Radiological staging in neuroblastoma : computed tomography or magnetic resonance imaging?

Purpose: To compare the effectiveness of computed tomography (CT) and magnetic resonance imaging (MRI) in the staging of neuroblastomas according to the International Neuroblastoma Risk Group Staging System (INRGSS). Material and methods: In this single-centre retrospective study we identified a total of 20 patients under the age of 18 years, who were admitted to our hospital with neuroblastoma between January 2005 and May 2018, and who had both CT and MRI examination. The INRGSS stages of tumours were evaluated by CT scan and MRI. Then, stages of tumours were described according to the INRGSS for CT and MRI, separately. The Spearman rank correlation test was used for statistical analysis. The p-value < 0.05 was considered as statistically significant. Results: The median age was 11 months, and the age range was one month to nine years. In our results; both MRI and CT were significant in the determination of radiological staging of NBL, p < 0.001 and p = 0.002, respectively. MRI was superior to CT in radiological staging. MRI was also superior for the detection of intraspinal extension, involvement of multiple body compartments, metastatic disease, and bone marrow infiltration. CT was more useful to consider the relationship between tumours and vascular structures. Conclusions: MRI and CT have high diagnostic accuracy rates in the staging of pre-treatment neuroblastomas. MRI is important in pre-treatment evaluation of neuroblastomas because of the higher detection of metastases as well as the lack of ionising radiation

Evaluation of the diagnostic and prognostic clinical values of circulating tumor DNA and cell-free DNA in pancreatic malignancies: a comprehensive meta-analysis

BackgroundThe diagnostic and prognostic clinical value of circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA) in pancreatic malignancies are unclear. Herein, we aimed to perform a meta-analysis to evaluate ctDNA and cfDNA as potential diagnostic and prognostic biomarkers.MethodsPRISMA reporting guidelines were followed closely for conducting the current meta-analysis. The PubMed/Medline, Scopus, and Web of Science (WoS) databases were scanned in detail to identify eligible papers for the study. A quality assessment was performed in accordance with the REMARK criteria. The risk ratios (RRs) of the diagnostic accuracy of ctDNA compared to that of carbohydrate antigen 19.9 (CA 19.9) in all disease stages and the hazard ratios (HRs) of the prognostic role of ctDNA in overall survival (OS) were calculated with 95% confidence intervals (CIs).ResultsA total of 18 papers were evaluated to assess the diagnostic accuracy and prognostic value of biomarkers related to pancreatic malignancies. The pooled analysis indicated that CA19.9 provides greater diagnostic accuracy across all disease stages than ctDNA or cfDNA (RR = 0.64, 95% CI: 0.50–0.82, p &lt; 0.001). Additionally, in a secondary analysis focusing on prognosis, patients who were ctDNA-positive were found to have significantly worse OS (HR = 2.00, 95% CI: 1.51–2.66, p &lt; 0.001).ConclusionThe findings of this meta-analysis demonstrated that CA19-9 still has greater diagnostic accuracy across all disease stages than KRAS mutations in ctDNA or cfDNA. Nonetheless, the presence of detectable levels of ctDNA was associated with worse patient outcomes regarding OS. There is a growing need for further research on this topic.Systematic review registrationhttps://doi.org/10.37766/inplasy2023.12.0092, identifier INPLASY2023120092

Clinical Significance Of DNA Repair Genes Expressions In Neurofibromatosis Type 1 Cases

