Arjen M. Rijken

Factors Influencing the Local Failure Rate of Radiofrequency Ablation of Colorectal Liver Metastases

BackgroundThe prognosis of patients with colorectal cancer is poor, especially when there is distant metastatic disease. Local ablation of tumor by radiofrequency ablation (RFA) has emerged as a safe and effective new treatment modality, but its long-term efficacy may be hindered by renewed local tumor growth at the site of RFA. The objectives of this study were to identify risk factors for local RFA failure and to define exclusion criteria for RFA treatment of colorectal liver metastases.MethodsA total of 199 lesions in 87 patients were ablated with RFA. Factors influencing local failure rates were identified and compared with data from the literature.ResultsThe local failure rate was 47.2%, and the average time to local disease progression was 6.5 months. Factors that significantly correlated with increased failure rates were metachronous occurrence of liver metastases, large mean lesion size, and central tumor location.ConclusionsBecause accurate electrode placement is pivotal in achieving adequate tumor necrosis, RFA should not be performed percutaneously when electrode placement is impaired. We suggest that lesions >5 cm and lesions located near great vessels or adjacent organs should be treated with open RFA, thus allowing vascular inflow occlusion and complete mobilization of the liver. Lesions that are difficult to reach by electrodes should be approached by an open procedure.

MARS treatment in posthepatectomy liver failure

Abstract Posthepatectomy liver failure (PHLF) is a dramatic complication following extensive liver resection or liver resection in a compromised liver, leading to death in 80% of cases. Molecular Adsorbent Recirculating System (MARS) is able to extract water and protein bound toxins out of the blood in liver failure patients. This paper describes the initial experience in the Netherlands using the MARS liver assist device in five patients with PHLF. In all patients, improvement of biochemical parameters was observed during MARS treatment along with clinical improvement in three patients. One patient survived. No clear guidelines for MARS treatment and prognostic factors for outcome after MARS treatment with regard to this patient group are available. In this paper, a MARS treatment regimen for PHLF is suggested based on literature and our own experience.

Resection of liver metastases in patients with breast cancer: Survival and prognostic factors

AIMS Patients with breast cancer metastasized to the liver have a median survival of 4-33 months and treatment options are usually restricted to palliative systemic therapy. The aim of this observational study was to evaluate the effectiveness and safety of resection of liver metastases from breast cancer and to identify prognostic factors for overall survival. METHODS Patients were identified using the national registry of histo- and cytopathology in the Netherlands (PALGA). Included were all patients who underwent resection of liver metastases from breast cancer in 11 hospitals in The Netherlands of the last 20 years. Study data were retrospectively collected from patient files. RESULTS A total of 32 female patients were identified. Intraoperative and postoperative complications occurred in 3 and 11 patients, respectively. There was no postoperative mortality. After a median follow up period of 26 months (range, 0-188), 5-year and median overall survival after partial liver resection was 37% and 55 months, respectively. The 5-year disease-free survival was 19% with a median time to recurrence of 11 months. Solitary metastases were the only independent significant prognostic factor at multivariate analysis. CONCLUSION Resection of liver metastases from breast cancer is safe and might provide a survival benefit in a selected group of patients. Especially in patients with solitary liver metastasis, the option of surgery in the multimodality management of patients with disseminated breast cancer should be considered.

Diagnostic and prognostic value of incidence of k-ras codon 12 mutations in resected distal bile duct carcinoma

Background and Objectives: The K‐ras gene is one of the most extensively investigated oncogenes in a wide variety of human tumors, but has rarely been studied in distal bile duct carcinoma (DBDC). We sought to investigate the diagnostic and prognostic value of K‐ras codon 12 mutations in this type of tumor.

