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Pediatric Neurosurgery 2023Embryonal tumors are highly malignant cancers of the central nervous system, with a relatively high incidence in infants and young children. Even with intensive... (Review)
Review
BACKGROUND
Embryonal tumors are highly malignant cancers of the central nervous system, with a relatively high incidence in infants and young children. Even with intensive multimodal treatment, the prognosis of many types is guarded, and treatment-related toxicity is significant. Recent advances in molecular diagnostics allowed the discovery of novel entities and inter-tumor subgroups, with opportunities for improved risk-stratification and treatment approaches.
SUMMARY
Medulloblastomas separate into four distinct subgroups with distinct clinicopathologic characteristics, and data from recent clinical trials for newly diagnosed medulloblastoma support subgroup-specific treatment approaches. Atypical teratoid rhabdoid tumor (ATRT), embryonal tumor with multilayered rosettes (ETMR), and pineoblastoma, as well as other rare embryonal tumors, can be distinguished from histologically similar tumors by virtue of characteristic molecular findings, with DNA methylation analysis providing a strong adjunct in indeterminate cases. Methylation analysis can also allow further subgrouping of ATRT and pineoblastoma. Despite the dire need to improve outcomes for patients with these tumors, their rarity and lack of actionable targets lead to a paucity of clinical trials and novel therapeutics.
KEY MESSAGES
(1) Embryonal tumors can be accurately diagnosed with pediatric-specific sequencing techniques. (2) Medulloblastoma risk stratification and treatment decisions should take into account molecular subgroups. (3) There is a dire need for a novel collaborative clinical trial design to improve outcomes is rare pediatric embryonal tumors.
Topics: Child, Preschool; Humans; Infant; Brain Neoplasms; Central Nervous System Neoplasms; Cerebellar Neoplasms; Medulloblastoma; Neoplasms, Germ Cell and Embryonal; Pineal Gland; Pinealoma; Rhabdoid Tumor; Clinical Trials as Topic
PubMed: 37245504
DOI: 10.1159/000531256 -
Biochemical Genetics Feb 2022miRNAs are evolutionarily conserved non-coding ribonucleic acids with a length of between 19 and 25 nucleotides. Because of their ability to regulate gene expression,... (Review)
Review
miRNAs are evolutionarily conserved non-coding ribonucleic acids with a length of between 19 and 25 nucleotides. Because of their ability to regulate gene expression, miRNAs have an important function in the controlling of various biological processes, such as cell cycle, differentiation, proliferation, and apoptosis. Owing to the long-standing regulative potential of miRNAs in tumor-suppressive pathways, scholars have recently paid closer attention to the expression profile of miRNAs in various types of cancer. Melatonin, an indolic compound secreted from pineal gland and some peripheral tissues, has been considered as an effective anti-tumor hormone in a wide spectrum of cancers. Furthermore, it induces apoptosis, inhibits tumor metastasis and invasion, and also angiogenesis. A growing body of evidence indicates the effects of melatonin on miRNAs expression in broad spectrum of diseases, including cancer. Due to the long-term effects of the regulation of miRNAs expression, melatonin could be a promising therapeutic factor in the treatment of cancers via the regulation of miRNAs. Therefore, in this review, we will discuss the effects of melatonin on miRNAs expression in various types of cancers.
Topics: Apoptosis; Humans; Melatonin; MicroRNAs; Neoplasms
PubMed: 34181134
DOI: 10.1007/s10528-021-10104-4 -
World Neurosurgery Sep 2019Surgical indications for patients with pineal cysts are controversial. There are absolute indications such as hydrocephalus or tectal compression; otherwise, it is...
BACKGROUND
Surgical indications for patients with pineal cysts are controversial. There are absolute indications such as hydrocephalus or tectal compression; otherwise, it is difficult to decide whether surgery would be beneficial when symptoms are not distinct.
OBJECTIVE
We tried to clarify the indications and clinical course of patients after resection of pineal cysts without ventriculomegaly.
METHODS
We reviewed our database for all patients operated on for pineal cyst without ventriculomegaly from 2003 to 2018. We studied the presenting symptoms, cyst size, surgical approach, extent of resection, and clinical and radiologic follow-up. Follow-up ranged from 3 months to 14 years (mean 3.74 years).
RESULTS
Forty-three patients underwent surgery for pineal cyst in absence of ventriculomegaly; 36 female patients, 7 male patients, mean age 25.63 years (±10.62 years, range 4-52 years). Presenting symptoms included headache (41/43), nausea and vomiting (31/43), dizziness (19/43), visual disturbances (10/43), and sleep disturbances (8/43). Mean cyst size was 15.7 mm (±4.9 mm, range 9-27 mm). In total, 41 of 43 patients reported a good outcome, represented by a Chicago Chiari Outcome Scale score of 11 or greater and only 2 of 43 patients reported a bad outcome, defined by Chicago Chiari Outcome Scale score of 10 or less.
