Abstract: Modern treatment principles for hepatocellular carcinoma have evolved from a single surgical resection to a comprehensive treatment with multidisciplinary involvement, multi-technology application, and multi-stage sequential approach. However, this concept is still far from being a consistent pursuit in clinical practice of hepatocellular carcinoma, and there is a lack of regular, substantial, and fruitful cooperation among related disciplines. The deeper reason for this is that physicians are becoming more and more specialized and look at hepatocellular carcinoma only from the perspective of their respective specialties, lacking in-depth thinking at the philosophical level. This article analyzes the humanistic orientation, fundamental principles, modern concepts and modal trade-offs that liver cancer treatment should have from four aspects: the essence of medicine, the positioning of the liver in the human body, the mechanism of liver cancer development, and the biological and pathological characteristics of liver cancer, respectively, to provide references on thinking and methods to further enhance the efficacy of liver cancer treatment. Liver cancer has a high incidence rate and great danger in China. Over the past half century, there has been tremendous progress in clinical basic research and treatment of liver cancer, and the treatment principle has developed from a single surgical resection to a comprehensive treatment with multidisciplinary participation, multi-technology application and multi-stage sequential treatment. The conceptual advancement has laid the foundation for further improving the efficacy, and at the same time, it has also raised higher requirements for the management of coordination and cooperation among clinical disciplines. However, at the present stage in China, the above concepts are far from being consistently pursued in liver cancer clinical practice, and the lack of regular, substantial and fruitful cooperation among related disciplines has considerably affected the scientific and standardized treatment of liver cancer in China, and problems such as over-treatment and under-treatment are common, and unsatisfactory curative effects are not uncommon. The authors believe that the main problem of liver cancer in China at the present stage is not the lack of in-depth understanding of liver cancer, nor the lack of exquisite technical level in treating liver cancer, but the obvious deviation in the way of thinking and level of understanding. In terms of thinking style, it is mainly point thinking or linear thinking, but not enough system thinking; in terms of cognitive level, physicians lack higher, more essential and systematic thinking about the meaning of life, the essence of medicine, the positioning of liver and its functions in the organism system, and the law of occurrence and development of liver cancer. The way of thinking and level of understanding, which are ultimately philosophical issues, are important issues that cannot be avoided in the clinical practice of liver cancer. This paper seeks to explore the proper way of thinking in treating liver cancer from a philosophical perspective, aiming to provide a platform of understanding beyond disciplinary portals for the implementation of modern treatment concepts for liver cancer and further enhance the scientific treatment level of liver cancer. I. Humanistic orientation of liver cancer treatment from the perspective of medical essence From the source, medicine is a natural manifestation of human nature, a natural act to maintain and promote human physical and mental health and life vitality. The essential characteristic of medicine is humanistic care. The professional behavior of doctors should always focus on the maintenance of the dignity of life, the care of the state of life and the respect for the value of life. These are both the starting point and the ending point of medicine. With the development and progress of medicine, the technical ability of doctors is getting stronger and stronger, and major traumatic surgery is becoming more and more common, and the potential harm to patients is getting bigger and bigger. At this time, if the doctor lacks sufficient humanistic feelings, necessary self-knowledge and humility, a slight negligence, the “double-edged sword” of surgery will cause irreparable harm to the patient. In this context, it is undoubtedly of great practical importance to think about the philosophical issues of the meaning of life and the nature of medicine, and to continuously use them to lead medical practice. ”We have gone so far that we have forgotten the purpose of our departure”. Factors such as the dilution of the humanistic spirit of physicians and the poor transformation of the medical model have led to an overtone of “cure” and a lack of humanistic feelings in the working methods of doctors. There are three main purposes for liver cancer patients to seek medical help: firstly, to prolong their survival time by eliminating the disease; secondly, to eliminate the disease without lowering or significantly lowering the quality of survival, and to maintain the value and dignity of their lives to the greatest extent; thirdly, the lower the medical cost, the better, and they do not want to be in a situation where “one person is cured and the whole family is poor. Third, the lower the medical cost, the better. For patients who have dignity and know how to care, the above three purposes should be the same, and the demand for quality of life and medical costs will never be lower than the desire