CEA, CA19-9, circulating DNA and circulating tumour cell kinetics in patients treated for metastatic colorectal cancer (mCRC).

BACKGROUND: We previously reported that CEA kinetics are a marker of progressive disease (PD) in metastatic colorectal cancer (mCRC). This study was specifically designed to confirm CEA kinetics for predicting PD and to evaluate CA19-9, cell-free DNA (cfDNA), circulating tumour DNA (ctDNA) and circulating tumour cell (CTC) kinetics. METHODS: Patients starting a chemotherapy (CT) with pre-treatment CEA > 5 ng/mL and/or CA19.9 > 30 UI/mL were prospectively included. Samples were collected from baseline to cycle 4 for CEA and CA19-9 and at baseline and the sixth week for other markers. CEA kinetics were calculated from the first to the third or fourth CT cycle. RESULTS: A total of 192 mCRC patients were included. CEA kinetics based on the previously identified >0.05 threshold was significantly associated with PD (p < 0.0001). By dichotomising by the median value, cfDNA, ctDNA and CA19-9 were associated with PD, PFS and OS in multivariate analysis. A circulating scoring system (CSS) combining CEA kinetics and baseline CA19-9 and cfDNA values classified patients based on high (n = 58) and low risk (n = 113) of PD and was independently associated with PD (ORa = 4.6, p < 0.0001), PFS (HRa = 2.07, p < 0.0001) and OS (HRa = 2.55, p < 0.0001). CONCLUSIONS: CEA kinetics alone or combined with baseline CA19-9 and cfDNA are clinically relevant for predicting outcomes in mCRC. TRIAL REGISTRATION NUMBER: NCT01212510.

Diagnostic value of CA19.9, circulating tumour DNA and circulating tumour cells in patients with solid pancreatic tumours.

BACKGROUND: The direct comparison of CA19.9, circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA) using endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has never been performed for the diagnosis of solid pancreatic tumours (SPTs). METHODS: We included 68 patients with a SPT referred for EUS-FNA. CTCs were analysed using size-based platform and ctDNA using digital PCR. The sensitivity, specificity, negative and positive predictive values were evaluated for each marker and their combination. RESULTS: SPTs corresponded to 58 malignant tumours (52 pancreatic adenocarcinoma (PA) and 6 others) and 10 benign lesions. The sensitivity and specificity for PA diagnosis were 73% and 88% for EUS-FNA, 67% and 80% for CTC, 65% and 75% for ctDNA and 79% and 93% for CA19.9, respectively. The positivity of at least 2 markers was associated with a sensitivity and specificity of 78% and 91%, respectively. CtDNA was the only marker associated with overall survival (median 5.2 months for ctDNA+ vs 11.0 months for ctDNA-, P=0.01). CONCLUSIONS: CA19.9 alone and in combination with ctDNA and/or CTC analysis may represent an efficient method for diagnosing PA in patients with SPTs. Further studies including a larger cohort of patients with both malignant and benign lesions will be necessary to confirm these promising results.

Circulating tumor cell isolation: the assets of filtration methods with polycarbonate track-etched filters.

Circulating tumor cells (CTCs) arise from primary or secondary tumors and enter the bloodstream by active or passive intravasation. Given the low number of CTCs, enrichment is necessary for detection. Filtration methods are based on selection of CTCs by size using a filter with 6.5 to 8 µm pores. After coloration, collected CTCs are evaluated according to morphological criteria. Immunophenotyping and fluorescence in situ hybridization techniques may be used. Selected CTCs can also be cultivated in vitro to provide more material. Analysis of genomic mutations is difficult because it requires adapted techniques due to limited DNA materials. Filtration-selected CTCs have shown prognostic value in many studies but multicentric validating trials are mandatory to strengthen this assessment. Other clinical applications are promising such as follow-up, therapy response prediction and diagnosis. Microfluidic emerging systems could optimize filtration-selected CTCs by increasing selection accuracy.

Post-mortem computed tomography compared to forensic autopsy findings: a French experience.

OBJECTIVES: The principal aim of our study was to establish concordance between post-mortem CT (PMCT) and forensic standard autopsy (SA) in detecting lesions according to different anatomical regions. A secondary aim was to determine the efficacy of PMCT in showing lethal lesions. METHODS: PMCTs were compared with autopsies in 236 cadavers in different contexts of death. PMCT findings were assessed by two independent radiologists. RESULTS: Concordance between PMCT and autopsy was almost perfect in showing skull, basal skull and hyoid bone fractures as well as in detecting facial, vertebral or pelvic fractures. Both examinations were discordant in demonstrating some intracranial injuries, vascular or organ wounds (more findings showed by autopsy), as well in showing free air in anatomical cavities (more findings detected by PMCT). Moreover, PMCT was effective in determining lethal lesions in the context of craniofacial trauma or after a gunshot wound. Concordance between the findings of the two radiologists was almost perfect for each type of lesion. CONCLUSION: PMCT could be considered as effective as SA in determining the cause of death in certain traumatic events. It was also effective in showing lethal lesions and could be a useful tool in reducing the number of SA. KEY POINTS: • Post-mortem CT is increasingly performed as an alternative/adjunct to formal autopsy. • More modern CT systems provide greater anatomical scope. • PMCT can usually determine the cause of most deaths following trauma. • Prospective studies are still required to establish an algorithm for forensic CT.

A brain penetration after Taser injury: controversies regarding Taser gun safety.

We report the case of a 27 year old man who was injured by a Taser gun device which penetrated the frontal part of the skull and damaged the underlying frontal lobe. Cerebral penetration was revealed by a brain CT scan. A neurosurgical procedure was required to remove the dart from the skull and brain and the evolution was successful allowing discharge of the patient one week later. There were no additional lesions, particularly electrifying lesion, as only one probe had penetrated the skull. We also observed the length of a Taser dart is sufficient to allow brain penetration. Fortunately, no infection or neurological complication occurred following brain injury. This case study underlines the potential risk induced by the use of Taser stun gun. Although generally regarded as a safe alternative, serious injuries have however been reported and questions regarding the safety of the device still remains unresolved.