Since Langenbuch performed the first liver resection in 1888, hepatic surgery has evolved tremendously and the safety of hepatectomy has improved significantly, with a perioperative mortality rate of less than 5%. At the same time, the “anatomical no-go areas” of liver surgery have been broken through one by one, and the indications for surgery have been greatly expanded. However, these hepatectomies are technically complex, difficult and risky, and there are more complications after surgery, which are usually called complex hepatectomy. It is generally believed that the complexity of hepatectomy is closely related to the size and location of the tumor, whether it invades important perihepatic vessels and the experience of the surgeon. There is no unified and clear definition of complex hepatectomy, and the following hepatectomies are usually classified as complex hepatectomy by most scholars.
(1) Huge tumors (>10 cm in diameter) requiring hemicolectomy or left/right trilobar hepatectomy.
(2) combined resection of segments IV, V and VIII of the liver (middle lobectomy)
(3) Hepatectomy in special areas, such as hepatic segment I and VIII resection.
(4) hepatectomy when the tumor invades the first and second hepatic hilum or inferior vena cava.
The complexity of these procedures lies in.
(1) the tumor is huge or in a special location, making intraoperative exposure difficult and surgical operation difficult
(2) The tumor is adjacent to or invades the major intrahepatic vascular structures, requiring careful preoperative planning of resection and delicate dissection.
(3) Reconstruction of important vessels such as hepatic vein or inferior vena cava is required at the same time.
Performing liver surgery under these circumstances may lead to injury of important vessels or bile ducts, causing fatal hemorrhage or postoperative liver failure. To ensure the smooth implementation of complex hepatectomy and reduce the occurrence of perioperative complications, surgeons with rich experience in hepatectomy, detailed preoperative assessment and thorough preoperative preparation, reasonable means of intraoperative hepatic blood flow control, flexible application of various hepatic dissection techniques and timely and effective postoperative complication management strategies are required.
I. Preoperative evaluation and decision making
Complex hepatectomy requires more thorough and precise preoperative evaluation and decision making, which mainly includes the following two aspects.
(1) Assessment of liver reserve function to understand the basic status of liver function and the potential risk of postoperative hepatic dysfunction, which helps to select suitable patients and formulate a reasonable resection range.
(2) Imaging assessment and decision making to evaluate the tumor stage, anatomical location and its relationship with large blood vessels and bold ducts inside and outside the liver, which helps to assess the possibility, complexity and risk of tumor resection, and also allows to calculate the remaining liver volume (FLR) after hepatectomy.
The application of preoperative virtualhepatectomy (virtualhepatectomy) software system based on imaging 3D reconstruction technology can better help surgeons to develop a reasonable surgical plan before surgery, thus further ensuring the effectiveness and safety of surgical resection.
1. Preoperative assessment of liver reserve function: The blood biochemical indexes commonly used in clinical practice are not suitable for the comprehensive assessment of liver reserve function. Various scoring systems have been applied to the evaluation of preoperative liver function, among which the application value of Child-Pugh liver function grading system has been fully affirmed and is still widely used in clinical practice, but due to the rough and general classification of this score, the actual liver reserve function of patients within the same level spans a large range, that is, there is the so-called floor and ceiling effect ( The floorandceilingeffect), therefore, cannot accurately and quantitatively reflect the reserve function of the liver. The end-stage liver disease model (themodel
The forend-stageliverdisease (MELD) scoring system is based on the international standard ratio (INR) of serum bilirubin concentration, creatinine, prothrombin time and liver disease, and has been widely used to assess the prognosis of patients with cirrhosis and the preoperative screening of liver transplant patients. Many scholars have also explored the value of the MELD score system for assessing the safety of hepatic resection, and the results showed that patients with hepatocellular carcinoma with cirrhosis who had a preoperative MELD score greater than 9 had a significantly higher mortality rate after hepatic resection. The MELD score can overcome the ceiling effect of the Child-Pugh liver function grading system to a certain extent and can be used as a complement to the Child score.
