<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/NCT02184182</url>
  </required_header>
  <id_info>
    <org_study_id>2934P</org_study_id>
    <nct_id>NCT02184182</nct_id>
  </id_info>
  <brief_title>Laparoscopic Microwave Ablation and Portal Vein Ligation for Staged Hepatectomy (LAPS)</brief_title>
  <acronym>LAPS</acronym>
  <official_title>Liver Resection After Portal Vein Ligation / Embolization and Transection Plane Devascularization With Radio Frequency / Microwave: Pilot Study on Primary and Secondary Liver Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Azienda Ospedaliera di Padova</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Azienda Ospedaliera di Padova</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      One of the limiting factors in the execution of a liver resection, in particular an extended&#xD;
      liver resection, it's represented by the future remnant liver (FRL) after hepatic surgery. In&#xD;
      cases of normal organ function an FRL of 25% is considered sufficient. In case of impaired&#xD;
      hepatic function or a history of chemotherapy, it is considered safe if at least of 40%.&#xD;
&#xD;
      Many strategies have been developed and proposed to increase the resectability in patients&#xD;
      undergoing major liver resections.&#xD;
&#xD;
      One of these is a new two-stage technique proposed recently by a group of German surgeons.&#xD;
      This approach consists in the ligation of the right portal vein associated with resection of&#xD;
      the liver along the falciform ligament (step 1). Step 2, after a period of 9 days (median -&#xD;
      5-25 days), after a volumetric CT to ensure an adeguate hypertrophy of the left lateral lobe&#xD;
      due to the combination of right portal occlusion and segment 4 devascularization, the patient&#xD;
      undergo a right trisectionectomy. The hypertrophy of the left lateral lobe is shown to be of&#xD;
      74%, higher than any other techniques of ligation or portal embolizatiol proposed in the&#xD;
      literature.&#xD;
&#xD;
      On the basis of the clinical experiences reported the investigators designed a new protocol&#xD;
      of two-stage hepatic resection for the treatment of primary or secondary tumors of the right&#xD;
      lobe. Step1: laparoscopic radio frequency / microwave ablation of the future transection&#xD;
      plane between segment 4 and left lateral lobe and surgical ligation or embolization of the&#xD;
      right portal vein. The ablation has the purpose to devascularize the segment 4 and has the&#xD;
      same significance of the resection of the liver along the falciform ligament described by the&#xD;
      Regensburg group.&#xD;
&#xD;
      Step2: After a period of time of 9 ± 2 days, following a volumetric CT showing an adequate&#xD;
      liver volume gain (ratio FRL / patient body weight&gt; 0.5), the patient undergo the&#xD;
      second-stage surgery: laparoscopic/ laparotomic right trisectionectomy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In patients with primary or metastatic liver tumors, the only potentially curative&#xD;
      therapeutic option is represented by hepatic resection. Nowdays extended resections can be&#xD;
      performed with acceptable morbidity and mortality. There is no unanimous definition on the&#xD;
      criteria of resectability and the ability to perform a more or less extensive liver resection&#xD;
      is deferred to the expertise of the center and the surgical team. The investigators will&#xD;
      consider a tumor resectable if the surgical procedure does not damage vital structures, the&#xD;
      normal function of the organ is preserved and and the tumor is completely removed (R0&#xD;
      resection). One of the limiting factors in the execution of a liver resection, in particular&#xD;
      if it is extended, it's represented by the future remnant liver (FRL) after hepatic&#xD;
      resection. In cases of normal organ function an FRL of 25% is considered sufficient. In case&#xD;
      of impaired hepatic function or a history of chemotherapy, it is considered safe if at least&#xD;
      of 40%.&#xD;
&#xD;
      Many methods have been developed and proposed to increase the resectability in patients&#xD;
      undergoing major liver resections. In case of bilobar tumor, a two-step approach (two-stage&#xD;
      hepatectomy)have been proposed. This procedure implies that one of the two lobes is initially&#xD;
      freed of disease by tumor resection or ablation. After achieving an adequate compensatory&#xD;
