Bing-Hui Yang

Surgery of small hepatocellular carcinoma. Analysis of 144 cases

A long‐term follow‐up study of 144 cases with surgically and pathologically proved small hepatocellular carcinoma (±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 < 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.

Prospective study of early detection for primary liver cancer

In order to evaluate the effectiveness of early detection for primary liver cancer (PLC), a randomized, prospective study was performed in Shanghai from 1992 to 1995. The study population was 35 through 55 years of age, with serum evidence of HBV infection or tory of chronic hepatitis. Seventeen thousand nine hundred and twenty individuals were randomly to allocated screening group and control group. In the screening group, every individual was checked up by serum AFP test and ultrasound every 6 months and in the control group, they were unchecked. After a mean time of 1.2 years, 38 patients with PLC in the screening group were detected while 18 patients with PLC occur in the control group. In patients from the screening group, 76.8% were in subclinical stage, 70.6% of them were treated by surgical resection with 1-, 2-year survival rate of 88.1% and 77.5%, respectively. However, in the control group, none of patients was in subclinical stage, none of the tumors resected, and none of patients survived over 1 year. The lead time was estimated to be 0.45 years. The cost for detecting an early stage PLC patient is RMB 12,600 (US

Inhibitory effect of the angiogenesis inhibitor TNP-470 on tumor growth and metastasis in nude mice bearing human hepatocellular carcinoma.

1,500). The study indicates that screening in the high risk population of PLC can detect patients in early stage, increase the resection rate and the survival rate. Screening program for PLC carried out in high risk populations is thus recommended.

Recurrence after resection of alpha-fetoprotein-positive hepatocellular carcinoma.

The antitumor and anti-metastatic effects of a potent angiogenesis inhibitor,O-(chloroacetyl-carbamoyl)fumagillol (TNP-470), was investigated in a highly metastatic model of human hepatocellular carcinoma—LCI-D20. Small pieces of LCI-D20 tumor tissue were implanted subcutaneously into the right axillary region of 24 nude mice; the mice were then randomized into two groups. To one group, TNP-470 30 mg/kg was given as a subcutaneous injection every other day from day 1 to day 15 and the mice were sacrificed on day 26. An antitumor effect of TNP-470 was clearly demonstrated by tumor weight (0.97±0.34 g compared to 2.04±0.34 g,P<0.001) and α-Fetoprotein value (93±59 μg/L compared to 769±282 μg/L,P<0.001). There was also an anti-metastatic effect of TNP-470. Lung metastases developed in only 1 of 12 mice in the treated group, while they developed in 6 of mice of the control group. No severe side-effect of TNP-470 was found in this study. In vitro study revealed that the purified hepatoma cells were insensitive to TNP-470 (the 50% inhibitory concentration was 43 μg/ml). These results suggest that the angiogenesis inhibitor TNP-470 has both strong antitumor and anti-metastatic effects on a human hepatocellular carcinoma model in nude mice.

Solitary minute hepatocellular carcinoma. A study of 14 patients

The long-term prognosis of surgery for hepatocellular carcinoma (HCC) is not yet satisfactory, the main reason being the high recurrence rate. The authors report the results of a long-term follow-up of 308 patients with HCC who became α-fetoprotein-(AFP)-negative after resection between 1975 and 1991. By March 1992, there was recurrence in 134 patients (43.5%). The 1-, 3-, 5- and 10-year recurrence rates were 9.2%, 38.8%, 54.9% and 85.0%, respectively. The 5-year survival rate was 49.7% for patients who had undergone a second hepatic resection (n=48). Analysis of factors influencing postoperative recurrence indicated that patients subjected to mass survey, with a lower γ-glutamyltransferase level, at an early stage of TNM classification, with a tumour of less than 5 cm, without tumour embolus, and with postoperative immunotherapy had a lower incidence of recurrence. It is concluded that the earlier the disease is diagnosed, the less the recurrence rate; adjuvant immunotherapy may reduce postoperative recurrence, and the early detection and resection of a recurrent tumour are important to prolonging survival further after curative resection of HCC.

Long-term results of surgery for small primary liver cancer in 514 adults

Fourteen patients with clinical Stage I hepatocellular carcinoma (T1NOMO) 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).

Characteristics and prognosis of primary liver cancer in young patients in China

During 1958–1993, 2030 patients with pathologically proven primary liver cancer (PLC) were retrospectively reviewed. Comparison between small PLC (<-5 cm,n=514) and large PLC (>5 cm,n=1516) revealed that small PLC had a higher resection rate (92.4% versus 49.1%), lower operative mortality (1.7% versus 5.2%), a higher percentage of single tumour nodules (78.0% versus 53.4%), a higher percentage of well encapsulated tumour (74.5% versus 35.8%) and higher survival rates after resection (5-year, 63.8% versus 36.6%; 10-year, 46.8% versus 28.5%). No significant difference was found between survival following limited resection (n=440) and lobectomy (n=34) in patients with small PLC. Re-resection of any subclinical recurrence or solitary pulmonary metastasis after small PLC resection was done in 70 cases. These results indicate that resection is still the modality of choice for treatment of small PLC; limited resection instead of lobectomy was the key to increasing resectability and decreasing operative mortality; re-resection of subclinical recurrence was important to prolong survival further.

Treatment of hepatocellular carcinoma: A summary of 33 years' experience

To investigate the clinicopathologic characteristics of primary liver cancer (PLC) in young adults, 77 patients aged 35 or younger were compared with 603 patients older than 35 years during the same period. In the young patients, PLC showed: (1) a low incidence detected at mass survey (young 15.6% vs older 28.7%,P<0.05); (2) a low level of history of hepatitis (young 36.8% vs older 66.3%,P<0.01); (3) a high incidence of positivity for hepatitis B surface antigen (HBsAg) (young 79.2% vs older 67.6%,P<0.05); (4) a relatively low incidence of associated cirrhosis (young 64.9% vs older 90.7%,P<0.01); (5) larger tumor size (PLC>5 cm; young 87.0% vs older 73.0%,P<0.01); and (6) a more advanced stage of the disease according to the TNM classification (stage III; young 29.9% vs older 18.2%,P<0.05). It is suggested that hepatitis B virus (HBV) may play an important role in the development of PLC without associated liver cirrhosis in young patients. Close periodic surveillance of young adults who are positive for HBsAg is important to detect PLC at an early stage.

Multimodality treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC), the most common type (90-95%) of primary liver cancer (PLC), causes 100,000 deaths every year in China. However, based on various strategies aimed at controlling this neoplasm, HCC has become “partly curable” instead of “incurable.” In China, hepatectomy for HCC started in the 1950s, liver cancer cell lines were established in the 1960s, field work in high risk areas, including epidemiology, etiology, and screening, have been conducted from the 1970s [1,2], and small HCC resection became an important clinical feature in the 1970s and 1980s [3–7]. During the past ten years, substantial progress has been made in the field of basic liver cancer research, studies have focused on the relation between hepatitis B virus (HBV) and HCC, a set of protooncogenes and HCC-related genes have been studied, and cytoreduction and sequential resection for unresectable HCC have become new trends [8].

Evaluation of Early Detection and Treatment of Hepatocellular Carcinoma

Abstract 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.