Techniques for assessing telomere length: A methodological review.

Telomeres are located at the ends of chromosomes and have specific sequences with a distinctive structure that safeguards genes. They possess capping structures that protect chromosome ends from fusion events and ensure chromosome stability. Telomeres shorten in length during each cycle of cell division. When this length reaches a certain threshold, it can lead to genomic instability, thus being implicated in various diseases, including cancer and neurodegenerative disorders. The possibility of telomeres serving as a biomarker for aging and age-related disease is being explored, and their significance is still under study. This is because post-mitotic cells, which are mature cells that do not undergo mitosis, do not experience telomere shortening due to age. Instead, other causes, for example, exposure to oxidative stress, can directly damage the telomeres, causing genomic instability. Nonetheless, a general agreement has been established that measuring telomere length offers valuable insights and forms a crucial foundation for analyzing gene expression and epigenetic data. Numerous approaches have been developed to accurately measure telomere lengths. In this review, we summarize various methods and their advantages and limitations for assessing telomere length.

A prospective multicenter assessor blinded pilot study using confocal laser endomicroscopy for intraoperative brain tumor diagnosis.

In this multi-center, assessor-blinded pilot study, the diagnostic efficacy of cCeLL-Ex vivo, a second-generation confocal laser endomicroscopy (CLE), was compared against the gold standard frozen section analysis for intraoperative brain tumor diagnosis. The study was conducted across three tertiary medical institutions in the Republic of Korea. Biopsy samples from newly diagnosed brain tumor patients were categorized based on location and divided for permanent section analysis, frozen section analysis, and cCeLL-Ex vivo imaging. Of the 74 samples from 55 patients, the majority were from the tumor core (74.3%). cCeLL-Ex vivo exhibited a relatively higher diagnostic accuracy (89.2%) than frozen section analysis (86.5%), with both methods showing a sensitivity of 92.2%. cCeLL-Ex vivo also demonstrated higher specificity (70% vs. 50%), positive predictive value (PPV) (95.2% vs. 92.2%), and negative predictive value (NPV) (58.3% vs. 50%). Furthermore, the time from sample preparation to diagnosis was notably shorter with cCeLL-Ex vivo (13 min 17 s) compared to frozen section analysis (28 min 28 s) (p-value < 0.005). These findings underscore cCeLL-Ex vivo's potential as a supplementary tool for intraoperative brain tumor diagnosis, with future studies anticipated to further validate its clinical utility.

Changes in the Epidemiologic Pattern of Primary CNS Tumors in Response to the Aging Population: An Updated Nationwide Cancer Registry Data in the Republic of Korea.

PURPOSE: Primary CNS tumors (PCNSTs) are tumors originating from the brain and surrounding tissues. These tumors account for a significant proportion of cancer deaths and morbidity globally. Accurate epidemiologic data are essential for shaping clinical practices, research priorities, and health care policies. This study presents the latest 2020 national data on PCNSTs from the Republic of Korea (ROK) and explores the trends in incidence and their societal implications in the context of an aging population. METHODS: This is a cross-sectional, observational study conducted using data sourced from the Korea National Cancer Incidence Database by the Korea Central Cancer Registry. The study analyzed national data on PCNSTs in the ROK for the years 2010, 2013, 2016, and 2020. RESULTS: In 2020, 15,568 new PCNST cases were diagnosed in the ROK. The overall crude rate was 30.32, and the age-standardized rate was 19.37 per 100,000 persons. A decade-long trend analysis revealed an increasing trend in newly diagnosed glioblastoma and lymphoma, and a decreasing trend in embryonal tumors, in relation to the aging population of the ROK. CONCLUSION: This study shows the significant impact of demographic shifts on the epidemiologic patterns of PCNSTs in the ROK. Our findings emphasize the need for collaborative efforts to address the rising challenges posed by the changing incidence of PCNSTs related to an aging population.

Factors Limiting Complete Resection in the Subarachnoid Space in Endoscopic Surgery for Giant Pituitary Adenoma.

