• Humans
• Retrospective Studies
• Neoadjuvant Therapy/adverse effects
• Carcinoembryonic Antigen
• Colorectal Neoplasms/pathology
• Prognosis
• Liver Neoplasms/drug therapy
• Liver Neoplasms/surgery
• Liver Neoplasms/pathology
• Hepatectomy

There are no optimal indication criteria for neoadjuvant chemotherapy (NAC) in patients with resectable colorectal liver metastases (CLM). The aim of this study was to prospectively assess the survival benefit of selective NAC administration in this patient population based on tumor characteristics.

Borderline resectable CLM (BR-CLM) were defined as four or more liver metastases, CLM larger than 5 cm, or CLM with concomitant resectable extrahepatic metastases. From 2010 to 2015, NAC was administered to BR-CLM patients. Upfront surgery without NAC was performed to patients having clearly resectable CLM (less than 3 lesions, smaller than 5 cm, and no extrahepatic metastases: CR-US group). Survival outcomes of the two groups were assessed.

The BR-NAC group comprised 73 patients and the CR-US group 172. All patients in the BR-NAC group underwent subsequent resection, as none showed disease progression or chemotherapy-associated liver damage. The 3- and 5-year overall survival rates of the CR-US group were 83.0% and 74.0%, while patients in the BR-NAC group had comparable 3-year and 5-year overall survivals (80.5% and 66.6%, P = 0.397).

Defining BR-CLM based on tumor characteristics optimizes patient selection for NAC. Favorable overall survival can be achieved by upfront surgery in patients with clearly resectable CLM and by NAC in patients with BR-CLM.

• Chemotherapy
• Colorectal cancer
• Liver metastases
• Liver resection

• Neoadjuvant chemotherapy
• angiogenesis inhibitor
• hepatectomy
• hepatotoxicity
• liver toxicity
• monoclonal antibody
• regeneration.

• Antineoplastic Combined Chemotherapy Protocols/adverse effects
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Colorectal Neoplasms/drug therapy
• Colorectal Neoplasms/pathology
• Colorectal Neoplasms/surgery
• Female
• Hepatectomy/adverse effects
• Humans
• Liver Neoplasms/drug therapy
• Liver Neoplasms/secondary
• Liver Neoplasms/surgery
• Male
• Middle Aged
• Neoadjuvant Therapy/adverse effects
• Postoperative Complications/etiology
• Retrospective Studies
• Treatment Outcome

Little is known about the safety of the anti-VEGF antibody bevacizumab in patients undergoing resection for colorectal liver metastases (CLM). This meta-analysis evaluates the impact of bevacizumab on parenchymal damage and functional recovery in patients undergoing resection for CLM.

The Medline, Embase and Cochrane Library were systematically searched for studies on preoperative chemotherapy with and without bevacizumab prior to resection of CLM. Studies that reported histological and/or clinical outcomes were eligible for inclusion. Meta-analyses were performed using a random effects model.

A total of 18 studies with a total sample size of 2430 patients (1050 patients with bevacizumab) were found. Meta-analyses showed a significant reduction in sinusoidal obstruction syndrome (SOS) (Odds ratio 0.50 [95 % confidence interval 0.37, 0.67]; p < 0.001; I² = 0 %) and hepatic fibrosis (0.61 [0.4, 0.86]; p = 0.004; I² = 7 %) after preoperative chemotherapy with bevacizumab. The reduced incidence of posthepatectomy liver failure in patients with bevacizumab treatment just failed to reach statistical significance (0.61 [0.34, 1.07]; p = 0.08 I² = 6 %). While there was no difference in perioperative morbidity and mortality, the incidence of wound complications was significantly increased in patients who received bevacizumab (1.81 [1.12, 2.91]; p = 0.02 I² = 4 %).

The combination of bevacizumab with cytotoxic chemotherapy is safe but increases the incidence of wound complications after resection of CLM. The reduction of SOS and hepatic fibrosis warrant further investigation and may explain the inverse association of bevacizumab administration and posthepatectomy liver failure.

The online version of this article (doi:10.1186/s12885-016-2095-6) contains supplementary material, which is available to authorized users.

Bevacizumab is a humanized monoclonal antibody targeting vascular endothelial growth factor (VEGF), often used in combinational chemotherapy regimens for the treatment of patients with colorectal liver metastases. However adverse events have been attributed to the use of bevacizumab including gastrointestinal perforations, thrombotic events, hypertension, bleeding, and wound healing complications. 53-year-old male, with a history of colorectal cancer with liver metastasis, receiving a combination of cytotoxic chemotherapy (FOLFIRI, irinotecan with fluorouracil and folinic acid) with bevacizumab presented as an emergency with an incarcerated incisional hernia. The last administration of chemotherapy and bevacizumab had taken place 2 weeks prior to this presentation. As the risk of strangulation of the bowel was increased, a decision was made to take the patient to theatre, although the hazard with respect to wound healing, haemorrhage, and infection risk was high due to the recent administration of chemotherapy with bevacizumab. The patient underwent an open repair of the incarcerated recurrent incisional hernia with placement of a biological mesh, and the postoperative recovery was uncomplicated with no wound healing or bleeding problems.

