Cause of death
Percentage (%)
Liver failure
30.0
Ascites
15.6
Sepsis
12.6
Bleeding
10.2
Cardiovascular
10.0
Gastrointestinal bleeding
4.4
Pulmonary complications
4.1
Bile leakage
2.4
Intra-abdominal abscess
0.9
Others
9.8
Complications | Percentage (%) |
|---|---|
Pulmonary complications | 27.8 |
Liver failure | 14.1 |
Bile leakage | 11.6 |
Intra-abdominal abscess | 11.3 |
Sepsis | 8.8 |
Bleeding | 6.1 |
Cardiovascular | 4.1 |
Ascites | 1.9 |
Gastrointestinal bleeding | 1.2 |
Others | 13.1 |
In the past decades, not only has the technique of open hepatectomy been refined, but also the other therapeutic methods have been developed. These techniques include radiofrequency ablation, microwave ablation, alcohol injection, and cryotherapy. The development of these technologies has enriched the treatment of liver cancer and reduced postoperative complications; for some patients with unresectable liver tumors, these techniques provide a selective method of treatment. However, mortality and morbidity rates differ depending on the surgical procedure. (1) Radiofrequency ablation techniques (including percutaneous, laparoscopic, and open surgical approaches), microwave ablation, and cryotherapy are rapidly gaining acceptance in the radiologic and surgical communities, particularly for patients who have inoperable tumors. These techniques are generally regarded as safe, effective, and minimally invasive; these procedures are also associated with less bleeding and have significantly lower morbidity and mortality rates than open surgical procedures [14–18]. A retrospective study in Japan [14] of 11688 radiofrequency ablations found that the mortality rate was 0.25 % and the morbidity rate was 4.5 %. After cryotherapy, the mortality and morbidity rates were 0.9–1.5 % and 6–29 %, respectively. (2) Living-donor liver resection is a special type of liver resection that is performed in healthy persons with normal liver parenchyma and function. The risk of postoperative morbidity is reduced, and mortality is rare. A study of 3565 cases of living-donor liver resection showed that the complication rate was only 8.4 % and the mortality rate was less than 0.1 % [19]. (3) Laparoscopic liver resection is becoming an attractive option for patients with liver disease and is considered to be a safe alternative to open surgical intervention. The complication rate was 10.5 %, and the mortality was 0.3 % in a meta-analysis that included 2804 patients [20]. However, most laparoscopic liver resections have been limited to tumors in the anterolateral segments. (4) Patients with hilar cholangiocarcinoma always have poor liver function, and the mortality and morbidity rates after major surgery are relatively high, ranging from 5.9 to 7.6 % and 22 to 77 %, respectively [21, 22]. The mortality and morbidity rates for different types of liver resection are displayed in Table 10.3.
Table 10.3
Short-term outcomes of liver resections
Surgical procedures | Morbidity (%) | Mortality (%) |
|---|---|---|
Radiofrequency ablation | 4.5–8.9 | 0.09–0.5 |
Open surgical | 9.9 | 0.5 |
Laparoscopic | 9.5 | 0.5 |
Percutaneous | 2.2–7.2 | 0.3 |
Microwave ablation | 7–14.2 | 0.7–2.3 |
Cryotherapy | 6–29 | 0.9–1.5 |
Laparoscopic liver resection | 10.5–21.7 | 0.3 |
Living-donor hepatectomy | 8.4–28 | <0.1 |
Hilar cholangiocarcinoma | 22–77 | 5.9–7.6 |
10.3 The Clavien-Dindo Classification of Surgical Complications
Although high-volume studies of liver resection are frequently reported worldwide, the reported rate of complications is highly variable, ranging from 14.5 to 42 %. One important cause of this variation is the absence of standard definitions and a widely accepted ranking system to classify surgical complications, which has hampered the interpretation of surgical outcome data and comparisons between different medical centers. In 2004, Clavien [23, 24] proposed a classification system for complications that is known as the Clavien-Dindo classification and is based on the therapy used to treat the complication (Table 10.4). This system is an important tool for quality assessment in surgery worldwide. Research from West China Hospital of Sichuan University [5] has summarized complications of liver resection, based on the Clavien-Dindo classification, in an analysis of 1543 cases of HCC liver resection; the results are displayed in Table 10.5.
