Perfusion-metabolism coupling in recurrent gliomas: a prospective validation study with 13N-ammonia and 18F-fluorodeoxyglucose PET/CT

Introduction

We assessed the validity of “perfusion-metabolism coupling” hypothesis in recurrent glioma with ¹³N-ammonia (¹³N-NH₃) PET/CT and ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET/CT.

Methods

Fifty-six consecutive patients (age, 38.8?±?12.1 years; 62.5 % males) with histologically proven and previously treated glioma presenting with clinical suspicion of recurrence were prospectively enrolled and evaluated with ¹³N-NH₃ PET/CT and ¹⁸F-FDG PET/CT. PET/CT images were evaluated both qualitatively and semiquantitatively. Tumor to white matter uptake ratio (T/W) and tumor to gray matter uptake ratio (T/G) were calculated and analyzed for both the modalities. A combination of clinico-radiological follow-up, repeated imaging, and biopsy (when available) were considered as the reference standard.

Results

Based on the reference standard, 27/56 patients had recurrence. ¹³N-NH₃ PET/CT and ¹⁸F-FDG PET/CT were concordant in 55/56 patients. Overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of ¹³N-NH₃PET/CT were 77.8, 86.2, 84.0, 80.7, and 82.1 %, respectively, and for ¹⁸F-FDG PET/CT were 77.8, 89.7, 87.5, 81.2, and 83.9 %, respectively. There was excellent agreement between results of ¹³N-NH₃ PET/CT and ¹⁸F-FDG PET/CT (??=?0.964; P?13N-NH₃ PET/CT and ¹⁸F-FDG PET/CT were not significantly different between high-grade and low-grade glioma (P?=?1.000). A strong positive correlation was noted between the uptake ratios derived on the two modalities (ρ?=?0.866, P?ρ?=?0.918, P?Conclusion A combination of ¹³N-NH₃ PET/CT and ¹⁸F-FDG PET/CT demonstrates that perfusion and metabolism are coupled in recurrent gliomas. These tracers target two different but interrelated aspects of the same pathologic process and can be used as surrogates for each other.     

Diagnostic accuracy of 18F-FDG PET/CT for detection of suspected recurrence in patients with oesophageal carcinoma

Purpose

To evaluate the role of ¹⁸F-FDG PET/CT in the detection of recurrence in patients with oesophageal carcinoma, suspected clinically or following conventional investigations.

Methods

This was a retrospective study. Data from 180 patients (age 56.3?±?10.4 years; 126 men, 54 women) with histopathologically proven oesophageal carcinoma (squamous cell 115, adenocarcinoma 59, neuroendocrine carcinoma 4, small cell 1, poorly differentiated 1) who had undergone 227 ¹⁸F-FDG PET/CT studies for suspected recurrence were analysed. Recurrence was suspected clinically or following conventional investigations. PET/CT images were revaluated by two nuclear medicine physicians in consensus. Findings were grouped into local, nodal and distant recurrence. Results were compared to those from contrast-enhanced (CE) CT when available (109 patients). Clinical/imaging follow-up (minimum 6 months) with histopathology (when available) was taken as the reference standard.

Results

Of the 227 ¹⁸F-FDG PET/CT studies,166 were positive and 61 were negative for recurrent disease. PET/CT showed local recurrence in 134, nodal recurrence in 115 and distant recurrence in 47, with more than one site of recurrence in 34. The PET/CT findings were true-positive in 153 studies, true-negative in 54, false-positive in 13 and false-negative in 7. The sensitivity of ¹⁸F-FDG PET/CT was 96 %, the specificity was 81 %, the positive and negative predictive values were 92 % and 89 %, respectively, and the accuracy was 91 %. PET/CT showed similar accuracy in patients with squamous cell carcinoma and in those with adenocarcinoma (P?=?0.181).¹⁸F-FDG PET/CT was more specific than CECT (67 % vs. 21 %; P?<?0.0001). PET/CT was superior to CECT for the detection of nodal recurrence (P?<?0.0001), but not local recurrence (P?=?0.093) or distant metastases (P?=?0.441).

Conclusion

¹⁸F-FDG PET/CT shows high accuracy in the detection of suspected recurrence in patients with oesophageal carcinoma. It is more specific than and is superior to CECT in the detection of nodal recurrence.     