CONCLUSIONS
We suggest that pineal cysts without ventriculomegaly are an indication for surgery when patients present with headache and/or visual disturbances and other causes have been excluded. Resolution of symptoms and quality of life in our cohort may denote a good indication for resection. However, we must admit that there is still no evidence to recommend this technique as a treatment of headache in these patients.
Topics: Adolescent; Adult; Central Nervous System Cysts; Child; Child, Preschool; Dizziness; Female; Headache; Humans; Magnetic Resonance Imaging; Male; Microsurgery; Middle Aged; Neurosurgical Procedures; Pineal Gland; Postoperative Period; Treatment Outcome; Young Adult
PubMed: 31154104
DOI: 10.1016/j.wneu.2019.05.200 -
Molecular Genetics & Genomic Medicine Jun 2021Pineal cyst is a benign lesion commonly occurring in people of any age. Until now, the underlying molecular alterations have not been explored.
BACKGROUND
Pineal cyst is a benign lesion commonly occurring in people of any age. Until now, the underlying molecular alterations have not been explored.
METHODS
We performed whole exome sequencing of 93 germline samples and 21 pineal cyst tissue samples to illustrate its genetic architecture and somatic mutations. The dominant and recessive inheritance modes were considered, and a probability was calculated to evaluate the significance of variant overrepresentation.
RESULTS
By analyzing pineal cyst as a Mendelian disease with a dominant inheritance pattern, we identified 42,325 rare germline variants, and NM_001004711.1:c.476A>G was highly enriched (FDR<0.2). By analyzing it as a recessive disorder, we identified 753 homozygous rare variants detected in at least one pineal cyst sample each. One STIM2 rare variant, NM_001169117.1:c.1652C>T, was overrepresented (FDR<0.05). Analyzing at a gene-based level, we identified a list of the most commonlymutated germline genes, including POP4, GNGT2 and TMEM254. A somatic mutation analysis of 21 samples identified 16 variants in 15 genes, which mainly participated in the biological processes of gene expression and epigenetic regulation, immune response modulation, and transferase activity.
CONCLUSION
These molecular profiles are novel for this condition and provide data for investigators interested in pineal cysts.
Topics: Adolescent; Adult; Cysts; Female; GTP-Binding Protein gamma Subunits; Germ-Line Mutation; Heterozygote; Homozygote; Humans; Male; Middle Aged; Phenotype; Pineal Gland; Ribonucleases; Ribonucleoproteins; Stromal Interaction Molecule 2; Exome Sequencing
PubMed: 33943042
DOI: 10.1002/mgg3.1691 -
World Neurosurgery Feb 2021Given the rarity of patients with pineal glioblastoma (GBM), clinical characteristics, treatment, and prognostic factors are not well characterized. This study aimed to...
OBJECTIVE
Given the rarity of patients with pineal glioblastoma (GBM), clinical characteristics, treatment, and prognostic factors are not well characterized. This study aimed to investigate these characteristics and identify the prognostic factors of overall survival (OS).
METHODS
A retrospective analysis of newly diagnosed patients with pineal GBM, including our 3 cases and an additional 44 cases from published articles, was conducted. Survival analysis was performed by Kaplan-Meier analysis and Cox regression analysis was used to determine the prognostic factors.
RESULTS
A total of 47 patients (28 males and 19 females) were enrolled, with a median age of 46 years (range, 5-74 years). Forty-four patients (90.9%) had preoperative obstructive hydrocephalus. Among 38 patients, 21 (55.3%) had distal leptomeningeal dissemination. Forty-five patients (95.7%) had resection/biopsy, 6 of whom had gross total resection, 22 had subtotal resection, 7 had partial resection, and 10 had biopsy. Adjuvant therapy included radiotherapy in 36 patients and chemotherapy in 27 patients. The median OS was 10.0 months. The 6-month, 1-year, and 2-year survival was 68.0%, 42.6%, and 17.0%, respectively. Cox regression analysis showed that patients receiving biopsy (P = 0.042) or chemotherapy (P = 0.029) had the better OS and these were regarded as independent prognostic factors. Further survival analysis showed that chemoradiotherapy had better survival benefit than other regimens.
