Seizures are among the most disabling neurological manifestations in patients with malignant brain tumours. Pakistan faces a substantial epilepsy treatment gap and lacks integrated neuro-oncology surveillance data. This study aimed to evaluate temporal trends in epilepsy recorded as a contributing cause of death among malignant brain tumour decedents in the United States and to propose a transferable surveillance model for countries with limited epidemiological infrastructure.

A retrospective population-based ecological time-trend study was conducted using the CDC WONDER Multiple Cause of Death database from 1999 to 2024. Death certificates listing malignant brain tumours (ICD-10 C71) as the underlying cause and epilepsy or status epilepticus (ICD-10 G40-G41) as contributing causes were included. Annual proportions of malignant brain tumour deaths with epilepsy co-reported were calculated with binomial standard errors. Joinpoint regression was used to estimate Annual Percent Change (APC), Average Annual Percent Change (AAPC), and 95% confidence intervals. Reporting adhered to the STROBE guideline.

The proportion of malignant brain tumour deaths with epilepsy or status epilepticus recorded as a contributing cause increased from 0.26% in 1999 to 1.45% in 2024, representing a 5.5-fold increase. No significant temporal change was observed between 1999 and 2005 (APC -7.36%; non-significant). This was followed by a significant increase between 2005 and 2020 (APC +13.05%; p=0.006), with a continued but non-significant rise from 2020 to 2024 (APC +5.13%). Overall, the average annual increase was significant (AAPC +6.53%; 95% CI 5.42-8.10; p<0.001).

Epilepsy was increasingly documented as a contributing cause of death among malignant brain tumour decedents in the United States over the 25-year study period, reflecting a persistent seizure burden in neuro-oncology. This reproducible population-based surveillance approach may help characterize epilepsy-related mortality and inform neuro-oncology surveillance strategies in countries lacking comprehensive registries, including Pakistan.

Prolonged length of hospital stay (LOS) after craniotomy for tumour resection is associated with increased healthcare costs, postoperative complications, and resource utilization. Identifying predictors of prolonged LOS may facilitate perioperative optimization and improve patient outcomes.

A retrospective cross-sectional study was conducted on 390 adult patients who underwent craniotomy for brain tumour resection between January 2019 and December 2023 at a single tertiary care center, Aga Khan University Hospital, Karachi. Data was collected after ERC approval from May to July 2024. Prolonged LOS was defined as hospitalization for ≥8 days. Demographic, clinical, radiological, operative, and postoperative variables were analyzed using univariate and multivariable logistic regression to identify independent predictors of prolonged LOS.

Of the 390 patients, 58 (14.9%) had prolonged hospitalization. On univariate analysis, prolonged LOS was associated with longer SCU/ICU stay, lower Karnofsky Performance Status (KPS), lower Glasgow Coma Scale (GCS), preoperative antiplatelet/anticoagulant use, greater blood loss, longer operative duration, perioperative transfusion, and general anaesthesia. On multivariable analysis, emergency admission (OR 2.85, 95% CI 1.33-6.07), transfer from another service (OR 6.07, 95% CI 1.04-35.43), and longer operative duration independently predicted prolonged LOS, while higher preoperative KPS was protective.

Emergency admission, inter-service transfer, prolonged operative duration, and poor preoperative functional status were independent predictors of prolonged hospital stay after craniotomy for tumour resection.

Optimizing functional status, improving operative efficiency, and implementing enhanced recovery pathways may help reduce LOS and improve resource utilization.

Brain and central nervous system (CNS) cancers represent a major cause of cancer-related mortality worldwide, with limited evidence describing subnational variation in Pakistan. This study aimed to evaluate ageand sex-specific provincial patterns of brain and CNS cancer mortality in Pakistan using Global Burden of Disease (GBD) 2023 estimates, spanning 1990 to 2023.

This ecological study used Global Burden of Disease (GBD) 2023 estimates of brain and central nervous system (CNS) cancer mortality in Pakistan from 1990 to 2023. Age-standardized mortality rates were analyzed by province (Punjab, Sindh, Khyber Pakhtunkhwa, Balochistan, Gilgit-Baltistan, Islamabad Capital Territory, and Azad Jammu & Kashmir), sex, and standard GBD age groups. Descriptive analyses were conducted to compare agestandardized mortality rates across provinces, sexes and age groups.