for survival time. Unfortunately, in the clinical treatment of liver cancer, doctors seem to pay more attention to the survival time of patients, and not enough attention to their survival quality, medical costs and other important issues. In the last decade, minimally invasive treatment represented by radiofrequency ablation (RFA) has become an effective and commonly used treatment for liver cancer. For early-stage hepatocellular carcinoma, the medium- and long-term efficacy of RFA or RFA-based minimally invasive treatment for hepatocellular carcinoma is not significantly different from that of hepatectomy and liver transplantation. This means that for early stage liver cancer, if there is no contraindication, RFA can be the first choice of treatment, which can effectively remove the liver cancer, maintain the quality of survival and reduce the medical cost to the greatest extent, so that surgery is not necessary. Unfortunately, technological advances have not changed surgeons’ thinking habits and working style to the extent they should, and surgeons are still as fond of “open surgery” as ever. It seems that they have really forgotten the “purpose of departure”. The liver is the largest substantive organ of the body, located in the middle of the “intestine-liver-lung” axis, and its venous ducts are the important “traffic channels” of the body. “There is no substitute for it, and it cannot be missing. The significant reduction of blood flow channels in the liver can lead to intestinal stasis, damage to the intestinal mucosal barrier, and changes in the microenvironment of the intestinal flora, exacerbating liver damage and forming a vicious circle. In addition, the liver has complex and diverse functions, supporting the body’s metabolism, detoxification, immunity and other important functions, and a slight failure of liver function will have a systemic impact on the body. As you can see, the liver is extremely important for the maintenance of the state of life or the care of the quality of life. In chronic liver disease or even cirrhosis, the functional reserve of the liver is significantly reduced and the intrahepatic venous channels are significantly destroyed. If the structure and function of the liver are not given extra care in the treatment of hepatocellular carcinoma, the whole body will be affected and other important organs will be damaged. As a result, even if liver cancer is completely removed, the patient’s quality of life will be seriously impaired and the therapeutic effect is often counterproductive. There is a common phenomenon in liver cancer wards: three patients with right hepatocellular carcinoma, same gender, similar age, cancer foci of about 5 cm in diameter and basically the same location, but with very different treatment plans. The first one was treated mainly by hepatectomy, the second one was treated mainly by RFA, while the third one was treated by liver transplantation. The reason for this is precisely because the three patients had very different liver function reserves. Although they grew similar hepatocellular carcinoma, the first patient had good liver function reserve and could tolerate hepatectomy well, so it was appropriate to prefer hepatectomy; the second had more obvious cirrhosis, but the liver function could still compensate better, plus the family economic condition was not rich, so it was suitable for minimally invasive treatment mainly by RFA; the third patient had heavy cirrhosis, obvious atrophy, accompanied by heavy portal hypertension, esophagogastric fundus Liver transplantation is undoubtedly the ideal treatment option, which can not only remove the cancerous foci to the greatest extent, but also completely eradicate the underlying liver diseases such as cirrhosis, which can kill multiple birds with one stone. The above case illustrates an important concept of modern liver cancer treatment: the fundamental principle of liver cancer treatment is to maintain the structure and function of liver to the greatest extent, and the treatment decision should be “liver-based treatment” rather than “cancer-based treatment”. The establishment of this concept is the reason why minimally invasive treatments such as RFA and liver transplantation have been highly recommended in China in the past decade or so, while the application of hepatectomy has become narrower and narrower. The development of liver cancer has the following two regular characteristics: First, the initial or young stage of liver cancer grows slowly, while the period of small liver cancer is usually longer; the larger the liver cancer is, the faster it develops. Secondly, in the early stage of hepatocellular carcinoma, metastasis within and outside the liver is less likely to occur. The above biological characteristics of hepatocellular carcinoma are mainly due to the power contrast between the immune status of the body and the immune escape of hepatocellular carcinoma. In the early stage of liver cancer, the immune system of the body is able to play a strong immunosuppressive role against the tumor, or the liver cancer at this stage is not yet more completely free from the control of the body’s immune system, while at the stage of middle and large liver cancer, the power contrast between the function of the body’s immune system and the immune tolerance of the tumor changes significantly and the tumor is able to progress rapidly. The above analysis shows the importance of two aspects of work for the treatment of liver cancer. One is the early diagnosis and treatment, and the other is the maintenance of