatocellular carcinoma (HCC) managed over 19 years in Hong Kong were retrospectively studied (mean diameter +/- standard deviation: 3.6 +/- 1.3 cm). Thirty-one patients were symptomatic and the majority (n = 33) of them had cirrhosis. When compared with 182 patients with large HCC operated within the same period, these patients with small HCC had a significantly higher incidence of spontaneously ruptured lesions (p less than 0.03). Following hepatic resection-major lobectomy (n = 19) and limited hepatic resection (n = 20), operative and hospital deaths occurred in 7.7% and 12.8% of patients, respectively. The size of the lesion had little influence on prognosis. The overall survival at 1, 3, and 5 years was 59%, 28%, and 11%, respectively, which was comparable to patients with large HCC greater than or equal to 5 cm. Further stratification of these 39 patients according to a diameter of greater than 3 cm (n = 22) or less than or equal to 3 cm (n = 17) showed no difference in long-term outcome. When compared with large tumors, frequent encapsulation (p less than 0.04) and less venous permeation (p less than 0.03) were encountered in small HCC. As the extent of hepatectomy had no effect on long-term outcome, limited hepatectomy for patients with small HCC is probably the procedure of choice. A 1 cm macroscopic resection margin is apparently adequate to ensure complete histological disease clearance.