Quantitative liver function tests can theoretically assess liver reserve function more objectively and accurately. Different quantitative liver function tests reflect different aspects of liver function, such as ion excretion, microsomal function, cytoplasmic function, and urea synthesis. There are several quantitative liver function tests, including indocyaninegreen (ICG) residual rate, galactose profile rate, aminopyrine breath test, lidocaine metabolite MEGX test, glucose tolerance test, etc. Among them, ICG residual rate is the most widely used in clinical practice, and ICGR15 can reflect liver reserve function in a more comprehensive and objective way, and can ICGR15 can reflect the liver reserve function in a more comprehensive and objective way, which can meet the requirement of accurate determination of liver reserve function before complex hepatectomy.
The literature reports that the occurrence of postoperative complications after hepatectomy is significantly correlated with the preoperative ICGR15 level, and some scholars believe that it is the only indicator that can predict liver failure and surgical death after hepatectomy. However, the results of ICG residual rate test are easily affected by intrahepatic blood shunts and biliary system obstruction and cannot reflect the true status of liver reserve function. In addition, iodine allergy, pregnancy, uremia, and history of dye allergy also limit its clinical application. In recent years, hepatobiliary nuclide imaging technique (99mTc?GSA test) has been used for quantitative assessment of liver reserve function, and it is believed that it can better assess the surgical risk of hepatectomy in patients with different underlying liver lesions. Since the 99mTc?GSA test is not limited by factors such as iodine allergy and jaundice, it can be used as a complementary tool to the ICG residual rate test.Makuuchi et al. proposed a preoperative decision tree for liver resection, the Makuuchi criteria (Makuuchicriteria), by combining the patient’s ascites condition, total serum bilirubin level and ICGR15 results: intractable ascites and hyperbilirubinemia are contraindications to hepatectomy, and the extent of hepatic resection is determined based on ICGR15 results. Selection of patients according to this criterion can greatly reduce the perioperative mortality of hepatectomy.
2. Preoperative imaging assessment: The complexity of complex hepatectomy is mainly reflected in the complex relationship between the tumor and the major blood vessels and bile ducts inside and outside the liver and how to preserve sufficient volume of functional residual liver tissue, so preoperative 3D image reconstruction of the liver by multi-detectorcomputedtomography (MD-CT) or MRI is particularly important. It is particularly important to reconstruct 3D images of the hepatic vein system. In particular, 3D images of the reconstructed hepatic venous system can estimate the outflow volume of each branch vein, and based on these parameters, the extent of resection and the venous branches to be preserved can be precisely determined, thus avoiding liver failure due to remaining liver congestion.
Some scholars have successively reported the feasibility assessment of preoperative hepatic mesolobectomy using 3D visualization liver dissection system, which not only shows the 3D relationship between the tumor and important intrahepatic veins, accurately calculates the volume of the liver to be resected and the size of the remaining volume, but also performs virtual liver resection as a preview of the actual surgery to truly achieve precise liver resection. The advent of virtual liver resection software not only solves the problem of accuracy of preoperative liver volume measurement (its measured liver volume differs from the actual one by only about 9mL), but also helps to select the best surgical resection plan preoperatively and further improves the safety of complex liver resection.
II. Intraoperative hepatic blood flow control
Intraoperative hemorrhage is the biggest obstacle to the successful implementation of complex hepatectomy. Intraoperative controlled low central venous pressure technique and hepatic flow blocking technique can reduce intraoperative bleeding and ensure the safety of surgery. The ideal hepatic flow blocking technique should be able to effectively control intraoperative bleeding while minimizing ischemia-reperfusion injury to the liver and systemic hemodynamic changes resulting from the blocked flow, and be simple and safe to perform. The existing hepatic flow blocking techniques have their own advantages and shortcomings, and should be selected rationally according to the surgical modality of liver resection and the specific condition of the patient.
Although the Pringle method is simple and effective, it can cause ischemia-reperfusion injury to residual liver tissue, stasis in the portal system and lead to intestinal bacterial translocation. The duration of a single block usually does not exceed 20 min and is usually applied to relatively simple hepatectomies for peripheral liver tumors. Selective access hepatic flow block, because it only blocks blood flow to the diseased side of the liver, can be used during regular hepatectomy not only to perform longer flow block, less intraoperative bleeding, less postoperative liver function impairment and fewer complications, especially for patients with combined cirrhosis. However, during resection of tumors adjacent to the second hepatic hilar or involving the hepatic vein, simple inflow blockade to the liver cannot effectively control bleeding from the hepatic venous system and prevent air embolism due to hepatic vein rupture.
