Radiofrequency ablation treatment for primary liver cancer
However, depending on the size, location, quantity and liver function of the tumor, less than 30% of primary liver cancer and 10%-20% of secondary liver cancer have the chance to be surgically resected, and RFA is getting more and more attention because of its advantages of less trauma, less pain, safety, effectiveness and easy operation. Since the 1960s, many scholars have conducted systematic research on the effect of hyperthermia on cancer cell killing, and a lot of experimental results have proved that tumor cells can be selectively killed by raising the temperature of tumor tissue to 41~45°C. In 1990, Rossi performed RF therapy on pig liver and produced an oval necrotic area of 1.4~1.8 cm, and in 1992, McGahan In 1993, Rossi et al. first reported the success of using radio frequency ablation (RFA) to treat 13 cases of primary liver cancer in humans, and now RFA has become a common clinical practice. Currently, RFA has become one of the commonly used clinical methods for the treatment of interstitial thermal destruction of liver cancer.
In clinical practice, it is necessary to choose appropriate interventional treatment for medium and large hepatocellular carcinoma because the risk of surgery is high and the possibility of surgical resection is low. livraghi et al. used radio frequency ablation for 126 medium and large hepatic tumors in 14 cases. After treatment, 60 lesions were completely necrotic (47.6%), 40 lesions were overwhelmingly necrotic (31.7%), and 26 lesions were partially necrotic (20.6%). Tumor size and morphology were determinants of treatment success, with complete necrosis rates of 71% and near-complete necrosis rates of 24% in 3.1-5.0 cm diameter, noninfiltrating tumors. Moderately sized and non-infiltrating tumors are significantly more effective than large, infiltrating tumors, but complete or near-complete necrosis can be achieved in most of the latter cases. Radiofrequency ablation is a safe and feasible treatment for medium- and large-sized hepatocellular carcinoma.
In patients with liver cancer with cirrhosis, the liver function reserve is reduced, which increases the risk of surgical treatment, and patients are prone to liver failure after surgery, and the risk of death is significantly increased. In most of these patients, radiofrequency ablation could achieve effective local control with few complications. The sclerotic liver tissues surrounding the cancer nodules are like heat insulation materials, which increase the heat storage in the cancer tissues during RF treatment, forming an “oven effect” and thus increasing the necrosis volume, so in some cases of combined cirrhosis, a single ablation can effectively treat non-invasive tumors.
The common site of metastasis of colon and rectal cancer is liver. Due to the existence of primary lesions, surgery is not the best choice for such patients, and radiofrequency ablation can be an effective method to treat liver metastases of colon and rectal cancer.
I. Basic principle and instrumentation
1.Basic principle
The high frequency radiofrequency wave generated by the radiofrequency generator sends out radiofrequency current through the electrode needle inserted into the tumor tissue, and then forms a circuit through the auxiliary electrode, which generates heat through the molecular friction and ion escape in the surrounding tissues. This leads to coagulative necrosis of tissues. (4) High temperature causes the vascular tissue around the tumor to coagulate and form a reaction zone, thus reducing or blocking the blood supply to the tumor and preventing the tumor from spreading. (6) To cause apoptosis of tumor cells.
2. Instrument and equipment
Radiofrequency treatment system mainly consists of three major parts: upper computer, lower computer and electrodes. The upper computer is PC, which is mainly used for real-time monitoring of resistance, power and electrode status during the operation. The lower computer is the RF generator, whose frequency should be greater than 300kHz to avoid RF stimulation of nerves and muscles. The electrode is composed of two parts, i.e. RF treatment electrode and auxiliary electrode. In order to avoid skin damage in the auxiliary electrode area caused by thermal deposition (heat sink), multiple auxiliary electrodes with pads of large surface area should be used, and they should not be too close to the treatment electrode. Radiofrequency electrode is the key technology of RFA. According to the different electrode design, monitoring index and RF generator power, it can be divided into Radionics, RITA and Radiotherpentics 3 types of RF therapy instruments.
