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Ophthalmology Science Mar 2022Gain of chromosome 6p has been associated with poor ocular survival in retinoblastoma and histopathologic grading of anaplasia with increased risk of metastatic spread...
PURPOSE
Gain of chromosome 6p has been associated with poor ocular survival in retinoblastoma and histopathologic grading of anaplasia with increased risk of metastatic spread and death. This study examined the correlation between these factors and other chromosomal abnormalities as well as results of whole genome sequencing, digital morphometry, and progression-free survival.
DESIGN
Retrospective cohort study from 2 United States tertiary referral centers.
PARTICIPANTS
Forty-two children who had undergone enucleation for retinoblastoma from January 2000 through December 2017.
METHODS
Status of chromosomes 6p, 1q, 9q, and 16q was evaluated with fluorescence in situ hybridization, the degree of anaplasia and presence of histologic high-risk features were assessed by ocular pathologists, digital morphometry was performed on scanned tumor slides, and whole genome sequencing was performed on a subset of tumors. Progression-free survival was defined as absence of distant or local metastases or tumor growth beyond the cut end of the optic nerve.
MAIN OUTCOME MEASURES
Correlation between each of chromosomal abnormalities, anaplasia, morphometry and sequencing results, and survival.
RESULTS
Forty-one of 42 included patients underwent primary enucleation and 1 was treated first with intra-arterial chemotherapy. Seven tumors showed mild anaplasia, 19 showed moderate anaplasia, and 16 showed severe anaplasia. All tumors had gain of 1q, 18 tumors had gain of 6p, 6 tumors had gain of 9q, and 36 tumors had loss of 16q. Tumors with severe anaplasia were significantly more likely to harbor 6p gains than tumors with nonsevere anaplasia ( < 0.001). Further, the hematoxylin staining intensity was significantly greater and that of eosin staining significantly lower in tumors with severe anaplasia ( < 0.05). Neither severe anaplasia ( = 0.10) nor gain of 6p ( = 0.21) correlated with histologic high-risk features, and severe anaplasia did not correlate to , , , or mutations in a subset of 14 tumors ( > 0.5). Patients with gain of 6p showed significantly shorter progression-free survival ( = 0.03, Wilcoxon test).
CONCLUSIONS
Gain of chromosome 6p emerges as a strong prognostic biomarker in retinoblastoma because it correlates with severe anaplasia, quantifiable changes in tumor cell staining characteristics, and extraocular spread.
PubMed: 36246172
DOI: 10.1016/j.xops.2021.100089 -
Frontiers in Oncology 2022Achieving maximal functionally safe resection of gliomas located within the eloquent speech areas is challenging, and there is a lack of literature on the combined use...
BACKGROUND
Achieving maximal functionally safe resection of gliomas located within the eloquent speech areas is challenging, and there is a lack of literature on the combined use of 5-aminolevulinic acid (5-ALA) guidance and awake craniotomy.
OBJECTIVE
The aim of this study was to describe our experience with the simultaneous use of 5-ALA fluorescence and awake speech mapping in patients with left frontal gliomas located within the vicinity of eloquent speech areas.
MATERIALS AND METHODS
A prospectively collected database of patients was reviewed. 5-ALA was administered at a dose of 20 mg/kg 2 h prior to operation, and an operating microscope in BLUE400 mode was used to visualize fluorescence. All patients underwent surgery using the "asleep-awake-asleep" protocol with monopolar and bipolar electrical stimulation to identify the proximity of eloquent cortex and white matter tracts and to guide safe limits of resection along with fluorescence guidance. Speech function was assessed by a trained neuropsychologist before, during, and after surgery.
