Ninos Ayez

Outcome of Microscopic Incomplete Resection (R1) of Colorectal Liver Metastases in the Era of Neoadjuvant Chemotherapy

BackgroundData from patients with colorectal liver metastases (CRLM) who received neoadjuvant chemotherapy before resection were reviewed and evaluated to see whether neoadjuvant chemotherapy influences the predictive outcome of R1 resections (margin is 0xa0mm) in patients with CRLM.MethodsBetween January 2000 and December 2008, all consecutive patients undergoing liver resection for CRLM were analyzed. Patients were divided into those who did and did not receive neoadjuvant chemotherapy. The outcome after R0 (tumor-free margin >0xa0mm) and R1 (tumor-free margin 0xa0mm) resection was compared.ResultsA total of 264 were eligible for analysis. Median follow-up was 34xa0months. Patients without chemotherapy showed a significant difference in median disease-free survival (DFS) after R0 or R1 resection: 17 [95% confidence interval (CI) 10–24] months versus 8 (95% CI 4–12) months (Pxa0<xa00.001), whereas in patients with neoadjuvant chemotherapy the difference in DFS between R0 and R1 resection was not significant: 18 (95% CI 10–26) months versus 9 (95% CI 0–20) months (Pxa0=xa00.303). Patients without chemotherapy showed a significant difference in median overall survival (OS) after R0 or R1 resection: 53 (95% CI 40–66) months versus 30 (95% CI 13–47) months (Pxa0<xa00.001). In patients with neoadjuvant chemotherapy, the median OS showed no significant difference: 65 (95% CI 39–92) months for the R0 group versus the R1 group, in whom the median OS was not reached (Pxa0=xa00.645).ConclusionsIn patients treated with neoadjuvant chemotherapy, R1 resection was of no predictive value for DFS and OS.

Is the Clinical Risk Score for Patients with Colorectal Liver Metastases Still Useable in the Era of Effective Neoadjuvant Chemotherapy

BackgroundSeveral clinical risk scores (CRSs) for the outcome of patients with colorectal liver metastases have been validated, but not in patients undergoing neoadjuvant chemotherapy. Therefore, this study evaluates the predictive value of these CRSs in this specific group.MethodsBetween January 2000 and December 2008, all patients undergoing a metastasectomy were analyzed and divided into two groups: 193 patients did not receive neoadjuvant chemotherapy (group A), and 159 patients received neoadjuvant chemotherapy (group B). In group B, the CRSs were calculated before and after administration of neoadjuvant chemotherapy. Results were evaluated by using the CRSs proposed by Nordlinger et al., Fong et al., Nagashima et al., and Konopke et al.ResultsIn groups A and B, the overall median survival was 43 and 47xa0months, respectively (Pxa0=xa00.648). In group A, all CRSs used were of statistically significant predictive value. Before administration of neoadjuvant chemotherapy, only the Nordlinger score was of predictive value. After administration of neoadjuvant chemotherapy, all CRSs were of predictive value again, except for the Konopke score.ConclusionsTraditional CRSs are not a reliable prognostic tool when used in patients before treatment with neoadjuvant chemotherapy. However, CRSs assessed after the administration of neoadjuvant chemotherapy are useful to predict prognosis.

Anatomical Versus Nonanatomical Resection of Colorectal Liver Metastases: Is There a Difference in Surgical and Oncological Outcome?

