Ye-Qin Yu

Clinical evaluation of cryosurgery in the treatment of primary liver cancer Report of 60 Cases

Cryosurgery with liquid nitrogen was employed for the treatment of 60 patients with primary liver cancer (PLC) at the Liver Cancer Research Unit, Zhong Shan Hospital, Shanghai Medical University, the Peoples Republic of China, from November 1973 to August 1987. Of 60 patients, subclinical stage amounted to 35% (21/60), moderate stage 55% (33/60) and late stage 10% (6/60). There were 21 cases with small PLC (⩽5 cm). The postoperative course was uneventful in all of the 60 patients. These was no operative mortality, and there was no complications such as rupture of tumor, secondary bleeding, bile leakage, or abdominal infection. The 1‐year, 2‐year, 3‐year, 4‐year, and 5‐year survival rates were 51.7% (30/58), 33.9% (19/56), 20.8% (11/53), 15.6% (7/45), and 11.4% (5/44), respectively, for the whole series. Among the 21 patients with tumor nodules ⩽5 cm in diameter, the 1‐year, 2‐year, 3‐year, 4‐year, and 5‐year survival rates were 76.2% (16/21), 61.9% (13/21), 50.0% (9/18), 41.2% (7/17), and 37.5% (6/16), respectively. These results indicate that hepatic cryosurgery is a promising, safe, and simple treatment for neoplastic disease of liver. Cryosurgery with liquid nitrogen can be considered the surgery of choice for nonresectable PLC in patients without jaundice, ascites, and noncompensated liver function, and the whole tumor mass can be involved in the frozen area.

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.

The role of cryosurgery in the treatment of hepatic cancer: a report of 113 cases

From November 1973 to June 1992, cryosurgery with liquid nitrogen (−196°C) was performed on 113 patients with hepatic cancer, including 107 patients with primary liver cancer (PLC) and 6 patients with secondary liver cancer (SLC). Of the 107 PLC patients, the subclinical stage constituted 30.8% (33/107), the moderate stage 61.7% (66/107), and the late stage 7.5% (8/107). There were 32 cases with small PLC (up to 5 cm). Liver cirrhosis was observed in 86.0% (92/107). We designed flat cryoprobes for freezing surface tumors, and single and multiple trocar cryoprobes for freezing tumors deep within the hepatic parenchyma. Intraoperative ultrasound was used for monitoring hepatic cryolesions. There were no operative mortalities and complications, such as rupture of a tumor, delayed bleeding, or bile leakage. The 5-year and 10-year survival rates were 22.0% and 8.2%, respectively, for the 107 PLC patients and 48.8% and 17.1%, respectively, for the 32 patients with small PLC. Of the 6 SLC patients, survival ranged from 2 months to 90 months (average, 23.2 months). One SLC patient has been well for 7 years and 6 months after cryosurgery. These results indicate that cryosurgery, the in situ freezing of cancer, is a safe and effective treatment for unresectable hepatic cancer.

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.

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.

Metastatic models of human liver cancer in nude mice orthotopically constructed by using histologically intact patient specimens.

In this study of orthotopic implantation of histologically intact surgical specimens, the authors constructed metastatic models of human hepatocellular carcinoma (HCC) in nude mice. Histologically intact human liver cancer specimens, derived from patients, were implanted directly into the liver of nude mice, and their orthotopic growth and metastases were observed. The transplantability and metastatic rate of two specimen groups (primary and metastatic lesions) were analysed. α-Fetoprotein (AFP) was also determined in transplanted tumours by an immunohistochemical method. Orthotopic growth was observed in 14 of 30 transplanted specimens and formation of metastases in 7 cases, which exhibited the variety of clinical behaviours seen in patients with HCC. These behaviours included local growth, regional invasion, spontaneous intrahepatic, lymph node and lung metastasis and peritoneal seeding. In two groups the growth rate of metastatic lesions following implantation was clearly higher than that of primary tumours. Chromosome analysis from locally growing tumours confirmed their morphologically human origin. An immunohistochemical study showed that implanted tumours originating from AFP-positive specimens maintained AFP expression. These results indicated that the animal models should prove valuable for developing new treatment modalities and studying the mechanism of metastasis of human HCC.

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).

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.