Κυριακή 2 Οκτωβρίου 2022

Molecular landscapes of longitudinal NF2/22q and non‐NF2/22q meningiomas show different life histories

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Abstract

Recurrence is a major complication of some meningiomas. Although there were many studies on biomarkers associated with higher grades or increased aggressiveness, few studies specifically examined longitudinal samples of primary meningiomas and recurrences from the same patients for molecular life history. We studied 99 primary and recurrent meningiomas from 42 patients by FISH for 22q, 1q, 1p, 3p, 5q, 6q, 10p, 10q, 14q, 18q, CDKN2A/B homozygous deletion, ALT (Alternative Lengthening of Telomere), TERT re-arrangement, targeted sequencing and TERTp sequencing. Although NF2 mutation and 22q were well known to be aetiological events in meningiomas, we found that in these paired meningiomas, combining the two events resulted in an NF2/22q group (57 tumors from 25 patients) which were almost mutually exclusive with those cases without these two changes (42 tumors from 17 patients) for NF2/22q. No other molecular changes were totally unique to NF2/22q or non-NF2/22q tumors. For molecular evolution, NF2/22q meningiomas had higher cytogenetic abnormalities than non-NF2/22q meningiomas (p = 0.003). Most of the cytogenetic changes in NF2/22q meningiomas were present from the outset whereas for non-NF2/22q meningiomas, cytogenetic events were uncommon in the primary tumors and most were acquired in recurrences. For non-NF2/22q tumors, CDKN2A/B homozygous deletion, 1q gain, 18p loss, 3p loss, and ALT were preferentially found in recurrences. Mutations were largely conserved between primary and recurrent tumors. Phylogenetic trees showed 11/11 patients with multiple recurrent tumors had a conserved evolutionary pattern. We conclude that for molecular life history, NF2 and 22q should be regarded as a group. NF2/22q recurring meningiomas showed more cytogenetic abnormalities in the primary tumors, whereas non-NF2/22q meningiomas showed C DKN2A/B deletion and other cytogenetic abnormalities and ALT at recurrences. Although chromosome 1p loss is a known poor prognostic marker in meningiomas, it was also associated with a shorter TBR (time between resection) in this cohort (p = 0.002).

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Genetic Polymorphism in the Tumor Necrosis Factor Alpha gene (G‐308A) is associated with Persistent Apical Periodontitis in Brazilians

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Abstract

Aim

To investigate if there was an association between genetic polymorphisms in TNF-⍺ and its receptors TNFRSF1A and TNFRSF1B with persistent apical periodontitis (PAP) in Brazilian subjects.

Methodology

Patients who had pulpal necrosis and apical periodontitis installed at the time of treatment, with at least one-year of follow-up after non-surgical root canal treatment were recalled. 378 subjects were included, 150 subjects with signs/symptoms of PAP and 228 subjects with root canal–treated teeth exhibiting healthy perirradicular tissues (healed). Genomic DNA was extracted from saliva and used for TNF-⍺ (rs1800629), TNFRSF1A (rs1800693) and TNFRSF1B (rs1061622) genotyping by real-time PCR. Genotypes and alleles frequencies were evaluated by c2 or Fisher's exact tests and odds ratio were implemented (𝛂= 5%).

Results

The genetic polymorphism in TNF-α (rs1800629) was associated as a protective factor for the development of PAP (p<0.05), once subjects who presented at least one allele A (AA+AG X GG), had a higher chance to lesion repair (p<0.05). The polymorphisms rs1800693 and rs1061622 in TNF receptors (TNFRSF1A and TNFRSF1B respectively) were not associated with the development of PAP (p>0.05).

Conclusions

The observed results demonstrate that polymorphism in TNF-α but not in its receptors is associated with PAP.

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Πέμπτη 29 Σεπτεμβρίου 2022

Long-term Locoregional Control With Unilateral Radiation for AJCC-7 T1-2N2b Tonsillar Cancer

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imageObjectives: Unilateral radiation to cervical nodes has been used as a de-escalation strategy in well-lateralized tonsil cancers. The efficacy of this approach with multiple ipsilateral nodes is not established. The study hypothesis was that unilateral radiation for American Joint Committee on Cancer (AJCC)-7 T1-2N2b tonsillar cancer results in a low rate of contralateral nodal failure. Materials and Methods: This study was a retrospective chart review of patients with AJCC-7 T1-2N2b tonsillar cancer from 2 academic institutions who were treated with unilateral radiation. The primary endpoint was the contralateral nodal failure rate. Locoregional control, overall survival, and the need for gastrostomy tube placement were additional endpoints. Results: The study cohort included 66 patients treated between 2005 and 2016. The median follow-up time was 80.9 months; contralateral nodal failure occurred in 2/66 (3.0%) patients at 4.1 and 20.9 months, respectively. Both patients underwent salvage treatment with long-term subsequent survival. Overall locoregional control at both 2 and 5 years was 93.9% and the median duration of control was not reached. Overall survival at 5 years was 92.4%. Conclusions: The use of unilateral radiation for AJCC-7 T1-2N2b tonsillar cancer resulted in low rates of contralateral nodal failure. This outcome demonstrates the safety of considering unilateral radiation treatment in patients with a relatively high ipsilateral nodal burden.
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The French FRACTURE database: A way to improve knowledge on management of children with very rare tumors

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Abstract

Introduction

Very rare pediatric tumors (VRTs), defined by an annual incidence ≤2 per million inhabitants, represent a heterogeneous group of cancers. Due to their extremely low incidence, knowledge on these tumors is scant. Since 2012, the French Very Rare Tumors Committee (FRACTURE) database has recorded clinical data about VRTs in France. This study aims: (a) to describe the tumors registered in the FRACTURE database; and (b) to compare these data with those registered in the French National Registry of Childhood Cancer (RNCE).

