xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05986383</url>
    </required_header>
    <id_info>
      <org_study_id>21408-0-03</org_study_id>
      <nct_id>NCT05986383</nct_id>
    </id_info>
    <brief_title>Multi-center Clinical Study on the Decision Tree of Precision Hepatectomy in China Precision Hepatectomy Decision Tree</brief_title>
    <official_title>A Prospective, Multi-center Clinical Study on the Safety and Effectiveness of Chinese Precision Hepatectomy Decision Tree</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Beijing Tsinghua Chang Gung Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>West China Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Second Affiliated Hospital, Sun Yat-Sen University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>The First Hospital of Jilin University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Meng Chao Hepatobiliary Hospital of Fujian Medical University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>LanZhou University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Southwest Hospital, China</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>The Affiliated Hospital of Qingdao University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Affiliated Hospital of Qinghai University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>The First Affiliated Hospital with Nanjing Medical University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Shenzhen People's Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Zhongshan Hospital Xiamen University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Beijing Tsinghua Chang Gung Hospital</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Liver failure (PHLF) after hepatectomy is a relatively serious postoperative complication.&#xD;
        Previous studies have shown that liver reserve function is related to PHLF. The &quot;Chinese&#xD;
        expert consensus decision tree for hepatectomy&quot; implemented recommends different surgical&#xD;
        methods according to the liver function of patients and the standardized residual functional&#xD;
        liver volume ratio, so as to achieve accurate hepatectomy and prolong the survival of&#xD;
        patients. In the retrospective study, it showed the safety and effectiveness of the decision&#xD;
        tree under the condition of extended hepatectomy indications, but it lacked prospective&#xD;
        research to evaluate. Therefore, this study intends to evaluate the safety and effectiveness&#xD;
        of hepatectomy under the guidance of Chinese expert consensus decision tree through&#xD;
        prospective research.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Hepatectomy is an effective treatment for primary liver cancer, with excellent efficacy and&#xD;
        controllable safety . The incidence of non fatal complications after Hepatectomy is as high&#xD;
        as 45%, ranging from less serious events to life-threatening complications, including&#xD;
        infection or sepsis, bleeding, leakage or cardiopulmonary events. Liver Function&#xD;
        Insufficiency is a serious complication, which is also described as Post hepatectomy Liver&#xD;
        failure (PHLF) after Hepatectomy. PHLF has many definitions. Balzan and his colleagues put&#xD;
        forward the &quot;50-50 standard&quot; in 2005, that is, on the fifth day after surgery, total&#xD;
        bilirubin&gt;50 μ mol/L (2.9 mg/dl) and prothrombin ratio&lt;50% (INR&gt;1.7) are met simultaneously.&#xD;
        The Sensitivity and specificity of this standard are 69.6% and 98.5% respectively , which was&#xD;
        confirmed as an effective predictor of death after Hepatectomy in 2009 . The &quot;Edinburgh&#xD;
        Standard&quot; proposed by Schindl et al. in 2005 is to divide the severity of PHLF according to&#xD;
        Hematology examination and clinical observation, which can be divided into&#xD;
        none/mild/moderate/severe . Mullen et al. proposed a peak postoperative bilirubin level&gt;120 μ&#xD;
        Mol/L), which can predict the death related to Liver failure, with a sensitivity of 93.3% and&#xD;
        a specificity of 94.3% . At present, the 2011 definition of the International Research Group&#xD;
        on Hepatosurgery (ISGLS) has been widely used as a standard to describe PHLF. According to&#xD;
        the international normalized ratio (INR), hyperbilirubin and other test indicators five days&#xD;
        after hepatectomy, and in combination with liver function, kidney function, respiratory&#xD;
        function, whether special assessment and special clinical treatment are required, the&#xD;
        severity of Liver failure in patients with cirrhosis after Hepatectomy is divided into A, B C&#xD;
        has three levels . The reported incidence of PHLF varies greatly, ranging from 0.7% to 34% ,&#xD;
        but recent reports have more commonly described it as between 8% and 12% . PHLF is an&#xD;
        important cause of death after Hepatectomy. In a large study, 70% of all patients who died&#xD;
        after liver resection met the PHLF criteria, while over 50% of patients had PHLF as the&#xD;
        direct cause of death. Moreover, nearly half of hospital deaths caused by PHLF occur within&#xD;