Substantial geographic variation in CNS cancer mortality was observed across Pakistan. The highest mortality rate was recorded in Gilgit-Baltistan (0.154, 95% UI: -0.359 to 1.006), followed by Punjab (0.146, 95% UI: -0.276 to 0.701), while the lowest rates were observed in Azad Jammu & Kashmir (0.021, 95% UI: -0.405 to 0.627)and Sindh (0.025, 95% UI: -0.374 to 0.572) representing a more than 7-fold provincial difference. Females demonstrated higher modelled mortality rates than males across most provinces, particularly in Punjab (0.192 [95% UI: -0.360 to 1.119] vs. 0.092 [95% UI: -0.406 to 0.883]). Age-specific analysis revealed peak mortality in the 20-39-year age group, with a decline in older age groups. Marked spatial heterogeneity was observed across provinces, with higher burden in northern regions.

Brain and CNS cancer mortality in Pakistan exhibits marked provincial, age-specific and sex-based disparities with higher burden among young adults, females and northern provinces. These findings underscore the need for targetted cancer surveillance, equitable resource allocation and region specific prevention and healthcare planning to address geographic disparities.

Supratentorial intraventricular tumours (SIVTs) represent rare and surgically demanding subset of intracranial neoplasms, characterized by heterogeneous pathology, deep anatomical location, and significant perioperative risk. Due to their low prevalence, robust outcome-data and evidence-based surgical guidelines remain scarce. This study evaluated clinical characteristics, surgical outcomes, and predictors of adverse events in a large single-center cohort.

A retrospective study was conducted on patients operated for SIVTs between April 2010 - April 2025. The data was collected between November 2025 - January 2026. Presenting complaints, radiological and surgical details, and postoperative complications were analyzed. Functional outcomes were assessed using the modified Rankin Scale (mRS). Multivariate logistic regression identified predictors of gross total resection (GTR) and postoperative ventriculoperitoneal shunt (VPS) dependence. Survival analysis was performed using Kaplan-Meier methods.

A total of 170 patients were included (mean age of 32.4 ± 15.7 years; 31(18.2%) were children). Headache 129(75.9%), nausea 68(40.0%), and vomiting 65(38.2%) were the most common presenting symptoms. Favourable preoperative mRS of 0-1 was noted in 133(79.6%) patients. Lateral ventricular tumours comprised 95(56%) of cases. GTR was achieved in 87/147(59.2%) patients. Postoperative complications occurred in 52/145(35.9%), including meningitis 9(6.2%), hydrocephalus 9(6.2%), and seizures 6(4.1%). No statistically significant predictors were identified for these complications. Multivariate logistic regression demonstrated that temporal transcortical- transventricular approach (OR 9.04; p=0.041) and low-grade tumours (OR 9.48; p=0.006) were independent predictors of GTR. Hydrocephalus at presentation showed a strong trend toward need of postoperative VPS (OR 7.68; p=0.054). During median follow-up of 13.8 months, recurrence was observed in 22.7% with a thirty-day mortality of 4.2%, both significantly worse in children and high-grade tumours.

Surgery for SIVTs carries meaningful risk but achieves favourable outcomes in most patients. Tumour grade and surgical approach are the strongest determinants of GTR, while preoperative hydrocephalus may guide anticipatory VP shunt planning. These findings can inform surgical decision-making and preoperative counselling in this rare tumour subset.

Glioblastoma (GB) exhibits marked histopathological heterogeneity, yet the influence of neuroanatomical location on its morphological and immunohistochemical characteristics remains poorly understood. We aimed to evaluate whether GBs arising in different anatomical compartments of the brain exhibit distinct histopathological and immunohistochemical phenotypes.

A retrospective observational study was conducted in the Department of Histopathology of Shifa International Hospital, Islamabad. Histopathology records of patients diagnosed with GB from 1st June 2021 till 1st June, 2026 were retrieved and data was collected from 1st June, 2026 till 20th June, 2026. GBs were categorized according to the intracranial location. Histopathological and immunohistochemical characteristics were considered phenotype-defining variables.