Classification | Definition |
|---|---|
I | Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic, or radiological interventions. Allowed therapeutic regimens are drugs such as antiemetics, antipyretics, analgesics, diuretics, and electrolytes, as well as physiotherapy. This grade also includes wound infections that are opened at the bedside |
II | Requiring pharmacological treatment with drugs other than those allowed for grade I complications. Blood transfusions and total parenteral nutrition are also included |
III | Requiring surgical, endoscopic, or radiological intervention |
IIIa | Intervention not under general anesthesia |
IIIb | Intervention under general anesthesia |
IV | Life-threatening complication (including CNS complications) requiring IC/ICU management |
IVa | Single organ dysfunction (including dialysis) |
IVb | Multi-organ dysfunction |
V | Death of a patient |
Table 10.5
The Clavien-Dindo classification of complications in HCC patients undergoing hepatectomy [5]
Complication grade | Cases (incidence) |
|---|---|
Grade I | 146 (9.5 %) |
Grade II | 193 (12.5 %) |
Grade IIIa | 58 (3.8 %) |
Grade IIIb | 13 (0.8 %) |
Grade IV | 31 (2 %) |
Grade V | 23 (1.5 %) |
10.4 Risk Factors for Short-Term Outcomes after Liver Resection
Many factors contribute to the development of complications and mortality, including the extent of liver damage, the general condition of the patient, comorbidities, and surgical factors. However, the influence of any single factor (such as the Child-Pugh score, the MELD score, the ICG-15 results, etc.) on adverse events is limited, although these factors have been identified as predictors of outcomes. Scoring systems have been proposed recently by many medical centers, but these systems have low sensitivity and specificity and have not been verified by other centers. Even for scoring systems that integrate important risk factors, the predictive ability for complications remains unsatisfactory [4, 8].
10.4.1 Liver-Related Risk Factors
10.4.1.1 Liver Function
The most frequently used indices for accessing liver function are the Child-Pugh score, the MELD score, and ICG-15. To prevent liver failure, liver resection is permitted when the Child-Pugh score is A. The risk of liver failure is associated with the MELD score. When the MELD score is <9, 9–10, or >10, the corresponding postoperative liver failure rates are 0.4, 3.8, and 20.3 % [25]. The use of ICG-15 is popular in Japan and Asia. Generally, liver resection of four segments is permitted when ICG-15 < 10 %, the resection of two to three segments is permitted when the ICG-15 is between 10 and 19 %, and the resection of one segment can be performed in patients whose ICG-15 is between 20 and 29 %.
10.4.1.2 Cirrhosis and Fibrosis
The cirrhotic liver tolerates acute tissue loss poorly, given its impaired function and decreased ability to regenerate. Fibrosis also affects the liver’s functional reserve and increases the risk of liver failure. Furthermore, patients with cirrhotic or fibrotic livers always have poor liver function, portal hypertension, ascites, and poor coagulation ability [10].
10.4.1.3 Steatohepatitis and Steatosis
Steatosis of the liver is another common condition and is usually related to obesity, diabetes mellitus, metabolic disorders, chemotherapy, and alcohol consumption [10]. Steatohepatitis is also the most frequent pathologic change in the liver parenchyma, with an incidence of 30 % in the western population. Among patients undergoing liver surgery, approximately 20 % of liver resection patients have steatosis, and this rate approaches to 25 % for living donors. Liver steatosis affects liver function and liver regeneration and commonly is considered to be a significant risk factor for liver failure after hepatic surgery [26]. One meta-analysis that included 1000 liver resections revealed a significant association between the degree of steatosis and an increased risk of postoperative complications and mortality [27]. Patients with at least 30 % steatosis had a significantly higher risk of postoperative complications (with a RR of 2.01) than patients without steatosis [27].
10.4.1.4 Portal Hypertension
Patients with portal hypertension always have accompanying poor liver function and cirrhosis, which contraindicate liver resection because of the higher risk of complications. However, recent studies have revealed that liver resection can be performed safely in patients with portal hypertension, with acceptably higher rates of liver failure and complications [28].
10.4.1.5 Tumor
Tumor size, tumor location, and the presence of vascular invasion are all associated with surgical injury and blood loss. In addition, the location of the tumor also affects the surgical plan and the postoperative blood supply and outflow. Tumors located in special segments such as the caudate lobe or segments VII and VIII are associated with increased operative difficulty and blood loss.
