Diagnosis and treatment of liver cancer

  The diagnosis of hepatocellular carcinoma has progressed from “post-mortem diagnosis” in the 1930s to “clinical diagnosis” and “sub-clinical diagnosis” in the 1970s. This progress is closely related to the introduction of new diagnostic methods in different periods; the first leap in liver cancer diagnosis was made by the use of AFP test in the late 1960s; the second leap in liver cancer diagnosis was made by the introduction of new localized diagnostic methods such as ultrasound imaging, CT and MRI in the 1980s by combining electronic computers and new technologies. The first leap improved the diagnosis of liver cancer from “clinical stage diagnosis” to “subclinical stage diagnosis”; the second leap improved the diagnosis of subclinical stage to the level of 1cm liver cancer, and made the diagnosis of clinical stage liver cancer more accurate, and the application of intraoperative ultrasound significantly improved the level of treatment. The application of intraoperative ultrasound has significantly improved the treatment level. The concept of “subclinical diagnosis” has completely updated the concept of liver cancer diagnosis in the past 100 years.  1) Hepatocellular carcinoma markers and laboratory tests: There have been many studies on serum hepatocellular carcinoma markers, and there are dozens of them. The main ones are: (1) alpha-fetoprotein (AFP) and its heterodimer; (2) various serum enzymes, such as GGT and its isoenzymes, ALD-A, AFU, AAT, ALP-Ⅰ, 5′-NPD-V, PyK, GST, etc.; (3) other markers such as DCP, ferritin and acidic ferritin. However, so far, there is no marker that exceeds AFP among various liver cancer markers, especially for early diagnosis, AFP has been validated for about 20 years. However, since 30% to 40% of liver cancer patients in China are AFP-negative, other markers still have their application value for AFP-negative liver cancer.  Ultrasonography (US): the most common and effective method for liver cancer diagnosis. It is a non-invasive localization, relatively inexpensive, reusable, non-radioactive, and highly sensitive. However, there are blind areas that are difficult to detect and are influenced by the background of other liver diseases, as well as by the operator’s anatomical knowledge and the meticulousness of the test and operation.  Electronic computerized X-ray body scan (CT): a routine item for the localization and diagnosis of liver cancer. Its diagnostic value is to clarify the location, number, size of lesions and their relationship with important blood vessels; to suggest the nature of lesions; to help localize radiotherapy; and to help understand whether there are cancer foci in the surrounding tissues and organs of liver. Magnetic resonance imaging (MRI): compared with CT, it is characterized by the ability to obtain cross-sectional, coronal and sagittal images; better resolution of soft tissues than CT; no radiological damage; and may be better than CT for differentiating benign and malignant intrahepatic occurrences, especially from hemangiomas. in addition, MRI can show the branches of the portal and hepatic veins without enhancement. Selective hepatic arteriography has become an important tool in the diagnosis of hepatocellular carcinoma. Radionuclide imaging: Radionuclide imaging used to be an important tool for the localization of hepatocellular carcinoma in the 60s and 70s. However, due to the introduction of ultrasound, CT, MRI and other imaging, radionuclide imaging has lagged behind the former in showing small lesions. In recent years, due to the application of single photon emission computed tomography (SPECT) and the application of monoclonal antibody for radioimmunoimaging, its importance has been regained.  (3) Laparoscopy and liver aspiration Laparoscopy has been used for many years to diagnose liver cancer, but in recent years, due to the progress of tumor marker and imaging technology, laparoscopy has been used less frequently. However, it still has some value for those who have unclear diagnosis, especially for those who are less likely to have hepatocellular carcinoma.   jaundice, ascites and cachexia; 6. portal vein trunk cancer thrombus often has periumbilical pain and abdominal distension; 7. AFP rise of 500μg/L or more without obvious abnormality of SGPT; 8. limited activity of right diaphragm limited elevation; 9. ultrasonography shows substantial occupancy with halo; 10. CT shows parenchymal occupancy without filling by contrast injection; 11. hepatic arteriography shows tumor vascular and tumor staining; 12. 99mTc-PMT shows positive scan is mostly hepatocellular carcinoma or hepatic adenoma.  (5) Diagnosis of subclinical hepatocellular carcinoma and small hepatocellular carcinoma: The diagnosis of subclinical hepatocellular carcinoma (i.e. those without symptoms) and small hepatocellular carcinoma (less than 5 cm in diameter) is mainly based on the joint analysis of AFP and ultrasonography and other localization diagnosis.  Treatment of hepatocellular carcinoma I. Surgical treatment Surgical treatment Surgical treatment is still the first choice for hepatocellular carcinoma. In recent years, due to the early diagnosis of liver cancer, localized diagnosis, tumor biology and several concepts of liver cancer surgery, the effectiveness of liver cancer surgical treatment has been significantly improved. Mainly include the following: surgical resection treatment: various intraoperative local treatments that cannot be resected: ① intraoperative hepatic artery portal vein chemotherapy and ligation; ② placement drug injection pump infusion chemotherapy; ③ intraoperative placement microwave radiation therapy; ④ intraoperative cryotherapy; ⑤ intraoperative electrochemical therapy; ⑥ triamcinolone acetonide plus liver perfusion chemotherapy; ⑦ sequential treatment of liver cancer.  II. Radiotherapy: In recent years, with the progress of research in radiation physics and radiation physiology, radiotherapy equipment has been advanced, and cobalt 60 gamma rays or X-rays from electron linear gas pedal and high-energy rays have been used. -The effect of radiotherapy for liver cancer has been significantly improved, and the side effects have been reduced to the lowest level. It mainly includes external radiation therapy and internal radiation therapy.  