Is sarcoma a complication of arterial femoro-popliteal bypass?

Angiosarcoma is a rare neoplasm comprising 1 to 2% of soft tissue sarcoma. This tumor has been associated with previous irradiation, exposure to toxins and the presence of foreign bodies. A case report of an epithelioid angiosarcoma that developed at the site of an arterial femoro-popliteal bypass using autologous vein is described. The initial presentation looked like a painful popliteal cyst. Chronic fibrosis secondary to the thrombosis could play a role in the tumorogenesis of this uncommon tumor. This case illustrates that sarcoma may be a late complication of vascular bypass and may have a rheumatologic presentation.     

Body mass index and response to tocilizumab in rheumatoid arthritis: a real life study

Several studies have suggested that obesity could have a negative effect on response to anti-tumor necrosis factor α (anti-TNFα) in rheumatoid arthritis (RA). Little is known about the impact of body mass index (BMI) on other biologic agents. We aimed to evaluate the effect of BMI on response to tocilizumab (TCZ) in RA. RA patients treated with TCZ were included in this multicenter retrospective study. BMI was calculated at the initiation of treatment. After 6 months of treatment, change from baseline in DAS28, pain on a visual analog scale, erythrocyte sedimentation rate and C-reactive protein level, and tender and swollen joints were analyzed. The primary endpoint was decrease in DAS28 ≥ 1.2. Secondary outcomes were good response and remission by EULAR criteria. At baseline, among 115 RA patients included, the median (interquartile range) BMI was 25.4 (22.0–28.8)?kg/m². The number of patients with normal weight, overweight, and obesity was 53 (46 %), 37 (32 %), and 25 (22 %), respectively. Baseline characteristics did not differ between the three subgroups of BMI. The median BMI did not differ between responders and non-responders for DAS28 decrease ≥1.2 (25.7 [22.1–29.9] vs 24.9 [22.0–27.1], P?=?0.38), EULAR good response (25.9 [22.8–30.0] vs 25.4 [22.0–28.4], P?=?0.61), and remission (25.1 [22.5–28.6] vs 25.4 [22.0–28.9], P?=?0.76). BMI did not affect the response to TCZ in RA. If confirmed, these results could be helpful for the selection of a biologic agent in obese RA patients.     

The Drosophila cacts2 mutation reduces presynaptic Ca2+ entry and defines an important element in Cav2.1 channel inactivation

Voltage-gated Ca2+ channels in nerve terminals open in response to action potentials and admit Ca2+, the trigger for neurotransmitter release. The cacophony gene encodes the primary presynaptic voltage-gated Ca2+ channel in Drosophila motor-nerve terminals. The cac(ts2) mutant allele of cacophony is associated with paralysis and reduced neurotransmission at non-permissive temperatures but the basis for the neurotransmission deficit has not been established. The cac(ts2) mutation occurs in the cytoplasmic carboxyl tail of the alpha1-subunit, not within the pore-forming trans-membrane domains, making it difficult to predict the mutation's impact. We applied a Ca2+-imaging technique at motor-nerve terminals of mutant larvae to test the hypothesis that the neurotransmission deficit is a result of impaired Ca2+ entry. Presynaptic Ca2+ signals evoked by single and multiple action potentials showed a temperature-dependent reduction. The amplitude of the reduction was sufficient to account for the neurotransmission deficit, indicating that the site of the cac(ts2) mutation plays a role in Ca2+ channel activity. As the mutation occurs in a motif conserved in mammalian high-voltage-activated Ca2+ channels, we used a heterologous expression system to probe the effect of this mutation on channel function. The mutation was introduced into rat Ca(v)2.1 channels expressed in human embryonic kidney cells. Patch-clamp analysis of mutant channels at the physiological temperature of 37 degrees C showed much faster inactivation rates than for wild-type channels, demonstrating that the integrity of this motif is critical for normal Ca(v)2.1 channel inactivation.     

Poor efficacy of TNF inhibitors in non-radiographic axial spondyloarthritis in the absence of objective signs: A bicentric retrospective study

Objective

To compare BASDAI 50 response rate to TNFi in axial spondyloarthritis (axSpA) depending on the presence or not of objective signs of axSpA and to look for predictive factors of TNFi efficacy.