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Pediatric Hematology and Oncology Mar 2019Retinoblastoma (RB) is the most common intraocular tumor of childhood. In low income countries, Time to diagnosis (TTD: interval between first symptom and diagnosis) has...
Retinoblastoma (RB) is the most common intraocular tumor of childhood. In low income countries, Time to diagnosis (TTD: interval between first symptom and diagnosis) has been associated with extraocular disease, metastasis and mortality. However, the relationship between TTD and prognosis is complex and not simply a linear correlation, particularly if TTD is <6 months. This systematic review aims to identify studies reporting TTD of retinoblastoma in Latin America, highlighting factors affecting TTD, alongside proposals and initiatives to obtain shorter intervals. The review also aims to discuss the methodology linked to cancer pathways studies. The study respected PRISMA recommendations, was registered on Prospero, an international database for systematic review registries under number CRD42017076777. MEDLINE/PUBMED, LILACS and SCIELO databases were searched. Studies from Latin America and the Caribbean, published between 1997 and 2017, reporting TTD and age at diagnosis of patients with retinoblastoma were selected. Nine studies were selected, concerning 1560 patients from Argentina, Brazil, Chile, Honduras, Mexico and Peru. The median TTD ranged from 3 to 5 months and the median age at diagnosis ranged from 16.5 to 22.2 months. A prolonged TTD was observed and was associated to damaging results on retinoblastoma outcomes, particularly increasing extraocular disease, and mortality rates. Methodological heterogeneity was observed and reiterates the importance of standardization of TTD studies, allowing more reliable comparisons and greater knowledge about retinoblastoma pathways before diagnosis. Reports on successful initiatives against delayed diagnosis were scarce, emphasizing a need for further studies.
Topics: Age Factors; Child, Preschool; Delayed Diagnosis; Early Detection of Cancer; Early Diagnosis; Eye Neoplasms; Humans; Infant; Infant, Newborn; Latin America; Prognosis; Retinoblastoma; Socioeconomic Factors; Time Factors
PubMed: 31014139
DOI: 10.1080/08880018.2019.1605432 -
Reproductive Biomedicine Online Apr 2019As all the structures of the human eye are characterized by sex hormone receptors, this study tested the hypothesis that assisted reproductive technology (ART) treatment...
As all the structures of the human eye are characterized by sex hormone receptors, this study tested the hypothesis that assisted reproductive technology (ART) treatment influences visual function and ocular morphology in women who have undergone ART treatment and children born as a result of ART treatment. A systematic literature search of all original articles published up to August 2018 was performed using the PubMed database, including all original studies available in the literature. Review articles, studies in which participants underwent mixed interventions (i.e. other than ART treatment), studies reporting data on ocular malformations in ART offspring, and studies written in languages other than English were excluded. All selected articles were analysed to assess the level of evidence according to the Oxford Centre for Evidence-Based Medicine 2011 guidelines, and the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation system. Although sparse data suggest that ART treatment can influence visual function and ocular morphology in women who have undergone ART treatment and children born as a result of ART treatment, the available evidence is inconclusive given its low level and quality. More high-quality research is needed to assess the potential interaction between ART treatment and the eye.
Topics: Adult; Child; Child, Preschool; Choroidal Neovascularization; Cornea; Eye; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Intraocular Pressure; Male; Myasthenia Gravis; Pregnancy; Reproductive Techniques, Assisted; Retina; Retinal Detachment; Retinal Vein; Retinoblastoma; Retinopathy of Prematurity; Vision, Ocular
PubMed: 30795976
DOI: 10.1016/j.rbmo.2018.11.007 -
PloS One 2019Risk of developing a malignancy when born premature is unknown. We hypothesised that risk of certain cancers might be increased in youth born preterm versus term. We... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Risk of developing a malignancy when born premature is unknown. We hypothesised that risk of certain cancers might be increased in youth born preterm versus term. We therefore performed a systematic review and meta-analysis to evaluate the incidence of malignancy in the context of preterm birth, according to various cancer types.
