• colorectal cancer
• liver synchronous metastasis
• one stage treatment
• outcomes
• simultaneous laparoscopic resection
• timing

• Computed tomography
• Liver tumour
• Resection planning
• Segmentation

• Abdomen
• Algorithms
• Hepatectomy
• Humans
• Imaging, Three-Dimensional
• Liver/diagnostic imaging
• Liver/surgery
• Liver Neoplasms/diagnostic imaging
• Liver Neoplasms/surgery
• Tomography, X-Ray Computed

Partial hepatectomy (PHx) is the gold standard for the treatment of colorectal cancer liver metastases. However, after removing a substantial amount of hepatic tissue, growth factors are released to induce liver regeneration, which may promote the proliferation of liver micrometastases or circulating tumour cells still present in the patient. The aim of this study is to assess the effect of PHx on the growth of liver metastases induced by intrasplenic cell inoculation as well as on in vitro proliferation of the same cancer cell line. Liver tumours were induced in 18 WAG/RijHsd male rats, by seeding 250,000 syngeneic colorectal cancer cells (CC531) into the spleen. The left lateral lobe of the liver was mobilized and in half of the animals it was removed to achieve a 40% hepatectomy. Twenty-eight days after tumour induction, the animals were sacrificed and the liver was removed and sliced to assess the relative tumour surface area (RTSA%). CC531 cells were cultured in presence of foetal calf serum, non-hepatectomised (NRS) or hepatectomized rat serum (HRS), and their proliferation rate at 24, 48, and 72 h was measured. RTSA% was significantly higher in animals which had undergone PHx than in the controls (non-hepatectomised) (46.98 ± 8.76% vs. 18.73 ± 5.65%; p < 0.05). Analysing each lobe separately, this difference in favour of hepatectomized animals was relevant and statistically significant in the paramedian and caudate lobes. But in the right lobe the difference was scarce and not significant. In vitro, 2.5% HRS achieved stronger proliferative rates than the control cultures (10% FCS) or their equivalent of NRS. In this experimental model, a parallelism has been shown between the effect of PHx on the growth of colorectal cancer cells in the liver and the effect of the serum on those cells in vitro.

• Hemihepatectomy
• Liver metastases
• Liver regeneration

• Colorectal liver metastases
• Extrahepatic tumor infestation
• Individualized treatment
• Liver surgery
• Treatment strategies

To evaluate the clinical value and efficiency of trans-arterial chemoperfusion (TACP) in patients with liver metastases from breast cancer (BC) and colorectal cancer (CRC).

We treated 36 patients with liver metastases of BC (n = 19, 19 females) and CRC (n = 17; 8 females, 9 males) with repeated TACP. The treatment interval was 4 wk. TACP was performed with gemcitabine (1000 mg/m²) and mitomycin (10 mg/m²), administered within 1 h after positioning the catheter tip in the hepatic artery. Before treatment, the size, location, tumour volume, vascularization and number of liver tumours were evaluated using magnetic resonance imaging (MRI). Tumour response was evaluated according to the Response Evaluation Criteria in Solid Tumors guidelines.

TACP using gemcitabine and mitomycin for metastases from CRC and BC was performed without any serious side effects. The follow-up MRI showed a therapeutic response in 84.2% of the BC patients - stable disease 47.4% and partial response 36.8%. A progression was seen in 15.8%. CRC patients showed a therapeutic response in 52.9% of cases. A progression of the disease was documented in 47.1% of the patients with CRC. These data show that TACP in patients with liver metastases of BC leads to a significantly better therapeutic response compared with CRC patients (P = 0.042). The median survival time was 13.2 mo for the BC patients, which is significantly longer than for CRC patients at 9.3 mo (P = 0.001).

TACP for liver metastases of BC appears to be a safe and effective palliative treatment with improved outcomes in comparison to patients with CRC.

• Colorectal neoplasms
• Breast neoplasms
• Neoplasm metastasis
• Neoplasms
• Drug therapy

• Colon cancer
• Liver metastases
• Long-term survival
• Lung metastases
• Rectal cancer

• Chemotherapy, Adjuvant
• Colorectal Neoplasms/mortality
• Colorectal Neoplasms/pathology
• Colorectal Neoplasms/surgery
• Combined Modality Therapy
• Female
• Humans
• Liver Neoplasms/mortality
• Liver Neoplasms/pathology
• Liver Neoplasms/secondary
• Liver Neoplasms/surgery
• Lung Neoplasms/mortality
• Lung Neoplasms/pathology
• Lung Neoplasms/secondary
• Lung Neoplasms/surgery
• Lymphatic Metastasis/pathology
• Male
• Metastasectomy
• Neoplasm Recurrence, Local/mortality
• Neoplasm Recurrence, Local/pathology
• Neoplasm Recurrence, Local/surgery
• Prognosis
• Retrospective Studies
• Survival Analysis

• Hepatectomy
• Liver failure
• Monocrotaline
• Oxaliplatin
• Pringle maneuver
• Sinusoidal obstruction syndrome (SOS)

• Colorectal metastases
• Elderly
• Liver resection
• Prognostic factors
• Survival

• Documentation
• Health Information Systems
• Humans
• Neoplasms/diagnosis
• Neoplasms/therapy
• Workflow

• Laparoscopic surgery
• Liver metastasis
• Minimal access

• Computer-assisted surgery
• Hepatectomy
• Liver neoplasms
• Liver segmentation
• Liver tumor

AIM: To offer an up-to-date review of all available treatment strategies for patients with synchronous colorectal liver metastases (CLM).