Indications and contraindications
1. Indications: ① single malignant tumor, generally less than 6cm in diameter, with the most ideal effect below 3cm; ② primary or secondary multiple small hepatocellular carcinoma, preferably less than 3 lesions; ③ large hepatocellular carcinoma, with liver function ChildA or B grade, without jaundice or ascites, or ChildC grade B after preparation; ④ surgical failure to resect, postoperative residual or recurrent hepatocellular carcinoma; ⑤ poor response or intolerance to chemotherapy and radiotherapy (5) those who do not respond well to or cannot tolerate chemotherapy or radiotherapy; (6) those who are older (generally >70 years old), in poor general condition, with diabetes mellitus, hypertension or heart disease and are not suitable for surgery; (7) those who have cancer foci after transplantation. Patients with total serum bilirubin lower than 51,3 μmol/L (3,Omg/L), plasma albumin higher than 30g/L, prothrombin time generally more than 50% of the normal control, platelets greater than 70×10/L, no hepatic encephalopathy, intractable ascites, active infection and extrahepatic dissemination, and negative pregnancy test are also required.
2. Contraindications: ① giant hepatocellular carcinoma or diffuse hepatocellular carcinoma; ② tumor in the hilar region. ③ Severe cardiac, cerebral, hepatic and renal insufficiency; ④ Coagulation dysfunction and severe bleeding tendency; ⑤ Infection in active stage; ⑥ Liver function grade C, with obvious jaundice, hepatic encephalopathy and intractable ascites; ⑦ Frequent fever and hyperemesis; ⑧ Main portal vein cancer embolism or extrahepatic dissemination; ⑨ Pregnant patients.
III. Intraoperative Methodology
The therapeutic electrode should be inserted into the tumor under the guidance of real-time imaging. Generally the electrode should be placed to the center of the tumor. Spread the multiple conductive electrodes and start the ablation treatment. The treatment can be performed using power control, temperature control, resistance control and manual control modes. The treatment procedure and time are decided according to the tumor volume and blood supply. Arata et al. used a sudden change in tissue resistance (roll-of) in the target area as the criterion for achieving efficacy. After the ablation is completed, the electrode probe should be cauterized when exiting 2 cm deep from the liver envelope to prevent postoperative bleeding and tumor implantation in the needle tract.
1. Selecting the best imaging guidance modality: At present, the most commonly used at home and abroad is ultrasound, and skilled imaging localization ability is important.
2. Choose the appropriate treatment route: ① Most of them can be done by percutaneous route, especially for tumor diameter less than 5cm. ② Tumors located on the liver surface are more suitable for trans-laparoscopic route. Ultrasound probe placed on the liver surface can detect lesions not detected by preoperative examination, and there are reports that the intraoperative detection rate reaches 37%. Hand-assisted laparoscopy can be used to temporarily block the hepatic artery and/or portal vein flow by Pringle maneuver to increase the extent of coagulative necrotic foci, but this route is technically difficult and costly. ③ RFA in open surgery, electrode needle placement is convenient, but the postoperative recovery time is long.
3. Selecting the best way to expand the range of necrotic foci: Goldberg et al. believed that the range of necrotic foci for ideal RFA treatment should include 0,5~1,0 cm of normal liver tissue around the tumor. The size of RF necrotic foci is positively correlated with current intensity and duration, negatively correlated with impedance, and closely correlated with tissue water content, tissue blood flow and heating rate, currently there are the following options to increase the range of necrotic foci: ① improve the RF generator to increase its output power, and Goldberg et al. (2) Improving the electrode needle from unipolar to bipolar, multipolar, and forming a larger necrotic area by increasing the contact area between the RF wave and the target; (3) Injecting saline into the target area before RF treatment. necrosis range; 6) In the treatment process, RF energy should be gradually increased, starting from low energy, which can make the heating and curing process of the tissues around the electrode proceed slowly, and also facilitate the heat dispersion and reduce the adverse effects caused by tissue charring; 7) Combined application with percutaneous anhydrous alcohol injection, freezing, percutaneous hepatic artery chemoembolization or surgical resection can increase the volume of necrosis foci.