METHODS
The study was designed per MOOSE and PRISMA guidelines. Articles were identified through November 2015. Observational studies exploring the association between childhood malignancy and birth characteristics were included. Of the 1658 records identified, 109 full text articles were evaluated for eligibility. Random effects meta-analyses were conducted on 10/26 studies retained; 95% confidence intervals were computed and adjusted following sensitivity analysis. Publication bias was evaluated using funnel plots, Begg's and Egger's tests.
RESULTS
No differences in risk of primary central nervous system tumor [OR 1.05; 95% CI 0.93-1.17, 5 studies, 580 cases] and neuroblastoma [OR 1.09; 95% CI 0.90-1.32, 5 studies, 211 cases] were observed in individuals born <37 versus ≥37 weeks' gestation. Preterm birth was consistently associated with hepatoblastoma [ORs 3.12 (95% CI 2.32-4.20), 1.52 (95% CI 1.1-2.1), 1.82 (95% CI 1.01-3.26), and 2.65 (95% CI 1.98-3.55)], but not leukemia, astrocytoma, ependymoma, medulloblastoma, lymphoma, nephroblastoma, rhabdomyosarcoma, retinoblastoma or thyroid cancer.
CONCLUSIONS
Children born premature may be at increased risk for hepatoblastoma but there is no strong evidence of an increased risk of primary central nervous system tumours or neuroblastoma. There is insufficient evidence to conclude whether prematurity modulates the risk of other childhood cancers.
Topics: Central Nervous System Neoplasms; Child; Female; Gestational Age; Hepatoblastoma; Humans; Incidence; Infant, Newborn; Infant, Premature; Liver Neoplasms; Male; Neoplasms; Neuroblastoma; Observational Studies as Topic; Pregnancy; Premature Birth; Risk Factors; Young Adult
PubMed: 30608983
DOI: 10.1371/journal.pone.0210366 -
Medicine Dec 2018Retinoblastoma (Rb) is the most common intra-ocular malignancy in children. The association of rs2279744, and rs937283 in MDM2 gene, and p21 rs1801270 polymorphism and... (Meta-Analysis)
Meta-Analysis
Retinoblastoma (Rb) is the most common intra-ocular malignancy in children. The association of rs2279744, and rs937283 in MDM2 gene, and p21 rs1801270 polymorphism and RB development have been demonstrated. To provide a comprehensive assessment of and to clarify associations between the 3 SNPs (MDM2 rs2279744, MDM2 rs937283, and p21 rs1801270) and the risk of RB, we performed a meta-analysis of all the eligible case-control studies. We searched English databases include PubMed, Embase, Google Scholar, and Cochrane Library, using an upper date limit of January 1, 2018. The association between MDM2 rs2279744, MDM2 rs937283, and p21 rs1801270 polymorphisms and the risk of RB were estimated by calculating a pooled OR and 95% CI under a homozygote comparison, heterozygote comparison, dominant model, and recessive model. The statistical power analysis was performed using G*Power. Our meta-analysis showed a significant association between RB susceptibility and MDM2 rs2279744 recessive model (OR = 1.427, 95%CI: 1.107-1.840, P = .006, I = 0%). Moreover, a significant link was observed between RB risk and MDM2 rs937283 homozygote comparison (OR = 0.471, 95%CI: 0.259-0.858, P = .014, I = 0%) and recessive model (OR = 0.587, 95%CI: 0.410-0.840, P = .004, I = 0%). However, no significant relationship between the p21 rs1801270 polymorphism and RB susceptibility was detected in any of the 4 models (P > .05). In conclusion, we found that significant association between the MDM2 rs2279744 polymorphism and increased RB risk, while MDM2 rs937283 polymorphism was associated with significantly decreased RB risk. However, as to the P21 rs1801270 polymorphism, a statistically significant association was not identified for RB.
