Retrospective real-life study on preoperative imaging for minimally invasive parathyroidectomy in primary hyperparathyroidism.

The objective of this study was to retrospectively evaluate preoperative imaging modalities for localization of parathyroid adenomas with a view to enable minimally invasive parathyroidectomy and in particular, to consider the contribution of 18F-fluorocholine-PET/CT. 104 patients with primary hyperparathyroidism, who underwent parathyroid surgery in a single centre during a 6-year period were included. Of these, 103 underwent ultrasound, 97 99mTc-Pertechnetate/SestaMIBI-SPECT, 20 MRI and 30 18F-fluorocholine-PET/CT. Based on surgical findings, sensitivities and specificities for correct lateralisation in orthotopic locations were: for ultrasound 0.75 (0.65-0.83) and 0.89 (0.81-0.94), for 99mTc-MIBI-SPECT 0.57 (0.46-0.67) and 0.97 (0.91-0.99), for MRI 0.60 (0.36-0.81) and 0.83 (0.59-0.96) and for 18F-fluorocholine-PET/CT 0.90 (0.73-0.98) and 0.90 (0.73-0.98). Correctly lateralized adenomas were significantly larger than those not found with ultrasound (p = 0.03) and SPECT (p = 0.002). Pre-operative PTH-levels were higher in single adenomas detected by scintigraphy than in those not (p = 0.02). 64 patients could be treated with a minimally invasive procedure. Cure after parathyroidectomy was obtained in 94% of patients. 18F-Fluorocholine-PET/CT could be shown to be a highly accurate modality to localize parathyroid adenomas preoperatively, obviating the need for total exploration in the majority of patients in whom ultrasound and scintigraphic results are discordant or both negative.

Chimeric antigen receptor T-cell therapy: design improvements and therapeutic strategies in cancer treatment.

Objectives: To summarize important findings from research on chimeric antigen receptor (CAR) T-cell immunotherapy in cancer. We discuss CAR design, cell products, toxicity management, heterogenous solid tumors and allogeneic transfer.Methods: A review of literature was conducted. The available literature was selected on original research, state-of-the art design, relevance to the objective and journal impact factor.Results: First-generation CARs provide patient T cells with tumor-specific antigen recognition. Second- and third-generation CARs incorporate costimulatory domains for enhanced T-cell persistence and antitumor activity. Fourth-generation CAR T cells (TRUCKs) include a cytokine production cassette, and hold promise in the treatment of heterogenous solid tumors. Transduced cell phenotype and subset composition are important factors. Suicide genes and safety switches are designed to decrease potential toxicity. Multi-specific CAR T cells can address heterogenous tumors. Allogeneic, off-the-shelf CAR T cells might reduce the production delay.Conclusion: CAR T cells have revolutionized the immunotherapeutic treatment of cancer: exciting results in refractory and relapsed B-cell malignancies have been published. Neurologic complications, solid tumor management and allogeneic constructs require further research. In conclusion, further design adjustments will enable CAR T cells to decisively reshape the field of cancer immunotherapy.