AMAÇ: Nörofibromatozis Tip 1 (NF1), çeşitli fenotiplere sahip, sık görülen otozomal dominant genetik bir hastalıktır. NF1 hastalarının klinik çeşitliliğinin genetik nedeni sorgulanmaktadır. DNA onarım genleri DNA' daki hataların onarımından sorumludur. Bu çalışmada DNA onarım genlerinin ekspresyonunu ve onların NF1 hastalarındaki klinik önemini nörofibrom, hamartomatöz lezyon, diğer tümörler ya da ailesel NF1 varlığı ile karşılaştırarak analiz etmek ve gen ekspresyonları ile klinik bulgular arasında ilişki olup olmadığını belirlemek amaçlandı. YÖNTEMLER: NF1' li hastalar ve NF1 ile birlikte malignitesi olan hastalar çalışmaya alındı. Kontrol grubu olarak da benzer yaş grubundaki her hangi bir hastalığı olmayan çocuklar ve NF1 ile ilgisi olmayan maligniteli olgular oluşturdu. Çalışma toplam 46 olgu içermekteydi: 36 NF1 hastası (30 çocuk; 6 ebeveyn), hiç bir hastalığı olmayan 8 kontrol olgusu, rabdomiyosarkomlu NF1 olmayan 2 kontrol olgusu çalışmaya alındı. Her bir hasta ve kontrol grubundan periferik kandan mononükleer hücre izolasyonu yapıldı. RNA izolasyonu ve cDNA dönüşümünden sonra, her bir olguda Real-Time PCR ile DNA onarımı ile ilişkili 84 genin ekspresyonu (standart array, SABiosciences) belirlendi. Ekspresyonların kontrol grubuna göre kat değişiklikleri ve T test ile p değeri karşılaştırmalı gruplarda değerlendirildi. BULGULAR: Araştırma grubunu 36 NF1 hastası, kontrol grubunu ise 8 sağlam çocuk ve 2 adet de NF1 ile ilişkisi olmayan maligniteli olgu (rabdomiyosarkom) oluşturmaktadır. 8 kontrol olgusunun yaş ortalaması 17±7,03 (10-30 yaş) (ortanca 13 yaş) idi. NF1 olgularının 17' si kadın 19' u erkekti. NF1' li olgularımız için tanı anındaki yaş ortalaması 10,08±8,86 (9 ay- 38 yaş) (ortanca 8 yaş) iken hastalarımızın çalışmaya alınan ebeveynlerinin yaş ortalaması 40,50±1,22 (39-42 yaş) (ortanca40 yaş) idi. 36 hastanın, 17' si nörofibromlu, 17' si hamartomatöz lezyonluydu. 1 hastada rabdomiyosarkom (RMS) gözlenmiş, 1 hasta meme kanseri ve 4 hasta da optik gliomluydu. NF1 olgularında, PNKP, RAD18, XAB2, XRCC3, XRCC4 ve XRCC5 genlerinin ekspresyonu kontrol grup ile karşılaştırıldığında azaldı (p&lt;0.05, T test). Nörofibromlu NF 1 olgularında, nörofibromsuz NF 1 olgularıyla karşılaştırıldığında POLB ekspresyonu artarken; ERCC3,LIG1,MGMT, MRE11A, MPG, MSH6, PARP2, PRKDC, RAD51B, RAD52, RPA3, SMUG1, TREX1, UNG ekspresyonu azaldı. RAD18 ailesel NF 1 varlığında ekspresyonu azalmış ve istatistiksel olarak önemli olduğu saptandı. Malign tümör olgularında NF 1' li ya da NF 1' siz gruplar karşılaştırıldığında gen ekspresyonunda kat değişiklikleri vardı. Maligniteli olgularda DDB2, MGMT, MLH1, POLB UNG, XPA ekspresyonları arttı. NF 1'li RMS olgusu ile NF 1' siz RMS olguları karşılaştırıldığında DDB2, MGMT, MLH1, POLB, UNG, XPA olmak üzere 6 genin ekspresyonu 10 kattan fazla artmış saptandı. SONUÇ: Bulgularımız NF 1 olgularındaki klinik bulgulardan tümör gelişimini öngörmek için DNA onarım sistemi ilişkili gen ekspresyon değişikliklerinin rolü olabileceğini göstermiştir. POLB nörofibrom varlığı belirteci, DDB2, MGMT, MLH1, POLB UNG, XPA malign tümör gözlenme belirteci olmaya aday genler olarak saptandı. Bu genlerin ekspresyonlarının daha geniş seri NF1li ve maligniteli olgularda çalışılması uygundur. OBJECTIVE: Neurofibromatosis Type 1 (NF1) is a a common autosomal dominant genetic disorder that has a variable phenotype. The genetical causes of clinical variability of NF1 patients is questioned. DNA repair genes are responsible for proofreading the missing in the DNA. We aimed to analyze expression of DNA repair genes and their clinical significance in NF1 patients; comparing exsistance of neurofibroma or hamartomatous lesions or other tumours or existance of NF1 in the family. The other aim of this study was to determine whether any relationship between gene expressions and clinical findings. METHODS: NF1 patients and malignancy with NF1 pateints were included and in this study. In the control gruop children that they are in the similar age group and they have no disease and no malignacy group were included. This study included total 46 cases. 36 NF1 patients (30 children; 6 parents), 8 control cases without any disease, two control cases with rhabdomyosarcoma without NF1 were included in this study. The mean age of control group was 17±7,03 (10-30 age) (median 13 age). In the NF1 pateints gruop 17 of them are female, and 19 are male. The mean age at diagnosis is 10,08±8,86 (9 months- 38 age)(median age 8) for children and 40,50±1,22 (39-42 age) (median age 40) for parents. Among 36 patients, 17 had neurofibromas, 17 had hamartomatous lesions. Rhabdomyosarcoma (RMS) was observed in one patient, breast cancer in one patient and four patients suffered optic glioma. Peripheral blood was obtained from each cases and mononuclear cells were separated. After RNA isolation and cDNA converting, expressions of 84 genes related with DNA Repair in standard array (SABiosciences) were determined by Real-Time PCR for each case. Fold changes and p values compared with control groups and fold changes evaluated with T test and p value in the comperative groups. RESULTS: 36 NF1 patients, 8 healthy children as a control and 2 cases no NF1 relationship with malignancy (rhabdomyosarcoma) were included in the study group. In NF1 cases PNKP, RAD18, XAB2, XRCC3, XRCC4 and XRCC5 genes were downregulated compared with control group. In NF1 cases having neurofibromas, POLB was over expressed; while ERCC3, LIG1, MGMT, MRE11A, MPG, MSH6, PARP2, PRKDC, RAD51B, RAD52, RPA3, SMUG1, TREX1, UNG were downregulated compared with the NF1 cases without neurofibromas (p&lt;0.05, T test). RAD18 is the downregulated and statistical significant gene for existence of NF1 in the family. There are gene expression fold change differences determined when malign tumor cases with/without NF1 were compared. DDB2, MGMT, MLH1, POLB UNG, XPA are increased. &nbsp; CONCLUSION: Our results may point toward a role of gene expression changes of DNA repair system to be predictive for clinical manifestations in NF1 cases