Topics: Cyclin-Dependent Kinase Inhibitor p21; Genetic Predisposition to Disease; Humans; Proto-Oncogene Proteins c-mdm2; Retinal Neoplasms; Retinoblastoma
PubMed: 30544467
DOI: 10.1097/MD.0000000000013547 -
European Journal of Dermatology : EJD Oct 2018In this review, the current knowledge of cutaneous squamous cell carcinogenesis (cSCC) is outlined based on an appraisal of the different features of cSCC, with...
In this review, the current knowledge of cutaneous squamous cell carcinogenesis (cSCC) is outlined based on an appraisal of the different features of cSCC, with particular emphasis on genetic alterations underlying aetiopathogenesis. When appropriate, diagnostic and/or prognostic biomarkers for cSCC are also considered. This review is intended to aid future investigation into the molecular characterization of cSCC.
Topics: Carcinogenesis; Carcinoma, Squamous Cell; Cell Cycle Proteins; Cyclin D1; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Microtubule-Associated Proteins; Mutation; Prevalence; Retinoblastoma Binding Proteins; Risk Assessment; Skin Neoplasms; Tumor Suppressor Protein p53; Ubiquitin-Protein Ligases
PubMed: 30530431
DOI: 10.1684/ejd.2018.3403 -
Urologia Internationalis 2019Leiomyosarcoma of the urinary bladder is exceedingly rare. Most clinicians come across only a few cases during their career, and information regarding treatment and... (Meta-Analysis)
Meta-Analysis
PURPOSE
Leiomyosarcoma of the urinary bladder is exceedingly rare. Most clinicians come across only a few cases during their career, and information regarding treatment and outcome is scattered in the scientific literature. Interested clinicians and patients have to undertake troublesome search for treatment and outcome information.
MATERIAL AND METHODS
We performed a systematic review of the literature using the PubMed and Web of Science databases and included all identified cases published in English language between 1970 and June 2018 into a meta-analysis. Prior to the literature search, key questions were formulated and with the data obtained, answers to these questions should be derived.
RESULTS
We analyzed clinical data of 210 cases of urinary bladder leiomyosarcoma revealed by this review and seen in our institution. The mean age of patients was 52 years. The majority (75%) of the tumors was classified as high-grade sarcomas. We found no report of a prior radiation therapy to the pelvic organs, but some authors suggested an association between cyclophosphamide treatment and the development of bladder leiomyosarcoma, especially in patients with retinoblastoma. For the whole sample, we determined 5- and 10-year cancer-specific cumulative mortality rates of 38 and 50%. Patients with high-grade sarcomas had a trend toward a higher mortality compared with low-grade tumors (p = 0.0280). The most promising treatment option seems to be surgery (radical or partial cystectomy) with negative resection margins, possibly supplemented by chemotherapy or radiation.
CONCLUSION
About half of patients with bladder leiomyosarcoma survived on the long run. Low-grade tumors may have a better outcome with, nevertheless, countable long-term mortality. For better assessment of that rare bladder tumor, its best treatment options, and the influence of neoadjuvant or adjuvant therapies on the outcome of patients, a larger series with long-term survival data is required.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cyclophosphamide; Cystectomy; Female; Humans; Leiomyosarcoma; Male; Middle Aged; Time Factors; Urinary Bladder; Urinary Bladder Neoplasms; Young Adult
PubMed: 30384363
DOI: 10.1159/000494357 -
Boletin Medico Del Hospital Infantil de... 2017This systematic review aims to report the current knowledge of retinoblastoma (Rb) and its implications in Mexico. We analyzed clinical and demographic data of patients...
BACKGROUND
This systematic review aims to report the current knowledge of retinoblastoma (Rb) and its implications in Mexico. We analyzed clinical and demographic data of patients with Rb at select hospitals with Rb programs or that treat and refer patients with Rb, and identified the gaps in practice. We propose solutions to improve diagnosis, provide adequate treatment, and improve patient uptake.