        30 days after surgery. In addition, the management cost of these postoperative complications&#xD;
        is high . Although there are already many treatment strategies that can save patients with&#xD;
        PHLF, the evidence for these treatment methods is still limited, and only a few conventional&#xD;
        methods are available for clinical use.&#xD;
  &#xD;
        Many preoperative factors may lead to PHLF. These have been extensively discussed in other&#xD;
        studies, including patient factors, disease pathology, intraoperative characteristics, and&#xD;
        postoperative course, but the most important factor that may affect the occurrence of PHLF is&#xD;
        the condition of the liver. On the one hand, it is the insufficient amount of remaining liver&#xD;
        tissue, accompanied by a decrease in liver regeneration ability in patients with cirrhosis.&#xD;
        The morphology, structure, and physiological function of regenerated liver cells are&#xD;
        incomplete, which can also affect the function of liver cells. At the same time,&#xD;
        postoperative liver reperfusion loss can also lead to insufficient liver functional liver&#xD;
        cell count. On the other hand, surgery directly leads to damage to the hepatic vascular&#xD;
        structure, changes in microcirculation structure, excessive inflammatory response after&#xD;
        surgery leading to liver microcirculation disorders, liver hypoperfusion, and further&#xD;
        exacerbating liver injury. Therefore, precise assessment of liver reserve function and&#xD;
        monitoring of liver microcirculation disorders during the perioperative period are of great&#xD;
        significance for selecting reasonable treatment methods, grasping the safe range of liver&#xD;
        resection, and reducing the incidence of postoperative liver failure in patients.&#xD;
  &#xD;
        Liver reserve function refers to the additional compensatory potential that the liver can&#xD;
        mobilize in response to increased physiological load. In the pathological state of liver&#xD;
        damage, the liver reserve function needs to meet the Functional requirement of body&#xD;
        metabolism, immunity and detoxification, as well as the needs of liver tissue repair and&#xD;
        regeneration. The reserve function of the liver mainly depends on the number of functional&#xD;
        liver cell populations and the integrity of their organizational structure. For decades, the&#xD;
        Child-Pugh score has been an important prognostic tool for patients with chronic liver&#xD;
        disease, used to stratify preoperative risk and to some extent remains a guiding factor for&#xD;
        clinical decision-making. The MELD score (the &quot;end stage liver disease model&quot;) can better&#xD;
        predict the prognosis of chronic liver disease. And MELD score is related to the early&#xD;
        prediction of incidence rate and mortality after Hepatectomy. Recently, the albumin bilirubin&#xD;
        (ALBI) score and its improvement have been proposed as an objective and evidence-based&#xD;
        clinical liver function assessment method. It has been proved to be a reliable assessment of&#xD;
        liver dysfunction in many studies , and is found to be superior to Child Pugh score in&#xD;
        predicting the outcome after Hepatectomy for liver cancer. The remaining liver volume (FLR)&#xD;
        is achieved by calculating the proportion of remaining liver tissue in the total liver&#xD;
        volume. To avoid PHLF, based on experience, it is recommended that the FLR be at least 20% of&#xD;
        the standard total liver volume, as the remaining parenchyma is normal . In addition, Truant&#xD;
        et al. found that patients with residual liver volume (RLV=FLR) related to body weight less&#xD;
        than 0.5% of their body weight had a significant risk of postoperative liver dysfunction and&#xD;
        death. If the liver is damaged through chemotherapy or existing liver diseases (such as&#xD;
        cirrhosis), it is necessary to increase FLR by at least 30% and 40%, respectively .&#xD;
  &#xD;
        However, although liver volume itself is important, it may not necessarily be related to&#xD;
        liver function. There are inherent limitations to liver capacity and Child Pugh score.&#xD;
        Compared to simple calculations of residual liver volume (FLR), the evaluation of functional&#xD;
        liver residual volume is better. Among the numerous tests to evaluate functional liver&#xD;
        capacity, indocyanine green clearance (ICG R15) is the most commonly used test, which can&#xD;
        minimize PHLF and mortality after Hepatectomy. In a large single center study, Professor&#xD;
        Yamin strictly applied bilirubin based algorithms and stratified them based on ICG clearance&#xD;
        rate, not only deciding which patients to undergo resection, but also deciding which type of&#xD;
        resection to perform. In a period of 10 years, excellent results have been achieved, with&#xD;
        only one patient having an extremely low mortality rate out of over a thousand resection&#xD;
        procedures. However, there are some limitations to ICG clearance, especially in patients with&#xD;