OBJECTIVES: Giant pituitary adenomas (>4 cm, GPAs) have presented great challenges to surgeons because the residual tumor in the subarachnoid space can cause hemorrhage or vessel injury following apoplexy. This study aimed to investigate the factors limiting surgical success in endoscopic skull base surgery (ESS) for GPAs. METHODS: ESS was performed on 67 consecutive patients with GPAs from 2010 to 2020. We retrospectively analyzed the clinical and radiologic features and surgical outcomes. Correlations between the tumor characteristics and extent of resection were statistically presented with odds ratios (ORs). RESULTS: Preoperative visual and hormonal impairments were present in 59 (88.1%) and 55 patients (82.1%), respectively. Gross total resection (GTR) was achieved in 58.2% of patients, and the tumor remained on the lateral side of the subarachnoid space or the cavernous sinus when complete resection failed. The tumor volume, maximal diameter, multilobulated shape, cavernous sinus invasion, posterior fossa extension, and extent of suprasellar lateral extension of tumors were significantly correlated with incomplete resection. In tumors with subarachnoid lateral extension, greater distances from the medial wall of the proximal cavernous internal carotid artery to the most lateral tumor significantly increased the risk of incomplete resection for the suprasellar lateral portion of the tumor, with an OR of 1.21. CONCLUSIONS: Considerable surgical planning in ESS for GPAs is crucial for complete resection and patient safety. We elucidated that lateral extension of tumors in the subarachnoid space hindered the surgical success of the suprasellar portion of the tumor.

The Warburg effect in patients with brain tumors: a comprehensive analysis of clinical significance.

PURPOSE: The Warburg Effect, referring to an elevation in serum lactate level attributable to increased tumor metabolism, is present in patients with brain tumors. This study comprehensively analyzes the Warburg effect in patients undergoing brain tumor resection. METHODS: We retrospectively analyzed the baseline intraoperative serum lactate levels of 2,053 patients who underwent craniotomies, including 415 with cerebral aneurysms and 1,638 with brain tumors. The brain tumor group was divided into subgroups based on the tumor pathology (extra-axial and intra-axial tumor) and the WHO tumor grade (high-grade and low-grade). RESULTS: Serum lactate level was significantly higher in the tumor group than in the aneurysm group (1.98 ± 0.97 vs. 1.09 ± 0.57 mmol/L, p < 0.001). The hyperlactatemia incidence (serum lactate level > 2.2 mmol/L) was higher in the tumor group (33.5 vs. 3.1%, p < 0.001). Severe hyperlactatemia (serum lactate level > 4.4 mmol/L) was found in 34 patients (2.1%) of only the tumor group. In patients with intra-axial tumors, serum lactate level was greater in high- than low-grade tumors (2.10 ± 1.05 vs. 1.88 ± 0.92 mmol/L, p = 0.006). Factors predictive of hyperlactatemia included supratentorial tumor location (odds ratio[95%CI] 2.926[2.127-4.025], p < 0.001) and a long tumor diameter (1.071[1.007-1.139], p = 0.028). In high-grade intra-axial brain tumor patients, there was a significant difference in overall survival between patients with hyperlactatemia than those without (p = 0.048). CONCLUSION: Our results show that brain tumor patients exhibit the Warburg effect and serum lactate may be a useful diagnostic and prognostic biomarker in patients with high-grade intra-axial brain tumors.

Changes of Resection Goal After Using 3-Dimensional Printing Brain Tumor Model for Presurgical Planning.

