mRNA expression profiles of colorectal liver metastases as a novel biomarker for early recurrence after partial hepatectomy.

BACKGROUND: Identification of specific risk groups for recurrence after surgery for isolated colorectal liver metastases (CRLM) remains challenging due to the heterogeneity of the disease. Classical clinicopathologic parameters have limited prognostic value. The aim of this study was to identify a gene expression signature measured in CRLM discriminating early from late recurrence after partial hepatectomy. METHODS: CRLM from two patient groups were collected: I) with recurrent disease ≤12 months after surgery (N = 33), and II) without recurrences and disease free for ≥36 months (N = 30). The patients were clinically homogeneous; all had a low clinical risk score (0-2) and did not receive (neo-) adjuvant chemotherapy. Total RNA was hybridised to Illumina arrays, and processed for analysis. A leave-one-out cross validation (LOOCV) analysis was performed to identify a prognostic gene expression signature. RESULTS: LOOCV yielded an 11-gene profile with prognostic value in relation to recurrent disease ≤12 months after partial hepatectomy. This signature had a sensitivity of 81.8%, with a specificity of 66.7% for predicting recurrences (≤12 months) versus no recurrences for at least 36 months after surgery (X2 P < 0.0001). CONCLUSION: The current study yielded an 11-gene signature at mRNA level in CRLM discriminating early from late or no relapse after partial hepatectomy.

The use of neo-adjuvant chemotherapy in patients with resectable colorectal liver metastases: Clinical risk score as possible discriminator.

AIM: The combination of surgery and chemotherapy (CTx) is increasingly accepted as an effective treatment for patients with colorectal liver metastases (CRLM). However, controversy exists whether all patients with resectable CRLM benefit from perioperative CTx. We investigated the impact on overall survival (OS) by neo-adjuvant CTx in patients with resectable CRLM, stratified by the clinical risk score (CRS) described by Fong et al. METHODS: Patients who underwent surgery for CRLM between January 2000 and December 2009 were included. We compared OS of patients with and without neo-adjuvant CTx stratified by the CRS. The CRS includes five prognosticators and defines two risk groups: low CRS (0-2) and high CRS (3-5). RESULTS: 363 patients (64% male) were included, median age 63 years (IQR 57-70). Prior to resection, 219 patients had a low CRS (neo-adjuvant CTx: N = 65) and 144 patients had a high CRS (neo-adjuvant CTx: N = 88). Median follow-up was 47 months (IQR 25-82). In the low CRS group, there was no significant difference in median OS between patients with and without CTx (65 months (95% CI 39-91) vs. 54 months (95% CI 44-64), P = 0.31). In the high CRS group, there was a significant difference in OS between patients with and without CTx (46 months (95% CI 24-68) vs. 33 month (95% CI 29-37), P = 0.004). CONCLUSION: In our series, patients with a high CRS benefit from neo-adjuvant CTx. In patients with a low risk profile, neo-adjuvant CTx might not be beneficial.

Prognostic value of circulating tumour cells for early recurrence after resection of colorectal liver metastases.

BACKGROUND: Despite good outcomes for many, a substantial group of patients undergoing metastasectomy for isolated liver metastases from colorectal cancer (CRC) experience early recurrence. We have investigated whether circulating tumour cell (CTC) detection can identify patients developing disease recurrence within 1 year after liver metastasectomy. METHODS: In CRC patients undergoing liver metastasectomy, 30 ml peripheral blood was withdrawn preoperatively. CTCs were detected by the CellSearch system after a density-gradient-based enrichment step. RESULTS: One hundred and seventy-three samples from 151 individual patients were analysed. In 75 samples (43%), CTCs were detected, 16% had ⩾3 CTCs/7.5 ml of blood. Eighty-two patients (47%) experienced early disease recurrence (<1 year). The 1-year recurrence rate between patients with or without detectable CTCs were similar (47% vs 48%) or with a low or high CTC count (<3 or ⩾3 CTCs/7.5 ml of blood) (50% vs 47%). Also disease-free and overall survival were similar between patients with or without CTCs. CONCLUSIONS: The presence of CTCs in preoperative peripheral blood samples does not identify patients at risk for early disease recurrence after curative resection of colorectal liver metastases. Other parameters are needed to better identify patients at high risk to relapse after liver metastasectomy for CRC.

Safety and efficacy of a novel, dry powder fibrin sealant for hemostasis in hepatic resection.