        perioperative jaundice and patients with impaired hemodynamics. Another aspect that reflects&#xD;
        the reserve function of the liver is the integrity of the tissue structure, which directly&#xD;
        determines the microcirculation structure of the liver. The complex functions of liver&#xD;
        biosynthesis, metabolism, detoxification, and host defense are closely dependent on a sound&#xD;
        liver microcirculation. Research has shown that microcirculation disorders are one of the&#xD;
        important pathogenesis of chronic liver disease, running through the entire disease&#xD;
        development process. Improving liver microcirculation is beneficial for the recovery of liver&#xD;
        function and helps to prevent and delay the formation of liver fibrosis and cirrhosis. The&#xD;
        Guidelines for the Diagnosis and Treatment of Liver failure (2012 Edition) mentioned that all&#xD;
        kinds of chronic liver disease patients have different degrees of liver microcirculation&#xD;
        disorders. Due to the increase of blood viscosity and the slowing of blood flow, the blood&#xD;
        perfusion and oxygen supply of microcirculation will inevitably be affected. It is difficult&#xD;
        for blood to enter and exit the liver, and the nutritional supply to liver cells cannot be&#xD;
        guaranteed, leading to further damage to liver cells, resulting in a vicious cycle. The&#xD;
        nutrients absorbed by the gastrointestinal tract are difficult to enter the liver, resulting&#xD;
        in indigestion; Drugs absorbed in the bloodstream are difficult to enter the liver and come&#xD;
        into contact with liver cells, making it difficult to effectively exert drug efficacy;&#xD;
        Metabolic waste is difficult to excrete from the liver, becoming toxins that remain in the&#xD;
        liver, leading to liver cell damage and accelerating the progression of liver disease. At&#xD;
        present, the main observation indicator reflecting liver microcirculation is effective liver&#xD;
        blood flow, which is also the &quot;functional liver blood flow&quot; studied in recent years.&#xD;
        Effective Hepatic Blood Flow (EHBF) refers to the blood flow of the liver that comes into&#xD;
        contact with liver cells and undergoes material exchange and metabolic function. Under the&#xD;
        condition of liver cirrhosis, due to changes in liver microcirculation structure and the&#xD;
        establishment of collateral circulation, there is arteriovenous shunt inside and outside the&#xD;
        liver. The effective blood flow of the liver (functional liver blood flow) is much lower than&#xD;
        the total liver blood flow (physical liver blood flow), and the clearance function of the&#xD;
        liver also decreases accordingly. The literature reports that using indocyanine green or&#xD;
        D-sorbitol as reagents for EHBF determination showed a significant decrease in EHBF in&#xD;
        patients with liver cirrhosis compared to normal individuals. Another study showed that EHBF&#xD;
        in patients with chronic liver failure was significantly lower than that in patients with&#xD;
        decompensated cirrhosis, and EHBF was closely related to the severity of HBV infection in&#xD;
        patients with chronic liver failure, which can be used to predict their 90 day mortality&#xD;
        rate. Therefore, EHBF is considered to reflect liver reserve function and also a marker of&#xD;
        liver ischemia.&#xD;
  &#xD;
        In order to improve the safety of liver resection, establishing a safe and effective liver&#xD;
        resection decision tree based on existing experience and data has always been a research&#xD;
        direction in liver and gallbladder surgery. In order to avoid Liver failure after&#xD;
        Hepatectomy, we should carefully consider whether to retain sufficient functional liver&#xD;
        volume before operation. However, there is no uniform standard for clinical hepatobiliary&#xD;
        Surgeon to evaluate liver reserve function before Hepatectomy. Each center proposes a variety&#xD;
        of hepatectomy decision systems based on Scientific theory and the center's practical&#xD;
        experience. At present, most of them refer to the Makuuchi standard of University of Tokyo in&#xD;
        Japan, the University of Zurich standard in Europe, the consensus decision tree of Chinese&#xD;
        experts on hepatectomy, in addition to Hong Kong, Fudan Zhongshan and other standards.&#xD;
  &#xD;
        The evaluation of liver reserve function proposed by the above standards refers to the Child&#xD;
        Pugh score, ICG15 minute retention rate (R15), or ICG plasma clearance rate (ICGK). However,&#xD;
        the Child Pugh score, ICGR15, and ICGK only reflect the number of functional liver cell&#xD;
        populations, and the integrity of liver tissue structure is not directly reflected. EHBF may&#xD;
        be able to supplement and improve liver reserve function.&#xD;
  &#xD;
        To sum up, previous studies have shown that liver reserve function is related to Liver&#xD;
        failure (PHLF) after Hepatectomy. The retrospective study of the Chinese expert consensus&#xD;