10.4.2 Patient-Related Risk Factors
10.4.2.1 Age
Elderly patients always have other diseases such as hypertension, diabetes mellitus, chronic obstructive pulmonary disease, etc. These comorbidities and poor physical condition can reduce the tolerance of elderly patients to surgery and increase the operative risk. Many studies have also suggested that patients over 65 or 70 years of age have higher morbidity and mortality rates after liver resection than younger patients [29, 30].
10.4.2.2 Body Mass Index (BMI)
With the prevalence of obesity continuously increasing worldwide, obesity and overweight have become increasing public health problems. In China, 36.2 % of adults were obese or overweight, while in the USA, this rate is as high as 66.2 % [31]. Obesity and overweight are not only associated with an increasing incidence of a number of conditions, including diabetes mellitus, cardiovascular disease, and nonalcoholic fatty liver disease, but also increase operative difficulty and operative time. A retrospective study that included 3960 liver resections found that obese patients seemed to have worse perioperative outcomes with higher rates of complications and mortality [32]. Data from our center indicate that although BMI did not increase the total complications, postoperative wound complications were more common in overweight and obese patients [33].
10.4.2.3 Comorbidities
The most common comorbidities in patients undergoing liver resection are chronic hepatitis B, hypertension, diabetes, chronic obstructive pulmonary disease, and cardiovascular disease. The Charlson comorbidity index is an effective method of integrating and assessing comorbidities that affect the vital organs. Higher Charlson index scores are associated with higher complication rates [34].
10.4.2.4 American Society of Anesthesiologists (ASA) Index
The ASA index is another method of assessing the degree of tolerance for surgery. Higher ASA scores are associated with higher surgical risks. Studies have suggested that patients with an ASA grade of III–VI have a 1.5- to twofold elevated risk for postoperative complications than patients with an ASA grade of I–II [5, 13].
10.4.3 Surgery-Related Risk Factors
10.4.3.1 Blood Loss
Blood loss during surgery plays a crucial role in postoperative short-term outcomes and is associated with mortality and morbidity. Many studies have shown that bleeding and subsequent blood transfusions are independent risk factors for complications [35]. Transfusions also contribute to immunosuppression, organ injury, and postoperative infection [36].
10.4.3.2 Occlusion of Blood Flow and Methods of Liver Resection
Occlusion of blood flow, especially the Pringer procedure, is the most important method of controlling bleeding during surgery. Although blood flow occlusion often results in gastrointestinal tract congestion, liver ischemia, and reperfusion injury, blood flow occlusion still can reduce postoperative morbidity and mortality. We conducted a study of 574 patients with hepatitis B-related HCC who underwent major hepatectomy and found that the amount of intraoperative blood loss in the no-occlusion group was greater than in the Pringer and the hemihepatic occlusion groups [37]. Presently, hemorrhage during liver resection can be well controlled, even without blood occlusion, with the use of equipment such as the Cavitron Ultrasonic Surgical Aspirator (Valleylab, Boulder, Colorado, USA), the water jet, and LigaSure.
10.4.3.3 Extent of Liver Resection
The extent of the liver resection affects blood loss and the risk of liver failure. Schindl’s study [38] identified a relative residual liver volume of 26.6 % as the cutoff value for severe hepatic dysfunction. However, the relative residual liver volume should be increased appropriately for patients with conditions such as cirrhosis that impair liver function. Suda [39] performed a study in patients with obstructive jaundice and suggested that the relative residual liver volume should be as high as 40 % to prevent liver failure. For patients with cirrhosis, a residual liver volume of 40–50 % is necessary [39]. In our study, we found that liver resection of more than three segments was associated with a 3.15-fold increased risk of complications, compared with resections of less than three segments [5].
10.4.3.4 Extrahepatic Procedures
Extrahepatic procedures, such as bowel resection, adrenalectomy, diaphragmatic resection, biliary tract exploration, and adhesion separation due to a prior operation, increase the risk of complications [13].
10.4.4 Other Risk Factors
Other factors, such as operative time, reoperation, and so on, have been identified as risk factors.
10.5 Bile Leakage
Bile leakage is one of the most frequent complications of liver resection, with an incidence of between 5.3 and 33 %. Bile leakage can result in peritonitis, liver abscess, and sepsis if prompt and reasonable treatment is not given [40]. Mild bile leaks can resolve on their own with sufficient peritoneal drainage; however, severe bile leakage always requires surgical intervention.