METHODS
A general review was conducted on PubMed of peer-reviewed literature on Rb in Mexico. Ophthalmology Department Heads or Directors of Rb programs at seven hospitals in Mexico were contacted for data available on their patients with Rb.
RESULTS
Five hospitals provided clinical data on 777 patients with Rb in a period spanning 2000-2015. Of the 122 patients with treatment, 83.4% underwent enucleation. From 33 to 45.3% of Rb tumors in Mexico reach an advanced intraocular stage of development. Knowledge of the disease is limited, despite the fact that the Mexican Retinoblastoma Group has elaborated Rb treatment guidelines and is developing a national Rb registry. Especially in the Southern states, prevalence and outcomes are comparable to African and Asian countries, and only few patients are referred to national treatment centers. Only three institutions have comprehensive Rb programs.
CONCLUSIONS
There is an immediate need in Mexico to expand primary care providers' knowledge of Rb and to expand and upgrade current Rb programs to meet the needs of the population adequately. Diagnosis and care of Rb patients in Mexico can also be improved by the establishment of a national Rb registry and a national early detection program, and by increased use of the national treatment protocol.
Topics: Early Detection of Cancer; Health Knowledge, Attitudes, Practice; Humans; Mexico; Practice Guidelines as Topic; Prevalence; Referral and Consultation; Registries; Retinal Neoplasms; Retinoblastoma
PubMed: 29364813
DOI: 10.1016/j.bmhimx.2016.08.002 -
Breast Cancer (Tokyo, Japan) Jan 2018The introduction of specific cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors significantly improved progression-free survival in hormone receptor-positive metastatic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The introduction of specific cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors significantly improved progression-free survival in hormone receptor-positive metastatic breast cancer. CDK 4/6 inhibitors induce cell cycle arrest via liberating the tumor suppressor retinoblastoma protein from CDK4/6 inhibitory effect. Preliminary studies suggested an increase in the hematological toxicities which might affect the quality of life in such palliative setting.
METHODS
We searched PubMed, ASCO, ESMO and San Antonio meeting databases for randomized phase II/III trials in metastatic breast cancer receiving CDK4/6 inhibitors with safety data provided on the incidence of hematological adverse effects.
RESULTS
Our search identified 1012 citations that were screened for relevance. Thirty-six studies were found to be potentially eligible. After excluding the ineligible studies, six studies were deemed to be eligible for meta-analysis. The risk ratio (RR) was 11.31 [95% confidence interval (CI) 8.06-15.87; p < 0.0001] for all-grade leucopenia, 14.86 (95% CI 11.37-19.41; p < 0.0001) for all-grade neutropenia, 9.04 (95% CI 3.78-21.63; p < 0.0001) for all-grade thrombocytopenia and 3.57 (95% CI 2.65-4.81; p < 0.0001) for all-grade anemia. The RR for grade 3/4 leucopenia was 33.86 (95% CI 14.59-78.57; p < 0.0001), for grade 3/4 neutropenia was 44.00 (95% CI 24.72-78.33; p < 0.0001), for grade 3/4 thrombocytopenia was 5.70 (95% CI 2.03-16.01; p = 0.001) and for grade 3/4 anemia was 2.80 (95% CI 1.45-5.41; p = 0.002). There was no significant increase in the RR of febrile neutropenia with RR of 3.29 (95% CI 0.93-11.57; p = 0.06).
CONCLUSION
Our analysis provides evidence that the use of CDK 4/6 inhibitors is associated with an increased risk of all-grade and high-grade hematological adverse events, which seems to be a class-effect, but not of febrile neutropenia compared with hormonal therapy alone.
