Trial Title:
Multi-center Clinical Study on the Decision Tree of Precision Hepatectomy in China Precision Hepatectomy Decision Tree
NCT ID:
NCT05986383
Condition:
Primary Liver Cancer
Metastatic Liver Cancer
Benign Liver Neoplasms
Hepatic Echinococcosis
Conditions: Official terms:
Echinococcosis
Echinococcosis, Hepatic
Liver Neoplasms
Study type:
Observational [Patient Registry]
Overall status:
Not yet recruiting
Study design:
Time perspective:
Prospective
Summary:
Liver failure (PHLF) after hepatectomy is a relatively serious postoperative
complication. Previous studies have shown that liver reserve function is related to PHLF.
The "Chinese expert consensus decision tree for hepatectomy" implemented recommends
different surgical methods according to the liver function of patients and the
standardized residual functional liver volume ratio, so as to achieve accurate
hepatectomy and prolong the survival of patients. In the retrospective study, it showed
the safety and effectiveness of the decision tree under the condition of extended
hepatectomy indications, but it lacked prospective research to evaluate. Therefore, this
study intends to evaluate the safety and effectiveness of hepatectomy under the guidance
of Chinese expert consensus decision tree through prospective research.
Detailed description:
Hepatectomy is an effective treatment for primary liver cancer, with excellent efficacy
and controllable safety . The incidence of non fatal complications after Hepatectomy is
as high as 45%, ranging from less serious events to life-threatening complications,
including infection or sepsis, bleeding, leakage or cardiopulmonary events. Liver
Function Insufficiency is a serious complication, which is also described as Post
hepatectomy Liver failure (PHLF) after Hepatectomy. PHLF has many definitions. Balzan and
his colleagues put forward the "50-50 standard" in 2005, that is, on the fifth day after
surgery, total bilirubin>50 μ mol/L (2.9 mg/dl) and prothrombin ratio<50% (INR>1.7) are
met simultaneously. The Sensitivity and specificity of this standard are 69.6% and 98.5%
respectively , which was confirmed as an effective predictor of death after Hepatectomy
in 2009 . The "Edinburgh Standard" proposed by Schindl et al. in 2005 is to divide the
severity of PHLF according to Hematology examination and clinical observation, which can
be divided into none/mild/moderate/severe . Mullen et al. proposed a peak postoperative
bilirubin level>120 μ Mol/L), which can predict the death related to Liver failure, with
a sensitivity of 93.3% and a specificity of 94.3% . At present, the 2011 definition of
the International Research Group on Hepatosurgery (ISGLS) has been widely used as a
standard to describe PHLF. According to the international normalized ratio (INR),
hyperbilirubin and other test indicators five days after hepatectomy, and in combination
with liver function, kidney function, respiratory function, whether special assessment
and special clinical treatment are required, the severity of Liver failure in patients
with cirrhosis after Hepatectomy is divided into A, B C has three levels . The reported
incidence of PHLF varies greatly, ranging from 0.7% to 34% , but recent reports have more
commonly described it as between 8% and 12% . PHLF is an important cause of death after
Hepatectomy. In a large study, 70% of all patients who died after liver resection met the
PHLF criteria, while over 50% of patients had PHLF as the direct cause of death.
Moreover, nearly half of hospital deaths caused by PHLF occur within 30 days after
surgery. In addition, the management cost of these postoperative complications is high .
Although there are already many treatment strategies that can save patients with PHLF,
the evidence for these treatment methods is still limited, and only a few conventional
methods are available for clinical use.
Many preoperative factors may lead to PHLF. These have been extensively discussed in
other studies, including patient factors, disease pathology, intraoperative
characteristics, and postoperative course, but the most important factor that may affect
the occurrence of PHLF is the condition of the liver. On the one hand, it is the
insufficient amount of remaining liver tissue, accompanied by a decrease in liver
regeneration ability in patients with cirrhosis. The morphology, structure, and
physiological function of regenerated liver cells are incomplete, which can also affect
the function of liver cells. At the same time, postoperative liver reperfusion loss can
also lead to insufficient liver functional liver cell count. On the other hand, surgery
directly leads to damage to the hepatic vascular structure, changes in microcirculation
structure, excessive inflammatory response after surgery leading to liver
microcirculation disorders, liver hypoperfusion, and further exacerbating liver injury.
Therefore, precise assessment of liver reserve function and monitoring of liver
microcirculation disorders during the perioperative period are of great significance for
selecting reasonable treatment methods, grasping the safe range of liver resection, and
reducing the incidence of postoperative liver failure in patients.
Liver reserve function refers to the additional compensatory potential that the liver can
mobilize in response to increased physiological load. In the pathological state of liver
damage, the liver reserve function needs to meet the Functional requirement of body
metabolism, immunity and detoxification, as well as the needs of liver tissue repair and
regeneration. The reserve function of the liver mainly depends on the number of
functional liver cell populations and the integrity of their organizational structure.