10.5.1 Definition and Grade
According to the International Study Group of Hepatobiliary and Pancreatic Surgeons [41], bile leakage is defined as a bilirubin concentration in the drain of at least three times the serum bilirubin concentration on or after postoperative day 3 or as the need for radiologic or operative intervention to treat biliary collections or bile peritonitis. Using this criterion, the severity of bile leakage was classified according to its effects on the clinical management of patients. Grade A bile leakage requires no change in clinical management. Grade B bile leakage requires active therapeutic intervention but is manageable without repeat laparotomy; in Grade C, repeat laparotomy is required to treat bile leakage.
10.5.2 Risk Factors for Bile Leakage
10.5.2.1 Bile Duct Injury
Bile duct injury often occurs at the time of hepatic inflow occlusion and liver resection. Bile leakage can happen when a bile duct injury is not detected or sufficiently repaired.
10.5.2.2 Insufficient Blood Supply to the Bile Duct
Excessive separation of the tissue around the biliary tree may injure the vascular supply to the bile duct. Insufficient blood supply after surgery can cause bile leakage, especially at the common bile duct and the common hepatic duct.
Inadequate suturing and repair of the liver section may omit small bile ducts, which is the most common cause of bile leakage. Another cause is partial necrosis and shedding of liver tissue, exposing the bile duct.
10.5.2.3 Postoperative Biliary Obstruction
Biliary obstruction can increase the bile duct pressure and cause bile leakage.
10.5.3 Clinical Manifestations
Bile leakage mainly presents clinically with persistent abdominal drainage of bile, with 100–300 mL of drainage every day. The presentation may be nonspecific when abdominal drainage remains unobstructed. Patients without peritoneal drainage tubes can present with distension, abdominal pain, or peritonitis (with abdominal tenderness and rebound tenderness). In addition, fever and elevated white blood cell counts are common. Severe cases present with sepsis. Identifying bile during a diagnostic puncture or laparotomy is diagnostic for bile leakage.
10.5.4 Treatment
The principle for treating bile leakage is to maintain the patency of bile drainage, prevent infection, and promote healing of the fistula.
10.5.4.1 Conservative Treatment
Conservative treatment is suitable for bile leakage without associated peritonitis. Treatment includes maintaining the patency of bile drainage, anti-infective treatments, nutritional support, and maintaining appropriate fluid and electrolyte balance. Most patients are cured after 2 weeks to 3 months of such treatment.
10.5.4.2 Percutaneous Puncture Drainage of the Abdominal Cavity [42]
For patients with biliary peritoneal effusions, percutaneous puncture drainage of the abdominal cavity should be performed with ultrasound or CT guidance.
10.5.4.3 Endoscopic Treatment
Endoscopic treatment includes endoscopic retrograde cholangiography (ERCP), endoscopic nasobiliary drainage (ENBD), and biliary stent placement [43]. ERCP and ENBD can reduce bile duct pressure and promote healing of the fistula. Many studies have shown that endoscopic treatments are minimally invasive, simple, and effective.
10.5.4.4 Abdominal Laparotomy
For patients with diffuse peritonitis, abdominal laparotomy should be performed in a timely fashion.
10.5.5 Prevention
10.5.5.1 Suturing the Liver Section
The main way to prevent bile leakage after liver resection is to suture the liver section and suture the transection of the bile duct; sometimes, repeated checking is necessary.
10.5.5.2 Bile Leakage Test
The bile leakage test is a common approach to reduce the risk of postoperative bile leakage. With this technique, after cholecystectomy and liver resection, a catheter is inserted through the cystic duct into the common bile duct, and the distal common bile duct is occluded. A solution is slowly injected into the biliary tree, and a clinical judgment is then made as to whether a bile leak is present on the transected surface of the liver. If so, the bile leak site will be closed steadily beforehand to avoid bile leakage. The solution used for the bile leakage test includes isotonic sodium, fat emulsion, indocyanine green, and methylene blue. A meta-analysis has found that the bile leakage test reduces the risk of postoperative bile leakage and does not increase the incidence of complications. Fat emulsion is the best choice of solution for the test [44].
10.5.5.3 Intraoperative Cholangiography
Intraoperative cholangiography can help to identify bile duct injury or stenosis and bile leakage.
10.6 Liver Failure
Liver failure is the most severe complication of liver resection. Although the reported incidence is only 2.6–14.1 % [4, 45, 46], this complication always has a poor prognosis and a high mortality rate of more than 50 % [46].
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