Methods

Data recorded in the FRACTURE database between January 1, 2012 and December 31, 2018 were analyzed. In addition, these data were compared with those of the RNCE database between 2012 and 2015 to evaluate the completeness of the documentation and understand any discrepancies.

Results

A total of 477 patients with VRTs were registered in the FRACTURE database, representing 97 histological types. Of the 14 most common tumors registered in the RNCE (772 patients), only 19% were also registered in the FRACTURE database. Total 39% of children and adolescent VRTs registered in the RNCE and/or FRACTURE database (323 of a total of 828 patients) were not treated in or linked to a specialized pediatric oncology unit.

Conclusion

VRTs represent many different heterogenous entities, which nevertheless account for 10% of all pediatric cancers diagnosed each year. Sustainability in the collection of these rare tumor cases is therefore important, and a regular systematic collaboration between the FRACTURE database and the RNCE register helps to provide a more exhaustive picture of these VRTs and allow research completeness for some peculiar groups of patients.

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Management of acute intra‐abdominal hemorrhage in ruptured hepatoblastoma with transarterial embolization using calibrated gelfoam particles

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Abstract

This brief report aims to evaluate the treatment outcome of transarterial embolization in ruptured hepatoblastoma complicated with acute intra-abdominal hemorrhage. Three children (mean age 6 years) with high-risk hepatoblastoma presented with rupture and acute intra-abdominal hemorrhage. In addition to aggressive fluid resuscitation and blood product support, super-selective embolization of the arteries with active bleeding or pseudoaneurysm was performed using calibrated gelfoam particles, with a technical success rate of 100%. Hemodynamic status and hemoglobin level were normalized in all patients within 2 days postembolization. The 30-day survival rate was 100%. No major complication was detected apart from mild elevation of alanine transaminase.

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Controlling Nutritional Status (CONUT) score is a prognostic marker for laryngeal cancer patients with curative resection

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Abstract

Background

To investigate the prognostic value of pre-treatment Controlling Nutritional Status (CONUT) score in laryngeal cancer.

Methods

Preoperative CONUT score was retrospectively calculated in 154 laryngeal cancer patients who underwent curative resection in our hospital from 2013 to 2016. The associations of CONUT with clinicopathological factors and survival were evaluated. The efficacy of CONUT score to predict prognosis was evaluated.

Results

The CONUT score was associated with body mass index (p = 0.033), neutrophil (p = 0.011), tumor size (p = 0.017), pTNM stage (p = 0.001), adjuvant radiotherapy (p < 0.001), negative pathologic factors (p < 0.001), and larynx preservation (p < 0.001). Patients with a higher CONUT score had worse overall survival (hazard ratio: 1.94, 95% confidence interval [CI]: 1.13–3.72, p = 0.039) and disease-free survival (hazard ratio: 2.16, 95% CI: 1.19–3.90, p = 0.011). The area under the curve of CONUT score (0.728) was higher than Preoperative Nutritional Index (0.72), platelet-to-lymphocyte ratio (0.675), and neutrophil-to-lymphocyte ratio (0.687).

Conclusion

The CONUT score can be useful for predicting survival in laryngeal cancer patients after curative resection.

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Risk of adverse neonatal outcomes among pregnant women with disabilities

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Abstract
Background
To compare risk of neonatal morbidities between women with and without documented disability and to evaluate mediation of these associations by pre-term birth and caesarean delivery.
Methods
Using data from the Consortium on Safe Labor (2002–2008; n = 223 385), we evaluated risk of 22 neonatal outcomes among singleton deliveries using ICD-9 codes to define physical (n = 1733), sensory (n = 250) and intellectual disability (n = 91). Adjusted relative risk (aRR) was estimated for each outcome among each category of disability, and among women with any disability using Poisson regression models with robust variance. Causal mediation methods evaluated pre-term birth and caesarean delivery as mediators.
Results
Compared with no disabili ty, neonates of women with any disability had higher risk of nearly all neonatal outcomes, including pre-term birth (aRR = 1.77; 95% CI 1.62–1.94), small for gestational age (SGA) (aRR = 1.25; CI 1.11–1.41), neonatal intensive care unit (NICU) admission (aRR = 1.70; CI 1.54–1.87), seizures (aRR = 2.81; CI 1.54–5.14), cardiomyopathy (aRR = 4.92; CI 1.15–20.95), respiratory morbidities (aRR ranged from 1.33–2.08) and death (aRR = 2.31; CI 1.38–3.87). Women with disabilities were more likely to have a maternal indication for pre-term delivery, including pre-pregnancy diabetes (aRR = 3.80; CI 2.84–5.08), chronic hypertension (aRR = 1.46; CI 0.95–2.25) and severe pre-eclampsia/eclampsia (aRR = 1.47; CI 1.19–1.81). Increased risk varied but was generally consistent across all disability categories. Most outcomes were partially mediated by pre-term birth, except SGA, and heightened risk remained for NICU admissions, respiratory distre ss syndrome, anaemia and a composite of any adverse outcome (aRR = 1.21; CI 1.10–1.32).
Conclusion
Neonates of women with disabilities were at higher risk of a broad range of adverse neonatal outcomes, including death. Risks were not fully explained by pre-term birth.
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