For decades, the Child-Pugh score has been an important prognostic tool for patients with
chronic liver disease, used to stratify preoperative risk and to some extent remains a
guiding factor for clinical decision-making. The MELD score (the "end stage liver disease
model") can better predict the prognosis of chronic liver disease. And MELD score is
related to the early prediction of incidence rate and mortality after Hepatectomy.
Recently, the albumin bilirubin (ALBI) score and its improvement have been proposed as an
objective and evidence-based clinical liver function assessment method. It has been
proved to be a reliable assessment of liver dysfunction in many studies , and is found to
be superior to Child Pugh score in predicting the outcome after Hepatectomy for liver
cancer. The remaining liver volume (FLR) is achieved by calculating the proportion of
remaining liver tissue in the total liver volume. To avoid PHLF, based on experience, it
is recommended that the FLR be at least 20% of the standard total liver volume, as the
remaining parenchyma is normal . In addition, Truant et al. found that patients with
residual liver volume (RLV=FLR) related to body weight less than 0.5% of their body
weight had a significant risk of postoperative liver dysfunction and death. If the liver
is damaged through chemotherapy or existing liver diseases (such as cirrhosis), it is
necessary to increase FLR by at least 30% and 40%, respectively .
However, although liver volume itself is important, it may not necessarily be related to
liver function. There are inherent limitations to liver capacity and Child Pugh score.
Compared to simple calculations of residual liver volume (FLR), the evaluation of
functional liver residual volume is better. Among the numerous tests to evaluate
functional liver capacity, indocyanine green clearance (ICG R15) is the most commonly
used test, which can minimize PHLF and mortality after Hepatectomy. In a large single
center study, Professor Yamin strictly applied bilirubin based algorithms and stratified
them based on ICG clearance rate, not only deciding which patients to undergo resection,
but also deciding which type of resection to perform. In a period of 10 years, excellent
results have been achieved, with only one patient having an extremely low mortality rate
out of over a thousand resection procedures. However, there are some limitations to ICG
clearance, especially in patients with perioperative jaundice and patients with impaired
hemodynamics. Another aspect that reflects the reserve function of the liver is the
integrity of the tissue structure, which directly determines the microcirculation
structure of the liver. The complex functions of liver biosynthesis, metabolism,
detoxification, and host defense are closely dependent on a sound liver microcirculation.
Research has shown that microcirculation disorders are one of the important pathogenesis
of chronic liver disease, running through the entire disease development process.
Improving liver microcirculation is beneficial for the recovery of liver function and
helps to prevent and delay the formation of liver fibrosis and cirrhosis. The Guidelines
for the Diagnosis and Treatment of Liver failure (2012 Edition) mentioned that all kinds
of chronic liver disease patients have different degrees of liver microcirculation
disorders. Due to the increase of blood viscosity and the slowing of blood flow, the
blood perfusion and oxygen supply of microcirculation will inevitably be affected. It is
difficult for blood to enter and exit the liver, and the nutritional supply to liver
cells cannot be guaranteed, leading to further damage to liver cells, resulting in a
vicious cycle. The nutrients absorbed by the gastrointestinal tract are difficult to
enter the liver, resulting in indigestion; Drugs absorbed in the bloodstream are
difficult to enter the liver and come into contact with liver cells, making it difficult
to effectively exert drug efficacy; Metabolic waste is difficult to excrete from the
liver, becoming toxins that remain in the liver, leading to liver cell damage and
accelerating the progression of liver disease. At present, the main observation indicator
reflecting liver microcirculation is effective liver blood flow, which is also the
"functional liver blood flow" studied in recent years. Effective Hepatic Blood Flow
(EHBF) refers to the blood flow of the liver that comes into contact with liver cells and
undergoes material exchange and metabolic function. Under the condition of liver
cirrhosis, due to changes in liver microcirculation structure and the establishment of
collateral circulation, there is arteriovenous shunt inside and outside the liver. The
effective blood flow of the liver (functional liver blood flow) is much lower than the
total liver blood flow (physical liver blood flow), and the clearance function of the
liver also decreases accordingly. The literature reports that using indocyanine green or
D-sorbitol as reagents for EHBF determination showed a significant decrease in EHBF in
patients with liver cirrhosis compared to normal individuals. Another study showed that
EHBF in patients with chronic liver failure was significantly lower than that in patients
with decompensated cirrhosis, and EHBF was closely related to the severity of HBV
infection in patients with chronic liver failure, which can be used to predict their 90
day mortality rate. Therefore, EHBF is considered to reflect liver reserve function and
also a marker of liver ischemia.
In order to improve the safety of liver resection, establishing a safe and effective
liver resection decision tree based on existing experience and data has always been a
research direction in liver and gallbladder surgery. In order to avoid Liver failure
after Hepatectomy, we should carefully consider whether to retain sufficient functional
liver volume before operation. However, there is no uniform standard for clinical
hepatobiliary Surgeon to evaluate liver reserve function before Hepatectomy. Each center
proposes a variety of hepatectomy decision systems based on Scientific theory and the
center's practical experience. At present, most of them refer to the Makuuchi standard of
University of Tokyo in Japan, the University of Zurich standard in Europe, the consensus
decision tree of Chinese experts on hepatectomy, in addition to Hong Kong, Fudan
Zhongshan and other standards.