        decision tree for hepatectomy also shows the safety and effectiveness of the decision tree in&#xD;
        the case of expanded hepatectomy indications, but there is a lack of forward-looking research&#xD;
        to evaluate it. Therefore, this study intends to evaluate the safety and effectiveness of&#xD;
        Hepatectomy under the guidance of the consensus decision tree of Chinese experts through&#xD;
        prospective research.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 2023</start_date>
    <completion_date type="Anticipated">March 2024</completion_date>
    <primary_completion_date type="Anticipated">March 2024</primary_completion_date>
    <study_type>Observational [Patient Registry]</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Other</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <target_duration>3 Months</target_duration>
    <primary_outcome>
      <measure>Postoperative liver failure rate (50-50 criteria)</measure>
      <time_frame>postoperative day 3 and postoperative day 5</time_frame>
      <description>The proportion of patients with Liver failure after Hepatectomy in all patients. Using the 50-50 standard.On the 5th day after surgery</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Postoperative liver failure rate (ISGLS criteria)</measure>
      <time_frame>postoperative day 3 and postoperative day 5</time_frame>
      <description>The proportion of patients with Liver failure after Hepatectomy in all patients. Adopting the ISGLS standard.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Value of indocyanine green retention test at 15 min (ICG-R15)</measure>
      <time_frame>postoperative day 3 and postoperative day 5</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Hepatic effective hepatic blood flow (EHBF)</measure>
      <time_frame>postoperative day 3 and postoperative day 5</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Postoperative remanent liver volume (mL)</measure>
      <time_frame>postoperative day 5</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Volume (mL) of blood loss during the operation</measure>
      <time_frame>the operation day</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Operation time (min)</measure>
      <time_frame>the operation day</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Hepatic inflow occlusion time (min) during the operation</measure>
      <time_frame>the operation day</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Postoperative serum albumin level (g/L)</measure>
      <time_frame>postoperative day 3 and postoperative day 5</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Postoperative serum ALT (U/L)</measure>
      <time_frame>postoperative day 3 and postoperative day 5</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Postoperative serum AsT (U/L)</measure>
      <time_frame>postoperative day 3 and postoperative day 5</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Postoperative serum total bilirubin (umol/L)</measure>
      <time_frame>postoperative day 3 and postoperative day 5</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Postoperative prothrombin time (sec)</measure>
      <time_frame>postoperative day 3 and postoperative day 5</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Postoperative INR value</measure>
      <time_frame>postoperative day 3 and postoperative day 5</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Postoperative periphery platelet amount</measure>
      <time_frame>postoperative day 3 and postoperative day 5</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Postoperative fasting plasma glucose (mmol/L)</measure>
      <time_frame>postoperative day 3 and postoperative day 5</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Child-pugh score</measure>
      <time_frame>postoperative day 3 and postoperative day 5</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Total postoperative complication rate</measure>
      <time_frame>postoperative day 14</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Clavien-Dindo grade of postoperative complications</measure>
      <time_frame>postoperative day 14</time_frame>
    </secondary_outcome>
    <number_of_groups>6</number_of_groups>
    <enrollment type="Anticipated">820</enrollment>
    <condition>Primary Liver Cancer</condition>
    <condition>Metastatic Liver Cancer</condition>
    <condition>Benign Liver Neoplasms</condition>
    <condition>Hepatic Echinococcosis</condition>
    <arm_group>
      <arm_group_label>Guoup 1</arm_group_label>
      <description>Liver function is Child Pugh A：If ICG-R15&lt;10%, the standardized residual functional liver volume ratio (RRS) ≥ 40%</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Guoup 2</arm_group_label>
      <description>Liver function is Child Pugh A：If ICG-R15 is 10% - 20%, RRS ≥ 60%</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Guoup 3</arm_group_label>
      <description>Liver function is Child Pugh A：If ICG-R15 is 21% - 30%, RRS ≥ 80%</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Guoup 4</arm_group_label>
      <description>Liver function is Child Pugh A：If ICG-R15 is 31%~40%, only minimal hepatectomy with hepatectomy rate less than 5% can be performed</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Guoup 5</arm_group_label>
