Supratotal Resection: An Emerging Concept of Glioblastoma Multiforme Surgery-Systematic Review And Meta-Analysis.

BACKGROUND: The severe neurologic tumor known as glioblastoma (GBM), also referred to as a grade IV astrocytoma, is rapidly progressive and debilitating. Supratotal resection (SpTR) is an emerging concept within glioma surgery, which aims to achieve a more extensive resection of the tumor than is possible with conventional techniques. METHODS: We performed a language-independent search of PubMed, Scopus, and Cochrane CENTRAL to identify all available literature up to August 2022 of patients undergoing SpTR assessing survival outcomes in comparison to other surgical modalities. RESULTS: After screening for exclusion, a total of 13 studies, all retrospective in design, were identified and included in our meta-analysis. SpTR was associated with significantly increased overall survival (hazard ratio 0.77, 95% CI 0.71-0.84; P < 0.01, I2 = 96%) and progression-free survival (hazard ratio 0.2, 95% CI 0.07-0.56; P = 0.002, I2 = 88%). CONCLUSION: SpTR is associated with greater overall survival and PFS when compared with other glioblastoma surgeries like GTR or SubTR.

Intrinsic and extrinsic apoptosis responses in leukaemia cells following daunorubicin treatment.

BACKGROUND: Daunorubicin is used clinically in the treatment of myeloma, acute lymphatic and myelocytic leukaemia. The toxic lesions caused by daunorubicin induce various modes of cell death, including apoptosis. Apoptosis is highly regulated programmed cell death that can be initiated mainly via two pathways, through death receptors (extrinsic) or involvement of the mitochondria (intrinsic). Induction of apoptosis via these pathways has been alluded following treatment with daunorubicin, but never compared in acute lymphoblastic leukaemia over a time course. METHODS: This study investigated the mechanisms of daunorubicin induced apoptosis in the treatment of CCRF-CEM, MOLT-4 (acute T-lymphoblastic leukaemia) and SUP-B15 (acute B-lymphoblastic leukaemia) cells. Cells were treated with daunorubicin for 4 h, and then placed in recovery medium (without daunorubicin) for 4 h, 12 h and 24 h. Apoptotic response was analysing using annexin-V expression, caspase activity, mitochondrial membrane potential change and an array to detect 43 apoptotic proteins. RESULTS: Daunorubicin induced apoptosis in all leukemic cell lines, but with different levels and duration of response. Both apoptosis levels and caspase activity increased after four hours recovery then declined in CCRF-CEM and MOLT-4 cells. However, SUP-B15 cells displayed initially comparable levels but remained elevated over the 24 h assessment period. Changes in mitochondrial membrane potential occurred in both MOLT-4 and CCRF-CEM cells but not in SUP-B15 cells. Expression of apoptotic proteins, including Bcl-2, Bax, caspase 3 and FADD, indicated that daunorubicin potentially induced both extrinsic and intrinsic apoptosis in both CCRF-CEM and MOLT-4 cells, but only extrinsic apoptosis in SUP-B15 cells. CONCLUSIONS: This study describes variations in sensitivities and timing of apoptotic responses in different leukaemia cell lines. These differences could be attributed to the lack of functional p53 in coordinating the cells response following cytotoxic treatment with daunorubicin, which appears to delay apoptosis and utilises alternative signalling mechanisms that need to be further explored.

Determination of the DNA repair pathways utilised by acute lymphoblastic leukaemia cells following daunorubicin treatment.

OBJECTIVE: DNA double strand breaks (DNA-DSBs) are among the most lethal DNA lesions leading to genomic instability and repaired by either homologous recombination (HR) or the non-homologous end joining (NHEJ) mechanisms. The purpose of this study was to assess the importance and the level of activation of non-homologous end joining (NHEJ) and homologous recombination (HR) DNA repair pathways in three cell lines, CCRF-CEM and MOLT-4 derived from T lymphocytes and SUP-B15 derived from B lymphocytes following treatment with chemotherapy agent daunorubicin. RESULTS: The Gamma histone H2AX (γH2AX) assay was used assess the effects of DNA-PK inhibitor NU7026 and RAD51 inhibitor RI-2 on repair of DNA-DSB following treatment with daunorubicin. In all cell lines, the NHEJ DNA repair pathway appeared more rapid and efficient. MOLT-4 and CCFR-CEM cells utilised both NHEJ and HR pathways for DNA-DSB repair. Whereas, SUP-B15 cells utilised only NHEJ for DSB repair, suggestive of a deficiency in HR repair pathways.

Time dependent response of daunorubicin on cytotoxicity, cell cycle and DNA repair in acute lymphoblastic leukaemia.

