Multisciplinary management of patients with liver metastasis from colorectal cancer

Colorectal cancer(CRC) is one of the leading causes of cancer-related death. Surgery, radiotherapy and chemotherapy have been till now the main therapeutic strategies for disease control and improvement of the overall survival. Twenty-five per cent(25%) of CRC patients have clinically detectable liver metastases at the initial diagnosis and approximately 50% develop liver metastases during their disease course. Twentythirty per cent(20%-30%) are CRC patients with metastases confined to the liver. Some years ago various studies showed a curative potential for liver metastases resection. For this reason some authors proposed the conversion of unresectable liver metastases to resectable to achieve cure. Since those results were published, a lot of regimens have been studied for resectability potential. Better results could be obtained by the combination of chemotherapy with targeted drugs, such as anti-VEGF and antiEGFR monoclonal antibodies. However an accurate selection for patients to treat with these regimens and to operate for liver metastases is mandatory to reduce the risk of complications. A multidisciplinary team approach represents the best way for a proper patient management. The team needs to include surgeons, oncologists, diagnostic and interventional radiologists with expertise in hepatobiliary disease, molecular pathologists, and clinical nurse specialists. This review summarizes the most important findings on surgery and systemic treatment of CRC-related liver metastases.

Digestive oncologist in the gastroenterology training curriculum

Until the late 1980s, gastroenterology (GE) was considered a subspecialty of Internal Medicine. Today, GE also incorporates Hepatology. However, Digestive Oncology training is poorly defined in the Hepatogastroenterology (HGE)-curriculum. Therefore, a Digestive Oncology curriculum should be developed and this document might be a starting point for such a curriculum. HGE-specialists are increasingly resisting the paradigm in which they play only a diagnostic and technical role in the management of digestive tumors. We suggest minimum endpoints in the standard HGE-curriculum for oncology, and recommend a focus year in the Netherlands for Digestive Oncology in the HGE-curriculum. To produce welltrained digestive oncologists, an advanced Digestive Oncology training program with specific qualifications in Digestive Oncology (2 years) has been developed. The schedule in Belgium includes a period of at least 6 mo to be spent in a medical oncology department. The goal ofthese programs remains the production of well-trained digestive oncologists. HGE specialists are part of the multidisciplinary oncological teams, and some have been administering chemotherapy in their countries for years. In this article, we provide a road map for the organization of a proper training in Digestive Oncology. We hope that the World Gastroenterology Organisation and other (inter)national societies will support the necessary certifications for this specific training in the HGE-curriculum.

Limited influences of chemotherapy on healthy and metastatic liver parenchyma

AIM: To examine the expression of E-cadherin, β-catenin,γ-catenin, VEGF, and p53 in 39 patients with hepatic metastasis from colorectal cancer immunohistochemically.METHODS: The patients were divided into two groups:those (n = 16) who had no chemotherapy for at least 6 mo before the liver resections and those (n = 23)who were treated with chemotherapy before liver resections. A score from 0 to 3 was given for the number of positive cells and from 0 to 3 for the intensity of staining in these cells, in both healthy and metastatic liver parenchyma.RESULTS: No significant differences in the expression of E-cadherin, β- and γ-catenin, VEGF and p53, could be observed between patients who received and did not receive chemotherapy, in both normal and metastatic liver parenchyma.CONCLUSION: Despite the assumption that chemotherapy had an effect on liver metastasis, no influences were noticed immunohistochemically.

Establishment of head and neck squamous cell carcinoma mouse models for cetuximab resistance and sensitivity

Aim:Acquired resistance to the targeted agent cetuximab poses a significant challenge in finding effective anti-cancer treatments for head and neck squamous cell carcinoma(HNSCC).To accurately study novel combination treatments,suitable preclinical mouse models for cetuximab resistance are key yet currently limited.This study aimed to optimize an acquired cetuximab-resistant mouse model,with preservation of the innate immunity,ensuring intact antibody-dependent cellular cytotoxicity(ADCC)functionality.Methods:Cetuximab-sensitive and acquired-resistant HNSCC cell lines,generated in vitro,were subcutaneously engrafted in Rag2 knock-out(KO),BALB/c Nude and CB17 Scid mice with/without Matrigel or Geltrex.Once tumor growth was established,mice were intraperitoneally injected twice a week with cetuximab for a maximum of 3 weeks.In addition,immunohistochemistry was used to evaluate the tumor and its microenvironment.Results:Despite several adjustments in cell number,cell lines and the addition of Matrigel,Rag2 KO and BALB/C Nude mice proved to be unsuitable for xenografting our HNSCC cell lines.Durable tumor growth of resistant SC263-R cells could be induced in CB17 Scid mice.However,these cells had lost their resistance phenotype in vivo.Immunohistochemistry revealed a high infiltration of macrophages in cetuximab-treated SC263-R tumors.FaDu-S and FaDu-R cells successfully engrafted into CB17 Scid mice and maintained their sensitivity/resistance to cetuximab.Conclusion:We have established in vivo HNSCC mouse models with intact ADCC functionality for cetuximab resistance and sensitivity using the FaDu-R and FaDu-S cell lines,respectively.These models serve as valuable tools for investigating cetuximab resistance mechanisms and exploring novel drug combination strategies.