Topics: Breast Neoplasms; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Drug-Related Side Effects and Adverse Reactions; Female; Hematologic Diseases; Humans; Prognosis; Protein Kinase Inhibitors
PubMed: 29147869
DOI: 10.1007/s12282-017-0818-4 -
ESMO Open 2016Loss of cell cycle control is a hallmark of cancer, and aberrations in the cyclin-dependent kinase-retinoblastoma (CDK-Rb) pathway are common in breast cancer (BC).... (Review)
Review
BACKGROUND
Loss of cell cycle control is a hallmark of cancer, and aberrations in the cyclin-dependent kinase-retinoblastoma (CDK-Rb) pathway are common in breast cancer (BC). Consequently, inhibition of this pathway is an attractive therapeutic strategy. The present review addresses efficacy and toxicity of CDK4/6 inhibition in BC.
METHODS
A literature search was carried out using PubMed and EMBASE; data reported at international meetings and clinicaltrials.gov were included.
RESULTS
Three specific CDK4/6 inhibitors palbociclib, abemaciclib and ribociclib are tested in clinical trials. A randomised phase II trial of palbociclib plus letrozole versus letrozole and a phase III of palbociclib plus fulvestrant versus fulvestrant showed significantly increased progression-free survival when compared with endocrine therapy alone in first-line and second-line treatment for advanced hormone receptor-positive HER2-negative BC. At the moment several phase III studies are ongoing with all three CDK4/6 inhibitors in hormone receptor-positive HER2-negative BC as well as other subtypes of BC. The predominant toxicity of agents was limited neutropenia. Other common adverse events were infections, fatigue and gastrointestinal toxicity. The toxicities seemed manageable. Yet data are too limited to differentiate between the compounds. Retinoblastoma protein (Rb) is considered a promising biomarker.
CONCLUSION
CDK4/6 inhibition might represent a substantial advance for patients with hormone receptor-positive HER2-negative BC. Results must be confirmed in phase III trials before any firm conclusions can be made regarding the future influence of CDK4/6 inhibition. There is an urgent need for prospective biomarker-driven trials to identify patients for whom CDK4/6 inhibition is cost-effective.
PubMed: 28848657
DOI: 10.1136/esmoopen-2016-000093 -
Neurosurgical Review Mar 2019We conducted a systematic review of 72 studies to characterize trilateral retinoblastomas. Kaplan-Meier analysis was used to estimate survival, and statistical...
We conducted a systematic review of 72 studies to characterize trilateral retinoblastomas. Kaplan-Meier analysis was used to estimate survival, and statistical significance was assessed by using a log-rank test. We analyzed 211 cases of trilateral retinoblastomas. The average age of onset of retinoblastoma was 0.79 ± 1.38 years, and the average latency period between the onset of retinoblastomas and trilateral retinoblastomas was 1.49 ± 1.76 years. The brain tumors were found before the retinoblastoma diagnosis in 6 cases (3.1%), concurrently in 61 cases (32.1%), and after the retinoblastoma diagnosis in 123 cases (64.7%). Pineal tumors were found in 155 cases (73.4%) and sellar tumors in 46 cases (21.8%). The overall median survival was 10.3 months (95% CI, 8.5-13) and the 5-year survival rate was 15.7%. Central nervous system symptoms were variable and associated with shorter survival in univariate and multivariate analyses. The survival time in patients who received high-dose chemotherapy with stem cell transplant was significantly longer (p = 0.0067) than that of with or without conventional chemotherapy. Twelve long-term survivors were reported, and of these, six patients were treated with high-dose chemotherapy with stem cell transplant and six patients were treated with conventional chemotherapy. It is important that survivors continue to undergo regular medical surveillance in order to detect trilateral retinoblastoma at a potentially curative stage. Trilateral retinoblastoma patients with an irradiation history had shorter survival than those without irradiation history for retinoblastoma. High-dose chemotherapy should be considered as a potential treatment option for trilateral retinoblastomas.
Topics: Child, Preschool; Female; Humans; Infant; Infant, Newborn; Kaplan-Meier Estimate; Male; Retinal Neoplasms; Retinoblastoma
PubMed: 28815312
DOI: 10.1007/s10143-017-0890-4