<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/NCT03270917</url>
  </required_header>
  <id_info>
    <org_study_id>NL36215.068.11*</org_study_id>
    <nct_id>NCT03270917</nct_id>
  </id_info>
  <brief_title>ORANGE SEGMENTS: Open Versus Laparoscopic Parenchymal Preserving Postero-Superior Liver Segment Resection</brief_title>
  <official_title>The ORANGE SEGMENTS - Trial: an International Multicentre Randomized Controlled Trial of Open Versus Laparoscopic Parenchymal Preserving Postero-superior Liver Segment Resection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Maastricht University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Queen Elizabeth Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>General Hospital Groeninge</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Liverpool University Hospitals NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>King's College Hospital NHS Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>San Raffaele University Hospital, Italy</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Newcastle-upon-Tyne Hospitals NHS Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Oslo University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Oxford University Hospitals NHS Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Derriford Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital Southampton NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Manchester University NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Moscow Clinical Scientific Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>San Camillo Hospital, Rome</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Fondazione Poliambulanza Istituto Ospedaliero</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Federico II University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Maastricht University Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The international and multicentre ORANGE SEGMENTS - Trial is a prospective, double blinded,&#xD;
      randomized controlled study comparing patients undergoing parenchymal preserving resection of&#xD;
      postero-superior liver segments (involving one or two of segments 4a, 7, 8). All patients&#xD;
      will be participating in an enhanced recovery programme.&#xD;
&#xD;
      Primary outcome is time to functional recovery. Secondary study parameters include hospital&#xD;
      length of stay, intraoperative blood loss, operation time, liver specific morbidity,&#xD;
      readmission percentage, resection margin, quality of life, body image and cosmesis , reasons&#xD;
      for delay of discharge after functional recovery, long term incidence of incisional hernias,&#xD;
      hospital and societal costs during one year, time to adjuvant chemotherapy initiation,&#xD;
      overall five-year survival.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Liver resection for colorectal metastasis is a potential curative therapy and has become the&#xD;
      standard of care in appropriately staged patients, offering five-year survival rates ranging&#xD;
      from 38 up to 61% in selected cases, with approximately 30% of patients surviving ten years&#xD;
      or more, compared to five-year survival rates of less than 5% for patients not amenable to&#xD;
      resection. Liver surgery is also a widely accepted treatment for symptomatic benign lesions&#xD;
      and those of uncertain nature or large size. Whilst the figures are a vast improvement on the&#xD;
      past, there is still a need to refine the treatment of these patients, including surgical&#xD;
      technique.&#xD;
&#xD;
      Open hepatectomy is the current standard of care for the management of primary and secondary&#xD;
      tumours. The open postero-superior liver segment resection requires a large incision to&#xD;
      achieve adequate access and proper control during resection. This has a significant impact on&#xD;
      patient's recovery and, in cases of small resections, this access may represent the major&#xD;
      component of surgical trauma. Advances in surgical technique and expertise now permit these&#xD;
      operations to be performed with minor incisions by using the laparoscopic approach. Although&#xD;
      the feasibility of laparoscopic hepatectomy has been established, only select centres use&#xD;
      this technique as their primary modality.&#xD;
&#xD;
      Laparoscopic liver resection was first reported in 1991. Over the past decades, the method&#xD;
      has gained wide acceptance for various liver resection procedures. Multiple retrospective&#xD;
      case series, patient cohorts, systematic reviews and meta-analyses have compared open with&#xD;
      laparoscopic liver surgery and indicate the laparoscopic approach to be safely applicable for&#xD;
      the resection of both malignant and benign liver lesions. Laparoscopic liver resection has&#xD;
      been associated with shorter hospital length of stay, reduced intraoperative blood loss, less&#xD;
      postoperative pain and earlier recovery. Despite this, concerns remain over operative times,&#xD;
      the ability to control haemorrhage laparascopically and long-term oncological outcomes.&#xD;
&#xD;