III. Chemotherapy: 95% of liver cancer patients have lost the chance of surgery at the time of diagnosis, and most of them still depend on chemotherapy. In the past, chemotherapy for hepatocellular carcinoma was not highly evaluated, especially the efficacy of systemic administration was very low. At present, it is considered that intubation chemotherapy is better than systemic combination chemotherapy and combination chemotherapy is better than single drug chemotherapy. Hepatic arterial cannulation chemotherapy is considered the best treatment for patients with hepatocellular carcinoma who are not suitable for surgical treatment.  IV. Interventional radiology: Interventional radiology techniques of percutaneous super-selective hepatic artery infusion chemotherapy and embolization, which emerged in the 1980s and developed rapidly, play a crucial role. Whether it is early limited hepatocellular carcinoma or middle or late stage hepatocellular carcinoma, this interventional radiology technique is a decisive treatment method and essential.  V. Immunotherapy Immunotherapy: BCG, small rod-shaped bacillus, levamisole, tumor vaccine, embryonic cells, thymidine, transfer factor and immune ribonucleic acid have been tried in China, but none of them has achieved obvious efficacy. In recent years, interferon, interleukin-II and lymphokine-activated killer cells have been used more frequently, which can improve the therapeutic effect of hepatocellular carcinoma in varying degrees alone or in combination with other therapies.  VI. Anhydrous alcohol injection therapy: In recent years, there have been many clinical reports on the treatment of liver cancer with anhydrous alcohol injection under B-ultrasound guidance. This therapy has obvious effects in shrinking lesions, controlling and delaying tumor growth, and is commonly used clinically because it does not require special conditions, is easy to operate, has few complications, is less painful to patients and is less expensive.  VII. Laser photodynamic therapy: local laser irradiation and simultaneous injection of chemotherapy drugs for liver cancer under ultrasound guidance has achieved better results.  VIII. Ultrasound-guided microwave coagulation therapy: this therapy is suitable for small hepatocellular carcinoma.  IX. Guided therapy: Guided therapy uses an antibody or compound with special affinity for liver cancer as a “carrier”, or through physical guidance such as magnetism, or through tumor vascular specific guidance such as iodine oil, and then combined with a “warhead” with tumor-killing effect (radionuclide, chemotherapy, etc.). The tumor-killing “warheads” (radionuclides, chemotherapeutic drugs, toxic proteins, BRM, etc.) are then cross-linked to achieve the goal of killing more tumors and damaging less normal tissue.  Complications of hepatocellular carcinoma Complications can be caused by hepatocellular carcinoma itself or coexisting cirrhosis, and are commonly seen in the late stage of the disease.  (a) Hepatic encephalopathy is often a terminal complication, accounting for 34.9% of the causes of death.  (b) Gastrointestinal bleeding accounts for 15.1% of the causes of death. Combined with cirrhosis or portal vein or hepatic vein cancer embolism can cause rupture and bleeding of esophageal or gastric fundic varices due to portal hypertension. It may also bleed due to gastrointestinal mucosal erosion and impaired coagulation mechanism.  (c) The incidence of rupture and bleeding of hepatocellular carcinoma nodules is about 9-14%. Hepatocellular carcinoma tissue necrosis and liquefaction may cause spontaneous rupture or rupture due to external force. If the rupture is limited to subperitoneal area, there may be sudden pain and rapid enlargement of liver. In mild cases, the bleeding stops after several days and the pain gradually decreases.  (4) Hemoperitoneum can be caused by direct infiltration of hepatocellular carcinoma on the diaphragmatic surface or by hematologic or lymphatic metastasis, commonly on the right side.  (v) Secondary infection is easily complicated by various infections, such as pneumonia, intestinal infection and fungal infection, due to long-term consumption of cancer and weakened resistance, especially after radiation and chemotherapy with decreased blood white blood cells.  The clinical research on liver cancer in the 1990s can still be summarized as “early, active, comprehensive and specific”, and the research on “specific treatment” may be an important trend, the goal of which will revolve around turning large liver cancer into small liver cancer and making more unresectable liver cancer resectable. The goal will be to turn large hepatocellular carcinomas into small hepatocellular carcinomas, to make more unresectable hepatocellular carcinomas resectable, and to transform more patients from incurable to partially curable.  There is an extremely promising future for “combination therapy”. Since it has not been proven that liver cancer is a single etiological factor, and different regions may have different combinations of etiological factors, it is difficult for the surface membrane antigenicity of liver cancer to be identical in different individuals, and it is difficult for monoclonal antibodies that are highly specific for a particular liver cancer cell to be adapted to different individuals.  ”Specific therapy” or “directed therapy” is one of the most attractive types of combination therapy. This new exploration, which has been in the clinic for more than 10 years, has already clarified several issues, although it is not yet mature. On the one hand, it has been proven that guidance therapy is a powerful weapon that can kill a large number of tumors, but on the other hand, it has been found that it is difficult to achieve 100% tumor elimination due to the interference of various physiological barriers and tumor blood supply, and antibody guidance has the risk of generating anti-antibody. In the next 10 years, more specific monoclonal antibodies may emerge, anti-antibody problems will be solved through chimeric antibody research, better warheads than 131I will emerge, including the application of BRM warheads, new ideas and approaches such as bifunctional antibodies will emerge, and there will be a possible integrated treatment program for clinical application.