<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/NCT01683357</url>
  </required_header>
  <id_info>
    <org_study_id>MTX-1STAGE LONG-TERM</org_study_id>
    <nct_id>NCT01683357</nct_id>
  </id_info>
  <brief_title>Prognosis of One-stage Hepatectomy for Bilobar Colorectal Metastases</brief_title>
  <official_title>LONG-TERM RESULTS AFTER ONE-STAGE ULTRASOUND-GUIDED HEPATECTOMY IN PATIENTS WITH MULTIPLE BILOBAR COLORECTAL LIVER METASTASES: TOWARDS NEW CONCEPTS OF RADICAL RESECTION BY MEANS OF AN INTENTION TO TREAT ANALYSES</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Milan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Milan</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      It is not rare that two-stage hepatectomy for multiple bilobar colorectal liver metastases&#xD;
      (CLM) be left incomplete because of disease progression or technical reasons. One-stage&#xD;
      hepatectomy seems a feasible and safe alternative, however, long-term results are lacking.&#xD;
      This study aims to provide evidence that one-stage hepatectomy compelling tumor exposure&#xD;
      provides adequate long-term results with low risk of local recurrences.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Eligibility Criteria The prospectively recruited cohort of patients herein analysed is the&#xD;
      result of a policy for which those patients considered resectable and presenting 4 or more&#xD;
      lesions, bilobar CLM were systematically approached in a one stage operation.&#xD;
&#xD;
      Patients were considered unresectable once there was concomitance of more than 3 lung&#xD;
      metastases, diffuse peritoneal carcinomatosis, and/or extra-hilar lymph node metastasis.&#xD;
&#xD;
      Outcome measures The primary outcome was the feasibility on an intention-to-treat basis. To&#xD;
      this purpose we studied the ratio between the number of patients surgically explored and&#xD;
      those who effectively received resection.&#xD;
&#xD;
      The secondary outcome was the safety of the procedure. To this purpose we studied morbidity,&#xD;
      mortality, amount of blood loss, rate of blood transfusions, and postoperative trend of liver&#xD;
      function tests.&#xD;
&#xD;
      The tertiary outcome measure was the reliability of the procedure from an oncological&#xD;
      standpoint. For this purpose we studied the following:&#xD;
&#xD;
        1. the rate of true local recurrence (cut-edge) after a minimum follow-up of 6 months;&#xD;
&#xD;
        2. the long-term follow-up, analysing the overall survival (survival after surgery), time&#xD;
           to recurrence (survival without recurrence), and time to liver recurrence (survival&#xD;
           without liver recurrence).&#xD;
&#xD;
        3. the overall survival compared with that based on an intention-to-treat criterion also&#xD;
           including the outcome of those patients who met the inclusion criteria but resulted&#xD;
           unresectable on exploration.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2001</start_date>
  <completion_date type="Actual">July 2012</completion_date>
  <primary_completion_date type="Actual">March 2012</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>feasibility on an intention-to-treat basis</measure>
    <time_frame>at the time of surgical intervention</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>safety of the procedure</measure>
    <time_frame>At 30 and 90 postoperative days</time_frame>
    <description>Peroperative morbidity and mortality as classified according with Dindo-Clavien classification (see ref.); Amount of intraoperative blood loss and blood transfusions.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>reliability of the procedure from an oncological standpoint</measure>
    <time_frame>6-months of minimum follow-up for local recurrences; 5 years actuarial curves for overall survival and time to recurrence</time_frame>
    <description>the rate of true local recurrence (cut-edge) after a minimum follow-up of 6 months;&#xD;
the long-term follow-up, analysing the overall survival (survival after surgery), time to recurrence (survival without recurrence), and time to liver recurrence (survival without liver recurrence).&#xD;
the overall survival compared with that based on an intention-to-treat criterion also including the outcome of those patients who met the inclusion criteria but resulted unresectable on exploration.</description>