      Initially, the left lateral segments of the liver were chosen for anatomic laparoscopic&#xD;
      resection, with good results. Many liver centres worldwide currently use laparoscopy for&#xD;
      resection of the anterior liver segments. Whilst case control studies would now seem&#xD;
      sufficient to allay such concerns in the context of minor liver resections and left lateral&#xD;
      sectionectomies, the adoption and dissemination of laparoscopy by hepatobiliary oncologic&#xD;
      surgeons for major hepatectomies and resections of postero-superior segments has been&#xD;
      restricted. Besides the relatively low volume of patients, major laparoscopic liver&#xD;
      resections are technically demanding, have a significant learning curve, are time consuming,&#xD;
      are thought to hold an increased morbidity risk and lack in evidence.&#xD;
&#xD;
      Nevertheless, a new impulse for the laparoscopic management of major liver lesions came after&#xD;
      the first reports of laparoscopic hemihepatectomies, which demonstrated that in expert hands&#xD;
      major anatomical laparoscopic liver resections are feasible with good efficacy and safety.&#xD;
      When comparing surgical procedures, one of the easiest to measure and often used outcomes is&#xD;
      the length of hospital stay; the time it takes for a patient to be discharged from the&#xD;
      hospital after an operation. On the whole, a median hospital length of stay of 6.0 to 13.1&#xD;
      days and 3.5 to 10.0 days have been observed after open and laparoscopic hepatic resections&#xD;
      in European centres respectively. For major surgery in expert centres, median duration of&#xD;
      hospital admission varied between 6 to 12.5 days for open surgery and 4 to 8.2 days for&#xD;
      laparoscopic resections. Concentrating on postero-superior liver segment resections, the&#xD;
      median hospital stay is 6 days (3-44 days) for those undergoing open compared with 4 days&#xD;
      (1-11 days) for those having laparoscopic resections.&#xD;
&#xD;
      Besides the immediate benefits to the patient, such as decreased intraoperative blood loss,&#xD;
      diminished postoperative pain, earlier recovery and reduced hospital length of stay,&#xD;
      laparoscopic liver surgery may also have the potential to improve outcomes in the longer term&#xD;
      by reducing complications, enhancing quality of life, improving cosmesis, ensuring early&#xD;
      commencement and completion of adjuvant therapies. However, level-1 evidence on all outcomes&#xD;
      is still to be presented.&#xD;
&#xD;
      Within the framework of optimized perioperative care, broader indications for hepatic surgery&#xD;
      and further adoption of laparoscopic liver resections, there is a clear need for a randomized&#xD;
      trial. Therefore, the multicentre and international ORANGE SEGMENTS - Trial has been designed&#xD;
      to provide evidence on the merits of laparoscopic versus open parenchymal preserving&#xD;
      postero-superior liver segment resection within an enhanced recovery programme in terms of&#xD;
      time to functional recovery, hospital length of stay, intraoperative blood loss, operation&#xD;
      time, resection margin, time to adjuvant chemotherapy initiation, readmission percentage,&#xD;
      (liver specific) morbidity, quality of life, body image, reasons for delay of discharge after&#xD;
      functional recovery, long term incidence of incisional hernias, hospital and societal costs&#xD;
      during one year and overall five-year survival.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">November 1, 2017</start_date>
  <completion_date type="Anticipated">December 1, 2026</completion_date>
  <primary_completion_date type="Anticipated">January 1, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Patients will be randomised to either the open or the laparoscopic treatment arm.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>The patient, ward physician and research investigator are blinded to the treatment intervention. A large abdominal dressing will be used to cover the incision(s) until postoperative day 4. Obviously, the surgeon and anaesthesiology team can not be blinded.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Time to functional recovery</measure>
    <time_frame>expected average of 4-10 days</time_frame>
    <description>Time until a patient is functionally recovered</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hospital length of stay</measure>
    <time_frame>30 days</time_frame>
    <description>Total length of hospital stay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intraoperative blood loss</measure>
    <time_frame>during procedure</time_frame>
    <description>Net intraoperative blood loss</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Operating time</measure>
    <time_frame>surgical time from incision until closure</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(Liver specific) morbidity</measure>
    <time_frame>1 year</time_frame>
    <description>Composite endpoint of liver specific morbidity (intra-abdominal bleeding, intra-abdominal abcess, ascites, postresectional liver failure, intra-operative mortality, bile leakage)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Readmission percentage</measure>