BACKGROUND: Conventional 2-Dimensional magnetic resonance imaging-based neuronavigation systems can improve the maximal safe resection in brain tumor surgery but can be unintuitive. A 3-Dimensional (3D)-printed brain tumor model allows for a more intuitive and stereoscopic understanding of brain tumors and adjacent neurovascular structures. This study aimed to identify the clinical efficacy of a 3D-printed brain tumor model in presurgical planning by focusing on differences in the extent of resection (EOR). METHODS: Thirty two neurosurgeons (14 faculty members, 11 fellows, 7 residents) randomly selected the two 3D-printed brain tumor models from the 10 manufactured models and performed presurgical planning following a standardized questionnaire. To compare the 2-Dimensional magnetic resonance imaging-based planning results with the 3D-printed model-based planning results, we analyzed the changing patterns and characteristics of the EOR. RESULTS: Of 64 randomly generated cases, the resection goal changed in 12 cases (18.8%). When the tumor was located intra-axially, the surgical posture required a prone position, and when the neurosurgeon was dexterous in surgery, there was a higher rate of EOR changes. 3D-printed models 2, 4, and 10, which all represented tumors in the posterior of the brain, had high rates of changing EOR. CONCLUSIONS: A 3D-printed brain tumor model could be utilized in presurgical planning to effectively determine the EOR.

Advances in Pituitary Surgery.

Pituitary surgery has advanced considerably in recent years with the exploration and development of various endoscopic approaches and techniques. Different endoscopic skull base approaches are being applied to access sellar tumors in different locations. Moreover, extracapsular dissection and cavernous sinus exploration have enabled gross total resection of sellar tumors where it could not have been achieved in the past. Techniques for skull base reconstruction have also progressed, allowing surgeons to remove larger and more complicated tumors than before. This review article discusses different endoscopic skull base approaches, surgical techniques for removing pituitary adenomas, and reconstruction methods for repairing postoperative low-flow and high-flow cerebrospinal fluid leakage.

Classification and Diagnosis of Adult Glioma: A Scoping Review.

Gliomas are primary central nervous system tumors that arise from glial progenitor cells. Gliomas have been classically classified morphologically based on their histopathological characteristics. However, with recent advances in cancer genomics, molecular profiles have now been integrated into the classification and diagnosis of gliomas. In this review article, we discuss the clinical features, imaging findings, and molecular profiles of adult-type diffuse gliomas based on the new 2021 World Health Organization Classifications of Tumors of the central nervous system.

Long-Term Outcomes of Indirect Bypass for 629 Children With Moyamoya Disease: Longitudinal and Cross-Sectional Analysis.

Background and Purpose- In pediatric moyamoya disease, there are few reports on the efficacy of surgical intervention for stroke prevention. We evaluated the long-term outcomes of indirect bypass surgery on a relatively large number of children with moyamoya disease in a single center. Methods- From August 1988 to December 2012, 772 children underwent indirect bypass surgery. This study included 629 patients who were followed up for >5 years, excluding patients with moyamoya syndrome. The mean clinical follow-up duration was 12 years (range, 5-29 years). Cross-sectional analysis was performed based on either Karnofsky Performance Scale or Lansky Play Performance Scale to evaluate overall clinical outcomes and factors associated with unfavorable outcomes. To analyze the longitudinal effect of surgery, the annual risk of symptomatic infarction or hemorrhage on the operated hemisphere after indirect bypass surgery was calculated with a person-year method, and the event-free survival rate was evaluated using the Kaplan-Meier method. Results- The overall clinical outcome was favorable in 95% of the patients. The annual risks of symptomatic infarction and hemorrhage on the operated hemispheres were 0.08% and 0.04%, respectively. Furthermore, the 10-year event-free survival rates for symptomatic infarction and hemorrhage were 99.2% and 99.8%. Conclusions- Indirect bypass surgery could provide satisfactory long-term improvement in overall clinical outcome and prevention of recurrent stroke in children with moyamoya disease.

Preservation of the Arachnoid Membrane During Encephaloduroarteriosynangiosis Reduces Postoperative Complications without Undermining the Surgical Outcome in Pediatric Moyamoya Disease.

