Ji-Zhen Lu

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.

Experience with liver resection after hepatic arterial chemoembolization for hepatocellular carcinoma

The use of percutaneous transcatheter hepatic arterial chemotherapy and embolization in the treatment of primary liver cancer has become increasingly popular in recent years. The authors employed this method, using a combination of cisplatin, mitomycin C, 5‐fluorouracil, and ethiodized oil (Lipiodol) or absorbable gelatin sponge in 30 patients with huge liver cancers (diameter range, 5.6–12.0 cm) as a preliminary treatment before liver resection. Significant tumor regression occurred after this treatment, converting these tumors into resectable lesions that were excised successfully later. Before surgery, chemoembolization was done once every 4–6 weeks. The patients underwent 1–5 treatment sessions (mean, 2.9) and then waited 1–4 months (mean, 2.4 months) before undergoing surgery. Alpha‐fetoprotein levels decreased to normal in seven patients. The tumor diameters were reduced by 31.6 ± 15.2% (2.3 ± 1.2 cm) and the percent tumor necrotic area ranged from 40–100%. Adhesions of the tumor to the diaphragm and thickening of the hepatoduodenal ligament and gallbladder wall were the primary operative findings, but they did not significantly complicate the surgery. There was one postoperative death from acute pulmonary embolism. The 1‐year, 2‐year, and 3‐year survival rates were 88.89%, 77.03%, and 77.03%, respectively. Although these patients still are being followed to assess their longterm survival, this treatment appears promising for patients with advanced huge liver cancers who hitherto have been denied surgery on grounds of unresectability. Cancer 1993; 71:62‐5.

Improved Survival with Resectionafter Transcatheter ArterialChemoembolization (TACE) for Unresectable Hepatocellular Carcinoma

Aim: This retrospective study was undertaken to analyze the outcome of hepatic resection in hepatocellular carcinomas (HCCs) that shrunk after transcatheter hepatic arterial chemoembolization (TACE) in 65 patients with unresectable HCCs between June 1987 and September 1996. Materials and Methods: Among these 65 patients, the median diameter of the tumor was 9.9 cm (5.6–20.0) prior to the first TACE, after 1–6 times of TACE (median 3) the median tumor diameter reduced to 3.7 cm (1.9–12.5) prior to resection. The duration between the last TACE treatment and sequential resection varied from 1 to 9 months (median 2.5). Serum α-fetoprotein (AFP) levels were abnormal in 39 out of the 65 patients. In AFP producing HCCs, the AFP level returned to normal (≤20 µg/l) in 14 out of 39 patients (35.9%). Hepatic segmentectomy, multiple hepatic segmentectomy or partial hepatic resection were performed in 61 patients, right hemihepatectomy in 1, left trisegmentectomy in 2, and left hemihepatectomy in 1. Results: Tumor necrosis ranged from 40 to 100% and pathologically and complete tumor necrosis occurred in 11 patients (16.9%). Of 14 patients with AFP levels decreased to normal, 10 still had microscopic living tumor foci. The 1-, 3- and 5-year survival rates of the 65 patients were 80.0, 65.0 and 56.0% respectively. Conclusion: TACE treatment can provide a chance of tumor resection for those patients with initially judged unresectable HCCs, and liver resection should be performed when the tumor has shrunk to be resectable, even when the AFP level has returned to normal.

Improved long-term survival for unresectable hepatocellular carcinoma (HCC) with a combination of surgery and intrahepatic arterial infusion of 131I-anti-HCC mAb. Phase I/II clinical trials

Abstract Resectional therapy has been accepted as the only curative therapy for hepatocellular carcinoma (HCC). Unfortunately, it is estimated that only 10% of HCC are resectable at the time of diagnosis. Cytoreduction and sequential resection offer a new hope for patients with unresectable HCC. Radioimmunotherapy (RIT) is an attractive approach for cytoreduction. We have previously shown that intrahepatic arterial 131I-labelled anti-HCC monoclonal antibody (131I-Hepama-1 mAb) could be used safely in combination with hepatic artery ligation for treatment of unresectable HCC, and encouraging results have been achieved. In this paper, the long-term survival and the prognostic factors in HCC patients treated with radioimmunotherapy will be analysed. Sixty-five patients with surgically verified unresectable HCC were treated with hepatic artery ligation plus hepatic artery cannulation and infusion from 1990 to 1992. Thirty-two patients were enrolled in a phase I–II clinical trial with infusion of 131I-radiolabelled anti-HCC monoclonal antibody (Hepama-1 mAb) via the hepatic artery (the RIT group). Another 33 patients formed the group treated with intrahepatic-arterial chemotherapy (the non-RIT group). T cell subsets were measured in 24 patients and human anti-(murine Ig) antibody (HAMA) were monitored in the RIT group. The 5-year survival rate was significantly higher in the RIT group than in the chemotherapy group, being 28.1% compared to 9.1% (P < 0.05); this was mainly a result of better cytoreduction and a higher sequential resection rate (53.1% compared to 9.1%). Significant prognostic factors in the RIT group included tumour capsule status and the number of tumour nodules. HAMA incidence and CD4+ T lymphocytes influenced short-term, but not long-term survival. It is suggested that intrahepatic-arterial RIT, using 131I-Hepama-1 mAb, combined with hepatic artery ligation might be an effective approach to improve long-term survival in some patients with unresectable HCC, which may successfully be made resectable by intra-arterial infusion of 131I-Hepama-1 mAb.