      <description>Liver function is Child Pugh A：If ICG-R15&gt;40%, only tumor resection is feasible</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Guoup 6</arm_group_label>
      <description>Liver function is Child Pugh B: only tumor resection is allowed</description>
    </arm_group>
    <eligibility>
      <study_pop>
        <textblock>
          1. CNLC stage Ⅰ a~Ⅱ b -- Ⅲ a (see the indications for hepatectomy of primary liver cancer&#xD;
               in the 2019 edition of the diagnostic and treatment specifications for primary liver&#xD;
               cancer);&#xD;
  &#xD;
                 1. CNLC stage Ⅰ a, Ⅰ b and Ⅱ a liver cancer with good liver reserve function&#xD;
  &#xD;
                 2. CNLC stage Ⅱ b liver cancer with tumor localized in the same segment or half of&#xD;
                    the liver on the same side.&#xD;
  &#xD;
                 3. The tumor is limited to the half-liver CNLC stage Ⅲ a liver cancer, and the&#xD;
                    portal vein branch tumor thrombus (Cheng's classification type I/II).&#xD;
  &#xD;
            2. Patients with benign liver neoplasms;&#xD;
  &#xD;
            3. Patients with metastatic liver cancer.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Age 18-70 years old, gender unlimited;&#xD;
  &#xD;
            2. Primary liver cancer patients who strictly comply with the clinical diagnostic&#xD;
               criteria of the &quot;Guidelines for the Diagnosis and Treatment of Primary Liver Cancer&quot;&#xD;
               (2019 version) or who have been confirmed by histopathological or cytological&#xD;
               examination, or patients with benign liver neoplasms, or metastatic liver cancer;&#xD;
  &#xD;
            3. Child-Pugh liver function rating A/B;&#xD;
  &#xD;
            4. ECOG PS score 0-2 points;&#xD;
  &#xD;
            5. The liver tumor can be resected (the remaining liver vessel structure is complete, the&#xD;
               liver volume is sufficient, and conforms to the decision system of safe hepatectomy);&#xD;
  &#xD;
            6. If the patient is HBV antigen positive and the HBV DNA is less than 1.0E+04 IU/ml,&#xD;
               routine antiviral treatment is required;&#xD;
  &#xD;
            7. Patients with portal hypertension can be included, and the severity can refer to&#xD;
               endoscopic esophageal varices or splenomegaly and hypersplenism;&#xD;
  &#xD;
            8. Use up to 3 antihypertensive drugs to fully control blood pressure (BP), which is&#xD;
               defined as BP&lt;=150/90 mm Hg (mmHg) during screening, and there is no change in&#xD;
               antihypertensive treatment within 1 week before the first cycle/day;&#xD;
  &#xD;
            9. The patient's expected survival period is more than 3 months;&#xD;
  &#xD;
           10. No pregnancy or pregnancy plan;&#xD;
  &#xD;
           11. No other contraindications for operation;&#xD;
  &#xD;
           12. Subjects voluntarily joined the study and signed the informed consent form, with good&#xD;
               compliance and cooperation in follow-up.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Extrahepatic metastasis of primary liver cancer;&#xD;
  &#xD;
            2. Diffuse liver cancer;&#xD;
  &#xD;
            3. Suffering from vascular liver diseases such as sinus obstruction syndrome, Budd-Chiari&#xD;
               syndrome and congenital vascular malformation;&#xD;
  &#xD;
            4. Patients with obstructive jaundice or cholestasis;&#xD;
  &#xD;
            5. Preoperative bilirubin&gt;50umol/L (2.9 mg/dL);&#xD;
  &#xD;
            6. Pregnant women;&#xD;
  &#xD;
            7. Have a history of mental illness or abuse of psychotropic substances;&#xD;
  &#xD;
            8. Joint HIV infected patients;&#xD;
  &#xD;
            9. With other malignant tumors;&#xD;
  &#xD;
           10. Floating population and other patients with poor compliance;&#xD;
  &#xD;
           11. Clinical trials involving other experimental drugs or devices within four weeks;&#xD;
  &#xD;
           12. The researcher believes that it is not suitable for enrollment.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>70 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Jiahong Dong, academician</last_name>
      <phone>18810108028</phone>
      <email>dongjiahong@mail.tsinghua.edu.cn</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>March 1, 2023</study_first_submitted>
    <study_first_submitted_qc>August 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 1, 2023</last_update_submitted>
    <last_update_submitted_qc>August 1, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Beijing Tsinghua Chang Gung Hospital</investigator_affiliation>
      <investigator_full_name>Jiahong Dong，MD</investigator_full_name>
      <investigator_title>Director</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Echinococcosis</mesh_term>
      <mesh_term>Echinococcosis, Hepatic</mesh_term>
      <mesh_term>Liver Neoplasms</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05986383
  org study id: 21408-0-03
  nct id: NCT05986383
  lead sponsor: 
  collaborator: 
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  is fda regulated drug: No
  is fda regulated device: No
  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.
