Thymidylate synthase: a predictive biomarker in resected colorectal liver metastases receiving 5-FU treatment.

AIM: To investigate the role of thymidylate synthase (TS) as a predictive biomarker in patients with resected colorectal liver metastases (CRLM). MATERIALS & METHODS: PubMed, EMBASE and Cochrane Library were queried up to June 2017. Meta-analysis was performed using random-effects model. Risk of bias was assessed using funnel plots. RESULTS: Six eligible studies were included, comprising a total of 542 patients. Meta-analysis demonstrated a trend to reduced overall survival in patients with resected CRLM with TS overexpression, with a hazard ratio of 1.13 (95% CI: 0.99-1.29; p = 0.08). In three studies where patients received systemic fluorouracil, the pooled hazard ratio was 2.25 (95% CI: 1.37-3.71; p = 0.001). CONCLUSION: TS appears to be a clinically relevant predictive biomarker in patients with resected CRLM receiving systemic 5-FU.

Parenchyma-sparing hepatectomy (PSH) versus non-PSH for bilobar liver metastases of colorectal cancer.

BACKGROUND: Preoperative interventions have increased the resectability of colorectal cancer (CRC) liver metastases. This retrospective study compares outcomes after liver resection for bilobar CRC metastases between patients who underwent parenchyma-sparing hepatectomy (PSH), i.e., segmentectomies and smaller resections on both lobes, and those treated with non-PSH, i.e., hemihepatectomy plus any resection on the other lobe. METHODS: A cohort of 119 patients who underwent liver resection for bilobar CRC metastases were included. Perioperative course and long-term survival were compared between 59 patients who underwent PSH and 60 patients who underwent non-PSH. Statistical analyses were done using Pearson's chi-square test, Fisher's exact test and the Mann-Whitney U test. Overall survival analysis was performed by the Kaplan-Meier estimator and Cox regression analysis. RESULTS: The median number of liver metastases was 2 in patients treated with PSH and 3 in those treated with non-PSH (P<0.01). Postoperative mortality, severe complications and radicality did not differ significantly between groups. Median intraoperative bleeding was 250 mL for PSH and 600 mL for non-PSH (P<0.001). Median operation time and hospital stay were significantly shorter for PSH. Overall survival was comparable between groups, also after adjustment for covariates. CONCLUSIONS: There were no significant differences in outcome, except for differences in bleeding, operation time and postoperative stay, favoring PSH. Furthermore, minimizing resection did not influence radicality. Hence, this study supports the use of PSH for bilobar CRC liver metastases when possible.

The Prognostic Role of Cancer Stem Cell Markers for Long-term Outcome After Resection of Colonic Liver Metastases.

BACKGROUND/AIM: To assess the expression of cancer stem cell (CSC) markers CD44, CD133 and CD24 in colon cancer liver metastases and analyse their predictive value for overall survival (OS) and disease-free survival (DFS) after liver resection. MATERIALS AND METHODS: Patients operated on for colon cancer liver metastases were included. CSC marker expression was determined through immunohistochemistry analysis. OS and DFS were compared between marker-positive and marker-negative patients. Multivariate analysis was performed to select predictive variables for OS and DFS. RESULTS: CD133-positive patients had a worse DFS than CD133-negative patients, with a median DFS of 12 and 25 months (p=0.051). Multivariate analysis selected CD133 expression as a significant predictor for DFS. CD44 and CD24 were not found to predict OS or DFS. CONCLUSION: CD133 expression in colonic liver metastases is a negative prognostic factor for DFS after liver resection. In the future, CD133 could be used as a biomarker for risk stratification, and possibly for developing novel targeted therapy.

Pattern of tumour growth of the primary colon cancer predicts long-term outcome after resection of liver metastases.