The literature reports that the application of selective hepatic vein blockade combined with Pringle’s method in hepatic resection can effectively prevent intraoperative hemorrhage and air embolism and reduce the incidence of postoperative complications and perioperative mortality, but this method still cannot avoid the potential damage that may result from Pringle’s method. Some scholars have reported that the use of selective access hepatic flow blockade for regular hepatectomy can significantly reduce intraoperative bleeding and postoperative complication rates. Alternating selective access to the liver combined with selective hepatic vein blockade can be used in middle lobe resection if the tumor does not involve the first hepatic hilar. Although total hepatic flow blockade can lead to hemodynamic disturbances, a modified total hepatic flow blockade technique is still required for hepatic resection of hepatic tumors that invade the inferior vena cava.
Since Belghiti et al. proposed the liverhangingmaneuver for hepatic resection, this method has been used in various hepatectomies, which has the advantages of shortening the time of hepatic resection, protecting the posterior inferior vena cava and reducing intraoperative bleeding. Recently, it has been reported that anterior approach hepatectomy using the liver suspension method for primary hepatocellular carcinoma patients can significantly reduce intraoperative bleeding and recent postoperative tumor recurrence rate compared with conventional surgical methods. Tong Ying et al [13] used selective complete hepatic blood flow blockade based on the hepatic suspension method in hemihepatectomy, which significantly reduced bleeding during hepatectomy and reduced the impairment of liver function compared with the Pringle method. Our experience is that in hemihepatectomy, selective access hepatic flow block combined with hepatic suspension is not significantly superior to selective access hepatic flow block alone.
In complex hepatectomy with high risk of bleeding, complex surgical operation and relatively long hepatic blood flow control time, the choice of hepatic blood flow blocking method should be flexible, and different blood flow blocking techniques can be appropriately used intraoperatively according to the surgical process and operational needs in order to effectively control bleeding while minimizing postoperative liver function impairment caused by ischemia-reperfusion injury.
III. Intraoperative ultrasound technique and liver parenchymal dissection technique
Makuuchi first reported the use of intraoperative ultrasound in hepatectomy as early as 1982 and highly emphasized the important value of intraoperative ultrasound in liver surgery. The intraoperative ultrasound probe placed directly on the liver surface can provide a clearer picture of the distribution of liver tumors and intrahepatic ducts, which not only allows precise staging of liver tumors, but also enables real-time intraoperative understanding of the relationship between tumors and important anatomical structures in the liver, so as to reconfirm or readjust the surgical resection path and avoid the occurrence of medically induced injuries, which is an important guarantee for the successful completion of complex hepatectomy. et al. reported that intraoperative ultrasound equipped with a special probe can clearly visualize the traffic branches between the hepatic veins. In liver-sparing hepatic resection (liver-sparingsurgery) for tumors located at the confluence of the hepatic vena cava, the need for venous reconstruction after hepatic vein resection can be determined by assessing the direction of portal vein branch flow in the corresponding area after finger compression of the hepatic vein to be resected.
Dissection of the liver parenchyma is a key step in liver resection, and the technique is closely associated with intraoperative or postoperative complications such as bleeding, biliary leakage, and postoperative hepatic insufficiency. In recent years, various new liver parenchymal dissection instruments have emerged to improve the accuracy and safety of liver resection. Complex liver surgery has raised higher requirements for bleeding control and preservation of normal liver tissues, and the selection of an appropriate liver dissection method is essential for successful completion of complex liver resection. The clamp method is still the most widely used method of liver dissection in China because of its no need for special equipment, simplicity and convenience. Its disadvantage is that the hepatic hilum needs to be blocked in the process of liver dissection, which is close to the important ductal structures, and sometimes it is difficult to distinguish and easy to cause misinjury, which cannot meet the careful dissection of important structures in the liver in complex hepatectomy. However, it is still a very effective method in case of hemorrhage during hepatic resection and the need for rapid separation of the liver.
