Treatment Of Primary Liver Cancer Research Articles

Caspase-3 gene transfected with LIGHT gene: can it be used for therapy of human hepatocellular carcinoma?

The aim of this study was to detect the expression of apoptosis factor caspase-3 in transferred HepG2 cells and provide feasible evaluation of the treatment for primary liver cancer with gene methods. The pcDNA4C-LIGHT cDNA was extracted from Escherichia coli JM-109; then, the pcDNA4C-LIGHT cDNA was transferred into the HepG2 cells by a cationic liposome mediated method. Meanwhile, the blank group was established as the control group and the HepG2 cells were collected after transfection at 12 h, 24 h, 48 h, 3 days and 5 days. The expression of caspase-3 was identified in the supernatants by ELISA. A standard curve was generated for the set of samples assayed. Statistical significance was analyzed by SPSS. The quantity of caspase-3 protein was the greatest at 48 h and the least on day 5. The secretion of caspase-3 did not increase in the control group. The coefficient of correlation was equal to 0.9986 and had evident significance. The pcDNA4C-LIGHT was effectively transfected in human HepG2 cells mediated by liposome. The expression of caspase-3 increased in the transfected group. This study provides necessary theoretic support for the treatment of liver cancer with gene methods.

Radionuclide Liver Cancer Therapies: From Concept to Current Clinical Status

Primary and secondary liver cancer have longtime been characterized by an overall poor prognosis since the majority of patients are not candidates for surgical resection with curative intent, systemic chemotherapy alone has rarely resulted in long-term survival, and the role of conventional external beam radiation therapy has traditionally been limited due to the relative sensitivity of the liver parenchyma to radiation. Therefore, a host of new treatment options have been developed and clinically introduced, including radioembolization techniques, which are the main topic of this paper. In these locoregional treatments liver malignancies are passively targeted because, unlike the normal liver, the blood supply of intrahepatic tumors is almost uniquely derived from the hepatic artery. These internal radiation techniques consist of injecting either yttrium-90 ((90)Y) microspheres, or iodine-131 ((131)I) or rhenium-188 ((188)Re) labeled lipiodol into the hepatic artery. Radioactive lipiodol is used exclusively for treatment of primary liver cancer, whereas (90)Y microsphere therapy is applied for treatment of both primary and metastatic liver cancers. Favorable clinical results have been achieved, particularly when (90)Y microspheres were used in conjunction with systemic chemotherapy. The main advantages of radiolabeled lipiodol treatment are that it is relatively inexpensive (especially (188)Re-HDD-lipiodol) and that the administration procedure is somewhat less complex than that of the microspheres. Holmium-166 ((166)Ho) loaded poly(L-lactic acid) microspheres have also been developed and are about to be clinically introduced. Since (166)Ho is a combined beta-gamma emitter and highly paramagnetic as well, it allows for both (quantitative) scintigraphic and magnetic resonance imaging.

Progress in research on the treatment of primary liver cancer with traditional Chinese medicine for activating blood to resolve stasis

Progress in research on the treatment of primary liver cancer with traditional Chinese medicine for activating blood to resolve stasis

Treatment of primary liver cancer by orthotopic liver transplantation

目的 探讨我国肝移植治疗原发性肝癌的手术适应证及效果.方法回顾性分析我院1999年2月至2004年连续施行的170例原位肝移植手术,对其中原发性肝癌62例的临床分期,手术方式及术后长期生存情况等进行分析,探讨手术指征及效果.结果 62例肝癌肝移植病人,随访1～39个月,住院期间死亡4例(6.45%),存活病例1、2、3年肿瘤复发转移率分别为29.31%,41.38%,58.06%;1、2、3年生存率分别为87.45%,65.59%,42.06%,进一步分析发现肿瘤直径<5cm者6例,全部无瘤生存;肿瘤伴门静脉主干癌栓者7例,除1例无瘤生存1年2个月外余均于1年内复发或死亡.结论晚期肝癌尚无门静脉主干癌栓者可作为我国肝移植指征,应进一步探索围手术期防治肝癌复发转移措施,进一步提高我国肝癌肝移植的疗效。

Treatment of Primary Liver Cancer with Postoperative After-Loading Radiotherapy and Gemcitabine

