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BACKGROUND Recently, the implementation of screening programs using α-fetoprotein (AFP) and ultrasonography in high risk populations has identified increasing numbers of patients with small hepatocellular carcinoma (small HCC). The aim of this study was to summarize the authors' experience in patients who underwent hepatectomy for small HCC and the factors that influence or improve long term survival. METHODS The study included 1000 patients who underwent hepatectomy for small HCC (≤ 5 cm) and compared them with 1366 patients who underwent hepatectomy for large HCC (> 5 cm) during the same period. A Cox proportional-hazards model was used for multivariate analysis of prognostic factors. RESULTS Comparison between patients with small HCC (n = 1000 patients) and patients with large HCC (n = 1366 patients) revealed that those with small HCC had a higher resection rate (93.6% [1000 of 1068 patients] vs. 55.7% [1366 of 2451 patients]; P 0.05). Reresection for subclinical recurrence or solitary pulmonary metastasis after small HCC resection was undertaken in 84 patients. CONCLUSIONS Resection is still the modality of first choice for the treatment of patients with small HCC. Minor resection instead of lobectomy was the key to increasing resectability and decreasing operative mortality, and reresection for subclinical recurrence or solitary pulmonary metastasis was important approach to prolonging survival further. Cancer 2001;91:1479–86. © 2001 American Cancer Society.

By 1996, 2898 patients with pathologically proven hepatocellular carcinoma (HCC) had been treated at the Liver Cancer Institute of Shanghai Medical University. The 5 year survival in the entire series was 36.2%, being increased from 4.8% in 1958-70, 12.2% in 1971-83, to 50.5% in 1984-96 and 274 patients had survived more than 5 years. The increase in the survival rate could be attributed to the decreasing mean tumour diameter (11.7, 10.5 and 9.5 cm, respectively) and multimodality treatment. In addition to small HCC resection (5 year survival 64.9%, n = 735) and large HCC resection (5 year survival 37.4%, n = 1050), the following deserves to be mentioned. First, the 5 year survival of unresectable HCC treated by palliative surgery increased from 0% to 7.2% to 20.0%, which was related to the increase in use of multimodality treatment, particularly in those followed by second-stage resection. Second, cytoreduction and sequential resection is a new field with a significant potential in the treatment of localized unresectable HCC in a cirrhotic liver. Cytoreduction can be achieved by surgery, such as hepatic artery ligation, cannulation, cryosurgery and their combination, and followed by intrahepatic arterial chemoembolization, targeting therapy or regional radiotherapy. Ninety of 647 patients with unresectable HCC so treated had marked shrinkage of tumour and received second-stage resection; the 5 year survival was 71.4%. Third, non-surgical cytoreduction was mainly achieved by transcatheter arterial chemoembolization (TACE); for 70 patients with second-stage resection following TACE, the 5 year survival was 56.0%. Finally, re-resection of subclinical recurrence of tumour after curative HCC resection was performed in 155 patients; the 5 year survival calculated from the first resection was 50.9%, which played an important role in increasing the 5 year survival in the resection group (from 13.0% to 29.5% to 56.2%). It is concluded that multimodality treatment with combined and sequential use of different modalities and repeated use of some modalities is of substantial benefit for localized unresectable HCC.

Subclinical hepatocellular carcinoma (SCHCC) is defined as HCC without obvious HCC symptoms and signs. During 1958–1991, 391 patients with SCHCC were analyzed. In the entire series, 1) 67.3% was detected by natural population screening using alpha-fetoprotein (AFP) serosurvey, while the others were discovered by high-risk population screening or regular health checkup using AFP and/or ultrasonography (US); 2) AFP > 20 μg/L was found in 77.6% of patients; 3) serum hepatitis B surface antigen (HBsAg) was positive in 68.9%; 4) associated liver cirrhosis occurred in 89.1%; 5) the median tumor size was 5 cm, and small HCC (≦ 5 cm) amounted to 61.1%; 6) resection was done in 81.4%, and limited resection was performed in the majority (71.3%); 7) re-resection for subclinical recurrence was done in 44 patients; and 8) cytoreduction and sequential resection was carried out in 13 patients with unresectable SCHCC. Comparison between SCHCC and clinical HCC (n = 1,251) revealed higher resectability (81.4% vs. 46.8%), lower operative mortality (1.9% vs. 6.0%), and higher 5-year survival (entire series: 50.7% vs. 20.6%; resection: 60.5% vs. 36.8%). It is concluded that the study of SCHCC has resulted in marked improvement of ultimate outcome of HCC; screening in high-risk populations using AFP and/or US, limited resection, and re-resection for subclinical recurrence are some of the key features. © 1993 Wiley-Liss, Inc.

Fourteen patients with clinical Stage I hepatocellular carcinoma (T1N0M0) were studied. All patients were asymptomatic, and their conditions were detected by alpha-fetoprotein (AFP) serosurvey and/or ultrasonography (US) either in the natural population in the early years of the study or in the high-risk population in the later years of the study. Cirrhosis was present in all patients. Radical resection was performed in all patients. There were no operative deaths or hospital deaths in this series. The 5-year survival rate after resection was 100%. There were seven long-term survivors in this series (14.2 years (alive), 11.3 years (alive), 8.8 years (alive), 8.8 years, 7.9 years, 7.6 years (alive), and 7.2 years after resection). The authors discuss aspects concerning early diagnosis, treatment, and prognosis of hepatocellular carcinoma (HCC).