OBJECTIVE: To identify significant predictive factors for overall survival (OS) and disease-free survival (DFS) after liver resection for colon cancer metastases, with special focus on features of the primary colon cancer, such as lymph node ratio (LNR), vascular invasion, and perineural invasion. METHODS: Patients operated for colonic cancer liver metastases between 2006 and 2014 were included. Details on patient characteristics, the primary colon cancer operation and metastatic disease were collected. Multivariate analysis was performed to select predictive variables for OS and DFS. RESULTS: Median OS and DFS were 67 and 20 months, respectively. 1-, 3- and 5-year OS were 97, 76, and 52%. 1-, 3- and 5-year DFS were 65, 42, and 37%. Multivariate analysis showed LNR to be an independent predictive factor for DFS but not for OS. Other identified predictive factors were vascular and perineural invasion of the primary colon cancer, size of the largest metastasis and severe complications after liver surgery for OS, and perineural invasion, number of liver metastases and preoperative CEA-level for DFS. Traditional N-stage was also considered to be an independent predictive factor for DFS in a separate multivariate analysis. CONCLUSIONS: LNR and perineural invasion of the primary colon cancer can be used as a prognostic variable for DFS after a concomitant liver resection for colon cancer metastases. Vascular and perineural invasion of the primary colon cancer are predictive for OS.

Tumour growth after portal vein embolization with pre-procedural chemotherapy for colorectal liver metastases.

BACKGROUND: For resection of colorectal cancer (CRC) liver metastases, pre-operative portal vein embolization (PVE) is used to increase the size of the future liver remnant (FLR) prior to advanced liver resection when indicated. PVE is speculated to cause tumour progression, but only a limited number of studies have analysed tumour growth after PVE in the context of pre-procedural chemotherapy, which was the aim of this retrospective study. METHODS: Patients treated with stabilizing chemotherapy and PVE before liver resection for CRC metastases were included. Tumour progression according to RECIST guidelines and a change in tumour volume was analysed on computed tomography (CT) scans prior to chemotherapy, before PVE and after PVE, respectively. RESULTS: Thirty-four patients were included, of whom 23 had bilobar disease. Of tumours in the embolized lobe, 3/34 showed progression after PVE as compared with 3/23 in the non-embolized lobe (P = 0.677). A decrease in tumour volume of 16% and 11% was noted in the embolized and non-embolized lobe, respectively (P = 0.368). Patients were off chemotherapy in a median of 16 days before PVE. There was a linear correlation between the growth of tumours and time between the end of chemotherapy and PVE (r = 0.25, P = 0.0005). CONCLUSION: The rate of progression of CRC liver metastases after PVE and pre-procedural chemotherapy was lower in the present study as compared with previous reports. This applies to tumours in both the embolized and non-embolized lobes and is associated with keeping the time between the end of chemotherapy and PVE short.

Limiting factors for liver regeneration after a major hepatic resection for colorectal cancer metastases.

BACKGROUND: Chemotherapy before resection of colorectal metastases in the liver is extensively used and has been shown to induce histopathological changes in the liver parenchyma, although little is known about the effect of chemotherapy on liver regeneration. The aim of this study was to determine if pre-operative chemotherapy influences the regenerated liver volume after a major liver resection. PATIENTS AND METHODS: This retrospective cohort study included 74 patients subjected to a major liver resection for colorectal metastases. Patients were divided into two groups depending on whether they had been treated with chemotherapy less than 3 months before surgery or not. Liver volumes were measured before and 1 year after resection. RESULTS: Pre-operative chemotherapy reduced volumetric liver regeneration (83 ± 2% versus 91 ± 2%; P = 0.007) as compared with patients without chemotherapy. There was a linear correlation between regenerated volume and time interval between the end of chemotherapy to resection (P = 0.031). CONCLUSIONS: Pre-operative chemotherapy in patients with colorectal liver metastases negatively affects volume regeneration after a partial hepatectomy. The time interval between chemotherapy and surgery determines the impact of these affects.