  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.
  observational model: Other
  time perspective: Prospective
  measure: Postoperative liver failure rate (50-50 criteria)
  time frame: postoperative day 3 and postoperative day 5
  description: The proportion of patients with Liver failure after Hepatectomy in all patients. Using the 50-50 standard.On the 5th day after surgery
  measure: Postoperative liver failure rate (ISGLS criteria)
  time frame: postoperative day 3 and postoperative day 5
  description: The proportion of patients with Liver failure after Hepatectomy in all patients. Adopting the ISGLS standard.
  measure: Value of indocyanine green retention test at 15 min (ICG-R15)
  time frame: postoperative day 3 and postoperative day 5
  measure: Hepatic effective hepatic blood flow (EHBF)
  time frame: postoperative day 3 and postoperative day 5
  measure: Postoperative remanent liver volume (mL)
  time frame: postoperative day 5
  measure: Volume (mL) of blood loss during the operation
  time frame: the operation day
  measure: Operation time (min)
  time frame: the operation day
  measure: Hepatic inflow occlusion time (min) during the operation
  time frame: the operation day
  measure: Postoperative serum albumin level (g/L)
  time frame: postoperative day 3 and postoperative day 5
  measure: Postoperative serum ALT (U/L)
  time frame: postoperative day 3 and postoperative day 5
  measure: Postoperative serum AsT (U/L)
  time frame: postoperative day 3 and postoperative day 5
  measure: Postoperative serum total bilirubin (umol/L)
  time frame: postoperative day 3 and postoperative day 5
  measure: Postoperative prothrombin time (sec)
  time frame: postoperative day 3 and postoperative day 5
  measure: Postoperative INR value
  time frame: postoperative day 3 and postoperative day 5
  measure: Postoperative periphery platelet amount
  time frame: postoperative day 3 and postoperative day 5
  measure: Postoperative fasting plasma glucose (mmol/L)
  time frame: postoperative day 3 and postoperative day 5
  measure: Child-pugh score
  time frame: postoperative day 3 and postoperative day 5
  measure: Total postoperative complication rate
  time frame: postoperative day 14
  measure: Clavien-Dindo grade of postoperative complications
  time frame: postoperative day 14
  arm group label: Guoup 1
  description: Liver function is Child Pugh A：If ICG-R15<10%, the standardized residual functional liver volume ratio (RRS) ≥ 40%
  arm group label: Guoup 2
  description: Liver function is Child Pugh A：If ICG-R15 is 10% - 20%, RRS ≥ 60%
  arm group label: Guoup 3
  description: Liver function is Child Pugh A：If ICG-R15 is 21% - 30%, RRS ≥ 80%
  arm group label: Guoup 4
  description: Liver function is Child Pugh A：If ICG-R15 is 31%~40%, only minimal hepatectomy with hepatectomy rate less than 5% can be performed
  arm group label: Guoup 5
  description: Liver function is Child Pugh A：If ICG-R15>40%, only tumor resection is feasible
  arm group label: Guoup 6
  description: Liver function is Child Pugh B: only tumor resection is allowed
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 70 Years
  healthy volunteers: No
  last name: Jiahong Dong, academician
  phone: 18810108028
  email: dongjiahong@mail.tsinghua.edu.cn
  responsible party type: Principal Investigator
  investigator affiliation: Beijing Tsinghua Chang Gung Hospital
  investigator full name: Jiahong Dong，MD
  investigator title: Director
  mesh term: Echinococcosis
  mesh term: Echinococcosis, Hepatic
  mesh term: Liver Neoplasms