the body’s immune function. As a corollary, the ideal treatment plan for liver cancer should not only be able to completely eliminate the tumor, but also maintain or promote the body’s immune function. The three currently recognized curative treatments for liver cancer – hepatectomy, liver transplantation and RFA – differ in their impact on the body’s immune function. After liver transplantation, the immune function is artificially suppressed to avoid immune rejection. At this time, as long as there is residual cancer tissue, tumor progression is prone to occur in an immunosuppressed environment, which is the most important reason for the strict requirements for liver transplantation indications for liver cancer. After liver resection, factors such as trauma, blood loss, negative nitrogen balance and reduced liver function will also cause the immune function of the body to present a certain degree of depression. The greater the surgical trauma, the more blood loss, the worse the nutritional status, the more severe the liver function damage, the worse the immune function of the body, and the less satisfactory the therapeutic effect will be. The principle of treating liver cancer is local thermal ablation, characterized by the fact that the ablated tumor tissues are left in situ and exposed to blood circulation. After RFA of liver cancer, tumor tissue components are absorbed into blood, which can be used as endogenous tumor antigens to further stimulate or amplify the anti-tumor immune response of the body on the basis of the original tumor immunity. The antigen-presenting function of dendritic cells, tumor-specific T lymphocyte activity, natural killer cell activity and liver blast cell activity are all significantly enhanced and have obvious inhibitory effects on tumor. When RFA is repeated in the short term, tumor antigens are again heavily exposed and memory T lymphocytes proliferate, which can stimulate a stronger and longer anti-tumor immune response. This also means that RFA treatment of liver cancer does not rely on simple tumor ablation, but immune enhancement is also an important mechanism. In recent years, some huge hepatocellular carcinomas, which are difficult to be removed surgically and even more difficult to be completely removed by RFA, have obtained unexpected and satisfactory results by repeated application of RFA, which seems to be a strong support for the above theory. One of the biological characteristics of hepatocellular carcinoma is multicentric growth, including simultaneous multicentric growth and heterochronic multicentric growth. The incidence of multicentric growth in hepatocellular carcinoma is reported to be as high as 50% in the literature. Considering intrahepatic metastasis, the likelihood of concurrent concurrent or heterochronic intra- and extrahepatic metastatic lesions and multicentric lesions is much higher than 50%. This also means that the development and progression of hepatocellular carcinoma is multistage, and any hepatocellular carcinoma lesion is only part of the disease, not the whole. Again, pathologically, the actual extent of the cancer foci is much greater than that shown on imaging. The extent of cancer foci includes at least three components: the primary cancer foci, the peri-cancerous micro-venous infiltrative foci, and the satellite foci. Generally speaking, the lower the degree of differentiation of hepatocellular carcinoma, the larger the cancer foci, the wider the extent of microvenous infiltration area, and the more satellite foci and the more distant from the main cancer foci. The study showed that among 48 cases of small hepatocellular carcinoma with diameter ≤3 cm, 16 cases (33.3%) had satellite foci; among them, 12 cases (75.0%) had satellite foci ≤1 cm, 3 cases (18.8%) had satellite foci 1-2 cm and 1 case (6.3%) had satellite foci >2.0 cm from the main carcinoma; among 65 cases of hepatocellular carcinoma with diameter >3 cm, 39 cases (65.0%) had satellite foci; among them, the Sasaki et al. studied 100 cases of hepatocellular carcinoma ≤5.0 cm in diameter and found that 46 cases (46.0%) had satellite foci with a mean distance of 1.0 cm (median 0.5 cm) from the main foci. It can be seen that hepatocellular carcinoma, in terms of occurrence characteristics, is often multicentric; in terms of development pattern, it often develops in stages; and in terms of pathological scope, it is often broad and unknowable. The above characteristics support the rationality of liver transplantation for the treatment of hepatocellular carcinoma, because the theoretical basis of this tool is based on the multicentric nature of hepatocellular carcinoma lesions, the multistage development and the broad pathology. However, the rationality of hepatectomy seems to be somewhat diminished, and the multicenter, staged, and broad features of hepatocellular carcinoma overshadow hepatectomy in terms of complete removal of lesions. In conclusion, medicine is both scientific, artistic, and humanistic. It is a never-ending scientific proposition how to coordinate various treatments for liver cancer in a scientific and reasonable manner to meet patients’ needs to the greatest extent. Under the background of “blossoming” of liver cancer treatment, it is necessary for us to stand higher, see more widely and think more comprehensively. Only in this way can we face up to the traditional constraints, get out of the current noise, condense advanced concepts, reflect the spirit of science, and return to the essence of medicine. Let philosophical thinking help us do a little better!