BACKGROUND: Encephaloduroarteriosynangiosis (EDAS) is a commonly used indirect revascularization operation method to treat pediatric patients with Moyamoya disease (MMD). Arachnoid dissection frequently has been performed during the EDAS operation to promote better revascularization. However, no studies have yet proven its surgical benefits. In this study, we investigated the impact of arachnoid preservation on the surgical outcome and postoperative complication by comparing pediatric patients with MMD who had the arachnoid membrane preserved during EDAS operation with those who had it dissected. METHODS: This was a retrospective cohort study based on a single surgeon's experience at a single institution. A total of 206 pediatric patients with MMD who underwent EDAS operation at Seoul National University Children's Hospital were recruited for the study. We compared the surgical outcome and the postoperation complication rate of these 2 groups. Furthermore, risk factors for postoperative complication were analyzed. RESULTS: The overall clinical outcome (P = 0.342) and the extent of revascularization of middle cerebral artery territories (P = 0.736) were not different between the arachnoid dissection group and the arachnoid preservation group. However, the postoperative infarction/hemorrhage rate was significantly greater in the arachnoid dissection group (P = 0.005). Arachnoid dissection (P = 0.011) and young age (<3 years old, P = 0.012) were significantly associated with increased risk of postoperative complications. CONCLUSIONS: Arachnoid preservation may help to reduce postoperative complications without decreasing the surgical outcome of EDAS. Furthermore, factors such as the patient's age should be taken into account when treating pediatric patients with MMD.

Local recurrence of brain metastasis reduced by intra-operative hyperthermia treatment.

PURPOSE: Brain metastasis is a common complication in cancer patients. Local recurrence after total resection of metastatic brain tumor has been frequently reported. In this study, we developed a new hyperthermia device and applied it to metastatic brain tumor patients intra-operatively to study if hyperthermia treatment could reduce local tumor recurrence. MATERIALS AND METHODS: A total of 63 metastatic brain patients were enrolled in the study with an informed consent obtained from every patient. After total resection of the tumor, the hyperthermia device was applied intra-operatively to the resection cavity. The surrounding brain tissue at 5 mm in depth from the tumor resection margin was raised to 42.5 °C for a total of 60 minutes (Clinical Research Information Service Registration Number: KCT0001308). RESULTS: A total of 10 local recurrences were observed in 63 patients who received hyperthermia treatment showing a local recurrence rate of 15.8%. It was significantly lower than the local recurrence rate of those who received conventional treatment (34%) when analyzed with one tailed z-test (p value: .001). Kaplan-Meier analysis also showed a significantly lower recurrence rate in the hyperthermia treatment group (p value: .0003). Complications included two cases of seizures and two cases of wound infection. CONCLUSIONS: Results of this study suggest that intra-operative hyperthermia treatment after total resection of metastatic brain tumor could reduce local recurrence of tumor. We believe that intra-operative hyperthermia treatment could be used as an adjuvant therapy to surgery and post-operative radiotherapy, or as a salvage treatment in patients who cannot receive further radiotherapy.

Decompressive craniectomy for herpes simplex encephalitis complicated by frank intracerebral hemorrhage: a case report and review of the literature.

BACKGROUND: Herpes simplex encephalitis is the most common type of sporadic encephalitis worldwide. Frank intracerebral hemorrhage complicating the disease course in herpes simplex encephalitis patients is rare, especially cases where surgical decompression is necessary. Here, we report a previously healthy female with herpes simplex encephalitis who underwent surgical decompression due to temporal lobe hemorrhage. CASE PRESENTATION: A previously healthy 34-year-old Korean female presented with fever, myalgia and severe headache. Brain MRI showed a high T2 signal intensity change and diffuse swelling of the right temporal lobe. Polymerase chain reaction testing of the cerebrospinal fluid confirmed the presence of herpes simplex virus 1. The patient was admitted for close observation and intravenous acyclovir. On hospital day 3, she had a sudden onset of vomiting and severe headache. Brain CT showed frank temporal lobe hemorrhage. Despite aggressive medical treatment, she became increasingly drowsy. Ultimately, she underwent emergency right decompressive craniectomy, expansile duraplasty and intracranial pressure monitor insertion. The patient recovered fully without any neurological deficits or neuropsychological problems. She was discharged after completion of 2 weeks of acyclovir and returned 2 months later for cranioplasty. CONCLUSIONS: Patients with severe herpes simplex encephalitis complicated by intracerebral hemorrhage or malignant cerebral edema should undergo aggressive medical treatment. Surgical decompression should also be actively considered in these severe cases to prevent further neurological deterioration.