RESULTS
In 28 patients operated with cortical mapping and 5-ALA guidance (12 Grade 4, 6 Grade 3, and 10 Grade 2 gliomas), Broca's area was identified in 23 cases and Wernicke's area was identified in 5 cases. Fluorescence was present in 14 cases. Six tumors had residual fluorescence due to the positive speech mapping in the tumor bed. Transient aphasia developed in 14 patients, and permanent aphasia developed in 4 patients. In 6 patients operated with cortical and subcortical speech mapping and 5-ALA guidance (4 Grade 4, 1 Grade 3, and 1 Grade 2 gliomas), cortical speech areas were mapped in 5 patients and subcortical tracts were encountered in all cases. In all cases, resection was stopped despite the presence of residual fluorescence due to speech mapping findings. Transient aphasia developed in 6 patients and permanent aphasia developed in 4 patients. In patients with Grade 2-3 gliomas, targeted biopsy of focal fluorescence areas led to upgrading the grade and thus more accurate diagnosis.
CONCLUSION
5-ALA guidance during awake speech mapping is useful in augmenting the extent of resection for infiltrative high-grade gliomas and identifying foci of anaplasia in non-enhancing gliomas, while maintaining safe limits of functional resection based on speech mapping. Positive 5-ALA fluorescence in diffuse Grade 2 gliomas may be predictive of a more aggressive disease course.
PubMed: 36212421
DOI: 10.3389/fonc.2022.940951 -
Advances in Cancer Diagnosis: Bio-Electrochemical and Biophysical Characterizations of Cancer Cells.Micromachines Aug 2022Cancer is a worldwide leading cause of death, and it is projected that newly diagnosed cases globally will reach 27.5 million each year by 2040. Cancers (malignant... (Review)
Review
Cancer is a worldwide leading cause of death, and it is projected that newly diagnosed cases globally will reach 27.5 million each year by 2040. Cancers (malignant tumors), unlike benign tumors are characterized by structural and functional dedifferentiation (anaplasia), breaching of the basement membrane, spreading to adjacent tissues (invasiveness), and the capability to spread to distant sites (metastasis). In the cancer biology research field, understanding and characterizing cancer metastasis as well as features of cell death (apoptosis) is considered a technically challenging subject of study and clinically is very critical and necessary. Therefore, in addition to the cytochemical methods traditionally used, novel biophysical and bioelectrochemical techniques (e.g., cyclic voltammetry and electrochemical impedance spectroscopy), atomic force microscopy, and electron microscopic methods are increasingly being deployed to better understand these processes. Implementing those methods at the preclinical level enables the rapid screening of new anticancer drugs with understanding of their central mechanism for cancer therapy. In this review, principles and basic concepts of new techniques suggested for metastasis, and apoptosis examinations for research purposes are introduced, along with examples of each technique. From our recommendations, the privilege of combining the bio-electrochemical and biosensing techniques with the conventional cytochemical methods either for research or for biomedical diagnosis should be emphasized.
PubMed: 36144024
DOI: 10.3390/mi13091401 -
Cancers Aug 2022(1) Background: Vena cava thrombus (VCT) is rare in Wilms tumor (WT) (4−10%). The aim of this study is to identify factors for an outcome to improve treatment for...
(1) Background: Vena cava thrombus (VCT) is rare in Wilms tumor (WT) (4−10%). The aim of this study is to identify factors for an outcome to improve treatment for better survival. (2) Methods: 148/3015 patients with WT (aged < 18 years) and VCT, prospectively enrolled over a period of 32 years (1989−2020) by the German Society for Pediatric Oncology and Hematology (SIOP-9/GPOH, SIOP-93-01/GPOH and SIOP-2001/GPOH), are retrospectively analyzed to describe clinical features, response to preoperative chemotherapy (PC) (142 patients) and surgical interventions and to evaluate risk factors for overall survival (OS). (3) Results: 14 VCT regressed completely with PC and another 12 in parts. The thrombus was completely removed in 111 (85.4%), incompletely in 16 (12.3%), and not removed in 3 (2.3%). The type of removal is unknown in four patients. Patients without VCT have a significantly (p < 0.001) better OS (97.8%) than those with VCT (90.1%). OS after complete resection is (89.9%), after incomplete (93.8%) and with no resection (100%). Patients with anaplasia or stage IV without complete remission (CR) after PC had a significantly worse OS compared to the remaining patients with VCT (77.1% vs. 94.4%; p = 0.002). (4) Conclusions: As a result of our study, two risk factors for poor outcomes in WT patients with VCT emerge: diffuse anaplasia and metastatic disease, especially those with non-CR after PC.