Clinical impact of different detection methods for disseminated tumor cells in bone marrow of patients undergoing surgical resection of colorectal liver metastases: a prospective follow-up study

BackgroundLarge number of patients with colorectal liver metastasis show recurrent disease after curative surgical resection. Identification of these high-risk patients may guide therapeutic strategies. The aim of this study was to evaluate whether the presence of disseminated tumor cells in bone marrow from patients undergoing surgical resection of colorectal liver metastases can predict clinical outcome.MethodsSixty patients with colorectal liver metastases were planned for a curative resection between 2001 and 2007. All patients underwent bone marrow aspiration before surgery. Detection of tumor cells was performed using immunocytochemical staining for cytokeratin (CK-ICC) combined with automated microscopy or indirectly using reverse transcription-polymerase chain reaction (RT-PCR).ResultsDisseminated tumor cells were found in 15 of the 46 patients (33%) using CK-ICC and in 9 of 44 of the patients (20%) using RT-PCR. Patients with negative results for RT-PCR had a significant better disease-free survival after resection of their liver metastases (p = 0.02). This group also showed significant better overall survival (p = 0.002). CK-ICC did not predict a worse clinical outcome.ConclusionsThe presence of disseminated tumor cells in bone marrow detected using RT-PCR did predict a worse clinical outcome. The presence of cells detected with CK-ICC did not correlate with poor prognosis.

Viable Tumor Tissue Adherent to Needle Applicators after Local Ablation: A Risk Factor for Local Tumor Progression

BackgroundLocal tumor progression (LTP) is a serious complication after local ablation of malignant liver tumors, negatively influencing patient survival. LTP may be the result of incomplete ablation of the treated tumor. In this study, we determined whether viable tumor cells attached to the needle applicator after ablation was associated with LTP and disease-free survival.MethodsIn this prospective study, tissue was collected of 96 consecutive patients who underwent local liver ablations for 130 liver malignancies. Cells and tissue attached to the needle applicators were analyzed for viability using glucose-6-phosphate-dehydrogenase staining and autofluorescence intensity levels of H&E stained sections. Patients were followed-up until disease progression.ResultsViable tumor cells were found on the needle applicators after local ablation in 26.7% of patients. The type of needle applicator used, an open approach, and the omission of track ablation were significantly correlated with viable tumor tissue adherent to the needle applicator. The presence of viable cells was an independent predictor of LTP. The attachment of viable cells to the needle applicators was associated with a shorter time to LTP.ConclusionsViable tumor cells adherent to the needle applicators were found after ablation of 26.7% of patients. An independent risk factor for viable cells adherent to the needle applicators is the omission of track ablation. We recommend using only RFA devices that have track ablation functionality. Adherence of viable tumor cells to the needle applicator after local ablation was an independent risk factor for LTP.

Prognostic value of cell proliferation (Ki-67 antigen) and nuclear DNA content in clinically resectable, distal bile duct carcinoma

AbstractBackground: The aim of this study was to investigate the prognostic value of cell proliferation (Ki-67 antigen) and DNA content in patients resected for distal bile duct carcinoma (DBDC). Methods: Formalin-fixed tumor specimens of 35 patients with resected DBDC and a long-term clinical follow-up were analyzed. MIB-1 antibody was used for Ki-67 antigen detection to determine the proportion of proliferating cells. DNA content was measured using flow cytometry. Results: A significant correlation was found between a low MIB-1 index (<20%) and survival (P<.05). Of the 35 tumor specimens, 34 specimens were evaluable by flow cytometry: 22 carcinomas were diploid (65%), and 12 were aneuploid (35%). The median DNA index of aneuploid tumors was 1.36 (range, 1.09 to 1.76). No correlation of DNA-ploidy with survival time was found. Conclusion: In contrast to DNA-ploidy pattern, Ki-67 antigen expression showed prognostic significance in resectable DBDC. A Ki-67 positive ratio of ⩾20% was associated with decreased survival time.

Epidermal growth factor receptor (EGFR) and prostaglandin-endoperoxide synthase 2 (PTGS2) are prognostic biomarkers for patients with resected colorectal cancer liver metastases.

