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Magnetic resonance imaging flowmetry demonstrates portal vein dilatation subsequent to oxaliplatin therapy in patients with colorectal liver metastasis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
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2013 (English)In: HPB, ISSN 1365-182X, E-ISSN 1477-2574, Vol. 15, no 4, 265-272 p.Article in journal (Refereed) Published
Abstract [en]

Objectives: 

Sinusoidal injury (SI) after oxaliplatin-based therapies for colorectal liver metastasis (CRLM) can increase postoperative morbidity. Preoperative methods to estimate SI are lacking. The aim of this study was to identify SI by evaluating portal vein haemodynamics.

Methods: 

Magnetic resonance imaging flowmetry (MRIF) was used to estimate portal vein haemodynamics in 29 patients with CRLM before liver surgery. Sinusoidal injury was evaluated from resected non-tumorous liver parenchyma according to the combined vascular injury (CVI) score of ≥3.

Results: 

All patients with SI (six of 29) received oxaliplatin; however, a significant association could not be proven (P= 0.148). Oxaliplatin-treated patients showed portal vein dilatation in both the SI and non-SI groups compared with patients who had not received oxaliplatin (Bonferroni corrected P= 0.003 and P= 0.039, respectively). Mean portal velocity tended to be lower in patients with SI compared with oxaliplatin-treated patients without SI (Bonferroni corrected P= 0.087). A mean portal velocity of ≤14.35 cm/s together with a cross-section area of ≥1.55 cm2 was found to predict SI with sensitivity of 100% and specificity of 78%.

Conclusions: 

Oxaliplatin treatment was associated with portal vein dilatation. Patients with SI showed a tendency towards decreased mean portal flow velocity. This may indicate that SI is associated with an increased resistance to blood flow in the liver parenchyma. Portal vein haemodynamic variables estimated by MRIF can identify patients without SI non-invasively.

Place, publisher, year, edition, pages
2013. Vol. 15, no 4, 265-272 p.
National Category
Medical and Health Sciences Basic Medicine
Research subject
Pathology
Identifiers
URN: urn:nbn:se:uu:diva-190126DOI: 10.1111/j.1477-2574.2012.00540.xISI: 000315902600004OAI: oai:DiVA.org:uu-190126DiVA: diva2:583064
Conference
This manuscript was presented at the 10th World IHPBA Congress, Paris, 1–5 July 2012.
Available from: 2013-01-07 Created: 2013-01-07 Last updated: 2017-12-06Bibliographically approved
In thesis
1. Colorectal Cancer Liver Metastases: Effects of Chemotherapy on Liver Parenchyma and Resections
Open this publication in new window or tab >>Colorectal Cancer Liver Metastases: Effects of Chemotherapy on Liver Parenchyma and Resections
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Current multimodal treatment of colorectal cancer liver metastasis often combines liver resections with preoperative chemotherapy with a 5-year survival of 40-50%. Preoperative chemotherapy includes conversion of initially non-resectable situation and control of micrometastatic disease. Despite its potential advantages also problems with associated steatosis, steatohepatitis and sinusoidal injury has been discussed. Paper I focused on prospective steatosis evaluation prior to resections using proton MR spectroscopy, most sensitive non-invasive method. Proton MR spectroscopy showed high concordance with digital quantification of steatosis and was also able to predict steatohepatitis with 100% sensitivity and 89% specificity without knowing lobular inflammation or hepatocyte ballooning. Paper II focused on portal vein hemodynamics changes in patients treated with oxaliplatin-based treatment and with sinusoidal injury. Magnetic resonance imaging flowmetry demonstrated portal vein dilatation associated with oxaliplatin treatment. Patients with SI showed a tendency towards decreased mean portal flow velocity. Portal vein flow was not changed. This may indicate that SI is associated with an increased resistance to blood flow in the liver parenchyma and stasis in splanchnic system. Paper III attempted to enlighten the effects of FOLFOX treatment on human liver tissue 6 weeks after treatment cessation by quantification of protein expression changes using label-free global proteome analysis. Deep proteome analysis identified 5891 proteins, where machine learning algorithm identified 3% of classifying proteins, associated with changes in DNA replication through upregulation of the minichromosome maintenance complex and with the innate immune response. Significant changes were observed in 1% of proteins, associated with DNA replication and cell cycle entry. Results support the hypothesis that liver has already regenerated from the FOLFOX treatment injury after 6 weeks. Paper IV aimed to identify possible patient, disease and chemotherapy characteristics associated with liver specific and severe general complications in a retrospective single centre cohort composed of 516 consecutive resections. Chemotherapy with more than 4 cycles of oxaliplatin was associated with post-hepatectomy hemorrhage. Underlying liver disease and diabetes mellitus were associated with 90-day mortality. Size of resection, intraoperative blood loss and transfusions were verified as independent predictors of liver specific complications to resections.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2014. 53 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1041
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-233790 (URN)978-91-554-9066-9 (ISBN)
Public defence
2014-11-22, Museum Gustavianum, Auditorium Minus, Akademigatan 3, Uppsala, 09:00 (English)
Opponent
Supervisors
Available from: 2014-10-30 Created: 2014-10-10 Last updated: 2015-01-23

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Urdzik, JozefBjerner, TomasWanders, AlkwinDuraj, FransHaglund, UlfNorén, Agneta

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