Is antigen specificity the key to efficient adoptive T-cell therapy?

Adoptive transfer of T cells remains a promising approach in melanoma. Initial clinical trials performed with polyclonal tumor-infiltrating lymphocyte gave limited clinical results. Nonetheless, encouraging results have been reported in adjuvant setting (stage III melanoma), and when tumor-infiltrating lymphocytes were associated with lymphodepleting regimens. Specificity of adoptive cell therapy has been achieved with the infusion of antigen specific cytotoxic T-lymphocyte clones, associated with some clinical responses. Antigen specificity can also be obtained by the allogeneic transfer of high-avidity T-cell receptors into autologous T cells. We propose an alternative strategy based on the selection of antigen-specific T cells with magnetic beads coated with HLA-peptide multimers. Future improvements of adoptive melanoma immunotherapy may be achieved by its association with other therapeutic strategies such as targeted therapy against signaling pathways.     

The effect of genital and lower urinary tract symptoms on steroid receptor expression in women with genital prolapse

Introduction and hypothesis  

This study evaluates the expression of estrogen receptor (ER) isoforms alpha (α) and beta (β) and progesterone receptor (PR) in vaginal and periurethral tissue in women with genital prolapse in relation to genital and lower urinary tract symptoms (LUTS).     

Prospective electrocardiography-triggered CT angiography of the great thoracic vessels in infants and toddlers with congenital heart disease: feasibility and image quality

PurposeTo investigate feasibility and image quality and to calculate radiation dose estimates for computed tomography angiography (CTA) of the great thoracic vessels in infants and toddlers with congenital heart disease (CHD) using end-systolic prospective electrocardiography-triggered sequential dual-source data acquisition.MethodsThis study was institutional review board approved; informed consent was obtained. Twenty children (age 1.2 ± 1.1 years) underwent 22 prospective ECG-triggered sequential dual-source CTA examinations (Somatom Definition, Siemens) with tube current (250 mAs/rot) centered at 250 ms past the R-peak in the cardiac cycle (end-systole). Tube voltage was set to 80 kV. Image quality was evaluated by two readers independently using a four-point grading scale (4 = excellent, 1 = non-diagnostic). Radiation dose estimates were calculated from the dose-length-product (DLP).ResultsAll CT images showed diagnostic image quality (mean score 3.67 ± 0.67, κ = 0.85). Stair-step artifacts were present in one and breathing artifacts in 4 patients, with neither impairing diagnostic image quality. Mean heart rate (bpm) was 107.6 ± 12.1 (76–130), mean heart rate variability (bpm) was 2.5 ± 2.0 (1–9). Mean scan length (mm) was 90.7 ± 22.7 (50–134). Mean estimated effective dose was 0.32 ± 0.11 mSv.ConclusionProspective ECG-triggered sequential dual source CTA is feasible in infants and toddlers with CHD, thereby allowing almost motion-free imaging of the great thoracic vessels with the benefit of a low radiation dose.     

Increased incidence of Leydig cell tumours of the testis in the era of improved imaging techniques

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Leydig cell tumours (LCTs) of the testis are rare tumours, accounting for 1–3% of all testicular neoplasms. Our data indicate that using scrotal ultrasound with high resolution imaging in routine checkups leads to an earlier detection of LCTs. Most patients underwent an organ‐sparing surgery and no androgen deprivation was observed.

OBJECTIVE

? To report an observed high frequency of Leydig cell tumours (LCTs) diagnosed at our centre.

PATIENTS AND METHODS

? Charts of all patients who underwent surgery for a testicular tumour between 1999 and 2008 at our department were searched and data from patients with LCT were collected. ? Before surgery all patients underwent ultrasound and complete staging. In all but two patients with LCT an organ‐sparing surgery was performed. Surgery was performed under ultrasound or palpation guidance. ? All patients underwent postoperative follow‐up. We retrospectively reviewed surgical technique, histology, epidemiology and outcome in all LCT patients.

RESULTS

? In the study period, 197 testicular tumours were surgically removed of which 29 were diagnosed as LCT (14.7% of 197; further study group) in 25 patients. Mean age of patients with LCT was 45 years (range 21–68 years). ? Tumour size ranged from 1.2 to 80 mm (mean 10.23 mm). In two patients (8%) the lesion was palpable whereas incidental diagnosis was made in seven patients (28%). ? In the remaining patients diagnosis was made by ultrasound performed for testicular pain (six patients, 24%) or during infertility or erectile dysfunction evaluation (10 patients, 40%). ? Definitive histology reported no malignant histopathological features in all but one patient; this particular patient experienced tumour progression after 2 months and died from advanced disease 1 year later. All other patients are free of disease after a mean follow up of 56 months (range 7–93 months). ? During this period one patient developed a second LCT on the contralateral side; another patient had a recurrence within the same testicle, but on the opposite pole. Both underwent a subsequent organ‐sparing tumour resection.

CONCLUSION

? The percentage of LCT (14.7% of all testicular tumours removed) was significantly higher than expected from the literature. One possible explanation for this phenomenon is the increasing use of better ultrasound technology and the subsequent increased detection of small nodules that have not been found in historical series. Use of ‘observation‐only’ for very small lesions detected at infertility clinics is under debate.