PurposeMetastasectomy is a common treatment option for patients with colorectal lung metastases (CLM). Challenges exist with margin assessment and identification of small nodules, especially during... Show morePurposeMetastasectomy is a common treatment option for patients with colorectal lung metastases (CLM). Challenges exist with margin assessment and identification of small nodules, especially during minimally invasive surgery. Intraoperative fluorescence imaging has the potential to overcome these challenges. The aim of this study was to assess feasibility of targeting CLM with the carcinoembryonic antigen (CEA) specific fluorescent tracer SGM-101.MethodsThis was a prospective, open-label feasibility study. The primary outcome was the number of CLM that showed a true positive fluorescence signal with SGM-101. Fluorescence positive signal was defined as a signal-to-background ratio (SBR) ≥ 1.5. A secondary endpoint was the CEA expression in the colorectal lung metastases, assessed with the immunohistochemistry, and scored by the total immunostaining score.ResultsThirteen patients were included in this study. Positive fluorescence signal with in vivo, back table, and closed-field bread loaf imaging was observed in 31%, 45%, and 94% of the tumors respectively. Median SBRs for the three imaging modalities were 1.00 (IQR: 1.00–1.53), 1.45 (IQR: 1.00–1.89), and 4.81 (IQR: 2.70–7.41). All tumor lesions had a maximum total immunostaining score for CEA expression of 12/12.ConclusionThis study demonstrated the potential of fluorescence imaging of CLM with SGM-101. CEA expression was observed in all tumors, and closed-field imaging showed excellent CEA specific targeting of the tracer to the tumor nodules. The full potential of SGM-101 for in vivo detection of the tracer can be achieved with improved minimal invasive imaging systems and optimal patient selection. Show less
Purpose: It is suggested that tumour markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) could be used to predict the stage of pancreatic cancer. However, optimal cut-off... Show morePurpose: It is suggested that tumour markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) could be used to predict the stage of pancreatic cancer. However, optimal cut-off values for CEA and CA19-9 are disputable. This study aimed to assess the value of CEA and CA19-9 serum levels at diagnosis of pancreatic ductal adenocarcinoma (PDAC) as predictors for the advanced stage of PDAC in patients discussed at pancreatic multidisciplinary team (MDT) meetings. Methods: Patients with suspected PDAC discussed at MDT meetings from 2013 to 2017 were reviewed, in order to determine optimal cut-off values of both CEA and CA19-9. Results: In total, 375 patients were included. Optimal cut-off values for predicting advanced PDAC were 7.0 ng/ml for CEA and 305.0 U/ml for CA19-9, resulting in positive predictive values of 83.3%, 73.6%, and 91.4% for CEA, CA19-9 and combined, respectively. Both tumour markers were independent predictors of advanced PDAC, demonstrated by an odds ratio of 4.21 (95% CI:1.85-9.56; p = 0.001) for CEA and 2.58 for CA19-9 (95% CI:1.30-5.14; p = 0.007). Conclusions: CEA appears to be a more robust predictor of advanced PDAC than CA19-9. Implementing CEA and CA19-9 serum levels during MDT meetings as an additional tool for establishing tumour resectability is worthwhile for tailored diagnostics. Show less
The studies described in this thesis focus on the feasibility of using carcinoembryonic antigen (CEA) as a target for immunotherapy of colorectal cancer and on the balance between anti-tumor... Show moreThe studies described in this thesis focus on the feasibility of using carcinoembryonic antigen (CEA) as a target for immunotherapy of colorectal cancer and on the balance between anti-tumor immunity and autoimmune pathology. The potential of CEA as a target antigen for immunotherapy of cancer is conceivably restricted by the fact that CEA is expressed in several abundant and vital tissues, including intestine and stomach, and is even routinely found in the serum of healthy individuals. We demonstrate that the CEA-specific CD4+ T-cell repertoire in CEA-tg mice is severely limited compared to wild-type mice and that this CD4+ T-cell tolerance for CEA was induced by the thymus. In addition we showed that CEA was expressed in medullary thymic epithelial cells (mTEC) in both mice and human beings. The latter suggests that the CEA-specific T-cell repertoire may also be tolerized in people. In further studies we have focussed on possibilities to overcome tolerance of CEA by reconstituting the T-cell repertoire of CEA-tg mice by adoptive transfer of the T-cell repertoire of CEA-immunized wild-type mice into tumor-bearing CEA-tg mice. Adoptive transfer in combination with immune modulation can result in efficient eradication of CEA-positive tumors. However, in order to prevent hazardous CEA-specific autoimmune reactions, the choice of the right immune modulation protocol is critical. Show less