  </other_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">58</enrollment>
  <condition>Liver Metastases</condition>
  <arm_group>
    <arm_group_label>Multiple Bilobar CLM</arm_group_label>
    <description>Patients selected for hepatectomy because carrier of multiple (&gt; or = to 4), bilobar CLM</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Hepatectomy</intervention_name>
    <description>Intraoperative ultrasound (IOUS) criteria for tumor-vessel relations let maximizing the preservation of the hepatic vascular skeleton. Contact between colorectal liver metastases and a major intrahepatic vessel is not by itself a criteria for vessel resection: tumor exposure is not contraindicated.&#xD;
If resection of a hepatic vein (HV), resection of the liver parenchyma drained by that vein is considered or not based on color-flow IOUS findings (hepatofugal blood flow in the feeding portal branch, evidence or not of communicating veins between adjacent HVs, evidence or not of accessory HVs).&#xD;
Parenchymal transection is performed under intermittent clamping by the Pringle maneuver. Drains are always inserted and a chest tube is inserted in patients undergoing thoracophrenolaparotomy.</description>
    <arm_group_label>Multiple Bilobar CLM</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with multiple (&gt; or = to 4) and bilobar colorectal liver metastases&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Those patients considered resectable and presenting 4 or more CLM, involving both liver&#xD;
        lobes are systematically approached in a one stage operation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patients carriers of more than 3 lung metastases, and/or diffuse peritoneal carcinomatosis,&#xD;
        and/or extra-hilar lymph node metastasis&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Guido Torzilli, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Milan, Humanitas Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Humanitas Cancer Center</name>
      <address>
        <city>Rozzano</city>
        <state>Milano</state>
        <zip>20089</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Wicherts DA, Miller R, de Haas RJ, Bitsakou G, Vibert E, Veilhan LA, Azoulay D, Bismuth H, Castaing D, Adam R. Long-term results of two-stage hepatectomy for irresectable colorectal cancer liver metastases. Ann Surg. 2008 Dec;248(6):994-1005. doi: 10.1097/SLA.0b013e3181907fd9.</citation>
    <PMID>19092344</PMID>
  </reference>
  <reference>
    <citation>Adam R, Laurent A, Azoulay D, Castaing D, Bismuth H. Two-stage hepatectomy: A planned strategy to treat irresectable liver tumors. Ann Surg. 2000 Dec;232(6):777-85. doi: 10.1097/00000658-200012000-00006.</citation>
    <PMID>11088072</PMID>
  </reference>
  <reference>
    <citation>Narita M, Oussoultzoglou E, Jaeck D, Fuchschuber P, Rosso E, Pessaux P, Marzano E, Bachellier P. Two-stage hepatectomy for multiple bilobar colorectal liver metastases. Br J Surg. 2011 Oct;98(10):1463-75. doi: 10.1002/bjs.7580. Epub 2011 Jun 28.</citation>
    <PMID>21710481</PMID>
  </reference>
  <reference>
    <citation>Jaeck D, Oussoultzoglou E, Rosso E, Greget M, Weber JC, Bachellier P. A two-stage hepatectomy procedure combined with portal vein embolization to achieve curative resection for initially unresectable multiple and bilobar colorectal liver metastases. Ann Surg. 2004 Dec;240(6):1037-49; discussion 1049-51. doi: 10.1097/01.sla.0000145965.86383.89.</citation>
    <PMID>15570209</PMID>
  </reference>
  <reference>
    <citation>Minagawa M, Makuuchi M, Torzilli G, Takayama T, Kawasaki S, Kosuge T, Yamamoto J, Imamura H. Extension of the frontiers of surgical indications in the treatment of liver metastases from colorectal cancer: long-term results. Ann Surg. 2000 Apr;231(4):487-99. doi: 10.1097/00000658-200004000-00006.</citation>
    <PMID>10749608</PMID>
  </reference>
  <reference>
    <citation>Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004 Aug;240(2):205-13. doi: 10.1097/01.sla.0000133083.54934.ae.</citation>
    <PMID>15273542</PMID>
  </reference>
  <results_reference>
    <citation>Torzilli G, Procopio F, Botea F, Marconi M, Del Fabbro D, Donadon M, Palmisano A, Spinelli A, Montorsi M. One-stage ultrasonographically guided hepatectomy for multiple bilobar colorectal metastases: a feasible and effective alternative to the 2-stage approach. Surgery. 2009 Jul;146(1):60-71. doi: 10.1016/j.surg.2009.02.017.</citation>