      hypertrophy of the lobe freed by the tumor (usually 4-6 weeks),a contralateral liver&#xD;
      resection can be done to treat the remnant tumor.&#xD;
&#xD;
      To increase the FRL another approach is to occlude the portal branches towards one of liver&#xD;
      lobes. This can be done with a surgical ligation (laparotomy or laparoscopy) or&#xD;
      radiologically, using portal embolization. The technique allows to increase from 10% to 46%&#xD;
      of the FRL with the possibility of obtaining a resection R-0 in 70-100% of cases. It is&#xD;
      unclear whether there is any difference between the methods of portal occlusion (ligation vs&#xD;
      embolization). To further increase hypertrophy after portal occlusion in liver tumors&#xD;
      occupying the right liver, some researchers proposed to embolize the portal branches of&#xD;
      segment 4th together with the right portal vein.&#xD;
&#xD;
      The group of Regensburg has introduced a new technique in two stages for tumors of the right&#xD;
      lobe, which combines the methods mentioned above. This two-stage approach consists in the&#xD;
      ligation of the right portal vein associated with resection of the liver along the falciform&#xD;
      ligament (step 1). Step 2, after a period of 9 days (median - 5-25 days), after a volumetric&#xD;
      CT to ensure an adeguate hypertrophy of the left lateral lobe, the patient undergo a right&#xD;
      trisectionectomy. The hypertrophy of the left lateral lobe is shown to be of 74%, higher than&#xD;
      any other techniques of ligation or portal embolizatiol proposed in the literature.&#xD;
&#xD;
      The rationale of this technique is the complete portal devascularization of the right lobe&#xD;
      plus segment 4 that produce a greater stimulus to hypertrophy of the left lateral segments.&#xD;
      This occurs in less time than other methods above described and allows to reduce the&#xD;
      timeframe between the two steps and minimizes the risk of interprocedural progression of the&#xD;
      underlying disease (incidence of drop outs in the two-stage hepatectomy of 20% for&#xD;
      progression disease).&#xD;
&#xD;
      The morbidity of this two-stage approach was 44% (complications of Clavien grade III and IV)&#xD;
      that mimics the data reported in the literature for extended hepatic resections (20-50%). The&#xD;
      12%mortality rate was similar to one described by Lang et al for left trisegmentectomies.&#xD;
&#xD;
      On the basis of the clinical experiences reported the investigators designed a new protocol&#xD;
      of two-stage hepatic resection for the treatment of primary or secondary tumors of the right&#xD;
      lobe. Step1: laparoscopic radio frequency / microwave ablation of the future transection&#xD;
      plane between segment 4 and left lateral lobe and surgical ligation or embolization of the&#xD;
      right portal vein. The ablation has the purpose to devascularize the segment 4 and has the&#xD;
      same significance of the resection of the liver along the falciform ligament described by the&#xD;
      Regensburg group.&#xD;
&#xD;
      Step2: After a period of time of 9 ± 2 days, following a volumetric CT showing an adequate&#xD;
      liver volume gain (ratio FRL / patient body weight&gt; 0.5), the patient undergo the&#xD;
      second-stage surgery: laparoscopic/ laparotomic right trisectionectomy&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>June 2014</start_date>
  <completion_date type="Anticipated">June 2017</completion_date>
  <primary_completion_date type="Anticipated">June 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of R0 resections</measure>
    <time_frame>30days after Step2</time_frame>
    <description>Percentage of operations in which a complete oncological radicality (R0) is achived</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Perioperative mortality (3 months)</measure>
    <time_frame>3 moths</time_frame>
    <description>Percentage of perioperative mortality (3 months)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Perioperative complication (Clavien Classification)</measure>
    <time_frame>1 month</time_frame>
    <description>Percentage of perioperative complication described using Clavien Dindo Classification</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to progression</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>12 and 24 months</time_frame>