BACKGROUND: Daunorubicin is commonly used in the treatment of acute lymphoblastic leukaemia (ALL). The aim of this study was to explore the kinetics of double strand break (DSB) formation of three ALL cell lines following exposure to daunorubicin and to investigate the effects of daunorubicin on the cell cycle and the protein kinases involved in specific checkpoints following DNA damage and recovery periods. METHODS: Three ALL cell lines CCRF-CEM and MOLT-4 derived from T lymphocytes and SUP-B15 derived from B lymphocytes were examined following 4 h treatment with daunorubicin chemotherapy and 4, 12 and 24 h recovery periods. Cell viability was measured via MTT (3-(4,5-dimethylthiazol-2-yl)-2-5 diphenyltetrazolium bromide) assay, reactive oxygen species (ROS) production by flow cytometry, double stranded DNA breaks by detecting γH2AX levels while stages of the cell cycle were detected following propidium iodide staining and flow cytometry. Western blotting was used to detect specific proteins while RNA was extracted from all cell lines and converted to cDNA to sequence Ataxia-telangiectasia mutated (ATM). RESULTS: Daunorubicin induced different degrees of toxicity in all cell lines and consistently generated reactive oxygen species. Daunorubicin was more potent at inducing DSB in MOLT-4 and CCRF-CEM cell lines while SUP-B15 cells showed delays in DSB repair and significantly more resistance to daunorubicin compared to the other cell lines as measured by γH2AX assay. Daunorubicin also causes cell cycle arrest in all three cell lines at different checkpoints at different times. These effects were not due to mutations in ATM as sequencing revealed none in any of the three cell lines. However, p53 was phosphorylated at serine 15 only in CCRF-CEM and MOLT-4 but not in SUP-B15 cells. The lack of active p53 may be correlated to the increase of SOD2 in SUP-B15 cells. CONCLUSIONS: The delay in DSB repair and lower sensitivity to daunorubicin seen in the B lymphocyte derived SUP-B15 cells could be due to loss of function of p53 that may be correlated to increased expression of SOD2 and lower ROS production.

Ossification and hypertrophy of ligamentum flavum at thoracic spine.

BACKGROUND: Hypertrophy of the ligamentum flavum is a pathological condition that causes neurological symptom (radiculopathy and / or myelopathy) and usually occurs in the thoracic,2 less frequently in the cervical spine that commonly involves thoracic spine. This study was conducted to analyse the clinical presentation and outcome of surgery of ossified ligamentum flavum at thoracic spine. METHODS: This case series was conducted at Department of Neurosurgery, Liaquat University of Medical and Health Sciences Jamshoro, from January 2010 to December 2012. Patients who presented with thoracic myelopathy due to ossified ligamentum flavum were included. All the patients, after detailed history, clinical examination and radiological investigation under went decompressive laminectomy at the appropriate level. Pre-operative, post-operative and neurolog'ifti', 06 months follow up was recorded. The patients having thoracic myelopathy due to other causes were excluded from the study. SPSS-10 was used to analyse the data. RESULTS: A total of 15 patients were admitted and operated (9 males, 6 females. (M:F ratio of 1.5:1). The majority of patients were in 6th decade. Backache and lower limb weakness was the presenting feature. Overall improvement in preoperative neurological status was seen in 9 (60%) patients. Neurology remained unchanged in 4 (26.6%) patients and worsened in 2 (13.3%) patients. CONCLUSION: The disease is common in 5th and 6th decade. Preoperative duration of symptoms significantly correlates with recovery.

Ventriculoperitoneal shunt blockage.

BACKGROUND: Hydrocephalus is the abnormal accumulation of cerebrospinal fluid within the ventricles and subarachnoid spaces, resulting in increased intracranial pressure. The treatment of choice is placement of ventriculoperitoneal shunt. Ventriculoperitoneal shunt blockage is not an uncommon complication. Objective of the study was to find out the frequency, causes and site of ventriculoperitoneal blockage and to compare it with other studies. METHODS: This case series study was conducted at Department of Neurosurgery Liaquat University Hospital, Jamshoro, from April 2008 to March 2012. The records of 53 patients between 40 days to 45 years age presenting with blocked ventriculoperitoneal shunt were included. All the patients underwent thorough clinical examination and radiological investigations, and shunt revision done. The retrieved data was collected on proforma. Frequencies and percentages were calculated for categorical data. RESULTS: Out of 53 patients 28 were males, 25 patients were females. Age of patients ranged from 40 days to 45 years. Time interval between the ventriculo-peritoneal shunt placement and blockage of shunt ranged from 2 weeks to 9 years. Out of 53 patients, 32 (69.37%) patients had obstruction at distal catheter, whereas 21 (39.62%) patients had ventricular catheter blockage. CONCLUSION: Ventriculo-peritoneal shunt blockage is one of the most common complications of shunt placement procedure. In this study most of the patients (69.37%) had distal catheter obstruction. Majority (35.84%) of the patients presented with shunt obstruction within one year of shunt placement. Shunt obstruction is common in children less than 3 years age.