Surgical oncology has progressed from regional cancer therapy to curative resection during the period from 19th to 20th centuries. Based on the recent advances in early diagnosis of solid tumors, minimally invasive surgery with organ preservation has attracted more attention. Hepatic cancer surgery has also progressed from lobectomy of large liver cancer in the 1950s to limited resection of small liver cancer in the 1970s, which reflected the influence of "concept of minimally invasive surgery". In the recent years, regional cancer therapies for liver cancer develop rapidly, and it is considered as an extension of this "concept". It is predicted that this "concept" will further influence the pattern of liver cancer treatment. However, the implication of this "concept" on cancer treatment will be limited by the biological characteristics of cancer cells. Multimodality combination treatment, biotherapy and studies on metastatic recurrence will probably the key issues to further enhance this "concept" on cancer treatment.

In the 20th century, major progresses were made for treatment of hepatocellular carcinoma: standard resection, radiotherapy and chemotherapy were applied in the 1950s; liver transplantation emerged in the 1960s, and the positive clinical results for the treatment of hepatocellular carcinoma were proved in the 1990s; the survival rates were significantly increased due to local resection for small liver cancer in the 1970s and local tumor therapies benefited the patients more in the 1980s. But the purpose of these procedures was only to destroy the tumors. In the past half century, the survival rate of liver cancer patients in our hospital increased every ten years. It is predicted that in the 21st century, the purpose of improving the outcome of treatment for liver cancer will elaborate to manipulating procedures between tumor and the human body on the basis of destroying the tumors. There are various ways to improve the therapeutic results for hepatocellular carcinoma. For example, these efforts can be achieved by developing and using new therapeutic methods. In the early 21st century, further biological study is the key point to influence the clinical progress for hepatocellular carcinoma. Although to destroy the tumors is basic and important, the most important thing is how to regulate the relationship between residual tumors and the human body.

The 5-year survival rates of small liver cancer resection were no longer improved in the past 40 years,indicating the importance of studies on cancer metastasis.Several important issues of cancer metastasis will be delineated:(1)Changing concepts of cancer metastasis:Cancer metastasis is a systemic issue,metastatic potential of cancer originated from pri-mary tumor,cancer stem cell is the key component of cancer metastasis,metastatic potential also influenced by immuneinflammatory microenvironment,metastatic potential is an alterable event.(2) The pro-metastatic effect of cancer eradication:In Liver Cancer Institute of Fudan University,experimental studies using human hepatocellular carcinoma nude mice model with high metastatic potential indicated that palliative resection,radiotherapy,chemotherapy,hepatic artery ligation and molecular targeted therapies that target to VEGF (eg.Sorafenib) promoted the metastatic potential of residual cancer,mainly via hypoxia,inflammation and immuno-suppression with different molecular alterations.Interestingly,effective intervention that inhibits metastasis and prolongs survival has been found using clinical available drugs in experimental studies.Such as cytokine (interferon),anti-inflammatories (aspirin and zoledronic acid),herbal medicine (Songyou Yin) and Tanshinone Ⅱ A,a novel tripeptide-tyroserleutide,etc.(3) Systemic intervention,including nervous system,immunotherapy,endocrinal intervention,as well as metabolic intervention,etc.were briefly discussed.

Purpose:Tumor growth and metastasis depend on angiogenesis, which is regulated by stimulating and inhibitory factors. Evaluation of angiogenesis of tumor is of value in predicting prognosis, and anti angiogenic therapy is a promising treatment of cancer. Genetic bases for angiogenesis control and search for new angiogenesis inhibitory factors remain to be studied in the future. Studies on relationship between angiogenic factors, such as vascular endothelial growth factors and basic fibroblast growth factors, and angiogenesis induced by hepatocellular carcinoma(HCC) are summarized in this paper. Experimental studies imply that anti angiogenic therapy will become a new modality in the treatment of HCC.

The development and progression of tumors are closely related to the tumor microenvironment.As one of the most important com-ponents in tumor microenvironment,cancer-associated fibroblasts (CAFs)play an important role in carcinogenesis,angiogenesis,inva-sion,and metastasis of tumors.The role of CAFs in the development and progression of hepatocellular carcinoma (HCC)is reviewed by dis-cussing how CAFs are recruited and activated in the tumor microenvironment and how CAFs promote tumor angiogenesis and regulate tumor immunity.This review may provide new approaches for the treatment of HCC.

Mutations detection of circulating tumor DNA can be divided into quantitative and qualitative classifications:the forumer mainly detects the total amount of circulating DNA (serum or plasma),whereas the latter mainly detects the specific genetic variations in serum or plasma DNA,such as gene mutations,methylations of tumor suppressor genes,and microsatellite alterations,etc.Both of them may reflect the tumor presence and disease severity.In this paper,mutations detection and its clinical significance of circulating tumor DNA in patients with hepatocellular carcinoma are reviewed.

The biological characteristic of carcinomas is determined both by the stromal microenvironment and the oncogene or anti-oncogene.The tumor stroma is also known as the reactive stroma which is composed of base member,immunocell,capillary,fibroblasts and ECM.Fibroblasts are the majority of tumor stromal cells.The relationship between fibroblasts and the initiation,progression of carcinoma has being in the spot light.In this review,we summarized the advance in the study of carcinoma-associated fibroblasts.

The models of both auxiliary partial orthotopic liver transplantation(APOLT)andacute liver failure were established.Acute liver failure in rats was successfully induced by partialhepatectomy of 75%with the remnant liver ischemia for 50 min.In treated group,the recipientsunderwent APOLT before the remnant liver(the right superior and inferior lobes)receiving tem-porary ischemia for 50 min.The experimental results showed that the 5-day survival rate of therats with acute liver failure was only 3%,while in the rats receiving APOLT,the 5-day survivalrate of the recipients and the liver graft was 80%and 73%,respectively.The liver function re-turned near tO normal level on the 5th postoperative day.It is suggested that acute liver failure in-duced by major liver resection with remnant liver ischemia in rat is an ideal model and APOLTmight provide an exact support for experimental acute liver failure in rat.

The aim of this study was to evaluate the role of vascular endothelial growth factor (VECF) and its receptor flk-1 system in angiogenesis and progression of human hepatocellular carcinoma (HCC) in vivo, the flk-1 dominant-negative mutant was cloned into the retroviral expression vector pLXSN, and was then packaged by PA317 cells to produce ecotropic retroviruses expressing mutated receptor constructs. 50mm_3 of LCI D-20 intact tissue were subcutaneously or orthotopically implanted in nude mice respectively. At day 1,3,5 after implantation, growing tumor were injected with 0.1 ml retroviral supematants into the site of tumor implantation. Tumor volumes, vascular density and lung metastasis were investigated. The results showed that the transfectants by flk-1 TM formed very small tumors after 21 days, which were less than 10 folds in size compared with control. There were hardly visible vessels in flk-1 TM transfected tumor tissue, whereas rich neovascularization could be found in control. The metastatic nodules in lungs were markedly decreased by dominant-negative flk-l TM (P

China ; Humans ; Liver Neoplasms ; prevention & control ; therapy