IV. Clinical efficacy
The symptoms of patients can be improved to different degrees after RFA treatment. The survival rates of primary hepatocellular carcinoma at 1, 2, 3 and 5 years after treatment are 94%, 86%, 68% and 40% respectively; the effect of metastatic hepatocellular carcinoma is not as good as primary, and the recurrence rate can reach 50% after 1 year. The factors of tumor recurrence after surgery are: ① tumor size; ② whether the blood vessels are invaded; ③ the scope of ablation. Recurrence is not related to the number of tumors.
Radiofrequency ablation is a new technique, and long-term clinical follow-up results are not yet available. In 1996, Oss et al. reported their experience of treating 50 cases of hepatocellular carcinoma within 7 years. 39 cases of HCC nodes were less than 3 cm in length and 11 cases of liver metastatic nodes were less than 3 or 5 cm in length. 1 to 8 treatments were done and the average follow-up time was 22 or 6 months. The reported survival rates at 1, 2, 3 and 5 years were 94%, 86%, 68% and 40%, respectively. 41% of HCC patients had recurrence of liver tumor, and only 2 patients with liver metastases survived cancer-free, and no treatment-related complications were seen. In Peking University Cancer Hospital, FA treatment was performed in 144 cases of primary cancer and 87 cases of M. C with 474 foci in 231 cases in the last 3 years. All cases were confirmed by biopsy or pathology. Among the primary hepatocellular carcinoma, 80,0% (115 cases) were advanced cases of stage III-IV. There were 173 male cases and 58 female cases, age 24-87 years, mean 58,8 years. The tumor size (the largest foci in each case) ranged from 1,2 to 10,8 cm, with a mean of 4,2 cm. 61 liver tumors were larger than 3,5 cm, among which 4 cases of 8-10,8 cm giant tumors were palliatively partially ablated. Enhanced CT examination at 1d or 30d after FA treatment was used as a criterion to evaluate the effective tumor inactivation. The FA efficacy of 227 liver tumors in our group and the survival rate of 186 cases at follow-up are shown in Table 10-3 and Table 10-4.
It is generally believed that the effect of RFA is greatly influenced by tumor size, and the rate of complete tumor necrosis after radiofrequency ablation for tumors >5 cm in diameter does not exceed 50%, so most authors do not recommend RFA for liver cancer >5-6 cm in diameter. however, Zhai Bo et al. of the Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University summarized 441 cases of larger primary liver cancer (tumor maximum diameter ≥4 cm) that lost the opportunity for surgery The treatment outcome and experience after ultrasound-guided radiofrequency ablation. RESULTS: The rate of complete tumor necrosis after radiofrequency ablation was 72,9 . The complication rate associated with radiofrequency ablation was 2O,9 , and the rate of serious complications was 9,5 . There were 7 deaths related to radiofrequency ablation. During the follow-up period of 1 to 62 months, 379 tumors ≥4 cm in diameter in 359 patients were effectively followed up, among which 302 tumors were completely necrotic after surgery and 130 tumors were locally recurrent during the follow-up period, with a local recurrence rate of 43,0 . The median survival period for tumors 4-5 cm in diameter was 27 months, and the survival rates at 1, 3 and 5 years were 78, 2%, 48, 1% and 17, 6%, respectively; the median survival period for tumors 5-6 cm in diameter was 18 months, and the survival rates at 1, 3 and 5 years were 66, 3%, 36, 4% and 9, 7%, respectively; the median survival period for tumors ≥6 cm in diameter was 11 months, and the survival rates at 1, 3 and 5 years were 53, 6%, 28, 1%, respectively. It is believed that radiofrequency ablation is a more effective local treatment for unresectable large primary hepatocellular carcinoma, but the indications should be strictly controlled.