BackgroundThe increased use of neoadjuvant chemotherapy and minimally invasive therapies for recurrence in patients with colorectal liver metastases (CLM) makes a surgical strategy to save as much liver volume as possible pivotal. In this study, we determined the difference in morbidity and mortality and the patterns of recurrence and survival in patients with CLM treated with anatomical (AR) and nonanatomical liver resection (NAR).MethodsFrom January 2000 to June 2008, patients with CLM who underwent a resection were included and divided into two groups: patients who underwent AR, and patients who underwent NAR. Patients who underwent simultaneous radiofrequency ablation in addition to surgery and patients with extrahepatic metastasis were excluded. Patient, tumor, and treatment data, as well as disease-free and overall survival (OS) were compared.ResultsEighty-eight patients (44%) received AR and 113 patients (56%) underwent NAR. NAR were performed for significant smaller metastases (3 vs. 4xa0cm, Pxa0<xa00.001). The Clinical Risk Score did not differ between the groups. After NAR, patients received significantly less blood transfusions (20% vs. 36%, Pxa0=xa00.012), and the hospital stay was significantly shorter (7 vs. 8xa0days, Pxa0<xa00.001). There were no significant differences in complications, positive resection margins, or recurrence. For the total study group, estimated 5-year disease-free and OS was 31 and 44%, respectively, with no difference between the groups.ConclusionsOur study resulted in no significant difference in morbidity, mortality, recurrence rate, or survival according to resection type. NAR can be used as a save procedure to preserve liver parenchyma.

Long-term results of the "liver first" approach in patients with locally advanced rectal cancer and synchronous liver metastases

BACKGROUND: There are no reports available on the long-term outcome of patients with the “liver first” approach. OBJECTIVES: The aim of this study was to present the long-term results of the “liver first” approach in our center. DESIGN: This study is a retrospective analysis. SETTING: This study was conducted at a tertiary referral center. PATIENTS: Patients from May 2003 to March 2009 were included. INTERVENTIONS: Patients with locally advanced rectal cancer and synchronous liver metastases were first treated for their liver metastases. If the treatment was successful, patients underwent neoadjuvant chemoradiotherapy and surgery for the rectal cancer. If metastases could not be resected, resection of the rectal primary was not routinely performed. MAIN OUTCOME MEASURES: The primary outcome measured was long-term results of the “liver first” approach. RESULTS: Of the 42 patients included (median age, 61 years), all but one (98%) started with neoadjuvant chemotherapy. In total, 31 (74%) patients completed the “liver first” approach. In 11 patients, curative therapy was not possible because of unresectable metastases; in 10 of these patients (91%), the primary tumor was not resected. LIMITATIONS: This study was limited because it was a retrospective analysis without a control group. CONCLUSIONS: By applying the “liver first” approach, the majority of this group of patients (74%) could undergo curative treatment of both metastatic and primary disease in combination with optimal neoadjuvant therapy. This strategy may avoid unnecessary rectal surgery in patients with incurable metastatic disease. In this selected patient group, long-term survival may be achieved with a 5-year survival rate of 67%.

Neo-adjuvant chemotherapy followed by surgery versus surgery alone in high-risk patients with resectable colorectal liver metastases: The CHARISMA randomized multicenter clinical trial

BackgroundEfforts to improve the outcome of liver surgery by combining curative resection with chemotherapy have failed to demonstrate definite overall survival benefit. This may partly be due to the fact that these studies often involve strict inclusion criteria. Consequently, patients with a high risk profile as characterized by Fong’s Clinical Risk Score (CRS) are often underrepresented in these studies. Conceptually, this group of patients might benefit the most from chemotherapy. The present study evaluates the impact of neo-adjuvant chemotherapy in high-risk patients with primary resectable colorectal liver metastases, without extrahepatic disease. Our hypothesis is that adding neo-adjuvant chemotherapy to surgery will provide an improvement in overall survival (OS) in patients with a high-risk profile.Methods/DesignCHARISMA is a multicenter, randomized, phase III clinical trial. Patients will be randomized to either surgery alone (standard treatment, arm A) or to 6 cycles of neo-adjuvant oxaliplatin-based chemotherapy, followed by surgery (arm B). Patients must be ≥ 18 years of age with liver metastases of histologically confirmed primary colorectal carcinoma. Patients with extrahepatic metastases are excluded. Liver metastases must be deemed primarily resectable. Only patients with a CRS of 3–5 are eligible. The primary study endpoint is OS. Secondary endpoints are progression free survival (PFS), quality of life, morbidity of resection, treatment response on neo-adjuvant chemotherapy, and whether CEA levels can predict treatment response.DiscussionCHARISMA is a multicenter, randomized, phase III clinical trial that will provide an answer to the question if adding neo-adjuvant chemotherapy to surgery will improve OS in a well-defined high-risk patient group with colorectal liver metastases.Trial registrationThe CHARISMA is registered at European Union Clinical Trials Register (EudraCT), number: 2013-004952-39, and in the “Netherlands national Trial Register (NTR), number: 4893.