• bevacizumab
• colorectal
• liver metastases
• surgical complications

• bevacizumab
• neoadjuvant chemotherapy
• poor risk
• rectal cancer

• Adult
• Aged
• Antibodies, Monoclonal, Humanized/administration & dosage
• Antibodies, Monoclonal, Humanized/adverse effects
• Antineoplastic Combined Chemotherapy Protocols/administration & dosage
• Antineoplastic Combined Chemotherapy Protocols/adverse effects
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Bevacizumab
• Capecitabine
• Chemotherapy, Adjuvant
• Deoxycytidine/administration & dosage
• Deoxycytidine/adverse effects
• Deoxycytidine/analogs & derivatives
• Drug Administration Schedule
• Female
• Fluorouracil/administration & dosage
• Fluorouracil/adverse effects
• Fluorouracil/analogs & derivatives
• Humans
• Male
• Middle Aged
• Multimodal Imaging
• Neoadjuvant Therapy/methods
• Organoplatinum Compounds/administration & dosage
• Organoplatinum Compounds/adverse effects
• Oxaliplatin
• Oxaloacetates
• Patient Selection
• Positron-Emission Tomography
• Prospective Studies
• Rectal Neoplasms/drug therapy
• Risk Assessment
• Risk Factors
• Tomography, X-Ray Computed
• Treatment Outcome

AIM: To assess the impact of preoperative neoadjuvant bevacizumab (Bev) on the outcome of patients undergoing resection for colorectal liver metastases (CLM).

METHODS: Eligible trials were identified from Medline, Embase, Ovid, and the Cochrane database. The data were analyzed with fixed-effects or random-effects models using Review Manager version 5.0.

RESULTS: Thirteen nonrandomized studies with a total of 1431 participants were suitable for meta-analysis. There was no difference in overall morbidity and severe complications between the Bev + group and Bev - group (43.3% vs 36.8%, P = 0.06; 17.1% vs 11.4%, P = 0.07, respectively). Bev-related complications including wound and thromboembolic/bleeding events were also similar in the Bev + and Bev - groups (14.4% vs 8.1%, P = 0.21; 4.1% vs 3.8%, P = 0.98, respectively). The incidence and severity of sinusoidal dilation were lower in patients treated with Bev than in patients treated without Bev (43.3% vs 63.7%, P < 0.001; 16.8% vs 46.5%, P < 0.00, respectively).

CONCLUSION: Bev can be safely administered before hepatic resection in patients with CLM, and has a protective effect against hepatic injury in patients treated with oxaliplatin chemotherapy.

• Colorectal cancer
• Liver metastases
• Bevacizumab
• Postoperative complication
• Sinusoidal dilatation

• Adult
• Aged
• Aged, 80 and over
• Angiogenesis Inhibitors/administration & dosage
• Angiogenesis Inhibitors/adverse effects
• Antibodies, Monoclonal, Humanized/administration & dosage
• Antibodies, Monoclonal, Humanized/adverse effects
• Bevacizumab
• Chemotherapy, Adjuvant
• Chi-Square Distribution
• Colorectal Neoplasms/mortality
• Colorectal Neoplasms/pathology
• Drug Administration Schedule
• Female
• Hepatectomy/adverse effects
• Hepatectomy/mortality
• Humans
• Liver Neoplasms/drug therapy
• Liver Neoplasms/mortality
• Liver Neoplasms/secondary
• Liver Neoplasms/surgery
• Liver Neoplasms/therapy
• Male
• Middle Aged
• Neoadjuvant Therapy
• Odds Ratio
• Risk Factors
• Treatment Outcome

• Humans
• Antineoplastic Combined Chemotherapy Protocols/adverse effects
• Colorectal Neoplasms/drug therapy
• Colorectal Neoplasms/pathology
• Fatty Liver/chemically induced
• Liver Neoplasms/drug therapy
• Liver Neoplasms/secondary
• Prognosis

• Wellcome Trust
• WT090974MA Wellcome Trust

Colorectal cancer (CRC) is one of the cancer models and most of the carcinogenic steps are presently well understood. Therefore, successful preventive measures are currently used in medical practice. However, CRC is still an important public health problem as it is the third most common cancer and the fourth most frequent cause of cancer death worldwide. Nowadays, pathologic stage is a unique and well-recognized prognostic indicator, however, more accurate indicators of the biologic behavior of CRC are expected to improve the specificity of medical treatment. Angiogenesis plays an important role in the growth and progression of cancer but its role as a prognostic factor is still controversial. Probably the most important clinical implication of tumor angiogenesis is the development of anti-angiogenic therapy. The goal of this review is to critically evaluate the role of angiogenic markers, assessed by either endoglin-related microvessel density or expression of vascular endothelial growth factor family members in the CRC setting and discuss the role of these angiogenic markers in anti-angiogenic therapies.

• Angiogenesis
• Colorectal cancer
• Colorectal cancer treatment
• Endoglin
• Prognosis
• Vascular endothelial growth factor

As colorectal cancer and colorectal liver metastases become a serious public health problem, new treatment modalities are needed in order to achieve better results. In the last decade there has been very important progress in oncology, with new and more effective chemotherapeutic agents administered alone or in combination improving the resectability rate in up to 40% of patients with colorectal liver metastases. Advances in interventional radiology, in particular, with the use of portal vein embolization and radiofrequency thermal ablation are new strategies allowing major liver resections and treatment of small liver metastases or early recurrences. Surgery, however, remains the gold standard strategy with intention to treat. In this review article we will describe the advanced role of surgery in the multidisciplinary approach to colorectal liver metastases, and the clinical problems the liver surgeon has to deal with, such as the resectability of the metastases, the presence of bilobar liver lesions and extrahepatic disease, the impact of chemotherapy in already resectable liver metastases, the problem of vanishing metastases after chemotherapy and the dilemma of staged or combined liver and colon operations and which organ first in the clinical scenario of synchronous colorectal liver metastases.

• Metastases
• Liver metastases
• Colorectal cancer
• Surgery