The evaluation of liver reserve function proposed by the above standards refers to the
Child Pugh score, ICG15 minute retention rate (R15), or ICG plasma clearance rate (ICGK).
However, the Child Pugh score, ICGR15, and ICGK only reflect the number of functional
liver cell populations, and the integrity of liver tissue structure is not directly
reflected. EHBF may be able to supplement and improve liver reserve function.
To sum up, previous studies have shown that liver reserve function is related to Liver
failure (PHLF) after Hepatectomy. The retrospective study of the Chinese expert consensus
decision tree for hepatectomy also shows the safety and effectiveness of the decision
tree in the case of expanded hepatectomy indications, but there is a lack of
forward-looking research to evaluate it. Therefore, this study intends to evaluate the
safety and effectiveness of Hepatectomy under the guidance of the consensus decision tree
of Chinese experts through prospective research.
Criteria for eligibility:
Study pop:
1. CNLC stage Ⅰ a~Ⅱ b -- Ⅲ a (see the indications for hepatectomy of primary liver
cancer in the 2019 edition of the diagnostic and treatment specifications for
primary liver cancer);
1. CNLC stage Ⅰ a, Ⅰ b and Ⅱ a liver cancer with good liver reserve function
2. CNLC stage Ⅱ b liver cancer with tumor localized in the same segment or half of
the liver on the same side.
3. The tumor is limited to the half-liver CNLC stage Ⅲ a liver cancer, and the
portal vein branch tumor thrombus (Cheng's classification type I/II).
2. Patients with benign liver neoplasms;
3. Patients with metastatic liver cancer.
Sampling method:
Non-Probability Sample
Criteria:
Inclusion Criteria:
1. Age 18-70 years old, gender unlimited;
2. Primary liver cancer patients who strictly comply with the clinical diagnostic
criteria of the "Guidelines for the Diagnosis and Treatment of Primary Liver Cancer"
(2019 version) or who have been confirmed by histopathological or cytological
examination, or patients with benign liver neoplasms, or metastatic liver cancer;
3. Child-Pugh liver function rating A/B;
4. ECOG PS score 0-2 points;
5. The liver tumor can be resected (the remaining liver vessel structure is complete,
the liver volume is sufficient, and conforms to the decision system of safe
hepatectomy);
6. If the patient is HBV antigen positive and the HBV DNA is less than 1.0E+04 IU/ml,
routine antiviral treatment is required;
7. Patients with portal hypertension can be included, and the severity can refer to
endoscopic esophageal varices or splenomegaly and hypersplenism;
8. Use up to 3 antihypertensive drugs to fully control blood pressure (BP), which is
defined as BP<=150/90 mm Hg (mmHg) during screening, and there is no change in
antihypertensive treatment within 1 week before the first cycle/day;
9. The patient's expected survival period is more than 3 months;
10. No pregnancy or pregnancy plan;
11. No other contraindications for operation;
12. Subjects voluntarily joined the study and signed the informed consent form, with
good compliance and cooperation in follow-up.
Exclusion Criteria:
1. Extrahepatic metastasis of primary liver cancer;
2. Diffuse liver cancer;
3. Suffering from vascular liver diseases such as sinus obstruction syndrome,
Budd-Chiari syndrome and congenital vascular malformation;
4. Patients with obstructive jaundice or cholestasis;
5. Preoperative bilirubin>50umol/L (2.9 mg/dL);
6. Pregnant women;
7. Have a history of mental illness or abuse of psychotropic substances;
8. Joint HIV infected patients;
9. With other malignant tumors;
10. Floating population and other patients with poor compliance;
11. Clinical trials involving other experimental drugs or devices within four weeks;
12. The researcher believes that it is not suitable for enrollment.
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Start date:
August 2023
Completion date:
March 2024
Lead sponsor:
Agency:
Beijing Tsinghua Chang Gung Hospital
Agency class:
Other
Collaborator:
Agency:
West China Hospital
Agency class:
Other
Collaborator:
Agency:
Second Affiliated Hospital, Sun Yat-Sen University
Agency class:
Other
Collaborator:
Agency:
The First Hospital of Jilin University
Agency class:
Other
Collaborator:
Agency:
Meng Chao Hepatobiliary Hospital of Fujian Medical University
Agency class:
Other
Collaborator:
Agency:
LanZhou University
Agency class:
Other
Collaborator:
Agency:
Southwest Hospital, China
Agency class:
Other
Collaborator:
Agency:
The Affiliated Hospital of Qingdao University
Agency class:
Other
Collaborator:
Agency:
Affiliated Hospital of Qinghai University
Agency class:
Other
Collaborator:
Agency:
The First Affiliated Hospital with Nanjing Medical University
Agency class:
Other
Collaborator:
Agency:
Shenzhen People's Hospital
Agency class:
Other
Collaborator:
Agency:
Zhongshan Hospital Xiamen University
Agency class:
Other
Source:
Beijing Tsinghua Chang Gung Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05986383