A Novel Implantable Cerebrospinal Fluid Reservoir : A Pilot Study.

OBJECTIVE: The purpose of this pilot study was to examine the safety and function of the newly developed cerebrospinal fluid (CSF) reservoir called the V-Port. METHODS: The newly developed V-Port consists of a non-collapsible reservoir outlined with a titanium cage and a connector for the ventricular catheter to be assembled. It is designed to be better palpated and more durable to multiple punctures than the Ommaya reservoir. A total of nine patients diagnosed with leptomeningeal carcinomatosis were selected for V-Port insertion. Each patient was followed up for evaluation for a month after the operation. RESULTS: The average operation time for V-Port insertion was 42 minutes and the average incision size was 6.6 cm. The surgical technique of V-Port insertion was found to be intuitive by all neurosurgeons who participated in the pilot study. There was no obstruction or leakage of the V-Port during intrathecal chemotherapy or CSF drainage. Also, there were no complications including post-operative intracerebral hemorrhage, infection and skin problems related to the V-Port. CONCLUSION: V-Port is a safe and an easy to use implantable CSF reservoir that addresses problems of other implantable CSF reservoirs. Further multicenter clinical trial is needed to prove the safety and the function of the V-Port.

Cervical Spine Chondroma Compressing Spinal Cord: A Case Report and Literature Review.

Chondromas are benign tumor of cartilaginous tissue that is rarely found in spine. The authors document a rare case of a 72 year old male patient with a cervical spinal chondroma compressing the spinal cord. The patient had symptoms of motor and sensory deficits, dysphagia and dysarthria. C1 and C2 laminotomy was done and the spinal tumor was removed. The patient gradually recovered from his previous symptom after the surgery.

Mobile phone use, blood lead levels, and attention deficit hyperactivity symptoms in children: a longitudinal study.

BACKGROUND: Concerns have developed for the possible negative health effects of radiofrequency electromagnetic field (RF-EMF) exposure to children's brains. The purpose of this longitudinal study was to investigate the association between mobile phone use and symptoms of Attention Deficit Hyperactivity Disorder (ADHD) considering the modifying effect of lead exposure. METHODS: A total of 2,422 children at 27 elementary schools in 10 Korean cities were examined and followed up 2 years later. Parents or guardians were administered a questionnaire including the Korean version of the ADHD rating scale and questions about mobile phone use, as well as socio-demographic factors. The ADHD symptom risk for mobile phone use was estimated at two time points using logistic regression and combined over 2 years using the generalized estimating equation model with repeatedly measured variables of mobile phone use, blood lead, and ADHD symptoms, adjusted for covariates. RESULTS: The ADHD symptom risk associated with mobile phone use for voice calls but the association was limited to children exposed to relatively high lead. CONCLUSIONS: The results suggest that simultaneous exposure to lead and RF from mobile phone use was associated with increased ADHD symptom risk, although possible reverse causality could not be ruled out.

Epidemiological characteristics of mobile phone ownership and use in korean children and adolescents.

OBJECTIVES: As public concern on possible harmful effects of mobile phone in children has been raised, information of epidemiological characteristics of mobile phone use in children and adolescents will be essential for public health policy. METHODS: Using three databases (n=21,693) collected from 2008 to 2011, we examined characteristics of mobile phone ownership and use, and socioeconomic positions (SEP) in Korean children and adolescents. RESULTS: The ownership rate and the amount of mobile phone use were higher in females than males, in higher school grades than lower grades, and at 2011 than 2008. The average age of first mobile phone ownership was shown to decrease from 12.5 years in currently high school students to 8.4 years in currently elementary school students at 2011. More than 90% of children in the 5th grade owned a mobile phone. More children owned a mobile phone in lower SEP communities than in higher SEP. Children with parents educated less than those with parents educated more were more likely to own and use mobile phone. CONCLUSIONS: Considering the epidemiological characteristics of mobile phone use, precautionary measures to prevent unnecessary exposure to mobile phones are needed in children and adolescents.