Is restaging with chest and abdominal CT scan after neoadjuvant chemoradiotherapy for locally advanced rectal cancer necessary

BackgroundThere is no evidence regarding restaging of patients with locally advanced rectal cancer after a long course of neoadjuvant radiotherapy with or without chemotherapy. This study evaluated the value of restaging with chest and abdominal computed tomographic (CT) scan after radiotherapy.MethodsBetween January 2000 and December 2010, all newly diagnosed patients in our tertiary referral hospital, who underwent a long course of radiotherapy for locally advanced rectal cancer, were analyzed. Patients were only included if they had chest and abdominal imaging before and after radiotherapy treatment.ResultsA total of 153 patients who met the inclusion criteria and were treated with curative intent were included. A change in treatment strategy due to new findings on the CT scan after radiotherapy was observed in 18 (12xa0%) of 153 patients. Twelve patients (8xa0%) were spared rectal surgery due to progressive metastatic disease.ConclusionsRestaging with a chest and abdominal CT scan after radiotherapy for locally advanced rectal cancer is advisable because additional findings may alter the treatment strategy.

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

AIMnThe 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.nnnMETHODSnPatients 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).nnnRESULTSn363 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).nnnCONCLUSIONnIn 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.

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.

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

BACKGROUNDnIdentification 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.nnnMETHODSnCRLM from two patient groups were collected: I) with recurrent disease ≤12 months after surgery (Nxa0=xa033), and II) without recurrences and disease free for ≥36 months (Nxa0=xa030). 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.nnnRESULTSnLOOCV 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 Pxa0<xa00.0001).nnnCONCLUSIONnThe current study yielded an 11-gene signature at mRNA level in CRLM discriminating early from late or no relapse after partial hepatectomy.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.

Surgery of the primary tumour in stage iv colorectal cancer with unresectable metastases

textabstractSurgery plays an important role in the treatment nof patients with limited metastatic disease of colorectal cancer (CRC). Long term survival and cure nis reported in 20−50% of highly selected patients nwith oligometastatic disease who underwent surgery. nThis paper describes the role of surgery of the nprimary tumour in patients with unresectable stage IV ncolorectal cancer. Owing to the increased efficacy nof chemotherapeutic regimens in stage IV colorectal ncancer, complications from unresected primary tumours are relatively infrequent. The risk of emergency nsurgical intervention is less than 15% in patients with nsynchronous metastatic disease who are treated with nchemotherapy. Therefore, there is a tendency among nsurgeons not to resect the primary tumour in case of nunresectable metastases. However, it is suggested that nresection of the primary tumour in case of unresectable nmetastatic disease might influence overall survival. nAll studies described in the literature (n = 24) are nnon-randomised and the majority is single-centre and nretrospective of nature. Most studies are in favour of nresection of the primary tumour in patients with symptomatic lesions. In asymptomatic patients the results nare less clear, although median overall survival seems nto be improved in resected patients in the majority of nstudies. The major drawback of all these studies is nthat primarily patients with a better performance status nand better prognosis (less metastatic sites involved) are nbeing operated on. Another limitation of these studies nis that few if any data on the use of systemic therapy nare presented, which makes it difficult to assess nthe relative contribution of resection on outcome. nProspective studies on this topic are warranted, and nare currently being planned. Conclusion: Surgery of nthe primary tumour in patients with synchronous nmetastasised CRC is controversial, although data from nthe literature suggest that resection might be a positive nprognostic factor for survival. Therefore prospective nstudies on the value of resection in this setting are nrequired.