    <description>Overall survival at 12 and 24 months after surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>disease free survival</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>hepatic diesease free survival</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Liver Tumors</condition>
  <arm_group>
    <arm_group_label>VLS ablation/portal ligation/hepatectomy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Step1:&#xD;
exploratory laparoscopy to exclude extrahepatic disease&#xD;
right portal vein ligation if surgically feasible&#xD;
RF/MW ablation on the future line of transection (of segment 4 close to left lateral lobe)&#xD;
radiological portal embolization within 48h form the laparoscopic procedure if the right portal vein ligation is not feasible CT volumetric scan to evaluate the left lateral lobe hypertrophy after 9±2 from Step 1&#xD;
Step 2: only if FRL/body weight &gt; 0.5&#xD;
- laparoscopic/laparotomic right trisectionectomy</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>VLS ablation/portal ligation/hepatectomy</intervention_name>
    <description>Step1:&#xD;
exploratory laparoscopy to exclude extrahepatic disease&#xD;
right portal vein ligation if surgically feasible&#xD;
RF/MW ablation on the future line of transection (of segment 4 close to left lateral lobe)&#xD;
radiological portal embolization within 48h form the laparoscopic procedure if the right portal vein ligation is not feasible&#xD;
CT volumetric scan to evaluate the left lateral lobe hypertrophy after 9±2 from Step 1&#xD;
Step 2: only if FRL/body weight &gt; 0.5&#xD;
- laparoscopic/laparotomic right trisectionectomy</description>
    <arm_group_label>VLS ablation/portal ligation/hepatectomy</arm_group_label>
    <other_name>VLS Ablation &amp; Portal Vein Ligation for Staged Hepatectomy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients aged between 18 and 70 years (M and F)&#xD;
&#xD;
          -  Liver tumors that interests the right hepatic lobe (segments 4,5,6,7,8) with possible&#xD;
             involvement of the caudate lobe (segment 1) or bilobar disease with less than 3&#xD;
             lesions in the left lateral lobe without vascular involvement and amenable to&#xD;
             surgically resectable or ablation in the Step1.&#xD;
&#xD;
          -  Absence of extrahepatic disease&#xD;
&#xD;
          -  Normal hepatic function (total bilirubin &lt;3 mg / dL)&#xD;
&#xD;
          -  Performance status: ECOG 0&#xD;
&#xD;
          -  In case of liver cirrhosis MELD score &lt;9&#xD;
&#xD;
          -  Patients without prior chemotherapy or with previous chemotherapy but with response&#xD;
             disease&#xD;
&#xD;
          -  Patients who give their consent to the intervention&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  CT Evidence of involvement of the major vessels in the future remnant liver&#xD;
&#xD;
          -  Presence of more than 3 nodules in the left lateral lobe&#xD;
&#xD;
          -  Presence of extrahepatic disease&#xD;
&#xD;
          -  Severe hepatic impairment&#xD;
&#xD;
          -  Age&gt; 70 years&#xD;
&#xD;
          -  Previous liver surgery (prior liver resections)&#xD;
&#xD;
          -  Patient receiving chemotherapy with documented disease progression&#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_official>
    <last_name>Umberto Cillo, MD PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Azienda Ospedaliera di Padova</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Umberto Cillo, MD, PhD</last_name>
    <phone>+390498211846</phone>
    <email>cillo@unipd.it</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Enrico Gringeri, MD, PHD</last_name>
    <phone>+390498211846</phone>
    <email>enrico.gringeri@unipd.it</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Chirurgia Epatobiliare e Trapianto Epatico - Azienda Ospedaliera di Padova</name>
      <address>
        <city>Padova</city>
        <zip>35100</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Umberto Cillo</last_name>
      <phone>+390498211846</phone>
      <email>cillo@unipd.it</email>
    </contact>
    <contact_backup>
      <last_name>Enrico Gringeri</last_name>
      <phone>+390498211846</phone>
      <email>enrico.gringeri@unipd.it</email>
    </contact_backup>
    <investigator>
      <last_name>Umberto Cillo</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Enrico Gringeri</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Domenico Bassi</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Riccardo Boetto</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Francesco Enrico D'Amico</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Marina Polacco</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <link>