CONCLUSIONS
In this study, we summarized the characteristics of patients with pineal GBM and showed the correlation between clinical characteristics and prognosis. This study may give readers a deep understanding of these rare GBMs and provide some references for future management.
Topics: Adolescent; Adult; Aged; Brain Neoplasms; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Child; Child, Preschool; Female; Glioblastoma; Humans; Male; Middle Aged; Neurosurgical Procedures; Pineal Gland; Pinealoma; Prognosis; Proportional Hazards Models; Radiotherapy, Adjuvant; Survival Rate; Young Adult
PubMed: 33186787
DOI: 10.1016/j.wneu.2020.11.016 -
Journal of Cellular Physiology Dec 2019Cervical cancer is one of the most common cancers between women and is known as the third leading cause of female cancer related deaths annually. Its detection in early... (Review)
Review
Cervical cancer is one of the most common cancers between women and is known as the third leading cause of female cancer related deaths annually. Its detection in early stages allows it to be a preventable and generally treatable disease. Increasing evidence revealed, a variety of internal and external factors are associated with initiation and progression of cervical cancer pathogenesis. Human papilloma virus infection is found as a major cause of cervical cancer. Other molecular and biochemical alterations as well as genetic and epigenetic changes are related cervical cancer progression. Current treatment options often have severe side effects and toxicities thus, new adjuvant agents having synergistic effects and ability to decrease different side effects and toxicities are needed. Melatonin is an indolamine compound secreted from the pineal gland which shows wide range anticancer activities. A large amount of studies indicated inhibitory effects of melatonin against various types of cancers. In addition, experimental evidence reports inhibitory effects of melatonin as an adjuvant therapy on cervical cancer by targeting a sequence of different molecular mechanisms. Herein, for first time, we summarized anticervical cancer effects of melatonin and its underlying molecular mechanisms.
Topics: Animals; Antineoplastic Agents; Female; Humans; Melatonin; Uterine Cervical Neoplasms
PubMed: 31131897
DOI: 10.1002/jcp.28865 -
Medical Sciences (Basel, Switzerland) Jan 2023Melanoma is the most aggressive type of skin cancer, with a greater risk of metastasis and a higher prevalence and mortality rate. This cancer type has been demonstrated... (Review)
Review
Melanoma is the most aggressive type of skin cancer, with a greater risk of metastasis and a higher prevalence and mortality rate. This cancer type has been demonstrated to develop resistance to the known treatment options such as conventional therapeutic agents and targeted therapy that are currently being used as the standard of care. Drug repurposing has been explored as a potential alternative treatment strategy against disease pathophysiologies, including melanoma. To that end, multiple studies have suggested that melatonin produced by the pineal gland possesses anti-proliferative and oncostatic effects in experimental melanoma models. The anticarcinogenic activity of melatonin is attributed to its ability to target a variety of oncogenic signaling pathways, including the MAPK pathways which are involved in regulating the behavior of cancer cells, including cell survival and proliferation. Additionally, preclinical studies have demonstrated that melatonin in combination with chemotherapeutic agents exerts synergistic effects against melanoma. The goal of this review is to highlight the mechanistic insights of melatonin as a monotherapy or combinational therapy for melanoma treatment.
Topics: Animals; Melatonin; Skin Neoplasms; Pineal Gland; Melanoma, Experimental; Signal Transduction
PubMed: 36649046
DOI: 10.3390/medsci11010009 -
Journal of Neurosciences in Rural... 2023Pineal cysts are usually benign, fluid-filled sacs and most pineal cysts are asymptomatic. Sudden death specifically related to pineal cysts is extremely uncommon. A...
Pineal cysts are usually benign, fluid-filled sacs and most pineal cysts are asymptomatic. Sudden death specifically related to pineal cysts is extremely uncommon. A literature review of the pertinent databases, including PubMed, Google Scholar, Scopus, and Web of Science, was carried out to review the existing literature describing sudden death in patients with pineal cysts. In the evaluation of 49 articles, it was found that four reports discussed the unexpected death of patients who had pineal cysts. A total of four cases of sudden death and a pineal cyst were reported. There were 75% females and a mean age of 29 (range: 20-45). Cyst size on average was 1.3 cm (1.2-1.5). In each case, the cause of death and the involvement of important brain structures were confirmed by autopsy results. A pathological analysis of the pineal region and the surrounding brain tissue revealed a variety of lesions. Vascular malformation was found in one case, adding another layer of complexity to the study of sudden death syndrome. In this research, the authors highlight the fact that patients with pineal cysts can experience serious, even fatal, complications. Increased vigilance and early detection through neuroimaging and neurological assessments are required due to the wide variety of clinical manifestations and underlying mechanisms. To explain the mechanism and enhance the management and prevention of sudden deaths associated with pineal cysts, additional research with larger sample sizes is required.