    <time_frame>1 year</time_frame>
    <description>Total percentage of patients being readmitted</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Resection margin</measure>
    <time_frame>1 year</time_frame>
    <description>Residual tumor cells in resection border</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life</measure>
    <time_frame>1 year</time_frame>
    <description>The physical, social and emotional well-being of the patient</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body image and cosmesis</measure>
    <time_frame>1 year</time_frame>
    <description>The aesthetic appearance of the scars associated with the operation and its influence on the patient self-view</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reasons for delay of discharge after functional recovery</measure>
    <time_frame>1 year</time_frame>
    <description>All reasons that may cause delay in discharge after the patient has recovered functionally, such as administrative reasons, patient confidence, logistics problems, etc.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incisional herniation</measure>
    <time_frame>1 year</time_frame>
    <description>Cicatricial hernia</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital and societal costs</measure>
    <time_frame>1 year</time_frame>
    <description>All costs that are associated with the operation, including in-hospital costs and out of hospital costs, such as home care, work absence, etc.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to adjuvant chemotherapy initiation</measure>
    <time_frame>1 year</time_frame>
    <description>The time it takes to start adjuvant chemotherapy after the patient has been operated</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall five-year survival</measure>
    <time_frame>5 years</time_frame>
    <description>Five-year survival</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">250</enrollment>
  <condition>Liver Surgery</condition>
  <arm_group>
    <arm_group_label>Open</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Open liver surgery</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Laparoscopy</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Laparoscopic liver surgery</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Parenchymal preserving postero-superior liver segment resection</intervention_name>
    <description>Parenchymal preserving liver segment resection of one or two of the postero-superior liver segments (4A, 7 or 8).</description>
    <arm_group_label>Laparoscopy</arm_group_label>
    <arm_group_label>Open</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients requiring a parenchymal sparing liver resection (including wedge resections&#xD;
             and full segmentectomies) involving one or two of segments 4a/7/8 for accepted&#xD;
             indications . A segment 6/7 resection would also be eligible.&#xD;
&#xD;
          -  Able to understand the nature of the study and what will be required of them.&#xD;
&#xD;
          -  Men and non-pregnant, non-lactating women, aged 18 years and older.&#xD;
&#xD;
          -  BMI between and including 18-35 kg/m2&#xD;
&#xD;
          -  Patients with ASA physical status I-II-III.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inability to give (written) informed consent.&#xD;
&#xD;
          -  Patients requiring other liver surgery than a parenchymal sparing resection involving&#xD;
             one or two of segments 4a, 7, 8.&#xD;
&#xD;
          -  Patients requiring parenchymal sparing liver resection involving segment 1. This is&#xD;
             due to the high level of technical difficulty.&#xD;
&#xD;
          -  Patients with hepatic lesion(s), that are located with insufficient margin from&#xD;
             vascular or biliary structures to be operated laparoscopically.&#xD;
&#xD;
          -  Patients with ASA physical status IV-V.&#xD;
&#xD;
          -  Repeat hepatectomy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mohammed Abu Hilal, Prof.</last_name>
    <role>Study Chair</role>
    <affiliation>University Hospital Southampton NHS Foundation Trust</affiliation>
  </overall_official>
  <overall_official>
    <last_name>John Primrose, Prof.</last_name>
    <role>Study Chair</role>
    <affiliation>University Hospital Southampton NHS Foundation Trust</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>General Hospital Groeninge</name>
      <address>
        <city>Kortrijk</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Poliambulanza Hospital</name>
      <address>
        <city>Brescia</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>San Raffaele Hospital</name>
      <address>
        <city>Milan</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>San Camillo-Forlanini Hospital</name>
      <address>
        <city>Rome</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Academic Medical Center</name>
      <address>
        <city>Amsterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maastricht University Medical Center+</name>
      <address>
        <city>Maastricht</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Oslo</name>