    <url>http://www.fegatochirurgia.com</url>
    <description>Online resource of Chirurgia Epatobiliare e Trapianto Epatico, Università degli Studi di Padova</description>
  </link>
  <reference>
    <citation>Schnitzbauer AA, Lang SA, Goessmann H, Nadalin S, Baumgart J, Farkas SA, Fichtner-Feigl S, Lorf T, Goralcyk A, Horbelt R, Kroemer A, Loss M, Rummele P, Scherer MN, Padberg W, Konigsrainer A, Lang H, Obed A, Schlitt HJ. Right portal vein ligation combined with in situ splitting induces rapid left lateral liver lobe hypertrophy enabling 2-staged extended right hepatic resection in small-for-size settings. Ann Surg. 2012 Mar;255(3):405-14. doi: 10.1097/SLA.0b013e31824856f5.</citation>
    <PMID>22330038</PMID>
  </reference>
  <reference>
    <citation>Lang H, Sotiropoulos GC, Brokalaki EI, Radtke A, Frilling A, Molmenti EP, Malago M, Broelsch CE. Left hepatic trisectionectomy for hepatobiliary malignancies. J Am Coll Surg. 2006 Sep;203(3):311-21. doi: 10.1016/j.jamcollsurg.2006.05.290. Epub 2006 Jul 13.</citation>
    <PMID>16931303</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>Farges O, Belghiti J, Kianmanesh R, Regimbeau JM, Santoro R, Vilgrain V, Denys A, Sauvanet A. Portal vein embolization before right hepatectomy: prospective clinical trial. Ann Surg. 2003 Feb;237(2):208-17. doi: 10.1097/01.SLA.0000048447.16651.7B.</citation>
    <PMID>12560779</PMID>
  </reference>
  <reference>
    <citation>Tartter PI. The association of perioperative blood transfusion with colorectal cancer recurrence. Ann Surg. 1992 Dec;216(6):633-8. doi: 10.1097/00000658-199212000-00004.</citation>
    <PMID>1466616</PMID>
  </reference>
  <reference>
    <citation>Donati M, Stavrou GA, Oldhafer KJ. Current position of ALPPS in the surgical landscape of CRLM treatment proposals. World J Gastroenterol. 2013 Oct 21;19(39):6548-54. doi: 10.3748/wjg.v19.i39.6548.</citation>
    <PMID>24151380</PMID>
  </reference>
  <reference>
    <citation>Lang H, Sotiropoulos GC, Fruhauf NR, Domland M, Paul A, Kind EM, Malago M, Broelsch CE. Extended hepatectomy for intrahepatic cholangiocellular carcinoma (ICC): when is it worthwhile? Single center experience with 27 resections in 50 patients over a 5-year period. Ann Surg. 2005 Jan;241(1):134-43. doi: 10.1097/01.sla.0000149426.08580.a1.</citation>
    <PMID>15622001</PMID>
  </reference>
  <reference>
    <citation>Are C, Iacovitti S, Prete F, Crafa FM. Feasibility of laparoscopic portal vein ligation prior to major hepatectomy. HPB (Oxford). 2008;10(4):229-33. doi: 10.1080/13651820802175261.</citation>
    <PMID>18806869</PMID>
  </reference>
  <reference>
    <citation>de Santibanes E, Alvarez FA, Ardiles V. How to avoid postoperative liver failure: a novel method. World J Surg. 2012 Jan;36(1):125-8. doi: 10.1007/s00268-011-1331-0.</citation>
    <PMID>22045448</PMID>
  </reference>
  <reference>
    <citation>van Lienden KP, Hoekstra LT, Bennink RJ, van Gulik TM. Intrahepatic left to right portoportal venous collateral vascular formation in patients undergoing right portal vein ligation. Cardiovasc Intervent Radiol. 2013 Dec;36(6):1572-1579. doi: 10.1007/s00270-013-0591-5. Epub 2013 Mar 13.</citation>
    <PMID>23483283</PMID>
  </reference>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>June 23, 2014</study_first_submitted>
  <study_first_submitted_qc>July 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 9, 2014</study_first_posted>
  <last_update_submitted>July 8, 2014</last_update_submitted>
  <last_update_submitted_qc>July 8, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 9, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Azienda Ospedaliera di Padova</investigator_affiliation>
    <investigator_full_name>Prof. Umberto Cillo</investigator_full_name>
    <investigator_title>full professor of general surgery, MD, PhD</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <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/NCT02184182
org study id: 2934P
nct id: NCT02184182
lead sponsor: 
has dmc: No
One of the limiting factors in the execution of a liver resection, in particular an extended
      liver resection, it's represented by the future remnant liver (FRL) after hepatic surgery. In
      cases of normal organ function an FRL of 25% is considered sufficient. In case of impaired
      hepatic function or a history of chemotherapy, it is considered safe if at least of 40%.