PubMed: 36010917
DOI: 10.3390/cancers14163924 -
Arab Journal of Urology 2022To evaluate whether p53, cyclin A and ki67 immunohistochemical (IHC) assay can be used as predictors for Wilms' tumor (WT) unfavorable outcomes.
OBJECTIVE
To evaluate whether p53, cyclin A and ki67 immunohistochemical (IHC) assay can be used as predictors for Wilms' tumor (WT) unfavorable outcomes.
METHODS
It is a non-concurrent cohort study including patients who underwent nephrectomy for WT from January 2000 to December 2015 in a tertiary referral center. Over a 5- year follow-up, unfavorable events, including relapse and cancer-specific mortality (CSM), were recorded. P53, cyclin A, and ki67 IHC assay were carried out for formalin-fixed paraffin-embedded WT samples.
RESULTS
After excluding those who did not meet the inclusion criteria, 75 patients were enrolled. Of the patients, 15/75 (20%) experienced WT relapse while 11/75 (14.6%) died of WT over five years. Unfavorable histology (UFH), including prominent blastemal components and anaplasia, was found in 15/75 (20%) children.Cyclin A immunopositivity was associated with high rates of relapse and CSM. P53 and ki67 positive IHC assay did not show any statistically significant association with unfavorable outcomes. Other risk factors e.g. advanced staging, UFH, extracapsular extension, tumor rupture, lymphadenopathy, and venous thrombosis were not associated with poor prognosis. However, the presence of residual tumors was accompanied by lower survival rates.
CONCLUSION
Cyclin A IHC assay can be used as a predictor of WT recurrence and CSM. Further studies with prospective patterns and a larger sample size are needed. WT: Wilms' tumor, UFH: unfavorable histology, IHC: immunohistochemical, PI: proliferation index, RFS: relapse-free survival, CSS: cancer-specific survival, FH: favorable histology, CSM: cancer-specific mortality, CDK: cyclin-dependent kinase.
PubMed: 35935912
DOI: 10.1080/2090598X.2022.2058240 -
Neurologia May 2023No formal indication currently exists for seizure prophylaxis in neurosurgical oncology patients. Neither have specific recommendations been made on the use of... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
No formal indication currently exists for seizure prophylaxis in neurosurgical oncology patients. Neither have specific recommendations been made on the use of antiepileptic drugs (AED) in seizure-free patients with meningiomas scheduled for surgery. AEDs are generally prescribed on a discretionary basis, taking into consideration a range of clinical and radiological risk factors. We present a systematic review and meta-analysis exploring the effectiveness of antiepileptic prophylaxis in patients with meningioma and no history of seizures.
METHODS
We performed a systematic review of the PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Embase, and clinicaltrials.gov databases. Of a total of 4368 studies initially identified, 12 were selected for extraction of data and qualitative analysis. Based on the clinical data presented, we were only able to include 6 studies in the meta-analysis. We performed heterogeneity studies, calculated a combined odds ratio, evaluated publication bias, and conducted a sensitivity analysis.
RESULTS
AED prophylaxis in patients with meningioma and no history of seizures did not significantly reduce the incidence of post-operative seizures in comparison to controls (Mantel-Haenszel combined odds ratio, random effects model: 1.26 [95% confidence interval, 0.60-2.78]; 2041 patients). However, we are unable to establish a robust recommendation against this treatment due to the lack of prospective studies, the presence of selection bias in the studies reviewed, the likelihood of underestimation of seizure frequency during follow-up, and the strong influence of one study on the overall effect.
CONCLUSIONS
Despite the limitations of this review, the results of the meta-analysis do not support the routine use of seizure prophylaxis in patients with meningioma and no history of seizures.
Topics: Humans; Meningioma; Phenytoin; Anticonvulsants; Incidence; Meningeal Neoplasms
PubMed: 35781420
DOI: 10.1016/j.nrleng.2022.03.002 -
Biomedicines Apr 2022This research aimed to investigate the interrelationship of carbohydrate metabolism parameters and immunohistochemical characteristics of glial tumors. Tumor tissue,...