V. Follow-up observation
Some authors use ultrasound to observe the blood supply, monitor the changes of tumor markers and puncture biopsy to observe the efficacy. Ultrasound examination at the time of treatment can help to determine the efficacy of high blood supply HCC, but it is not helpful for M. C. Ultrasound is of limited value in determining whether there is tumor residue or survival in ablation foci, and can only provide reference based on changes in tumor size and the presence or absence of blood flow; strong echogenicity of the tumor can be seen one month after surgery, and the tumor begins to shrink after 3 months. However, ultrasound is more sensitive to detect new lesions next to ablation foci, and micro lesions. Liu Jibin and Sobat reported that ultrasonography after FA can help to detect residual tumor and evaluate the efficacy.
After 1 month, CT showed the coagulated necrotic foci as hypodense areas with clear margins, and the delayed images could distinguish the necrotic foci from the residual tumors. 2-3 months after surgery, the tumors were gradually shrunken, and further shrunken after 6 months, indicating that they had been mechanized. If the tumor foci gradually increase in size and there is tumor infiltration around the ablation area, local recurrence can be confirmed. The morphology and CT values of recurrent tumors vary with tumor type. High blood supply tumors show enhancement at the ablated tumor margin or elsewhere in the liver; low blood supply tumors show enlargement of the original ablated area, nodular growth at the tumor margin, or a hypodense ring at the ablated tumor margin. More systematic CT scanning is also used to detect extrahepatic lesions, and in addition, CT can be applied to understand the efficacy of tumor margins. For larger tumors it is necessary to perform enhanced CT examination within 24h after ablation, which can determine whether the ablation is complete and whether there are complications, and if residual activity is found in the lesion, it can be supplemented with timely treatment; while it is difficult to identify the congested band formed around the ablated tissue and the residual tumor after 24h CT examination. CT examination is mainly combined with tumor marker examination as well as color ultrasound and tumor size measurement to comprehensively evaluate the tumor survival status, and the results are more reliable; multi-point aspiration biopsy is still needed for lesions to be retreated if necessary. The current study reports that M and contrast-enhanced M examinations are more sensitive for determining tumor residual or recurrence.
The main purpose of active follow-up of postoperative patients is to detect tumor recurrence as early as possible for timely treatment. If the recurrence is limited to intrahepatic, re-ablation is effective; if extrahepatic metastasis or extensive intrahepatic lesions occur, comprehensive treatment such as systemic chemotherapy or embolization chemotherapy should be combined.
VI. Complications
Livraghi et al. reported a mortality rate of 0.3% and an overall complication rate of 7.6%, with no significant differences between different treatment routes. livraghi classified complications into four types: thermal injury, mechanical injury, infection, and other unexplained complications. 1997 American Society of Cardiovascular and Radiological Sciences Complications of RFA are defined as those that occur during the 30-day perioperative period or are confirmed by delayed imaging and can be judged to be caused by RFA. Any untreated complication that could endanger the patient’s life, lead to other serious accidents or disability, and prolong hospitalization is considered a major complication. Others are secondary complications, and common unintended effects that do not require treatment are side effects’.
1. Causes of death
The mortality rate of RFA is reported to be about 0.3%, and the common causes of death are: gastrointestinal perforation, sepsis, hemorrhage due to tumor rupture, liver failure due to bile duct stenosis and myocardial infarction, etc.
2. Main complications
(1) Gastrointestinal perforation: the incidence is about 0.3%, which often occurs in patients with previous history of right upper abdominal surgery, chronic cholecystitis, tumor within 1 cm from the liver envelope and close to the gastrointestinal tract, and manifests as abdominal pain, fever and elevated white blood cell count 2 to 4 days after RFA. Perforation is most likely to occur in the colon, and relatively less in the stomach and small intestine.
(2) Abdominal bleeding: the incidence is about 0.5%, and bleeding is likely to occur in patients with cirrhosis, etc., from the ablation area, liver metastases, needle tracts, rupture of intrahepatic hematoma.
(3) Liver abscess: the incidence is about 0.3%, often occurs in patients with diabetes mellitus or gas in the biliary tract, preoperative antibiotics should be used prophylactically, once it occurs, drainage, anti-infection or even surgery is feasible.