Background:Resection of colorectal cancer liver metastasis (CRCLM) with curative intent has long-term benefit in ∼40% of cases. Prognostic biomarkers are needed to improve clinical management and reduce futile surgeries. Expression of epidermal growth factor receptor (EGFR) and prostaglandin-endoperoxide synthase 2 (PTGS2; also known as cyclooxygenase-2) has been associated with carcinogenesis and survival. We investigated the prognostic value of EGFR and PTGS2 expression in patients with resected CRCLM.Methods:Formalin-fixed paraffin-embedded CRCLM tissue and corresponding primary tumour specimens from a multi-institutional cohort of patients who underwent liver resection between 1990 and 2010 were incorporated into tissue microarrays (TMAs). TMAs were stained for EGFR and PTGS2 by immunohistochemistry. The hazard rate ratio (HRR) for the association between expression in CRCLM and overall survival was calculated using a 500-fold cross-validation procedure.Results:EGFR and PTGS2 expression could be evaluated in 323 and 351 patients, respectively. EGFR expression in CRCLM was associated with poor prognosis (HRR 1.54; P<0.01) with a cross-validated HRR of 1.47 (P=0.03). PTGS2 expression was also associated with poor prognosis (HRR 1.60; P<0.01) with a cross-validated HRR of 1.63 (P<0.01). Expression of EGFR and PTGS2 remained prognostic after multivariate analysis with standard clinicopathological variables (cross-validated HRR 1.51; P=0.02 and cross-validated HRR 1.59; P=0.01, respectively). Stratification for the commonly applied systemic therapy regimens demonstrated prognostic value for EGFR and PTGS2 only in the subgroup of patients who were not treated with systemic therapy (HRR 1.78; P<0.01 and HRR 1.64; P=0.04, respectively), with worst prognosis when both EGFR and PTGS2 were highly expressed (HRR 3.08; P<0.01). Expression of PTGS2 in CRCLM was correlated to expression in patient-matched primary tumours (P=0.02, 69.2% concordance).Conclusions:EGFR and PTGS2 expressions are prognostic molecular biomarkers with added value to standard clinicopathological variables for patients with resectable CRCLM.

Large variation in the utilization of liver resections in stage IV colorectal cancer patients with metastases confined to the liver

BACKGROUND Surgical resection of both the primary tumor and all metastases is considered the only chance of cure for patients with stage IV colorectal cancer. The aim of this study was to investigate change over time in the utilization of liver resections, as well as possible institutional variations. PATIENTS AND METHODS All patients diagnosed with stage IV colorectal cancer with metastases confined to the liver (n = 1617) between 2004 and 2012 were selected from the population-based Eindhoven Cancer Registry. The proportion of patients undergoing liver resection was investigated. Institutional variation in the period 2010-2012 was analyzed using logistic regression. Kaplan-Meier and Cox regression analyses were used to analyze overall survival. RESULTS The proportion of patients undergoing liver metastasectomy increased over time from 8% in 2004 to approximately 24% in 2012. There was a wide inter-hospital variation in the proportion of patients that underwent a liver resection (range: 14-34%) in the period 2010-2012. Liver resection was more often performed in younger patients and in rectal cancer patients. Median overall survival in patients undergoing liver resection was 55 months. Adjusted for potential confounders, resection of liver metastases was strongly associated with improved overall survival (HR 0.32, 95%CI 0.25-0.40). DISCUSSION This study shows that despite the excellent long-term prognosis for patients with stage IV colorectal cancer after liver resection, there is still a large institutional variation in the utilization of this potentially curative therapy.

Laparoscopic Liver Resection in the Netherlands: How Far Are We?

Background: The objective of this study was to provide a systematic review on the introduction of laparoscopic liver surgery in the Netherlands, to investigate the initial experience with laparoscopic liver resections and to report on the current status of laparoscopic liver surgery in the Netherlands. Methods: A systematic literature search of laparoscopic liver resections in the Netherlands was conducted using PubMed/MEDLINE. Analysis of initial experience with laparoscopic liver surgery was performed by case-control comparison of patients undergoing laparoscopic left lateral sectionectomy matched with patients undergoing the open procedure in the Netherlands between the years 2000 and 2008. Furthermore, a nationwide survey was conducted in 2011 on the current status of laparoscopic liver surgery. Results: The systematic review revealed only 6 Dutch reports on actual laparoscopic liver surgery. Matched case-control comparison showed significant differences in the length of hospital stay, blood loss and operation time. Complications did not differ significantly between the two groups (26 vs. 21%). The 2011 survey showed that 21 centers in the Netherlands performed formal liver resections and that 49 (5% of total) laparoscopic liver resections were performed in 2010. Conclusion: The systematic review revealed that very few laparoscopic liver resections were performed in the Netherlands in the previous millennium. The matched case-control comparison of laparoscopic and open left lateral resection showed a reduction in hospital length of stay with comparable morbidity. The laparoscopic technique has been slowly adopted in the Netherlands, but its popularity seems to increase in recent years.