This research aimed to investigate the interrelationship of carbohydrate metabolism parameters and immunohistochemical characteristics of glial tumors. Tumor tissue, peritumoral area, and adjacent noncancerous tissue fragments of 20 patients with gliomas of varying degrees of anaplasia were analyzed. The greatest differences in the carbohydrate metabolism compared to adjacent noncancerous tissues were identified in the tumor tissue: reduction in the levels of lactate and glycogen synthase kinase-3β. Significant differences with adjacent noncancerous tissues for the peritumoral zone were not found. The activity of the carbohydrate metabolism enzymes was different depending on the immunohistochemical glioma profile, especially from Ki 67 level. Bioinformatic analysis of the interactions of immunohistochemical markers of gliomas and carbohydrate metabolism enzymes using the databases of STRING, BioGrid, and Signor revealed the presence of biologically significant interactions with glycogen synthase kinase 3β, hexokinase, glucose-6-phosphate dehydrogenase, and transketolase. The established interconnection of glycolysis with methylation of the promoter of O-6-methylguanine-DNA-methyltransferase (MGMT) of gliomas can be used to increase chemotherapy efficiency.
PubMed: 35625744
DOI: 10.3390/biomedicines10051007 -
Journal of Hepatology Oct 2022Hepatoblastoma (HB) and hepatocellular carcinoma (HCC) are the predominant liver cancers in children, though their respective treatment options and associated outcomes...
BACKGROUND & AIMS
Hepatoblastoma (HB) and hepatocellular carcinoma (HCC) are the predominant liver cancers in children, though their respective treatment options and associated outcomes differ dramatically. Risk stratification using a combination of clinical, histological, and molecular parameters can improve treatment selection, but it is particularly challenging for tumors with mixed histological features, including those in the recently created hepatocellular neoplasm not otherwise specified (HCN NOS) provisional category. We aimed to perform the first molecular characterization of clinically annotated cases of HCN NOS.
METHODS
We tested whether these histological features are associated with genetic alterations, cancer gene dysregulation, and outcomes. Namely, we compared the molecular features of HCN NOS, including copy number alterations, mutations, and gene expression profiles, with those in other pediatric hepatocellular neoplasms, including HBs and HCCs, as well as HBs demonstrating focal atypia or pleomorphism (HB FPAs), and HBs diagnosed in older children (>8).
RESULTS
Molecular profiles of HCN NOS and HB FPAs revealed common underlying biological features that were previously observed in HCCs. Consequently, we designated these tumor types collectively as HBs with HCC features (HBCs). These tumors were associated with high mutation rates (∼3 somatic mutations/Mb) and were enriched with mutations and alterations in key cancer genes and pathways. In addition, recurrent large-scale chromosomal gains, including gains of chromosomal arms 2q (80%), 6p (70%), and 20p (70%), were observed. Overall, HBCs were associated with poor clinical outcomes.
CONCLUSIONS
Our study indicates that histological features seen in HBCs are associated with combined molecular features of HB and HCC, that HBCs are associated with poor outcomes irrespective of patient age, and that transplanted patients are more likely to have good outcomes than those treated with chemotherapy and surgery alone. These findings highlight the importance of molecular testing and early therapeutic intervention for aggressive childhood hepatocellular neoplasms.
LAY SUMMARY
We molecularly characterized a class of histologically aggressive childhood liver cancers and showed that these tumors are clinically aggressive and that their observed histological features are associated with underlying recurrent molecular features. We proposed a diagnostic algorithm to identify these cancers using a combination of histological and molecular features, and our analysis suggested that these cancers may benefit from specialized treatment strategies that may differ from treatment guidelines for other childhood liver cancers.
Topics: Carcinoma, Hepatocellular; Child; Chromosome Aberrations; Hepatoblastoma; Humans; Liver Neoplasms; Mutation; Young Adult
PubMed: 35577029
DOI: 10.1016/j.jhep.2022.04.035 -
SAGE Open Medical Case Reports 2022Anaplastic thyroid carcinoma accounts for 3%-4% of thyroid malignancies worldwide and is aggressive in nature with a median survival of 6 months at diagnosis. A...