      Many strategies have been developed and proposed to increase the resectability in patients
      undergoing major liver resections.

      One of these is a new two-stage technique proposed recently by a group of German surgeons.
      This approach consists in the ligation of the right portal vein associated with resection of
      the liver along the falciform ligament (step 1). Step 2, after a period of 9 days (median -
      5-25 days), after a volumetric CT to ensure an adeguate hypertrophy of the left lateral lobe
      due to the combination of right portal occlusion and segment 4 devascularization, the patient
      undergo a right trisectionectomy. The hypertrophy of the left lateral lobe is shown to be of
      74%, higher than any other techniques of ligation or portal embolizatiol proposed in the
      literature.

      On the basis of the clinical experiences reported the investigators designed a new protocol
      of two-stage hepatic resection for the treatment of primary or secondary tumors of the right
      lobe. Step1: laparoscopic radio frequency / microwave ablation of the future transection
      plane between segment 4 and left lateral lobe and surgical ligation or embolization of the
      right portal vein. The ablation has the purpose to devascularize the segment 4 and has the
      same significance of the resection of the liver along the falciform ligament described by the
      Regensburg group.

      Step2: After a period of time of 9 ± 2 days, following a volumetric CT showing an adequate
      liver volume gain (ratio FRL / patient body weight> 0.5), the patient undergo the
      second-stage surgery: laparoscopic/ laparotomic right trisectionectomy.
In patients with primary or metastatic liver tumors, the only potentially curative
      therapeutic option is represented by hepatic resection. Nowdays extended resections can be
      performed with acceptable morbidity and mortality. There is no unanimous definition on the
      criteria of resectability and the ability to perform a more or less extensive liver resection
      is deferred to the expertise of the center and the surgical team. The investigators will
      consider a tumor resectable if the surgical procedure does not damage vital structures, the
      normal function of the organ is preserved and and the tumor is completely removed (R0
      resection). One of the limiting factors in the execution of a liver resection, in particular
      if it is extended, it's represented by the future remnant liver (FRL) after hepatic
      resection. In cases of normal organ function an FRL of 25% is considered sufficient. In case
      of impaired hepatic function or a history of chemotherapy, it is considered safe if at least
      of 40%.

      Many methods have been developed and proposed to increase the resectability in patients
      undergoing major liver resections. In case of bilobar tumor, a two-step approach (two-stage
      hepatectomy)have been proposed. This procedure implies that one of the two lobes is initially
      freed of disease by tumor resection or ablation. After achieving an adequate compensatory
      hypertrophy of the lobe freed by the tumor (usually 4-6 weeks),a contralateral liver
      resection can be done to treat the remnant tumor.

      To increase the FRL another approach is to occlude the portal branches towards one of liver
      lobes. This can be done with a surgical ligation (laparotomy or laparoscopy) or
      radiologically, using portal embolization. The technique allows to increase from 10% to 46%
      of the FRL with the possibility of obtaining a resection R-0 in 70-100% of cases. It is
      unclear whether there is any difference between the methods of portal occlusion (ligation vs
      embolization). To further increase hypertrophy after portal occlusion in liver tumors
      occupying the right liver, some researchers proposed to embolize the portal branches of
      segment 4th together with the right portal vein.

