Resection of colorectal liver metastases - Impact of preoperative chemotherapy

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

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Sammanfattning

Background
Colorectal cancer is a leading cause of cancer related death worldwide. 20-30 % of patients will develop colorectal liver metastases (CRLMs). Surgical resection is the mainstay of treatment for CRLMs, and is often combined with perioperative chemotherapy, which can prolong progression-free survival after resection. Moreover, observation of CRLMs response to preoperative chemotherapy can help to identify patients with progressive disease, which allows for treatment adjustment.

However, preoperative chemotherapy can induce liver parenchymal injury, which can negatively affect surgical outcome and be difficult to detect in the preoperative setting. In addition, a worse surgical outcome has also been reported in patients with low preoperative muscle mass. Little is known about whether preoperative chemotherapy worsens skeletal muscle depletion.
Aims
To investigate effects of preoperative chemotherapy on the liver and preoperative muscle mass in patients undergoing liver resection for CRLMs, and to investigate whether diffusion-weighted magnetic resonance imaging (MRI) can be used to assess response in CRLMs to preoperative chemotherapy.

Patients and methods
In study I, liver volume measurements were conducted on pre- and postoperative computed tomography (CT) or MRI images in 74 patients who underwent major liver resections for CRLMs. In study II, intraoperative measurement of liver microcirculation was performed using sidestream dark-field imaging in 40 patients before and after liver resection. In study III, liver and spleen elastography was performed in 35 patients before and after liver resection. In study IV, measurement of skeletal muscle mass was carried out on pre- and posttreatment CT images in 97 patients undergoing neoadjuvant chemotherapy for CRLMs. In study V, measurements of the apparent diffusion coefficient (ADC) on pre- and postchemotherapy diffusion-weighted MRI in 49 CRLMs in 27 patients were conducted and compared to the metastases’ pathological chemotherapy response.

Results and conclusions
Preoperative chemotherapy for CRLMs negatively affects the liver volume regeneration after a liver resection. The sooner the resection is carried out after the cessation of chemotherapy, the greater the impact on regeneration. Patients with a transient postoperative liver insufficiency have a lower liver volume regeneration than others.

A major liver resection leads to an increase in sinusoidal blood velocity and increase in liver and spleen stiffness. Hepatic microcirculation is altered in patients with liver parenchymal injury.

Patients lose muscle mass during neoadjuvant chemotherapy, and muscle loss impairs the conditions for adjuvant chemotherapy.

After preoperative chemotherapy, an increase in ADC occurs in both pathological responding and non-responding CRLMs, and in study V, there was no difference in the relative change of ADC between the pathological responding and non-responding CRLMs.
Originalspråkengelska
KvalifikationDoktor
Tilldelande institution
  • Institutionen för kliniska vetenskaper, Lund
Handledare
  • Sturesson, Christian, handledare
  • Andersson, Roland, Biträdande handledare
Tilldelningsdatum2021 okt. 22
UtgivningsortLund
Förlag
ISBN (tryckt)978-91-8021-113-0
StatusPublished - 2021

Bibliografisk information

Defence details
Date: 2021-10-22
Time: 13:00
Place: Föreläsningssal 2, Centralblocket, Entrégatan 7, Skånes Universitetssjukhus i Lund. Join by Zoom: https://lu-se.zoom.us/j/69531598576
External reviewer(s)
Name: Viborg Mortensesn, Frank
Title: professor
Affiliation: Aarhus University, Denmark

Ämnesklassifikation (UKÄ)

  • Kirurgi

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