Objective: To evaluate the curative effectiveness of postoperative after-loading radiotherapy with the use of gemcitabine in 22 patients with primary liver cancer. Methods: From Oct. 1999 to Dec. 2001, 22 patients with primary liver cancer underwent postoperative after-loading radiotherapy 3-10 days after hepatectomy and chemotherapy using gemcitabine (1400 mg every week for 3 weeks, repeated after one week interval, total cycles were 6) and compared with 22 cases of sole hepatectomy. Three-six catheters were placed for irradiation after hepatectomy. The single-dose of after-loading radiotherapy was 10 Gy, 2-4 sessions per person. Results: The rate of AFP negative-reversion was 100% (17/17) in the treated group, higher than in control group (62.5%, 10/16, P<0.05). In the treated group, the 1-year relapse rate, metastasis rate and survival rate were 18.2% (4/22), 0 and 100% (22/22) respectively, while in the control group they were 45.5% (10/22), 13.6% (3/22) and 77.3% (17/22) respectively. There were significant differences between the two groups in relapse rate, metastasis rate and survival rate within a year (P<0.05). Conclusion: Postoperative after-loading radiotherapy with gemcitabine is an effective way for the treatment of primary liver cancer.

A Critical Evaluation of Hepatic Resection in Cirrhosis: Optimizing Patient Selection and Outcomes

Hepatic resection has long been the mainstay of treatment of primary liver cancers, particularly hepatocellular carcinoma (HCC). Because of the high incidence of cirrhosis in patients with HCC, the use of resection was initially limited by the ability of the cirrhotic liver to sustain the surgical insult and the mass reduction. Today, hepatectomy in cirrhosis is undergoing a remarkable evolution. Although surgical and anesthetic improvements have increased the safety of this option, the rapid development of alternative therapies has decreased the need for it. Local excision for small HCC is likely to be replaced by image-guided, percutaneous ablative techniques. Furthermore, total replacement of a cirrhotic liver may be a more effective long-term cure than resection. Unquestionably, resection remains the optimal approach for patients with large tumors and healthy underlying liver function. The role of rapidly evolving new approaches will remain the subject of intensive inquiry in the years to come. In this report, we have attempted to clarify current practice with respect to the evaluation, selection, and technique of resection in cirrhosis, and identify areas of active inquiry.

Report of the 15th follow-up survey of primary liver cancer.

In the 15th Nationwide follow-up survey of primary liver cancer, 18,843 newly registered patients (1998-1999) and 18,405 follow-up patients from 791 hospitals in Japan were analyzed. Of the newly registered patients, approximately 95% were patients with hepatocellular carcinoma (HCC) and 3.3% had intrahepatic cholangiocarcinoma (ICC). The patients were assessed using 194 items that were related to epidemiological and clinicopathological factors, diagnosis, and treatment. Furthermore, the survival rates of all of the newly registered patients in the 10th-15th follow-up survey were calculated for each histological type, background factor(s) and treatment, respectively. In patients with hepatocellular carcinoma, the survival rates of patients who underwent hepatectomy, ethanol injection therapy, microwave coagulation therapy, or transcatheter arterial embolization were calculated by tumor size, tumor number, and clinical stage. This follow-up survey will be helpful to assess the progress of research and medical practice in the treatment of primary liver cancer.

Right trisectionectomy for primary liver cancer.

To evaluate the value of right trisectionectomy, previously named right trisegmentectomy, in the treatment of primary liver cancer by summarizing our 13-year experience for this procedure. Thirty three primary liver cancer patients undergoing right trisectionectomy from Apr. 1987 to Dec. 1999 were investigated retrospectively. The impacts in survival of patients by cancerous biological behavior, such as tumor thrombi and satellite nodules, were discussed respectively. All right trisectionectomies were performed under normothermic interruption of porta hepatis at single time. Ultrasonic dissector (CUSA system 200) was used in dissection of hepatic parenchyma from Nov. 1992, instead of finger fracture. 1-, 3- and 5-year survival rates were 71.9 %, 40.6 % and 34.4 %, respectively. The longest survival term with free cancer was 150 months (alive). There were no significant differences in survival curves between cases with and without tumor thrombi (right branch of portal vein) and satellite nodules. Operative mortality was 3.0 % (1/33). Main surgical complications occurred in 5 cases. Right trisectionectomy should be regarded as an effective and safe procedure for huge primary liver cancers and is worth using more widely.

Some therapeutic concepts converse of primary liver cancer in China

Since 1990’s, comprehensive therapy predominated by surgery has become the maintrend in the treatment of primary liver cancer (PLC). We elucidate concepts converse of operative indication, operative mode, postoperative anti-recurrence, approach of comprehensive treatment and therapeutic model in PLC. These new concepts have gradually involved in clinical diagnosis and treatment, which promotes the advance in hepatic surgery.

Progress in research of liver surgery in China.