If the principle of shallow to deep and front to back can be followed, most of the hepatectomy can be completed without blocking the hepatic blood flow, but the disadvantage is that the speed of hepatic dissection is slow and it is easy to cause misinjury, as well as bleeding and bile leakage due to scorch off after surgery. The principle of ultrasonic suction knife (CUSA) is high-frequency vibration (23,000 times/s) to produce tissue crushing, combined with flushing and suction to preserve the cleanliness of the operative field, which can clearly show various ducts in the section, resulting in safe ligation and less bleeding, especially suitable for fine dissection of deep liver and ducts in the hilar region, which can maximize the preservation of normal liver tissue and meet the requirements of precise hepatectomy. Its disadvantage is that it has no hemostasis and slow dissection speed, especially when cirrhosis is obvious.
Waterjet uses the cutting force generated by a high-pressure water jet within a certain pressure range to cut tissue. It can cut through the liver parenchyma while preserving the larger blood vessels and bile duct structures in it, facilitating accurate cutting, ligation and suturing. The new head has suction and electrocoagulation functions, which makes it easier and faster in liver dissection and maintains a clear anatomy of the liver section.Rau et al. compared 31 cases of liver dissection using the water jet knife with 30 cases using CUSA, and the water jet knife took less time to dissect the liver and significantly reduced intraoperative and postoperative blood transfusion. However, the tissue of severe cirrhosis was tougher, and liver resection time was significantly longer and bleeding was significantly more.
The Ligasure vascular closure system uses high-frequency electrical energy combined with jaw pressure to rapidly denature the collagen and elastin of the duct wall, causing permanent closure of the duct. saiura et al. demonstrated through a randomized clinical trial that the application of the Ligasure system can shorten the time to liver dissection and thus reduce surgical bleeding. The disadvantage is that it does not preserve as much normal liver parenchyma as possible. A recent meta-analysis showed that there was no significant difference in intraoperative bleeding and postoperative complication rates between the clamp method and various other liver dissection techniques, while the operative time was significantly reduced.
In conclusion, various hepatic dissection instruments have their own characteristics and techniques, and understanding and mastering the techniques related to various instruments and rational selection and combined use of various hepatic dissection instruments can improve the safety of complex hepatectomy. When performing complex hepatectomy, the clamping method or electrocoagulation method can be used to dissect the superficial tissues of the liver, and the CUSA or waterjet can be used to dissect the liver in deep areas or important anatomical structures, which can not only perform fine dissection of important liver ducts, but also save the operation time.
IV. Resection and reconstruction of hepatic vein and inferior vena cava
In the past, liver tumors with hepatic vein involvement were often considered unresectable because of their high surgical risk and poor surgical prognosis. Currently, hemihepatectomy (or enlarged hepatectomy) and hepatic resection with preservation of liver parenchyma plus hepatic vein resection are often used for such patients. The former is suitable for patients with good hepatic compensation and sufficient remaining liver volume, while the latter is the ideal procedure for patients with chronic liver disease.
The literature reports that ligation of the hepatic vein trunk allows the establishment of intrahepatic traffic branches through the hepatic blood sinusoids and short hepatic veins to keep the venous outflow tract unobstructed, thus not adversely affecting the post-hepatectomy period. However, in recent years, with the accumulation of experience in living liver transplantation, it has been confirmed that obstruction of the hepatic venous outflow tract will lead to acute stasis and loss of function in the drainage area where the hepatic veins are located, resulting in parenchymal failure in the drainage area and serious infectious complications, especially in patients with cirrhosis. Therefore, reconstruction of the hepatic vein after hepatectomy, especially reconstruction of the middle hepatic vein, has been increasingly emphasized in complex hepatectomy. It has been reported that the anastomosis of the V and VIII branches of the middle hepatic vein with the inferior vena cava is an important factor affecting the function of the remaining right hepatic half during left hepatectomy including the middle trunk vein.55,56 However, reconstruction is not necessary after all hepatic vein resections, and in addition, hepatic vein reconstruction may increase surgical bleeding and operative time, resulting in increased postoperative complications.