      The group of Regensburg has introduced a new technique in two stages for tumors of the right
      lobe, which combines the methods mentioned above. This two-stage approach consists in the
      ligation of the right portal vein associated with resection of the liver along the falciform
      ligament (step 1). Step 2, after a period of 9 days (median - 5-25 days), after a volumetric
      CT to ensure an adeguate hypertrophy of the left lateral lobe, the patient undergo a right
      trisectionectomy. The hypertrophy of the left lateral lobe is shown to be of 74%, higher than
      any other techniques of ligation or portal embolizatiol proposed in the literature.

      The rationale of this technique is the complete portal devascularization of the right lobe
      plus segment 4 that produce a greater stimulus to hypertrophy of the left lateral segments.
      This occurs in less time than other methods above described and allows to reduce the
      timeframe between the two steps and minimizes the risk of interprocedural progression of the
      underlying disease (incidence of drop outs in the two-stage hepatectomy of 20% for
      progression disease).

      The morbidity of this two-stage approach was 44% (complications of Clavien grade III and IV)
      that mimics the data reported in the literature for extended hepatic resections (20-50%). The
      12%mortality rate was similar to one described by Lang et al for left trisegmentectomies.

      On the basis of the clinical experiences reported the investigators designed a new protocol
      of two-stage hepatic resection for the treatment of primary or secondary tumors of the right
      lobe. Step1: laparoscopic radio frequency / microwave ablation of the future transection
      plane between segment 4 and left lateral lobe and surgical ligation or embolization of the
      right portal vein. The ablation has the purpose to devascularize the segment 4 and has the
      same significance of the resection of the liver along the falciform ligament described by the
      Regensburg group.

      Step2: After a period of time of 9 ± 2 days, following a volumetric CT showing an adequate
      liver volume gain (ratio FRL / patient body weight> 0.5), the patient undergo the
      second-stage surgery: laparoscopic/ laparotomic right trisectionectomy
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of R0 resections
time frame: 30days after Step2
description: Percentage of operations in which a complete oncological radicality (R0) is achived
measure: Perioperative mortality (3 months)
time frame: 3 moths
description: Percentage of perioperative mortality (3 months)
measure: Perioperative complication (Clavien Classification)
time frame: 1 month
description: Percentage of perioperative complication described using Clavien Dindo Classification
measure: Time to progression
time frame: 12 months
measure: Overall survival
time frame: 12 and 24 months
description: Overall survival at 12 and 24 months after surgery
measure: disease free survival
time frame: 12 months
measure: hepatic diesease free survival
time frame: 12 months
arm group label: VLS ablation/portal ligation/hepatectomy
arm group type: Experimental
description: Step1:
exploratory laparoscopy to exclude extrahepatic disease
right portal vein ligation if surgically feasible
RF/MW ablation on the future line of transection (of segment 4 close to left lateral lobe)
radiological portal embolization within 48h form the laparoscopic procedure if the right portal vein ligation is not feasible CT volumetric scan to evaluate the left lateral lobe hypertrophy after 9±2 from Step 1
Step 2: only if FRL/body weight > 0.5
- laparoscopic/laparotomic right trisectionectomy
intervention type: Procedure
intervention name: VLS ablation/portal ligation/hepatectomy
description: Step1:
exploratory laparoscopy to exclude extrahepatic disease
right portal vein ligation if surgically feasible
RF/MW ablation on the future line of transection (of segment 4 close to left lateral lobe)
radiological portal embolization within 48h form the laparoscopic procedure if the right portal vein ligation is not feasible
CT volumetric scan to evaluate the left lateral lobe hypertrophy after 9±2 from Step 1
Step 2: only if FRL/body weight > 0.5
- laparoscopic/laparotomic right trisectionectomy
arm group label: VLS ablation/portal ligation/hepatectomy
other name: VLS Ablation & Portal Vein Ligation for Staged Hepatectomy
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Umberto Cillo, MD PhD
role: Study Chair
affiliation: Azienda Ospedaliera di Padova
last name: Umberto Cillo, MD, PhD
phone: +390498211846
email: cillo@unipd.it
last name: Enrico Gringeri, MD, PHD
phone: +390498211846
email: enrico.gringeri@unipd.it
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: Italy
url: http://www.fegatochirurgia.com
description: Online resource of Chirurgia Epatobiliare e Trapianto Epatico, Università degli Studi di Padova
citation: Schnitzbauer AA, Lang SA, Goessmann H, Nadalin S, Baumgart J, Farkas SA, Fichtner-Feigl S, Lorf T, Goralcyk A, Horbelt R, Kroemer A, Loss M, Rummele P, Scherer MN, Padberg W, Konigsrainer A, Lang H, Obed A, Schlitt HJ. Right portal vein ligation combined with in situ splitting induces rapid left lateral liver lobe hypertrophy enabling 2-staged extended right hepatic resection in small-for-size settings. Ann Surg. 2012 Mar;255(3):405-14. doi: 10.1097/SLA.0b013e31824856f5.