Liver surgery, was started in the late 1950s in China and has developed rapidly in the past 40 years[1]. The study on the diagnosis and treatment of primary liver cancer in China underwent four stages: ① In the 1950s, the anatomical study of the liver lay a solid foundation for liver resection[2]. ② In the 1960s and 1970s, studies mainly focused on the detecting methods of AFP and other tumor markers, clinical and pathologic characterion of small liver cancer and epidemiology of liver cancer. ③ In the 1980s, imaging diagnostic techniques, such as CT, MRI, DSA, Doppler ultrasonography, etc., and new therapeutics[3], such as hepatic artery chemo-embolization, percutaneous intra-tumoral ethanol injection, hepatic artery ligation with targeted chemotherapy[4], and some new concepts such as radical regional resection, re-operation of the recurrent liver cancer, two-stage resection, the combined surgical management of liver cancer complicated with hepatic duct thrombus, splenomegaly and portal hypertension were introduced. These comprehensive treatment further improved the liver cancer surgery. ④ In the 1990s, attention was mainly focused on the biotherapy and liver transplantation. The progress in the diagnosis and treatment of primary liver cancer in recent years are summarized as follows.

Development in the interventionsl herbal treatment of primary liver cancer

Development in the interventionsl herbal treatment of primary liver cancer

Cryotherapy for primary liver cancer.

Between November 1973 and December 1996, the in situ freezing of tumor, i.e., cryotherapy, was performed with liquid nitrogen (-196 degrees C) on 235 patients with primary liver cancer (PLC). There were no operative mortalities or severe complications. The 5-year survival was 39.8% for the 235 PLC patients, and 55.4% for the 80 patients with small PLC (< or = 5 cm). When analyzed with respect to treatment modalities without considering the size of the tumor, the 5-year survival was 26.9% for 78 PLC patients treated by cryotherapy alone; 39.6% for 58 PLC patients treated by cryotherapy plus hepatic artery ligation and perfusion; 46.0% for 27 PLC patients treated by cryotherapy for residual tumor plus resection of the main tumor; and 60.4% for 72 PLC patients treated by cryotherapy followed by resection of the frozen tumor. These results indicate that cryotherapy is a safe and effective treatment for PLC.

Treatment of unresectable primary liver cancer: with reference to cytoreduction and sequential resection.

Unquestionably, progress has been made in the early detection and early treatment of primary liver cancers (PLCs), although most remain unresectable, mainly because the cancer is advanced and coexists with liver cirrhosis, particularly in Oriental patients. Thanks to the progress of regional cancer therapy, a multidisciplinary approach, and changing concepts about surgical oncology, it has been proved that some unresectable but not far advanced PLCs are potentially convertible to being resectable, particularly those cancers confined to the right lobe of a cirrhotic liver. A retrospective analysis of 571 unresectable PLCs revealed the following: (1) There was an increase in 5-year survivals in the series, from 0% during the 1960s (n = 61), to 4.8% during the 1970s (n = 163), to 21.2% during the 1980s (n = 347). It might be a result of the increase in double- or triple-modality treatments in these series (from 9.8%, to 19.6%, to 70.3%, respectively) and in the sequential resection rate after cytoreduction (from 0%, to 2.5%, to 14.7%). (2) The combination of hepatic artery ligation, hepatic artery cannulation and infusion, and intrahepatic arterial radioimmunotherapy has resulted in better shrinkage of the tumor, a higher sequential resection rate, and a higher 5-year survival (28.2%). (3) Of the 55 patients who had initially unresectable PLCs and yielded "cytoreduction and sequential resection," the 5-year survival was 58.5%. It is concluded that cytoreduction and sequential resection might be an important approach to improving the prognosis of patients with unresectable PLCs.

Alternating chemotherapy and fractionated radiotherapy as a modality for the treatment of primary liver cancer

Alternating chemotherapy and fractionated radiotherapy were carried out in 32 patients with surgically proven unresectable primary liver cancer (PLC). After initial surgical intervention of hepatic artery ligation and cannulation, the tumor was localized with silver clips. The cisplatin 20 mg was infused via a hepatic artery catheter per day on the first 3 consecutive days. Fractionated radiation (18MV straight linear accelerator) of 250 cGy, twice a day with an interval of 6 hours, was then followed on the 8th, 9th and 10th days. The cycle was repeated 3 or 4 times. The shrinkage of tumors and decrease of AFP level were observed in 100% (32/32) and 90.5% (19/21) of the patients respectively. A second-stage resection was done in 37.5% (12/32) of the patients. The 1-, 3- and 5-year survival rates after resection were 96.7%, 67.5% and 67.5% respectively. It is suggested that this modality is a choice of therapies which can convert some unresectable large PLC to resectable ones.

