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Diagnostic Value of Diffusion-weighted Magnetic Resonance in High-risk Colorectal and Appendiceal Neoplasms

ABSTRACT: Diffusion-weighted magnetic resonance imaging (DWI/MRI) has been described in recent literature as a highly sensitive and specific modality for the detection of peritoneal metastases PM. It has been demonstrated to be superior to CT for patients with known peritoneal disease from colorectal and gynaecological malignancies as a staging tool for cytoreductive surgery. It was also demonstrated to be superior for the detection of PM for gastric cancer patients otherwise considered with a resectable tumor. However, the literature is scarce on the role of DWI/MRI in the detection of peritoneal recurrence for patients with high-risk features, either colorectal cancer (CRC) or appendiceal neoplasms (AN). The aim of this study is to prospectively assess the added value of whole-body DWI/MRI (WB-DWI/MRI) to CT and diagnostic laparoscopy for detection of PM in the follow-up of patients presenting with CRC or AN and high-risk features for peritoneal recurrence and evaluate how it correlates with intraoperative findings.

DISEASE(S): Peritoneal Neoplasms,Carcinoma,Appendix Cancer,Colorectal Cancer,Appendix Neoplasm,Appendiceal Neoplasms,Peritoneal Carcinomatosis,Neoplasms,Peritoneal Metastases

PROVIDER: 461 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:The aim of the study is to assess the value of whole body diffusion weighted MR imaging (WB-DWI) as a non-invasive method. On one hand for pretreatment lesion detection and post-therapeutic tumor recurrence but also for early therapy monitoring with the intention to early identify patients with a poor tumor response. Our research group demonstrated that this technique is accurate in patients with head and neck cancer it could differentiate between viable tumor tissue and inflammatory or necrotic tissue at variable time points after completion of radiotherapy. In the literature it is stated that DWI can also predict the response to chemotherapeutic therapy. This is only true for focal MRI images (eg only in liver). This study aims to determine whether the whole body technique can efficiently be used because the distribution of metastases is systemic. The study includes two phases: In a first phase, a baseline study will be conducted; all possible injury types will be gathered to determine the variability in signal characteristics to finally determine appropriate thresholds to differentiate between benign and malignant lesions. This should allow us later on to perform prospective studies. In a second phase, different applications such as: * pretherapeutic staging * Detection of post-therapy recurrence * Early evaluation of systemic cytotoxic therapy. The results of the DW-MRI will be compared with those of PET, CT and conventional MRI which are now routinely performed for the diagnosis of colorectal tumors. The scans will be performed in a group of patients on a 3 Tesla MR system. This system is fully approved by the European and American standards and the patients will not be exposed to radiation or contrast agents. In principle, all patients treated for gastrointestinal cancer were included after informed consent from the patient. This study is important to investigate whether DWI is accurate in the pre-therapeutic injury detection and staging of gastrointestinal tumors compared with PET / CT and DWI. In addition it is important to predict the outcome after therapy.

Project description:Peritoneal dialysis (PD) is the worldwide recognized preferred dialysis treatment for children affected by end-stage kidney disease (ESKD). However, due to the unphysiological composition of PD fluids, the peritoneal membrane (PM) of these patients may undergo structural and functional alterations, which may cause fibrosis. Several factors may accelerate this process and primary kidney disease may have a causative role. In particular, patients affected by corticoresistant primary focal segmental glomerulosclerosis), a rare glomerular disease leading to nephrotic syndrome and ESKD, seem more prone to develop peritoneal fibrosis. The mechanism causing this predisposition is still unrecognized. To better define this condition, we carried out, for the first time, a new comprehensive comparative proteomic mass spectrometry analysis of mesothelial exosomes from peritoneal dialysis effluent (PDE) of 6 pediatric patients with focal segmental glomerular sclerosis (FSGS) versus 6 patients affected by other primary renal diseases (No FSGS). Our omic study demonstrated that, despite the high overlap in the protein milieu between the two study groups, machine learning allowed a complete distinction of the whole proteomic exosome mesothelial content of FSGS versus No FSGS (with 100% accuracy). Out of the 2490 identified proteins, 40% (995) were involved in epithelial-mesenchymal transition (EMT)/fibrosis and in the transforming growth factor-β pathway. Additionally, the Weight Gene Co-expression Network Analysis algorithm identified that some of the discriminative proteins (TIMP1, CTHRC1, SPARC, CHMP4B, COL5A2, ANXA13, FNC2 and CENP-E) were also highly correlated to PD vintage, fibrosis, EMT and non-neoplastic PM disease. All together our data demonstrated that mesothelial cells of FSGS patients are more prone to activate a pro-fibrotic machinery with exosomes having a primary role in this process. Moreover, they indicated that identified FSGS-associated elements in mesothelial exosome protein could be employed as potential new biomarkers of mesothelial integrity. Finally, our results highlighted that in FSGS patients particular attention should be paid to use more biocompatible dialysis solution, reduce the length of time on PD and personalize PD regimens to minimize the risk of rapid loss of PM function or development of encapsulating peritoneal sclerosis.

Project description:While hyperthermia has been shown to be an effective adjuvant anti-tumor treatment to radiotherapy, we still do not completely understand effects thermoradiotherapy on tumor phenotype or how these effects vary among different tumors. Here, we performed gene expression analysis in 22 spontaneous canine sarcomas before and after the first hyperthermia treatment that was administered as an adjuvant to radiotherapy. Diffusion weighted MRI (DWI) was done prior to the treatment course and at the end of therapy. Using supervised analysis, we identified significant correlation of DWI with several genes involved in VEGF signaling, telomerase, Wnt pathways and fatty acid synthesis. When the change of gene expression caused by treatment was examined, we found that thermoradiotherapy led to the induction of well known cycle regulators p21 and mdm2 and reduced cellular proliferation in most treated tumors. We also identified two tumor subtypes with dramatic differences in the gene expression response and treatment response at the end of therapy. In the subtype with strong expression and increase in DWI, the mRNA level of hsp70, POT1 and centrosomal proteins was significantly higher. In the other subtype with modest response to hyperthermia, levels of CD31, vWF and transferrin was noted to be significantly higher. It is also possible to build a predictive model based on the pre-treatment gene expression to predict the likely treatment response of the tumors. The differential expression between the two tumor subtypes was used to interrogate connectivity map and identify linkages to an HDAC inhibitor and geldanamycin, an HSP90 inhibitor. Both HDAC inhibitors and hsp90 inhibitor geldanamycin are shown to synergerize with thermoradiotherapy in reducing cell survival in clonogenic assays. Taken together, the gene expression studies of hyperthermia-treated spontaneous canine tumors shed mechanistic insights into the heterogeneity of thermoradiotherapy response and identified pathway-targeting compounds with synergistic potential to enhance its therapeutic benefits. To our knowledge, this is one of the first successful attempts to link genomic and functional imaging changes together. This is the first demonstration of using such associations to understand the connection between cellular and physiologic responses to treatment. gene expression analysis in 22 spontaneous canine sarcomas before and after the first hyperthermia treatment that was administered as an adjuvant to radiotherapy.

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Diagnostic Value of Diffusion-weighted Magnetic Resonance in High-risk Colorectal and Appendiceal Neoplasms

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