BACKGROUND/AIMS: Fibrocaps is a dry powder fibrin sealant containing human plasma-derived fibrinogen and thrombin. The safety, efficacy, and application methods for Fibrocaps were evaluated in an exploratory, first-in-human, noncomparative, clinical study. METHODS: Patients with minor bleeding/oozing after elective partial hepatic resection had Fibrocaps applied to the bleeding site either directly from the vial or from a spray device, with manual pressure applied using a cellulose, collagen, or gelatin sponge, if needed. Safety was evaluated at screening and postoperative days 1, 2, and 5, and weeks 4 and 12. The formation of anti-thrombin antibodies was assessed at baseline, and after 4 and 12 weeks. Time to hemostasis (TTH) within 10 min was determined. RESULTS: Twenty-nine patients were treated with Fibrocaps; 6 experienced serious adverse events that were not related to the course of treatment. Adverse events occurring in >10% of patients were nausea, constipation, hypotension, obstipation, hypokalemia, and postoperative pain. Most adverse events were mild or moderate in severity. No patient developed anti-thrombin antibodies. The percentage of patients who achieved hemostasis was 93%; the median TTH was 3.8 min (range 0.3-10.3). Manual pressure was applied with Fibrocaps in 19 patients and considered beneficial in most. CONCLUSION: Fibrocaps was well tolerated in patients undergoing elective hepatic resection and resulted in rapid hemostasis. These safety and efficacy results support further clinical testing of this ready-to-use fibrin sealant as an adjunct to surgical hemostasis.

Preoperative FDG-PET-scan in patients with resectable colorectal liver metastases does not improve overall survival: a retrospective analyses stratified by clinical risk score.

BACKGROUND: The aim of this study was to determine whether selection with fluorine-18-deoxyglucose positron emission tomography (FDG-PET) imaging would result in an improved outcome in surgically treated patients with curative resection of colorectal liver metastases (CRLM), stratified by the clinical risk score (CRS) of Fong et al. [Ann Surg 1999;230:309-318]. PATIENTS AND METHODS: Between January 2000 and December 2009, all patients who underwent resection for CRLM from two different university teaching hospitals in the Netherlands were analysed. Patients were stratified by the CRS. RESULTS: In total 613 patients were eligible for analysis. There was no statistical difference in median disease-free survival (DFS) between patients with and without an FDG-PET scan in both low CRS [17 months (95% CI 12-22) vs. 14 months (95% CI 11-17), p = 0.332] and high CRS [14 months (95% CI 7-21) vs. 9 months (95% CI 8-10), p = 0.073]. There was no statistical difference in median overall survival (OS) between patients with and without an FDG-PET scan in both low CRS [64 months (95% CI 54-74) vs. 54 months (95% CI 42-66), p = 0.663] and high CRS [39 months (95% CI 23-55) vs. 41 months (95% CI 34-48), p = 0.903]. CONCLUSION: The present study could not demonstrate that patients selected by an FDG-PET scan before liver resection, and stratified by CRS, have an improvement in DFS or OS.

The basilic vein and the cephalic vein perform equally in upper arm arteriovenous fistulae.

OBJECTIVE: To compare the brachiocephalic (BC) and basilic vein transposition (BVT) arteriovenous fistula (AVF) with regard to maturation, patency, blood flow and complication rates. DESIGN: A retrospective chart review. MATERIALS AND METHOD: Between January 2000 and December 2010, consecutive patients undergoing BC or BVT AVF were included. Patient characteristics were collected retrospectively from digital patient files and a prospective database of haemodialysis patients. RESULTS: A total of 173 autologous upper arm AVFs (87 BC and 86 BVT) were created in 151 patients. Mean (±SEM) follow-up was 19 ± 1.4 months (range 0-100). There were no differences between the groups in respect to brachial artery and cubital fossa vein diameters, time to first use, flow and the number of secondary interventions. Operative time was significantly longer (P < 0.001) and the mid upper arm vein diameter before bifurcation greater (P = 0.038) in BVT patients. The 1- and 2-year primary patency rates for the whole cohort was 40.8% and 30.2% with secondary patency rates of 78.0% and 72.4%. There was no difference between the groups for these outcomes (P = 0.951, P = 0.516, respectively). CONCLUSION: With the exception of the efferent vein diameter in the mid upper arm and operative time, there was no difference between a BC and BVT AVF.

Body composition and outcome in patients undergoing resection of colorectal liver metastases.

BACKGROUND: Recent evidence suggests that depletion of skeletal muscle mass (sarcopenia) and an increased amount of intra-abdominal fat (central obesity) influence cancer statistics. This study investigated the impact of sarcopenia and central obesity on survival in patients undergoing liver resection for colorectal liver metastases (CLM). METHODS: Diagnostic imaging from patients who had hepatic resection for CLM in one centre between 2001 and 2009, and who had assessable perioperative computed tomograms, was analysed retrospectively. Total cross-sectional areas of skeletal muscle and intra-abdominal fat, and their influence on outcome, were analysed. RESULTS: Of the 196 patients included in the study, 38 (19·4 per cent) were classified as having sarcopenia. Five-year disease-free (15 per cent versus 28·5 per cent in patients without sarcopenia; P = 0·002) and overall (20 per cent versus 49·9 per cent respectively; P < 0·001) survival rates were lower for patients with sarcopenia at a median follow-up of 29 (range 1-97) months. Sarcopenia was an independent predictor of worse recurrence-free (hazard ratio (HR) 1·88, 95 per cent confidence interval 1·25 to 2·82; P = 0·002) and overall (HR 2·53, 1·60 to 4·01; P < 0·001) survival. Central obesity was associated with an increased risk of recurrence in men (P = 0·032), but not in women (P = 0·712). CONCLUSION: Sarcopenia has a negative impact on cancer outcomes following resection of CLM.