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Neoadjuvant chemotherapy does not affect future liver remnant growth and outcomes of associating liver partition and portal vein ligation for staged hepatectomy
Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
UCL, England.
UCL, England.
Vizgen De La Arrixaca University Hospital, Spain.
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2017 (English)In: Surgery, ISSN 0039-6060, E-ISSN 1532-7361, Vol. 161, no 5, p. 1255-1265Article in journal (Refereed) Published
Abstract [en]

Background. The only potentially curative treatment for patients with colorectal liver metastases is hepatectomy. Associating liver partition and portal vein ligation for staged hepatectomy has emerged as a method of treatment for patients with inadequate future liver remnant. One concern about associating liver partition and portal vein ligation for staged hepatectomy is that preoperative chemotherapy may negatively affect the volume increase of the future liver remnant and outcomes. Methods. This study from the International Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy Registry (NCT01924741) includes 442 patients with colorectal liver metastases registered from 2012-2016. Future liver remnant hypertrophy (absolute increase, percent increase, and kinetic growth rate) and clinical outcome were analyzed retrospectively in relation to type and amount of chemotherapy. The analyzed groups included patients with no chemotherapy, 1 regimen of chemotherapy, amp;gt; 1 regimen, and a group that received monoclonal antibodies in addition to chemotherapy. Results. Ninety percent of the patients received neoadjuvant oncologic therapy including 42% with 1 regimen of chemotherapy, 44% with monoclonal antibodies, and 4% with amp;gt; 1 regimen. Future liver remnant increased between 74-92% with the largest increase in the group with 1 regimen of chemotherapy. The increase in milliliters was between 241 mL (amp;gt; 1 regimen) and 306 mL (1 regimen). Kinetic growth rate was between 14-18% per week and was greatest for the group with 1 regimen of chemotherapy. No statistical significance was found between the groups with any of the measurements of future liver remnant hypertrophy. Conclusion. Neoadjuvant chemotherapy, including monoclonal antibodies, does not negatively affect future liver remnant growth. Patients with colorectal liver metastases who might be potential candidates for associating liver partition and portal vein ligation for staged hepatectomy should be considered for neoadjuvant chemotherapy. (Surgery 2017;161:1255-65.)

Place, publisher, year, edition, pages
MOSBY-ELSEVIER , 2017. Vol. 161, no 5, p. 1255-1265
National Category
Surgery
Identifiers
URN: urn:nbn:se:liu:diva-137854DOI: 10.1016/j.surg.2016.11.033ISI: 000400318000011PubMedID: 28081953OAI: oai:DiVA.org:liu-137854DiVA, id: diva2:1104924
Available from: 2017-06-02 Created: 2017-06-02 Last updated: 2020-04-28
In thesis
1. Colorectal Liver Metastases – Different Aspects on Treatment with Associated Liver Partition and Portal Vein Ligation for Staged Hepatectomy and on Portal Vein Occlusion
Open this publication in new window or tab >>Colorectal Liver Metastases – Different Aspects on Treatment with Associated Liver Partition and Portal Vein Ligation for Staged Hepatectomy and on Portal Vein Occlusion
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Introduction: For patients with colorectal liver metastases (CRLM), the only treatment with a possibility for long-term survival and cure is radical resection. The majority of patients are at the time of diagnosis not assessed as resectable because they have advanced disease in the liver or unresectable extrahepatic disease or are too frail to withstand liver surgery. Patients who at the time of diagnosis are not assessed as resectable may be treated with conversion chemotherapy to downsize the tumor burden and render the patient eligible for resection. One concern with chemotherapy administered preoperatively has been the potential negative effect on the future liver remnant (FLR), especially for patients with a low volume of the FLR who are undergoing techniques to increase the volume. Established techniques to increase the volume are portal vein occlusion (PVO) and two-staged hepatectomy (TSH). A more recent method is Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS). Due to the relative novelty of ALPPS, the long-term oncological results are not known. For patients with CRLM, resection of liver metastases is more favorable from a health economic perspective than palliative treatment and results in a higher quality of life than palliative chemotherapy. For patients undergoing ALPPS as well as TSH, the data are scarce.

Aim: The aim of the first study was to determine whether preoperative chemotherapy has a negative impact on the volume increase for patients undergoing ALPPS. The aim of the second study was to analyze the temporal course of the volume increase in the FLR for patients undergoing PVO. The aim of the third study was to study the long-term outcome for patients randomized to ALPPS or TSH. The aim of the fourth study was to perform a health economic analysis of patients randomized to ALPPS or TSH.

Methods: The first study was based on data from the ALPPS registry, which is an international registry initiated 2012. All patients included in the registry between 2012 and 2016 were included. The patients were divided into the following four groups: no preoperative chemotherapy, 1 regimen of neoadjuvant chemotherapy, more than 1 regimen, and more than 1 regimen with the addition of monoclonal antibodies. The volume increase between interventions 1 and 2 was analyzed. In the second study, a retrospective analysis was performed of patients randomized to TSH. Forty-eight patients were included. The volume increase of the FLR was analyzed as the kinetic growth rate (KGR). The KGR was calculated from PVO until radical hepatectomy or exclusion, as well as between the first and second radiological evaluations. In the third and fourth studies, patients randomized to ALPPS and TSH were included. In the third study, survival, as well as factors affecting the outcome, were analyzed. In the fourth study, a calculation of resource use was performed, as was an analysis of health-related quality of life (HRQoL) for the groups.

Results: In the first study, it was found that chemotherapy had no negative impact on the volume increase for patients undergoing ALPPS. In the second study, it was found that the volume increase of the FLR was largest the first week after ALPPS. In the third study, it was found that patients randomized to ALPPS had a longer survival than those randomized to TSH. Of the factors affecting the outcome, resection of liver metastases had a significant impact. In the fourth study, no significant difference could be found in resource use or HRQoL for patients randomized to ALPPS over TSH.

Conclusion: Patients with advanced CRLM undergoing ALPPS should receive preoperative chemotherapy, if indicated. For those undergoing PVO, early evaluation is crucial to evaluate the volume increase, and for those with insufficient increase, additional techniques to increase the volume should be considered. Resection of liver metastases is an important factor to improve the outcome. Further studies are warranted to conclude whether ALPPS or TSH is most effective from a health economic perspective.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2020. p. 105
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1738
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-165372 (URN)10.3384/diss.diva-165372 (DOI)9789179298609 (ISBN)
Public defence
2020-05-29, Eken, Building 421, Campus US, Linköping, 09:00 (Swedish)
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Available from: 2020-04-28 Created: 2020-04-28 Last updated: 2020-05-06Bibliographically approved

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Hasselgren, KristinaWalter, LarsSandström, PerBjörnsson, Bergthor
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Division of Surgery, Orthopedics and OncologyFaculty of Medicine and Health SciencesDepartment of Surgery in LinköpingResearch & Development Unit in Local Health Care
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