gms | German Medical Science

Background: Even after intended curative liver resection for colorectal liver metastases, tumor recurrence occurs in about 50% of patients. Basic research suggests that the process of hepatic regeneration also stimulates outgrowths of micrometastases or circulating tumor cells. However patient data whether volumetric liver regeneration and regrowth induces tumor recurrence is lacking. Therefore this study aims to elucidate if a fast liver regeneration enables tumor recurrence.

Materials and methods: Liver regrowth was measured on pre- and postoperative CT scans. 58 Patients with a formal right or left hemihepatectomy and suitable pre- and postoperative (2-3 months, 5-7 months and 11-14 months) CT scans were included from our prospective database of colorectal liver metastases. The future remnant liver volume and subsequent liver volumes were measured, liver regeneration calculated for each time point and correlated with clinical patient data including recurrence of liver metastases and overall survival of the patients.

15 patients had died until last follow-up with a median follow-up of the surviving patients of 42 months (range 2 to 103 months).

Results: 37 (63,8%) men and 21 (36,2%) women with a mean age of 58,7 ± 11,0 years (range 28-74) were included. 45 patients (77,6%) underwent a right and 13 patients (22,4%) a left hemihepatectomy. 77,6% had a R0, 12,1% R1 and 10,3% Rx-resection. 75,9% of the patients received preoperative chemotherapy.

The postoperative liver volume for left hemihepatectomies was 1066 cm³ and 532cm³ for right hemihepatectomies (p<0,001). The highest rate of liver regeneration was directly postoperative (2-3 month) with 17,45% for left and 109,92% right side resections, but still increased until 11-14 month with finally 21% and 122,64%. Regeneration after left hemihepatectomies increased to a final volume of 1409 ± 367,18 cm³ and right hemihepatectomies increased to 1266 ± 242 cm³ (p= 0,088).

Volume increase was independent of gender, primary tumor stage, localization and number of metastases as well as preoperative chemotherapy (p>0.05)

Neither absolute nor relative amount of liver regeneration (< or >median) at the chosen timepoints had a significant influence on the overall survival (all p>0.5). However patients with an early strong regeneration showed a shorter median OS with 56 months (95% CI 33,2-78,8) than patients with less regeneration and OS of 103,0 months (95% CI 18.8-187,2), statistical significance could not be observed (p= 0,165).

79,3% of patients had a tumor recurrence (p=0,592) and 50% got recurrent liver metastases (p=0,753), independent of liver regeneration. The median time for recurrent liver metastases was 9 months (range 1 to 46 months).

Conclusion: We could not confirm that a higher rate of liver regeneration is correlated with a recurrence of liver metastases and thus lower overall survival, as suspected in animal trials.

It is therefore questionable if a mice tumor model, where a tumor reoccurs within days or weeks is comparable with the human being and a course of disease extending over years.

In our study an early high rate of regeneration might influence tumor recurrence and shorter OS without reaching statistical significance possibly due to a small number of patients.

While future studies with bigger cohorts are warranted, surgical resection of CRC liver metastases remains the only curative treatment regardless of the speed of liver regeneration.