    <PMID>19541011</PMID>
  </results_reference>
  <results_reference>
    <citation>Torzilli G, Montorsi M, Donadon M, Palmisano A, Del Fabbro D, Gambetti A, Olivari N, Makuuchi M. &quot;Radical but conservative&quot; is the main goal for ultrasonography-guided liver resection: prospective validation of this approach. J Am Coll Surg. 2005 Oct;201(4):517-28. doi: 10.1016/j.jamcollsurg.2005.04.026.</citation>
    <PMID>16183489</PMID>
  </results_reference>
  <results_reference>
    <citation>Torzilli G, Garancini M, Donadon M, Cimino M, Procopio F, Montorsi M. Intraoperative ultrasonographic detection of communicating veins between adjacent hepatic veins during hepatectomy for tumours at the hepatocaval confluence. Br J Surg. 2010 Dec;97(12):1867-73. doi: 10.1002/bjs.7230. Epub 2010 Aug 26.</citation>
    <PMID>20799289</PMID>
  </results_reference>
  <results_reference>
    <citation>Torzilli G, Montorsi M, Del Fabbro D, Palmisano A, Donadon M, Makuuchi M. Ultrasonographically guided surgical approach to liver tumours involving the hepatic veins close to the caval confluence. Br J Surg. 2006 Oct;93(10):1238-46. doi: 10.1002/bjs.5321.</citation>
    <PMID>16953487</PMID>
  </results_reference>
  <results_reference>
    <citation>Torzilli G, Palmisano A, Procopio F, Cimino M, Botea F, Donadon M, Del Fabbro D, Montorsi M. A new systematic small for size resection for liver tumors invading the middle hepatic vein at its caval confluence: mini-mesohepatectomy. Ann Surg. 2010 Jan;251(1):33-9. doi: 10.1097/SLA.0b013e3181b61db9.</citation>
    <PMID>19858707</PMID>
  </results_reference>
  <results_reference>
    <citation>Torzilli G, Procopio F, Donadon M, Del Fabbro D, Cimino M, Montorsi M. Safety of intermittent Pringle maneuver cumulative time exceeding 120 minutes in liver resection: a further step in favor of the &quot;radical but conservative&quot; policy. Ann Surg. 2012 Feb;255(2):270-80. doi: 10.1097/SLA.0b013e318232b375.</citation>
    <PMID>21975322</PMID>
  </results_reference>
  <results_reference>
    <citation>Torzilli G, Donadon M, Marconi M, Botea F, Palmisano A, Del Fabbro D, Procopio F, Montorsi M. Systematic extended right posterior sectionectomy: a safe and effective alternative to right hepatectomy. Ann Surg. 2008 Apr;247(4):603-11. doi: 10.1097/SLA.0b013e31816387d7.</citation>
    <PMID>18362622</PMID>
  </results_reference>
  <results_reference>
    <citation>Torzilli G, Del Fabbro D, Palmisano A, Donadon M, Bianchi P, Roncalli M, Balzarini L, Montorsi M. Contrast-enhanced intraoperative ultrasonography during hepatectomies for colorectal cancer liver metastases. J Gastrointest Surg. 2005 Nov;9(8):1148-53; discussion 1153-4. doi: 10.1016/j.gassur.2005.08.016.</citation>
    <PMID>16269386</PMID>
  </results_reference>
  <verification_date>September 2012</verification_date>
  <study_first_submitted>September 4, 2012</study_first_submitted>
  <study_first_submitted_qc>September 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 11, 2012</study_first_posted>
  <last_update_submitted>September 6, 2012</last_update_submitted>
  <last_update_submitted_qc>September 6, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 11, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Milan</investigator_affiliation>
    <investigator_full_name>Prof. Guido Torzilli</investigator_full_name>
    <investigator_title>Director Liver Surgery Unit, Humanitas Cancer Center - Associate Professor, University of Milan</investigator_title>
  </responsible_party>
  <keyword>Liver Metastases</keyword>
  <keyword>Surgery</keyword>
  <keyword>Intraoperative Ultrasound</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Liver Neoplasms</mesh_term>
  </condition_browse>
  <!-- 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/NCT01683357
org study id: MTX-1STAGE LONG-TERM
nct id: NCT01683357
lead sponsor: 
has dmc: No
It is not rare that two-stage hepatectomy for multiple bilobar colorectal liver metastases
      (CLM) be left incomplete because of disease progression or technical reasons. One-stage
      hepatectomy seems a feasible and safe alternative, however, long-term results are lacking.
      This study aims to provide evidence that one-stage hepatectomy compelling tumor exposure
      provides adequate long-term results with low risk of local recurrences.