      <address>
        <city>Oslo</city>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Moscow Clinical Scientific Center</name>
      <address>
        <city>Moscow</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aintree University Hospital</name>
      <address>
        <city>Aintree</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen Elizabeth Hospital</name>
      <address>
        <city>Birmingham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>King's College Hospital</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Manchester Royal Infirmary</name>
      <address>
        <city>Manchester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Freeman Hospital</name>
      <address>
        <city>Newcastle</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oxford University Hospitals</name>
      <address>
        <city>Oxford</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Derriford Hospital</name>
      <address>
        <city>Plymouth</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Southampton</name>
      <address>
        <city>Southampton</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>Norway</country>
    <country>Russian Federation</country>
    <country>United Kingdom</country>
  </location_countries>
  <removed_countries>
    <country>Germany</country>
  </removed_countries>
  <reference>
    <citation>Coles SR, Besselink MG, Serin KR, Alsaati H, Di Gioia P, Samim M, Pearce NW, Abu Hilal M. Total laparoscopic management of lesions involving liver segment 7. Surg Endosc. 2015 Nov;29(11):3190-5. doi: 10.1007/s00464-014-4052-2. Epub 2015 Jan 13.</citation>
    <PMID>25582963</PMID>
  </reference>
  <reference>
    <citation>Cipriani F, Shelat VG, Rawashdeh M, Francone E, Aldrighetti L, Takhar A, Armstrong T, Pearce NW, Abu Hilal M. Laparoscopic Parenchymal-Sparing Resections for Nonperipheral Liver Lesions, the Diamond Technique: Technical Aspects, Clinical Outcomes, and Oncologic Efficiency. J Am Coll Surg. 2015 Aug;221(2):265-72. doi: 10.1016/j.jamcollsurg.2015.03.029. Epub 2015 Mar 27.</citation>
    <PMID>25899733</PMID>
  </reference>
  <reference>
    <citation>Scuderi V, Barkhatov L, Montalti R, Ratti F, Cipriani F, Pardo F, Tranchart H, Dagher I, Rotellar F, Abu Hilal M, Edwin B, Vivarelli M, Aldrighetti L, Troisi RI. Outcome after laparoscopic and open resections of posterosuperior segments of the liver. Br J Surg. 2017 May;104(6):751-759. doi: 10.1002/bjs.10489. Epub 2017 Feb 13.</citation>
    <PMID>28194774</PMID>
  </reference>
  <reference>
    <citation>Zheng B, Zhao R, Li X, Li B. Comparison of laparoscopic liver resection for lesions located in anterolateral and posterosuperior segments: a meta-analysis. Surg Endosc. 2017 Nov;31(11):4641-4648. doi: 10.1007/s00464-017-5527-8. Epub 2017 Apr 7.</citation>
    <PMID>28389796</PMID>
  </reference>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>August 28, 2017</study_first_submitted>
  <study_first_submitted_qc>August 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 1, 2017</study_first_posted>
  <last_update_submitted>December 10, 2021</last_update_submitted>
  <last_update_submitted_qc>December 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 30, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Parenchymal preserving</keyword>
  <keyword>Postero-superior</keyword>
  <keyword>Laparoscopy</keyword>
  <keyword>Hepatectomy</keyword>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT03270917
org study id: NL36215.068.11*
nct id: NCT03270917
lead sponsor: 
collaborator: 
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has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The international and multicentre ORANGE SEGMENTS - Trial is a prospective, double blinded,
      randomized controlled study comparing patients undergoing parenchymal preserving resection of
      postero-superior liver segments (involving one or two of segments 4a, 7, 8). All patients
      will be participating in an enhanced recovery programme.

      Primary outcome is time to functional recovery. Secondary study parameters include hospital
      length of stay, intraoperative blood loss, operation time, liver specific morbidity,
      readmission percentage, resection margin, quality of life, body image and cosmesis , reasons
      for delay of discharge after functional recovery, long term incidence of incisional hernias,
      hospital and societal costs during one year, time to adjuvant chemotherapy initiation,
      overall five-year survival.
Liver resection for colorectal metastasis is a potential curative therapy and has become the
      standard of care in appropriately staged patients, offering five-year survival rates ranging
      from 38 up to 61% in selected cases, with approximately 30% of patients surviving ten years
      or more, compared to five-year survival rates of less than 5% for patients not amenable to
      resection. Liver surgery is also a widely accepted treatment for symptomatic benign lesions
      and those of uncertain nature or large size. Whilst the figures are a vast improvement on the
      past, there is still a need to refine the treatment of these patients, including surgical
      technique.