PubMed: 38059255
DOI: 10.25259/JNRP_421_2023 -
International Journal of Surgery... Dec 2023The pineal region tumors are challenging for neurosurgeons and can lead to secondary hydrocephalus. The introduction of the exoscope has provided clinical interventions...
BACKGROUND
The pineal region tumors are challenging for neurosurgeons and can lead to secondary hydrocephalus. The introduction of the exoscope has provided clinical interventions with high image quality and an ergonomic system for pineal region tumor operations. In this study, the authors describe the exoscopic approach used to facilitate the surgical resection of pineal region tumors and relieve hydrocephalus.
MATERIALS AND METHODS
In this retrospective cohort study, we consecutively reviewed the clinical and radiological data of 25 patients with pineal region lesions who underwent three-dimensional exoscopic tumor resection at a single center.
RESULTS
The patient cohort consisted of 16 males and 9 females, with an average age of 34.6 years (range, 6-62 years; 8 cases aged ≤18). Pathological examination confirmed eight pineal gland tumors, four gliomas, nine germ cell neoplasms, two ependymomas, and two metastatic tumors. Preoperative hydrocephalus was present in 23 patients. Prior to tumor resection, external ventricular drainage (EVD) with Ommaya reservoir implantation was performed in 17 patients. Two patients received preoperative endoscopic third ventriculostomy (ETV), and five patients received a ventriculoperitoneal (VP) shunt, including one who received both procedures. Gross total resection was achieved in 19 patients (76%) in the 'head-up' park bench position using the exoscope. Eight patients (31.6%) with third ventricle invasion received subtotal resection, mainly in glioma cases, which was higher than those without invasion (0%), but not statistically significant ( P =0.278, Fisher's exact test). No new neurological dysfunction was observed after surgery. Two patients (8%) developed intracranial and pulmonary infections, and two patients (8%) suffered from pneumothorax. Hydrocephalus was significantly relieved in all patients postoperatively, and four patients with relapse hydrocephalus were cured during the long-term follow-up. Postoperative adjuvant management was recommended for indicated patients, and a mean follow-up of 24.8±14.3 months showed a satisfied outcome.
CONCLUSIONS
The exoscope is a useful tool for pineal region tumor resection and hydrocephalus relief, particularly with posterior third ventricle invasion, as total resection could be achieved without obvious complication. The special superiority of the exoscope for the indicated pineal region tumors should be highlighted.
Topics: Male; Female; Humans; Adult; Pinealoma; Retrospective Studies; Treatment Outcome; Neoplasm Recurrence, Local; Pineal Gland; Glioma; Ventriculostomy; Third Ventricle; Hydrocephalus; Brain Neoplasms
PubMed: 37755386
DOI: 10.1097/JS9.0000000000000707 -
JPMA. the Journal of the Pakistan... Nov 2022To provide information about brain tumour epidemiology in Pakistan and potential associated risk factors due to family, medical and social characteristics.
OBJECTIVES
To provide information about brain tumour epidemiology in Pakistan and potential associated risk factors due to family, medical and social characteristics.
METHODS
A retrospective cross-sectional nationwide study was designed by the Pakistan Society of Neuro-oncology, to include patients diagnosed with brain tumours in Pakistan retrospectively, from January 1, 2019- December 31, 2019. The study intended to involve data from all age groups for all brain tumour cases, irrespective of histopathology which would determine the national prevalence and incidence of these tumours.
RESULTS
A total of 2750 brain tumour cases were recorded, of which 1897 (69%) were diagnosed in the public sector. MRIs were a more common radiological study compared to CT scans. Gliomas were the most common tumours 778 (28.29%), while pineal tumours were the least common 19 (0.69%). The median age at diagnosis for males was 36 (24-49), while the median age at diagnosis for females was 37 (24-48). Hypertension was the most common co-morbidity in patients diagnosed with a brain tumour, 524 (51.89%), and smoking was the most frequent social behaviour, 355 (62.02%). Findings indicate a low metastasis frequency and few females seeking care.
CONCLUSIONS
The PBTES and the PBTC have presented an opportunity and platform for hospitals and health professionals to work together to strengthen cancer care health systems, ensure implementation of treatment guidelines and conduct regular cancer registration.
Topics: Male; Female; Humans; Retrospective Studies; Pakistan; Cross-Sectional Studies; Brain Neoplasms; Glioma
PubMed: 36591621
DOI: 10.47391/JPMA.11-S4-AKUB01