METHODS: A comprehensive literature search was performed to identify articles related to the management of patients with synchronous CLM. A search of the electronic databases PubMed, MEDLINE, and Google Scholar was conducted in September 2014. The following search terms were used: synchronous colorectal liver metastases, surgery, stage IV colorectal cancer, liver-first approach, and up-front hepatectomy. These terms were employed in various combinations to maximize the search. Only articles written in English were included. Particular attention was devoted to studies and review articles that were published within the last six years (2009-2014). Additional searches of the cited references from primary articles were performed to further improve the review. The full texts of all relevant articles were accessed by two independent reviewers.

RESULTS: Poor long-term outcomes of patients with synchronous CLM managed by a traditional treatment strategy have led to questions about the timing and sequence of possible therapeutic interventions. Thus, alternative paradigms called reverse strategies have been proposed. Presently, there are four treatment strategies available: (1) primary first approach (or traditional approach) comprises resection of the primary colorectal tumor followed by chemotherapy; subsequent liver resection is performed 3-6 mo after colorectal resection (provided that CLM are still resectable); (2) simultaneous resection of the primary colorectal tumor and CLM during a single operation presents intriguing options for a highly select group of patients, which can be associated with significant postoperative morbidity; (3) liver-first (or chemotherapy-first) approach comprises preoperative chemotherapy (3-6 cycles) followed by liver resection, adjuvant chemotherapy, and resection of the primary colorectal tumor (it is best suited for patients with asymptomatic primary tumors and initially unresectable or marginally resectable CLM); and (4) up-front hepatectomy (or “true” liver-first approach) includes liver resection followed by adjuvant chemotherapy, colorectal resection, and adjuvant chemotherapy (strategy can be offered to patients with asymptomatic primary tumors and initially resectable CLM).

CONCLUSION: None of the aforementioned strategies appears inferior. It is necessary to establish individual treatment plans in multidisciplinary team meetings through careful appraisal of all strategies.

• Colorectal cancer
• Liver-first approach
• Reverse strategy
• Simultaneous resection
• Up-front hepatectomy

• Antineoplastic Agents/administration & dosage
• Antineoplastic Agents/adverse effects
• Carcinoma/mortality
• Carcinoma/secondary
• Carcinoma/therapy
• Chemotherapy, Adjuvant
• Colectomy/adverse effects
• Colectomy/mortality
• Colorectal Neoplasms/mortality
• Colorectal Neoplasms/pathology
• Colorectal Neoplasms/therapy
• Drug Administration Schedule
• Hepatectomy/adverse effects
• Hepatectomy/mortality
• Humans
• Liver Neoplasms/mortality
• Liver Neoplasms/secondary
• Liver Neoplasms/therapy
• Neoadjuvant Therapy
• Neoplasm Staging
• Patient Selection
• Risk Factors
• Time Factors
• Treatment Outcome

Hepatic resection is the procedure of choice for curative treatment of colorectal liver metastases (CLM). Objectives of surgical strategy are low intraoperative blood loss, short liver ischemic times and minor postoperative morbidity and mortality. Blood loss is an independent predictor of mortality and compromises, in common with postoperative complications, long-term outcome after hepatectomy for CLM. The type of liver resection has no impact on the outcome of patients with CLM; wedge resections are not inferior to anatomical resections in terms of tumor clearance, pattern of recurrence or survival. Despite the lack of proof of survival benefit, routine lymphadenectomy has been advocated, allowing the detection of microscopic lymph node metastases and with prognostic value. In experienced hands, minimally invasive liver surgery is safe with acceptable morbidity and mortality and oncological results comparable to open hepatic surgery, but with reduced blood loss and earlier recovery. The European Colorectal Metastases Treatment Group recommended treating up front with chemotherapy for patients with both resectable and unresectable CLM. However, neoadjuvant chemotherapy can induce damage to the remnant liver, dependent on the number of chemotherapy cycles. Therefore, in our opinion, preoperative chemotherapy should be reserved for patients whose CLM are marginally resectable or unresectable. A meta analysis of randomized trials dealing with perioperative chemotherapy for the treatment of resectable CLM demonstrated a benefit of systemic chemotherapy but did not answer the question of whether a neoadjuvant or adjuvant approach should be preferred. Analysis of the literature demonstrates that the results of specialized centers cannot be attained in the reality of comprehensive patient care. Reasons behind the commonly poorer results seen in cancer networks as compared with literature-based data are, on the one hand, geographical disparities in access to specialized surgical and medical care. On the other hand, a selection bias in the reports of the literature may be assumed. Studies of surgical resection for CLM derive almost exclusively from case series generally drawn from large academic centers where patient selection or surgical expertise is superior to what is found in many communities. Therefore, we may conclude that the comprehensive propagation of the standards outlined in this paper constitutes a major task in the near future to reduce the variations in survival of patients with CLM.