Anaplastic thyroid carcinoma accounts for 3%-4% of thyroid malignancies worldwide and is aggressive in nature with a median survival of 6 months at diagnosis. A 67-year-old lady with a hard goitre presented with compressive symptoms and mild hypothyroidism. Ultrasound scan revealed a Thyroid Imaging Reporting and Data System 5 lesion with suspicious left-sided cervical lymphadenopathy. Anaplastic carcinoma was diagnosed by fine needle aspiration cytology. Left-sided thyroid tumour with possible carotid sheath infiltration and left-sided cervical lymphadenopathy was seen on contrast-enhanced computed tomography of the neck. She underwent total thyroidectomy with therapeutic bilateral selective central and lateral cervical lymphadenectomy. Involvement of the aero-digestive tract and carotid sheath was not observed intra-operatively. Histology reported anaplastic carcinoma with deposits of papillary carcinoma in affected lymph nodes. Oncological management was commenced thereafter. Anaplastic thyroid carcinoma usually presents as advanced disease. However, current guidelines suggest a multimodal approach comprising of curative surgery whenever feasible with adjuvant radiotherapy and chemotherapy. For patients with stage IV/IV loco-regional disease as in our patient, total thyroidectomy with therapeutic lymphadenectomy to achieve R0/R1 resection plus adjuvant therapy is the current accepted practice. For locally advanced disease, surgery maybe opted after down-staging. The aim is to resect tumour wholly and not merely de-bulking. The presence of papillary carcinoma in lymph nodes points towards anaplasia occurring in a background of differentiated thyroid carcinoma in our patient similar to what literature suggests. This has implications in post-operative thyroxine suppression and radioiodine ablative therapies.
PubMed: 35449526
DOI: 10.1177/2050313X221091399 -
Modern Pathology : An Official Journal... Sep 2022Correctly diagnosing a rare childhood cancer such as sarcoma can be critical to assigning the correct treatment regimen. With a finite number of pathologists worldwide...
Correctly diagnosing a rare childhood cancer such as sarcoma can be critical to assigning the correct treatment regimen. With a finite number of pathologists worldwide specializing in pediatric/young adult sarcoma histopathology, access to expert differential diagnosis early in case assessment is limited for many global regions. The lack of highly-trained sarcoma pathologists is especially pronounced in low to middle-income countries, where pathology expertise may be limited despite a similar rate of sarcoma incidence. To address this issue in part, we developed a deep learning convolutional neural network (CNN)-based differential diagnosis system to act as a pre-pathologist screening tool that quantifies diagnosis likelihood amongst trained soft-tissue sarcoma subtypes based on whole histopathology tissue slides. The CNN model is trained on a cohort of 424 centrally-reviewed histopathology tissue slides of alveolar rhabdomyosarcoma, embryonal rhabdomyosarcoma and clear-cell sarcoma tumors, all initially diagnosed at the originating institution and subsequently validated by central review. This CNN model was able to accurately classify the withheld testing cohort with resulting receiver operating characteristic (ROC) area under curve (AUC) values above 0.889 for all tested sarcoma subtypes. We subsequently used the CNN model to classify an externally-sourced cohort of human alveolar and embryonal rhabdomyosarcoma samples and a cohort of 318 histopathology tissue sections from genetically engineered mouse models of rhabdomyosarcoma. Finally, we investigated the overall robustness of the trained CNN model with respect to histopathological variations such as anaplasia, and classification outcomes on histopathology slides from untrained disease models. Overall positive results from our validation studies coupled with the limited worldwide availability of sarcoma pathology expertise suggests the potential of machine learning to assist local pathologists in quickly narrowing the differential diagnosis of sarcoma subtype in children, adolescents, and young adults.
Topics: Adolescent; Animals; Child; Humans; Machine Learning; Mice; Neural Networks, Computer; Pathologists; Rhabdomyosarcoma; Rhabdomyosarcoma, Embryonal; Young Adult
PubMed: 35449398
DOI: 10.1038/s41379-022-01075-x