Endovascular Treatment of Tracheoinnominate Artery Fistula: Case Report and Literature Review With Pooled Cohort Analysis.

To pool data from published cases of tracheoinnominate artery fistula (TIF) treated with surgical or endovascular techniques along with reporting a case of similar presentation. A total of 261 cases in 137 published case reports and case series were identified through a comprehensive systematic literature review. Data regarding patient characteristics, treatment, and follow-up were extracted. A local case of a 14-year-old boy with TIF due to longstanding tracheostomy treated with stent-graft placement was added to the data. Comparison of the complication rates between surgical vs endovascular interventions was done with the chi-square test. Factors associated with longer survival were assessed by the Cox regression analysis. Thirty-three (12.6%) of the reported cases were treated endovascularly, 137 (52.3%) were treated surgically, and 92 (35.1%) were reported with no definitive treatment. Mean age was 34 ± 22 years, and 61% were males. The mean time interval between tracheotomy placement and bleeding was 1 ± 2.5 years. A lower procedure-related complication (30% vs 50%, P = 0.045) and 30-day mortality (9% vs 23%, P = 0.008) rates had been reported with percutaneous approaches compared to surgery. No percutaneous procedure was reported prior to year 2000. In multivariate analysis stratified by publication year, a shorter tracheostomy-to-bleeding time (year) was significantly associated with higher hazards of death (hazard ratio: 1.22, P = 0.017). Type of intervention (percutaneous vs surgery) was not associated with postintervention survival (adjusted hazard ratio: 0.78, P = 0.558). Endovascular stent grafting can have a comparable postprocedural survival and lower complication rates vs open surgical repair in treatment of TIF.

[18F]CFA as a clinically translatable probe for PET imaging of deoxycytidine kinase activity.

Deoxycytidine kinase (dCK), a rate-limiting enzyme in the cytosolic deoxyribonucleoside (dN) salvage pathway, is an important therapeutic and positron emission tomography (PET) imaging target in cancer. PET probes for dCK have been developed and are effective in mice but have suboptimal specificity and sensitivity in humans. To identify a more suitable probe for clinical dCK PET imaging, we compared the selectivity of two candidate compounds-[(18)F]Clofarabine; 2-chloro-2'-deoxy-2'-[(18)F]fluoro-9-ß-d-arabinofuranosyl-adenine ([(18)F]CFA) and 2'-deoxy-2'-[(18)F]fluoro-9-ß-d-arabinofuranosyl-guanine ([(18)F]F-AraG)-for dCK and deoxyguanosine kinase (dGK), a dCK-related mitochondrial enzyme. We demonstrate that, in the tracer concentration range used for PET imaging, [(18)F]CFA is primarily a substrate for dCK, with minimal cross-reactivity. In contrast, [(18)F]F-AraG is a better substrate for dGK than for dCK. [(18)F]CFA accumulation in leukemia cells correlated with dCK expression and was abrogated by treatment with a dCK inhibitor. Although [(18)F]CFA uptake was reduced by deoxycytidine (dC) competition, this inhibition required high dC concentrations present in murine, but not human, plasma. Expression of cytidine deaminase, a dC-catabolizing enzyme, in leukemia cells both in cell culture and in mice reduced the competition between dC and [(18)F]CFA, leading to increased dCK-dependent probe accumulation. First-in-human, to our knowledge, [(18)F]CFA PET/CT studies showed probe accumulation in tissues with high dCK expression: e.g., hematopoietic bone marrow and secondary lymphoid organs. The selectivity of [(18)F]CFA for dCK and its favorable biodistribution in humans justify further studies to validate [(18)F]CFA PET as a new cancer biomarker for treatment stratification and monitoring.