For decades, unresectable primary liver cancer (PLC) determined by operation was incurable. However, a retrospective study of 24 years' materials with unresectable PLC indicated that 5-year survival of unresectable PLC has increased from 0% in 1966-1977 (n = 137) to 16.9% in 1978-1989 (n = 345). This encouraging improvement was mainly a result of cytoreduction therapy followed by sequential resection. Multimodality combination treatment with hepatic artery ligation, plus hepatic artery infusion with chemotherapy, plus radioimmunotherapy (or radiotherapy) yielded the highest sequential resection rate (30.6%) and 5-year survival (28.0%) as compared with double combination and single modality treatment. The 5-year survival of 33 patients receiving sequential resection after cytoreduction therapy was 63.2%. It is suggested that cytoreduction and sequential resection might offer a hope for surgically verified unresectable PLC.

From July 1958 to June 1978, a total of 333 cases with pathologically proven primary liver cancer (PLC) were admitted to the Zhong Shan Hospital, Shanghai Medical University, Shanghai, the people's Republic of China. Of these, 39.6% (132 of 333) were resected and 14.4% (19 of 132) survived over 10 years after resection for PLC. These 19 patients surviving over 10 years were investigated in this paper. All 19 patients underwent radical resection, including right hemihepatectomy in two cases, left hemihepatectomy in ten cases, left lateral segmentectomy in three cases, and local resection in four cases. By the end of June 1988, follow-up varied from 10 years and 1 month to 26 years and 7 months, with a mean follow-up of 15 years and 4 months. All 19 patients are still alive with free of disease. The longest survival patient had a tumor measuring 10 X 8 X 6 cm in size and underwent local resection. Upon follow-up after 26 years and 7 months, the patient was found to be still living and well. Two patients with intraperitoneal ruptured PLC have survived for 19 years and 4 months, and 16 years and 11 months, respectively, after resection of the tumors free of disease and have returned to work. Subclinical recurrence of PLC was discovered in one patient in whom reoperation with cryosurgery was carried out. The patient has been in good condition with negative alpha-fetoprotein (AFP) for 8 years and 10 months after cryosurgery. Subclinical solitary pulmonary metastasis was detected in two patients because of a secondary rise in AFP level. Reoperations were carried out and the metastatic tumors were removed. These two patients are still in good health with negative AFP 9 years and 6 months, and 10 years and 1 months, respectively, after reoperation. These results indicate that early and radical resection are the principal factors influencing long-term survival; reoperation for subclinical recurrence and solitary metastasis remains an important approach to prolong survival further; intraperitoneal rupture of PLC does not exclude the possibility of cure; new surgical techniques, such as cryosurgery and bloodless hepatectomy, have been shown to be effective in some patients.

A long-term follow-up study of 144 cases with surgically and pathologically proved small hepatocellular carcinoma (less than or equal to 5 cm) from 1967 to 1987 is reported. One hundred eight cases (75.0%) were detected by alpha-fetoprotein serosurvey and/or ultrasonography mainly in a high-risk population; 129 cases (89.6%) coexisted with cirrhosis. Resection was done in 132 cases (91.7%) with three (2.3%) operative deaths; cryosurgery, laser vaporization, and hepatic arterial chemotherapy were used in the rest. Limited resection was done in 67.4% of resections. Reresection of subclinical recurrence or solitary pulmonary metastasis was done in 21 cases. The 5-year and 10-year survival rates were 67.9% and 53.4% in the resection group but zero in the nonresection group. Survival was correlated negatively with tumor size, 5-year survival after resection was 84.6% in tumors less than or equal to 2 cm but 59.5% in tumors of 4.1 to 5 cm. The increase of resectability and reresection resulted in marked improved of 5-year survival from 43.5% in 1973 to 1977 to 63.3% in 1978 to 1982 in the entire series. No significant difference was found between survival of limited resection and lobectomy. Resection may be the modality of choice for treatment of small hepatocellular carcinomas with compensated liver function. Limited resection instead of lobectomy was the key to increased resectability and decreased operative mortality in cirrhotic livers. Reresection of subclinical recurrence was important to prolong survival further.

Sixty-six patients surviving over 5 years after resection of hepatocellular carcinoma (HCC) are investigated. Of them, subclinical stage amounted to 56.1% (37/66) and moderate stage to 43.9% (29/66). There were 35 cases with small HCC (less than or equal to 5 cm). Cirrhosis was present in 81.1% (54/66). Radical resection was performed in 98.5% (65/66) and palliative resection in 1.5% (1/66). Reoperation for subclinical recurrence and solitary pulmonary metastasis was done in 14 patients, and sequential resection of huge tumors, in three patients. By the end of June 1988, follow-up varied from 60 to 319 months (mean, 115 months); 80.3% of the patients (53/66) are still alive and free of disease; 19.7% (13/66) died with disease. The majority of long-term survivors have returned to their original work; some young patients got married after resection of small HCC 10 years ago, and some can even play football again. Some aspects to improve long-term survival are discussed.