      Open hepatectomy is the current standard of care for the management of primary and secondary
      tumours. The open postero-superior liver segment resection requires a large incision to
      achieve adequate access and proper control during resection. This has a significant impact on
      patient's recovery and, in cases of small resections, this access may represent the major
      component of surgical trauma. Advances in surgical technique and expertise now permit these
      operations to be performed with minor incisions by using the laparoscopic approach. Although
      the feasibility of laparoscopic hepatectomy has been established, only select centres use
      this technique as their primary modality.

      Laparoscopic liver resection was first reported in 1991. Over the past decades, the method
      has gained wide acceptance for various liver resection procedures. Multiple retrospective
      case series, patient cohorts, systematic reviews and meta-analyses have compared open with
      laparoscopic liver surgery and indicate the laparoscopic approach to be safely applicable for
      the resection of both malignant and benign liver lesions. Laparoscopic liver resection has
      been associated with shorter hospital length of stay, reduced intraoperative blood loss, less
      postoperative pain and earlier recovery. Despite this, concerns remain over operative times,
      the ability to control haemorrhage laparascopically and long-term oncological outcomes.

      Initially, the left lateral segments of the liver were chosen for anatomic laparoscopic
      resection, with good results. Many liver centres worldwide currently use laparoscopy for
      resection of the anterior liver segments. Whilst case control studies would now seem
      sufficient to allay such concerns in the context of minor liver resections and left lateral
      sectionectomies, the adoption and dissemination of laparoscopy by hepatobiliary oncologic
      surgeons for major hepatectomies and resections of postero-superior segments has been
      restricted. Besides the relatively low volume of patients, major laparoscopic liver
      resections are technically demanding, have a significant learning curve, are time consuming,
      are thought to hold an increased morbidity risk and lack in evidence.

      Nevertheless, a new impulse for the laparoscopic management of major liver lesions came after
      the first reports of laparoscopic hemihepatectomies, which demonstrated that in expert hands
      major anatomical laparoscopic liver resections are feasible with good efficacy and safety.
      When comparing surgical procedures, one of the easiest to measure and often used outcomes is
      the length of hospital stay; the time it takes for a patient to be discharged from the
      hospital after an operation. On the whole, a median hospital length of stay of 6.0 to 13.1
      days and 3.5 to 10.0 days have been observed after open and laparoscopic hepatic resections
      in European centres respectively. For major surgery in expert centres, median duration of
      hospital admission varied between 6 to 12.5 days for open surgery and 4 to 8.2 days for
      laparoscopic resections. Concentrating on postero-superior liver segment resections, the
      median hospital stay is 6 days (3-44 days) for those undergoing open compared with 4 days
      (1-11 days) for those having laparoscopic resections.

      Besides the immediate benefits to the patient, such as decreased intraoperative blood loss,
      diminished postoperative pain, earlier recovery and reduced hospital length of stay,
      laparoscopic liver surgery may also have the potential to improve outcomes in the longer term
      by reducing complications, enhancing quality of life, improving cosmesis, ensuring early
      commencement and completion of adjuvant therapies. However, level-1 evidence on all outcomes
      is still to be presented.

      Within the framework of optimized perioperative care, broader indications for hepatic surgery
      and further adoption of laparoscopic liver resections, there is a clear need for a randomized
      trial. Therefore, the multicentre and international ORANGE SEGMENTS - Trial has been designed
      to provide evidence on the merits of laparoscopic versus open parenchymal preserving
      postero-superior liver segment resection within an enhanced recovery programme in terms of
      time to functional recovery, hospital length of stay, intraoperative blood loss, operation
      time, resection margin, time to adjuvant chemotherapy initiation, readmission percentage,
      (liver specific) morbidity, quality of life, body image, reasons for delay of discharge after
      functional recovery, long term incidence of incisional hernias, hospital and societal costs
      during one year and overall five-year survival.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Patients will be randomised to either the open or the laparoscopic treatment arm.