• Liver metastases
• Colorectal cancer
• Surgery
• Chemotherapy
• Outcome

• Chemotherapy, Adjuvant
• Colorectal Neoplasms/drug therapy
• Colorectal Neoplasms/surgery
• Cooperative Behavior
• Hepatectomy
• Humans
• Interdisciplinary Communication
• Liver Neoplasms/drug therapy
• Liver Neoplasms/secondary
• Liver Neoplasms/surgery
• Minimally Invasive Surgical Procedures
• Patient Care Team

AIM: To investigate the effect of interstitial implantation of iodine-125 on the growth of adenocarcinoma of the large intestine and to explore potential mechanisms involved.

METHODS: Nude mice bearing HCT-116-xenografted tumors were randomly divided into two groups (n = 24 each): control group and experimental group. The control group underwent implantation of empty seeds, while the experiment group underwent implantation of iodine-125 seeds (14.8 MBq). On days 7, 14, 21 and 28 after implantation, mice were killed to calculate tumor growth, detect the expression of proliferating cell nuclear antigen (PCNA) in tumor tissue by immunohistochemistry, determine the apoptosis of tumor cells by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, and observe the ultrastructural changes of tumor cells by transmission electron microscopy (TEM).

RESULTS: On days 7, 14, 21 and 28 after implantation, both tumor volume and weight were significantly lower in the experiment group than in the control group (tumor volume on day 28: 497.3 mm3 ± 7.8 mm3 vs 947.2 mm3 ± 40.4 mm3, P < 0.01; tumor weight on day 28: 1.131 g ± 0.079 g vs 2.139 g ± 0.094 g, P < 0.01). The reduced rate of tumor growth in the experimental group was higher than that in the control group (on day 28: 47.12% vs 25.77%). The expression of PCNA in the experiment group decreased with time and was significantly lower on day 28 than that in the control group. On day 14, apoptotic bodies began to appear and then gradually increased in number, reaching the peak on day 28.

CONCLUSION: Interstitial implantation of iodine-125 seeds induces apoptosis but inhibits cell proliferation in HCT-116-xenografted tumors in nude mice.

• Iodine-125 seed
• Colorectal cancer
• Apoptosis
• Proliferating cell nuclear antigen

• Adult
• Aged
• Colorectal Neoplasms/pathology
• Colorectal Neoplasms/surgery
• Digestive System Surgical Procedures/methods
• Female
• Hepatectomy/methods
• Humans
• Hungary
• Liver Neoplasms/secondary
• Liver Neoplasms/surgery
• Male
• Middle Aged
• Retrospective Studies
• Treatment Outcome

The objective of this work is to evaluate a new concept of intraoperative three-dimensional (3D) visualization system to support hepatectomy. The Resection Map aims to provide accurate cartography for surgeons, who can therefore anticipate risks, increase their confidence and achieve safer liver resection.

In an experimental prospective cohort study, ten consecutive patients admitted for hepatectomy to three European hospitals were selected. Liver structures (portal veins, hepatic veins, tumours and parenchyma) were segmented from a recent computed tomography (CT) study of each patient. The surgeon planned the resection preoperatively and read the Resection Map as reference guidance during the procedure. Objective (amount of bleeding, tumour resection margin and operating time) and subjective parameters were retrieved after each case.

Three different surgeons operated on seven patients with the navigation aid of the Resection Map. Veins displayed in the Resection Map were identified during the surgical procedure in 70.1% of cases, depending mainly on size. Surgeons were able to track resection progress and experienced improved orientation and increased confidence during the procedure.

The Resection Map is a pragmatic solution to enhance the orientation and confidence of the surgeon. Further studies are needed to demonstrate improvement in patient safety.

Colorectal cancer is one of the most common cancers worldwide and the second most common type of cancer in the Western world. Colorectal cancer is the most common source of metastatic liver cancer, and liver metastasis is an important prognostic factor for colorectal cancer. Hepatic resection is the treatment of choice for colorectal liver metastases. The postoperative 5-year survival rate for patients with colorectal liver metastase now exceeds 50%. However, hepatic resection is indicated for only 10%-25% of patients with colorectal liver metastases. Therefore, non-surgical methods have attracted increasing attention. Permanent ¹²⁵I seed implantation is now becoming a hotspot for treatment of colorectal liver metastases. This review will focus on the recent advances in permanent ¹²⁵I seed implantation for colorectal liver metastases.

• Colorectal cancer
• Liver metastasis
• ¹²⁵I seed
• Brachytherapy