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

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.

Radioiodinated anti-hepatocellular carcinoma (HCC) ferritin Targeting therapy, tumor imaging and anti-antibody response in HCC patients with hepatic arterial infusion

SummaryRadioimmunoimaging and radioimmunotherapy with radioiodinated anti-(hepatocellular carcinoma ferritin) antibody (131I-or125I-FtAb) have been applied in patients with primary liver cancer. A total of 41 patients with surgically unresectable hepatocellular carcinoma (HCC) and receiving hepatic artery ligation and cannulation during exploratory laparotomy were treated with this regimen by intrahepatic arterial infusion. Compared with the control group, a decline of serum α-fetoprotein (65.7% versus 42.9%) and shrinkage of tumor (68.3% versus 33.9%) were observed in the treated group, and a higher second-look resection rate (31.7% versus 5.1%) and longer survival (1-year: 61.0% versus 37.3%, 3-year: 25.0% versus 6.9%) resulted. The administration of antibody through a hepatic arterial catheter (n=16) was compared with intravenous injection (n-17) in terms of the tumor-imaging sensitivity in 33 patients with liver cancer. The results indicated that hepatic arterial infusion was superior to intravenous injection. The sensitivity 7 days after the administration was 100% in the i.a. group and 76.5% in the i.v. group, the uptake ratio of tumor to liver being 1.74±0.57 in the former and 1.34±0.29 in the latter. Furthermore, intrahepatic arterial infusion revealed a lower anti-antibody detection rate than intravenous injection (0/14 versus 4/11).

Solitary minute hepatocellular carcinoma. A study of 14 patients

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).

Human anti-(murine Ig) antibody responses in patients with hepatocellular carcinoma receiving intrahepatic arterial 131I-labeled Hepama-1 mAb. Preliminary results and discussion

Human anti-(murine Ig) antibody (HAMA) responses were monitored in 32 patients with unresectable hepatocellular carcinoma (HCC) undergoing radioimmunotherapy using131I-labeled anti-HCC monoclonal antibody (Hepama-1 mAb) intrahepatic arterial infusion. Dosages of Hepama-1 mAb ranged from 5 mg to 20 mg and the mAb was radiolabeled with 0.74–4.00 GBq (20–108 mCi)131I (4–6 mCi/mg). T lymphocyte subsets were examined before and after radioimmunotherapy in 24 patients. In this series, 34.4% (11/32) of patients developed HAMA within 2–4 weeks after the infusion. All patients with a negative HAMA response (n=14). had CD4+ T lymphocyte subsets (T helper/inducer) much lower than those of the HAMA-positive (n=10) patients and the control group (n=40) (P<0.01) prior to infusion. The sequential resection and survival rates in the HAMA-negative group were also lower than that of the HAMA-positive group. Thus, the determination of T lymphocyte subsets might help to predict the HAMA response in HCC patients during radioimmunotherapy.

Resection of the primary liver cancer of the hepatic hilus

Primary liver cancer (PLC) of the hepatic hilus was designated as a tumor situated at the main branch of the portal vein or pedicle of the hepatic veins in contact with the intrahepatic vena cava. That is, the main tumor located at segment I, IV, V, or VIII and concentrating on the central part of the liver was called “the central type of PLC,” which differed from a tumor located at segment II, III, VI, or VII; the latter was called “the peripheral type of PLC.” Surgical treatment of the PLC has been significantly improved in the past two decades, but the resection of the central type of PLC is difficult and hazardous. This institution admitted 903 PLC from January 1970 to April 1988, of which 118 cases were the central type; 65 cases were resected successfully, a resectability of 55.1%. One patient died from sepsis within 1 month of operation (mortality 1.53%). The modes of operation for the different segments are described, and suggestions for improvements are presented. The survival rates were compared with a similar number of patients with the peripheral type of tumor in the same period and treated by the same surgeons. The results show noticeable differences. The one‐year, three‐year, and five‐year survival rates after resection were 70.9%, 43.2%, and 39.2% in the central type of PLC; they were 98.3%, 85.0%, and 76.4% in the peripheral type of PLC (P < 0.001). Further discussion of improvements in surgical techniques and mental awareness are suggested.

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

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.