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: The patient, ward physician and research investigator are blinded to the treatment intervention. A large abdominal dressing will be used to cover the incision(s) until postoperative day 4. Obviously, the surgeon and anaesthesiology team can not be blinded.
measure: Time to functional recovery
time frame: expected average of 4-10 days
description: Time until a patient is functionally recovered
measure: Hospital length of stay
time frame: 30 days
description: Total length of hospital stay
measure: Intraoperative blood loss
time frame: during procedure
description: Net intraoperative blood loss
measure: Operating time
time frame: surgical time from incision until closure
measure: (Liver specific) morbidity
time frame: 1 year
description: Composite endpoint of liver specific morbidity (intra-abdominal bleeding, intra-abdominal abcess, ascites, postresectional liver failure, intra-operative mortality, bile leakage)
measure: Readmission percentage
time frame: 1 year
description: Total percentage of patients being readmitted
measure: Resection margin
time frame: 1 year
description: Residual tumor cells in resection border
measure: Quality of life
time frame: 1 year
description: The physical, social and emotional well-being of the patient
measure: Body image and cosmesis
time frame: 1 year
description: The aesthetic appearance of the scars associated with the operation and its influence on the patient self-view
measure: Reasons for delay of discharge after functional recovery
time frame: 1 year
description: All reasons that may cause delay in discharge after the patient has recovered functionally, such as administrative reasons, patient confidence, logistics problems, etc.
measure: Incisional herniation
time frame: 1 year
description: Cicatricial hernia
measure: Hospital and societal costs
time frame: 1 year
description: All costs that are associated with the operation, including in-hospital costs and out of hospital costs, such as home care, work absence, etc.
measure: Time to adjuvant chemotherapy initiation
time frame: 1 year
description: The time it takes to start adjuvant chemotherapy after the patient has been operated
measure: Overall five-year survival
time frame: 5 years
description: Five-year survival
arm group label: Open
arm group type: Other
description: Open liver surgery
arm group label: Laparoscopy
arm group type: Other
description: Laparoscopic liver surgery
intervention type: Procedure
intervention name: Parenchymal preserving postero-superior liver segment resection
description: Parenchymal preserving liver segment resection of one or two of the postero-superior liver segments (4A, 7 or 8).
arm group label: Laparoscopy
arm group label: Open
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Mohammed Abu Hilal, Prof.
role: Study Chair
affiliation: University Hospital Southampton NHS Foundation Trust
last name: John Primrose, Prof.
role: Study Chair
affiliation: University Hospital Southampton NHS Foundation Trust
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country: Belgium
country: Italy
country: Netherlands
country: Norway
country: Russian Federation
country: United Kingdom
country: Germany
citation: Coles SR, Besselink MG, Serin KR, Alsaati H, Di Gioia P, Samim M, Pearce NW, Abu Hilal M. Total laparoscopic management of lesions involving liver segment 7. Surg Endosc. 2015 Nov;29(11):3190-5. doi: 10.1007/s00464-014-4052-2. Epub 2015 Jan 13.
PMID: 25582963
citation: Cipriani F, Shelat VG, Rawashdeh M, Francone E, Aldrighetti L, Takhar A, Armstrong T, Pearce NW, Abu Hilal M. Laparoscopic Parenchymal-Sparing Resections for Nonperipheral Liver Lesions, the Diamond Technique: Technical Aspects, Clinical Outcomes, and Oncologic Efficiency. J Am Coll Surg. 2015 Aug;221(2):265-72. doi: 10.1016/j.jamcollsurg.2015.03.029. Epub 2015 Mar 27.
PMID: 25899733
citation: Scuderi V, Barkhatov L, Montalti R, Ratti F, Cipriani F, Pardo F, Tranchart H, Dagher I, Rotellar F, Abu Hilal M, Edwin B, Vivarelli M, Aldrighetti L, Troisi RI. Outcome after laparoscopic and open resections of posterosuperior segments of the liver. Br J Surg. 2017 May;104(6):751-759. doi: 10.1002/bjs.10489. Epub 2017 Feb 13.
PMID: 28194774
citation: Zheng B, Zhao R, Li X, Li B. Comparison of laparoscopic liver resection for lesions located in anterolateral and posterosuperior segments: a meta-analysis. Surg Endosc. 2017 Nov;31(11):4641-4648. doi: 10.1007/s00464-017-5527-8. Epub 2017 Apr 7.
PMID: 28389796
responsible party type: Sponsor
sharing ipd: Undecided