An experimental study and clinical pilot trials on Yttrium-90 glass microspheres through the hepatic artery for treatment of primary liver cancer

Yttrium-90 (90-Y) glass microsphere is a new kind of radiation microsphere for internal radiation therapy of primary liver cancer (PLC). The study was carried out by administration of 35 microns nondegradable 90-Y glass microsphere through the hepatic artery for treatment of PLC. Six rabbits were injected with 185-1480 megabecquerels (MBq) of 90-Y glass microspheres, and three rabbits were injected with 35-300 mg of 89-Y glass microspheres for the toxic test. Eighteen patients received 2442-5550 MBq of 90-Y glass microspheres for the treatment of PLC. Whole blood counts, liver function, and imaging examination were performed. Pathologic examinations were performed on all rabbits. All rabbits were apparently well after absorbing 114.1-845.2 Gy 90-Y glass microspheres in the liver but showed transient degeneration of hepatocytes and portal fibrosis histologically. The mean absorbed dose in liver tissue of patients with PLC was 30.33 Gy, whereas that in tumor tissue was 88 Gy and the highest in tumor tissue, 186.36 Gy. The mean tumor:liver tissue ratio was 3:1; the highest, 14:1. Fourteen patients were still alive after half a year's follow-up and 6 of these 14 were still alive after 1 year. The rabbits could tolerate up to eight-fold of the upper limit of clinical dose (100 Gy). Good responses to the radiation therapy of 90-Y glass microspheres in patients with localized and hypervascular or vascular mass were achieved. Contraindications for the therapy were presence of massive hepatic arterioportal shunt and cancer emboli in the main portal vein. It is safe and applicable to deliver 90-Y glass microspheres in large doses through the hepatic artery for internal radiation treatment of PLC.

Resection of segment VIII of liver for treatment of primary liver cancer.

The close relationship of hepatic segment VIII to the right and middle hepatic veins and to the inferior vena cava makes liver cancer resection in this region extremely difficult. Resection of segment VIII was performed in 25 patients with primary liver cancer between January 1970 and May 1990. Most resections were performed with just porta hepatis occlusion, but some cases required the technique of total hepatic vascular exclusion, otherwise known as "bloodless hepatic resection." It involved control of both the suprahepatic and infrahepatic inferior vena cavae in addition to control of the porta hepatis. Major modifications to the original technique were made, and the 1-, 3-, and 5-year survival rates were 90.5%, 50.0%, and 37.5%, respectively. Two patients have survived 12 and 15 years, respectively. Both of them are alive to date and have returned to work.

Contributions to the treatment of primary liver cancer. 4'-epidoxorubicin and cisplatin studied in hepatocarcinoma cell cultures and in partially hepatectomized rats.

(1993). Contributions to the treatment of primary liver cancer. 4′-Epidoxorubicin and cisplatin studied in hepatocarcinoma cell cultures and in partially hepatectomized rats. Scandinavian Journal of Clinical and Laboratory Investigation: Vol. 53, No. 2, pp. 101-109.

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 long-term survival, this treatment appears promising for patients with advanced huge liver cancers who hitherto have been denied surgery on grounds of unresectability.

Treatment of primary liver cancer in Singapore A review of 3200 cases seen between January 1, 1977, and July 31, 1987

Between January 1977 and July 1987, 3200 patients with hepatocellular carcinoma (HCC) were studied in Singapore. HCC formed 90% of primary liver cancers seen in Singapore and is the second most common fatal malignancy seen in men in the country. Extensive clinical and basic research has defined certain treatment strategies. Of importance is the prompt detection of early nodular tumours, which can be resected. Resection, 'targetting' with anticancer drugs and, in selected cases, synchronised direct hepatic irradiation with adriamycin, used as a radiosensitiser, have been promising treatment methods. Biological modifiers, such as interferons and interleukins, offer potential for the future. Preliminary pilot studies suggest that interferons may prevent the development of HCC, but more studies are required. Similarly, selective localisation of anticancer agents with radio-isotopical agents opens opportunities for treatment.

The changing role of surgery in the treatment of primary liver cancer

For decades, the role of surgery in the treatment of primary liver cancer (PLC) was important but limited. However, a comparison of pathologically proven PLC during the three periods 1958-1966, 1967-1975, and 1976-1984 revealed that as a result of alpha fetoprotein (AFP) serosurvey, changing concepts in surgical oncology, and introduction of new surgical modalities, the role of surgery has become greater. The increasing proportion of subclinical PLC (0, 7.2, and 21.2%) has favored the increasing series resection rate (16.1, 34.7, and 39.6%) and palliative surgery (13.7, 17.0, and 29.8%). The results indicated that early resection, reoperation for subclinical recurrence, resection of huge PLC in stages, and combination of palliative surgery other than resection might be responsible for the increasing 5-year survival rate (1.7, 7.1, and 19.5%) in the entire series.