Eligibility Criteria The prospectively recruited cohort of patients herein analysed is the
      result of a policy for which those patients considered resectable and presenting 4 or more
      lesions, bilobar CLM were systematically approached in a one stage operation.

      Patients were considered unresectable once there was concomitance of more than 3 lung
      metastases, diffuse peritoneal carcinomatosis, and/or extra-hilar lymph node metastasis.

      Outcome measures The primary outcome was the feasibility on an intention-to-treat basis. To
      this purpose we studied the ratio between the number of patients surgically explored and
      those who effectively received resection.

      The secondary outcome was the safety of the procedure. To this purpose we studied morbidity,
      mortality, amount of blood loss, rate of blood transfusions, and postoperative trend of liver
      function tests.

      The tertiary outcome measure was the reliability of the procedure from an oncological
      standpoint. For this purpose we studied the following:

        1. the rate of true local recurrence (cut-edge) after a minimum follow-up of 6 months;

        2. the long-term follow-up, analysing the overall survival (survival after surgery), time
           to recurrence (survival without recurrence), and time to liver recurrence (survival
           without liver recurrence).

        3. the overall survival compared with that based on an intention-to-treat criterion also
           including the outcome of those patients who met the inclusion criteria but resulted
           unresectable on exploration.
observational model: Cohort
time perspective: Prospective
measure: feasibility on an intention-to-treat basis
time frame: at the time of surgical intervention
measure: safety of the procedure
time frame: At 30 and 90 postoperative days
description: Peroperative morbidity and mortality as classified according with Dindo-Clavien classification (see ref.); Amount of intraoperative blood loss and blood transfusions.
measure: reliability of the procedure from an oncological standpoint
time frame: 6-months of minimum follow-up for local recurrences; 5 years actuarial curves for overall survival and time to recurrence
description: the rate of true local recurrence (cut-edge) after a minimum follow-up of 6 months;
the long-term follow-up, analysing the overall survival (survival after surgery), time to recurrence (survival without recurrence), and time to liver recurrence (survival without liver recurrence).
the overall survival compared with that based on an intention-to-treat criterion also including the outcome of those patients who met the inclusion criteria but resulted unresectable on exploration.
arm group label: Multiple Bilobar CLM
description: Patients selected for hepatectomy because carrier of multiple (> or = to 4), bilobar CLM
intervention type: Procedure
intervention name: Hepatectomy
description: Intraoperative ultrasound (IOUS) criteria for tumor-vessel relations let maximizing the preservation of the hepatic vascular skeleton. Contact between colorectal liver metastases and a major intrahepatic vessel is not by itself a criteria for vessel resection: tumor exposure is not contraindicated.
If resection of a hepatic vein (HV), resection of the liver parenchyma drained by that vein is considered or not based on color-flow IOUS findings (hepatofugal blood flow in the feeding portal branch, evidence or not of communicating veins between adjacent HVs, evidence or not of accessory HVs).
Parenchymal transection is performed under intermittent clamping by the Pringle maneuver. Drains are always inserted and a chest tube is inserted in patients undergoing thoracophrenolaparotomy.
arm group label: Multiple Bilobar CLM
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Guido Torzilli, MD, PhD
role: Principal Investigator
affiliation: University of Milan, Humanitas Cancer Center
facility: 
country: Italy
citation: Wicherts DA, Miller R, de Haas RJ, Bitsakou G, Vibert E, Veilhan LA, Azoulay D, Bismuth H, Castaing D, Adam R. Long-term results of two-stage hepatectomy for irresectable colorectal cancer liver metastases. Ann Surg. 2008 Dec;248(6):994-1005. doi: 10.1097/SLA.0b013e3181907fd9.
PMID: 19092344
citation: Adam R, Laurent A, Azoulay D, Castaing D, Bismuth H. Two-stage hepatectomy: A planned strategy to treat irresectable liver tumors. Ann Surg. 2000 Dec;232(6):777-85. doi: 10.1097/00000658-200012000-00006.
PMID: 11088072
citation: Narita M, Oussoultzoglou E, Jaeck D, Fuchschuber P, Rosso E, Pessaux P, Marzano E, Bachellier P. Two-stage hepatectomy for multiple bilobar colorectal liver metastases. Br J Surg. 2011 Oct;98(10):1463-75. doi: 10.1002/bjs.7580. Epub 2011 Jun 28.