PMID: 22330038
citation: Lang H, Sotiropoulos GC, Brokalaki EI, Radtke A, Frilling A, Molmenti EP, Malago M, Broelsch CE. Left hepatic trisectionectomy for hepatobiliary malignancies. J Am Coll Surg. 2006 Sep;203(3):311-21. doi: 10.1016/j.jamcollsurg.2006.05.290. Epub 2006 Jul 13.
PMID: 16931303
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: Farges O, Belghiti J, Kianmanesh R, Regimbeau JM, Santoro R, Vilgrain V, Denys A, Sauvanet A. Portal vein embolization before right hepatectomy: prospective clinical trial. Ann Surg. 2003 Feb;237(2):208-17. doi: 10.1097/01.SLA.0000048447.16651.7B.
PMID: 12560779
citation: Tartter PI. The association of perioperative blood transfusion with colorectal cancer recurrence. Ann Surg. 1992 Dec;216(6):633-8. doi: 10.1097/00000658-199212000-00004.
PMID: 1466616
citation: Donati M, Stavrou GA, Oldhafer KJ. Current position of ALPPS in the surgical landscape of CRLM treatment proposals. World J Gastroenterol. 2013 Oct 21;19(39):6548-54. doi: 10.3748/wjg.v19.i39.6548.
PMID: 24151380
citation: Lang H, Sotiropoulos GC, Fruhauf NR, Domland M, Paul A, Kind EM, Malago M, Broelsch CE. Extended hepatectomy for intrahepatic cholangiocellular carcinoma (ICC): when is it worthwhile? Single center experience with 27 resections in 50 patients over a 5-year period. Ann Surg. 2005 Jan;241(1):134-43. doi: 10.1097/01.sla.0000149426.08580.a1.
PMID: 15622001
citation: Are C, Iacovitti S, Prete F, Crafa FM. Feasibility of laparoscopic portal vein ligation prior to major hepatectomy. HPB (Oxford). 2008;10(4):229-33. doi: 10.1080/13651820802175261.
PMID: 18806869
citation: de Santibanes E, Alvarez FA, Ardiles V. How to avoid postoperative liver failure: a novel method. World J Surg. 2012 Jan;36(1):125-8. doi: 10.1007/s00268-011-1331-0.
PMID: 22045448
citation: van Lienden KP, Hoekstra LT, Bennink RJ, van Gulik TM. Intrahepatic left to right portoportal venous collateral vascular formation in patients undergoing right portal vein ligation. Cardiovasc Intervent Radiol. 2013 Dec;36(6):1572-1579. doi: 10.1007/s00270-013-0591-5. Epub 2013 Mar 13.
PMID: 23483283
responsible party type: Principal Investigator
investigator affiliation: Azienda Ospedaliera di Padova
investigator full name: Prof. Umberto Cillo
investigator title: full professor of general surgery, MD, PhD
mesh term: Liver Neoplasms