Combined portal vein embolization and preoperative chemotherapy prior to liver resection for colorectal cancer metastases.

OBJECTIVE: Compare perioperative course and long-term mortality after liver resection for colorectal cancer (CRC) metastases between patients who had preoperative treatment with portal vein embolization (PVE) and chemotherapy or chemotherapy alone. METHODS: Among patients undergoing liver resection for CRC metastases following preoperative chemotherapy treatment, 17 patients who had received preoperative PVE (group A) were compared with 17 matched controls who had no PVE (group B). Perioperative course and long-term mortality were compared between groups A and B and between group A and the entire group of 75 cases with preoperative chemotherapy (group C). RESULTS: Baseline characteristics for the matched groups A and B were similar. Group C included less major resections. Median intraoperative bleeding was 1600 ml in group A, 1200 ml in group B, and 1000 ml in group C (p < 0.05 vs. group A). Median postoperative stay was comparable in all groups (8-9 days). Operation time was 542 min in group A and 464 min in group B (p < 0.01). Mortality after 30 days and 1, 2, and 5 years was similar in all groups. CONCLUSION: Perioperative outcome and long-term survival did not differ when comparing liver resection for CRC liver metastases preceded by PVE and chemotherapy or chemotherapy alone, except for the operation time. The study supports the safety of this "aggressive" combination approach in patients in need of tumor "downstaging" by chemotherapy and PVE to increase the remnant liver volume.

Influence of preoperative chemotherapy on the intraoperative and postoperative course of liver resection for colorectal cancer metastases.

BACKGROUND: Liver resection is a possibly curative treatment for colorectal cancer (CRC) liver metastases. Preoperative chemotherapy may make initially irresectable tumors resectable. The aim of this study was to compare perioperative course and short-term mortality after liver resection for CRC metastases between patients who were and were not treated with preoperative chemotherapy. METHODS: Patients who had undergone liver resection for CRC metastases were included. A total of 97 patients treated with preoperative chemotherapy (group A) were compared with 136 who were not (group B). Intraoperative bleeding, operating time, complications, duration of stay, and mortality were compared using Pearson's χ(2) test, Fisher's exact test, and the Mann-Whitney U-test. RESULTS: Mean intraoperative bleeding, duration of stay, and operating time were not significantly different. Complications occurred in 62.9% and 63.2% in groups A and B, respectively. The 30- and 90-day mortality rates were zero in group A, comparable to 1.5% in group B. CONCLUSIONS: There were no significant differences in the perioperative course or postoperative mortality when comparing CRC patients with or without chemotherapy prior to liver resection. Consequently, this study suggests that preoperative chemotherapy before liver resection for CRC metastases does not negatively influence perioperative outcome and can therefore be applied if "downstaging" is indicated.

Fast-track programmes for hepatopancreatic resections: where do we stand?

BACKGROUND: Fast-track (FT) programmes represent a series of multimodal concepts that may reduce surgical stress and speed up convalescence after surgery. The aim of this systematic review was to evaluate FT programmes for patients undergoing hepatopancreatic surgery. METHODS: PubMed, Embase and the Cochrane Library databases were searched for studies of FT vs. conventional recovery strategies for liver and pancreatic resections. RESULTS: For liver surgery, three cohort studies were included. Primary hospital stay was significantly reduced after FT care in two of the three studies. There were no significant differences in rates of readmission, morbidity and mortality. For pancreatic surgery, three cohort studies and one case-control study were included. Primary hospital stay was significantly shorter after FT care in three out of the four studies. One study reported a significantly decreased readmission rate (7% vs. 25%; P= 0.027), and another study showed lower morbidity (47.2% vs. 58.7%; P < 0.01) in favour of the FT group. There was no difference in mortality between the FT and control groups. CONCLUSIONS: FT rehabilitation for liver and pancreatic surgical patients is feasible. Future investigation should focus on optimizing individual elements of the FT programme within the context of liver and pancreatic surgery.