(4) Liver failure: the incidence is less than 0.1%, often caused by intraoperative radiofrequency treatment, the pursuit of complete inactivation of the tumor or the formation of cardiovascular thrombosis.
(5) Needle tumor implantation: the incidence is about 0.5%, most of them appear in 4 to l8 months after surgery, and they are likely to occur in patients with superficial tumor location which makes it inconvenient to burn the needle tract, deeper tumor and needle biopsy, high AFP base level and low differentiation. In order to reduce the occurrence, attention should be paid to the intraoperative change of the position of the therapeutic needle and the burning of the needle tract at the end of needle extraction.
(6) Pulmonary complications: the total incidence is about 0,2%, mostly occurring in the percutaneous treatment route, such as injury to the costal vessels resulting in hemothorax, accidental injury to the pleura resulting in pleural effusion, adult respiratory distress syndrome, etc. Other major complications include diaphragmatic paralysis, portal vein thrombosis, sepsis, acute cholecystitis, biliary tract injury, etc. For superficial tumors, difficult placement of electrode needles, long operation time or too many treatments, the complications are significantly increased, and among them, the number of treatments can significantly affect the complication rate.
3. Secondary complications and side effects
(1) Pain: Intraoperative pain is more common, especially when the tumor is superficially located or near the hepatic hilum, and when the pulse technique with higher output power is used. The severity of pain depends on the patient’s pain threshold and is not easy to predict. Pain may also occur immediately or within 3 days after surgery. If pain occurs after 3 days, potential complications should be ruled out by examination.
(2) Post-ablation syndrome: The manifestations are similar to those of influenza, such as low fever (usually not exceeding 38,8℃) and general malaise. If the scope of ablation is large, the symptoms may appear soon after the procedure, sometimes lasting 2 to 3 weeks, and even high fever and lethargy. Some scholars believe that this is caused by the release of tumor material in excess of its own excretory capacity during the ablation process, so some people call it “tumor lysis syndrome (TLS)”. Generally, symptomatic treatment is sufficient.
(3) Skin burns: common before the use of large area auxiliary electrodes, but now rare. However, those who have metal grafts or wasting with superficial tumor should pay special attention, because when the local temperature exceeds 47℃ it can cause second degree burns, and over 52℃ can lead to third degree burns.
Others are self-limiting abdominal bleeding, subperitoneal or intrahepatic hematoma, bilioma, biliary stenosis, gallbladder wall thickening, hepatic arteriovenous fistula, biliary portal fistula with biliary hemorrhage, electrode needle cannot be removed, and asymptomatic pleural effusion. Efforts to improve the operation technique and strengthen postoperative treatment of hepatoprotection, hemostasis and anti-infection should reduce the occurrence of complications.
VII Evaluation and outlook
Minimally invasive interventional therapy has become an important aspect of non-surgical treatment under the new paradigm of comprehensive tumor treatment, and RFA will undoubtedly play an important role, even replacing other treatments and becoming a standout.¨ RFA technology has just started in the past 10 years and needs to be further improved and optimized. (2) the treatment effect on tumors larger than 5 cm in diameter is not yet satisfactory; (3) there is a lack of effective monitoring means to accurately identify postoperative coagulative necrosis and focal remnants; (4) the biological characteristics of the stimulated tumor cells remaining after RFA treatment are affected, and whether their metastatic and infiltrative abilities have changed; (5) the limit of maximum destruction at one time when RFA is performed for giant hepatocellular carcinoma. RFA has been recognized as a safe and effective new method for the treatment of tumors. has been recognized in clinical practice at home and abroad. The introduction of RFA has greatly improved the quality of life and prolonged the survival of tumor patients. Perhaps in the future, RFA technique will replace traditional surgery to treat small hepatocellular carcinoma, and it is certain that with the improvement of technology and the update of instrumentation, this minimally invasive tumor treatment technique will make great development in the early 2 1 century.