PMID: 21710481
citation: Jaeck D, Oussoultzoglou E, Rosso E, Greget M, Weber JC, Bachellier P. A two-stage hepatectomy procedure combined with portal vein embolization to achieve curative resection for initially unresectable multiple and bilobar colorectal liver metastases. Ann Surg. 2004 Dec;240(6):1037-49; discussion 1049-51. doi: 10.1097/01.sla.0000145965.86383.89.
PMID: 15570209
citation: Minagawa M, Makuuchi M, Torzilli G, Takayama T, Kawasaki S, Kosuge T, Yamamoto J, Imamura H. Extension of the frontiers of surgical indications in the treatment of liver metastases from colorectal cancer: long-term results. Ann Surg. 2000 Apr;231(4):487-99. doi: 10.1097/00000658-200004000-00006.
PMID: 10749608
citation: Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004 Aug;240(2):205-13. doi: 10.1097/01.sla.0000133083.54934.ae.
PMID: 15273542
citation: Torzilli G, Procopio F, Botea F, Marconi M, Del Fabbro D, Donadon M, Palmisano A, Spinelli A, Montorsi M. One-stage ultrasonographically guided hepatectomy for multiple bilobar colorectal metastases: a feasible and effective alternative to the 2-stage approach. Surgery. 2009 Jul;146(1):60-71. doi: 10.1016/j.surg.2009.02.017.
PMID: 19541011
citation: Torzilli G, Montorsi M, Donadon M, Palmisano A, Del Fabbro D, Gambetti A, Olivari N, Makuuchi M. "Radical but conservative" is the main goal for ultrasonography-guided liver resection: prospective validation of this approach. J Am Coll Surg. 2005 Oct;201(4):517-28. doi: 10.1016/j.jamcollsurg.2005.04.026.
PMID: 16183489
citation: Torzilli G, Garancini M, Donadon M, Cimino M, Procopio F, Montorsi M. Intraoperative ultrasonographic detection of communicating veins between adjacent hepatic veins during hepatectomy for tumours at the hepatocaval confluence. Br J Surg. 2010 Dec;97(12):1867-73. doi: 10.1002/bjs.7230. Epub 2010 Aug 26.
PMID: 20799289
citation: Torzilli G, Montorsi M, Del Fabbro D, Palmisano A, Donadon M, Makuuchi M. Ultrasonographically guided surgical approach to liver tumours involving the hepatic veins close to the caval confluence. Br J Surg. 2006 Oct;93(10):1238-46. doi: 10.1002/bjs.5321.
PMID: 16953487
citation: Torzilli G, Palmisano A, Procopio F, Cimino M, Botea F, Donadon M, Del Fabbro D, Montorsi M. A new systematic small for size resection for liver tumors invading the middle hepatic vein at its caval confluence: mini-mesohepatectomy. Ann Surg. 2010 Jan;251(1):33-9. doi: 10.1097/SLA.0b013e3181b61db9.
PMID: 19858707
citation: Torzilli G, Procopio F, Donadon M, Del Fabbro D, Cimino M, Montorsi M. Safety of intermittent Pringle maneuver cumulative time exceeding 120 minutes in liver resection: a further step in favor of the "radical but conservative" policy. Ann Surg. 2012 Feb;255(2):270-80. doi: 10.1097/SLA.0b013e318232b375.
PMID: 21975322
citation: Torzilli G, Donadon M, Marconi M, Botea F, Palmisano A, Del Fabbro D, Procopio F, Montorsi M. Systematic extended right posterior sectionectomy: a safe and effective alternative to right hepatectomy. Ann Surg. 2008 Apr;247(4):603-11. doi: 10.1097/SLA.0b013e31816387d7.
PMID: 18362622
citation: Torzilli G, Del Fabbro D, Palmisano A, Donadon M, Bianchi P, Roncalli M, Balzarini L, Montorsi M. Contrast-enhanced intraoperative ultrasonography during hepatectomies for colorectal cancer liver metastases. J Gastrointest Surg. 2005 Nov;9(8):1148-53; discussion 1153-4. doi: 10.1016/j.gassur.2005.08.016.
PMID: 16269386
responsible party type: Principal Investigator
investigator affiliation: University of Milan
investigator full name: Prof. Guido Torzilli
investigator title: Director Liver Surgery Unit, Humanitas Cancer Center - Associate Professor, University of Milan
mesh term: Neoplasm Metastasis
mesh term: Liver Neoplasms