Melendez et al57 concluded that there are 5 independent risk factors affecting postoperative mortality: biliary ductitis, creatinine >1.3 mg/dL, total bilirubin >6 mg/dL, intraoperative bleeding >3 L, and hepatic or inferior vena cava reconstruction, and the presence of two of these risk factors would result in an operative mortality rate close to 100%. The presence of other risk factors must be excluded when performing hepatic or inferior vena cava reconstruction. There is no universally accepted selection criteria for hepatic vein reconstruction, but some scholars have reported that preoperative virtual hepatectomy liver imaging software calculates the non-congestedliverremnant (NCLR) volume after hepatic vein resection to select whether to perform hepatic vein reconstruction: normal liver function (ICGR15<10%), NCLR less than 40% of total liver volume, or hepatic vein reconstruction. Those with normal liver function (ICGR15<10%) and NCLR less than 40% of total liver volume, or those with hepatic insufficiency (ICGR1510-20%) and NCLR less than 50% of total liver volume require venous reconstruction.
Hepatic vein reconstruction is performed in various ways, including end-to-end anastomosis of the hepatic vein branches to the main trunk and end-to-side anastomosis to the vena cava, and in most cases hepatic flow block by Pringle’s method is sufficient without whole liver flow block. Materials used include the saphenous vein, external iliac vein, ovarian vein, resected portion of the portal vein58-60 , and circumferential polytetrafluoroethylene artificial vessels (Gore-Texgraft). kuang61 and Millis62 reported a high incidence of thrombotic complications using refrigerated vessels as interposition vessels. In contrast, it has been suggested that the refurbished saphenous vein is more suitable for reconstruction of the hepatic venous trunk. Improper way of outflow tract reconstruction leads to stenosis or obstruction, which will also cause liver stasis. In China, Yan Lunan et al. proposed that the reconstructed outflow tract vessels should be as short as possible to avoid angulation and distortion; the interposition vessels should be vertical when anastomosing with the inferior vena cava, with low resistance to blood flow and less likely to form thrombus, and the anastomosis between the hepatic vein trunk and IVC should be triangular, stable and less likely to be deformed by pressure, and proposed a multi-port vertical anastomosis pattern accordingly.
Malignant tumors of the liver located in the caudate lobe and the root of the hepatic vein are likely to involve the inferior vena cava, and the tumor may compress, invade, or even encircle the inferior vena cava, causing it to be compressed, displaced, or deformed, or the tumor invades along the hepatic vein to form a cancer thrombus. In 1980, Starzl was the first to report hepatocellular carcinoma invading the inferior vena cava, and hepatocellular carcinoma and part of the inferior vena cava were resected and reconstructed by allogeneic vein reconstruction.
In recent years, some scholars have reported that partial resection of the inferior vena cava in combination with hepatic resection can achieve more satisfactory results in some patients. It is still difficult to distinguish accurately the tumor compression or invasion of the inferior vena cava before surgery, and whether partial resection of the inferior vena cava is needed should be decided after intraoperative exploration. The main intraoperative risks of inferior vena cava resection are hemorrhage and air embolism. Intraoperative total hepatic flow block with or without veno-venous diversion is usually used, and the safe time frame for patients with normal liver function to tolerate total hepatic flow block is 20-120 min.
In situ hepatic cryoperfusion combined with veno-venous diversion can effectively alleviate the systemic hemodynamic disturbances and visceral stasis caused by total hepatic flow blockade. If the tumor only infiltrates part of the vein wall, only part of the vessel wall should be removed for repair or reconstruction, if the resected inferior vena cava wall exceeds 1/2 of the circumference and the stenosis is obvious after repair, artificial blood vessel or own vein can be used for patch repair. If the inferior vena cava wall is extensively infiltrated or completely obstructed, segmental resection of the inferior vena cava and reconstruction with autologous or allogeneic vessels and artificial vessels are feasible. The relationship between the tumor and the inferior vena cava can be further explored after liver parenchyma dissection, and venous resection can be avoided if it is locally compressed, but some scholars reported that resection of the involved inferior vena cava and reconstruction before liver resection can reduce the time of blood flow blockage into the liver.
In conclusion, with the rapid development of liver surgery, the connotation and extension of the concept of “complex hepatectomy” will continue to expand, new instruments will emerge, and laparoscopic and robotic surgery will make complex hepatectomy much less traumatic and further improve surgical skills and safety.