A total of 303 patients were included with 201(66.3%) males; having the mean age of 52.3±16.3 years. The temporal lobe was the commonest tumour location in 82(27.0%) cases. Nuclear atypia was identified in 297(98.0%), microvascular proliferation in 295(97.4%), hypercellularity in 223(73.6%), and pseudopalisading necrosis in 210(69.3%) cases. Distinct morphological patterns included spindle cell morphology in 79(26.1%), giant cell change in 55(18.2%), gemistocytic differentiation in 22(7.3%), epithelioid morphology in 16(5.3%), and clear-cell morphology in 11(3.6%) cases. A high Ki-67 labelling index was observed in 211(69.6%) tumours. Among the evaluated histopathological variables, fibrillary background demonstrated a significant association with anatomical compartment, occurring more frequently in temporal lobe glioblastomas than in tumours arising from other locations (p=0.020). Although tumours involving multiple cerebral lobes exhibited the highest frequency of a high Ki-67 labelling index in 46(88.5%) cases, the association between Ki-67 labelling index and anatomical compartment was not statistically significant (p>0.05).

GBs demonstrate compartment-specific histomorphological variation, with temporal lobe tumours showing a distinctive predilection for fibrillary background. The absence of significant regional differences in proliferative activity suggests that anatomical location primarily influences morphological phenotype rather than tumour proliferation. These findings provide insight into location-dependent histological diversity in GB and warrant further correlation with molecular alterations and clinical outcomes.

To describe the demographic characteristics, clinical presentation, radiological findings, tumour characteristics, histological subtypes, and associated complications (including comorbidities, raised intracranial pressure, and obstructive hydrocephalus) among children, adolescents, and young adults diagnosed with intracranial germ cell tumours..

This retrospective cohort study included all patients up to the age of 25 years diagnosed with IGCTs, through tissue biopsy, MRI, CSF cytology, and serum/CSF tumour markers (AFP and β-hCG), at the Aga Khan University Hospital, Karachi. Data were collected on presenting complaints, tumour characteristics, surgical intervention, chemoradiotherapy regimen, and outcomes.

Twelve patients were identified; 7 (58.3%) were male, with a mean age at diagnosis of 13.25 ± 6,78 years. Germinomas accounted for 7/12 (58.3%) cases and non-germinomatous germ cell tumours (NGGCTs) for 5/12 (41.7%), including immature and mature teratoma, yolk sac tumour, and mixed germ cell tumour. Most tumours were found in the pineal region 7/12 (58.3%). The most frequent presenting symptoms were headache 9/12 (75.0%), vomiting 8/12 (66.7%), and visual abnormalities 6/12(50.0%).Isolated AFP increase was seen in 5/12 (41.7%) patients and half were tumour marker negative. Chemotherapy was administered in 10/12 (83.3%) patients, most commonly carboplatin-etoposide7/12 (60%), followed by ICE-based regimens 4/12(30%). Radiotherapy was delivered in 5(41.7%), primarily using IMRT or VMAT, including whole-brain, ventricular, or craniospinal protocols with tumourbed boost based on disease extent. Overall survival was 11/12 (91.7%), with one mortality in a patient with yolk sac tumour.

This study serves as the first comprehensive characterization of IGCTs in Pakistan, demonstrating favourable outcomes similar to international studies.

Ependymomas are neuroepithelial tumours capable of CSF dissemination, leading to spinal drop metastases. The incidence, risk factors, and clinical impact of this dissemination remain unclear. This study evaluated the incidence, predictors, and outcomes of drop metastases in patients with cranial and spinal ependymomas treated over a 25-year period.

A retrospective cross-sectional study was conducted at Aga Khan University Hospital, Karachi including all patients with histologically confirmed cranial or spinal ependymomas who underwent surgery between 1st June 2000 to 30th June 2025. Demographic, clinical, radiological, pathological, and follow-up data were reviewed. Drop metastases were identified by contrast-enhanced whole-neuroaxis MRI and/or positive CSF cytology. Univariable and multivariable logistic regression analyses were performed.

Preoperative spinal drop metastases were detected in 8/75 (10.7%) patients with available MRI. Detection was significantly higher with whole-neuroaxis MRI done in 5 out of 12 patients (41.7%) than spine-only MRI done in 3 out of 28 patients (10.7%) or brain-only MRI (p < 0.001). Tumour location was significantly associated with preoperative spinal drop metastases, with infratentorial and spinal tumours demonstrating higher dissemination rates than supratentorial tumours (p = 0.045). Histopathological subtype was also significantly associated with metastasis, with myxopapillaryependymoma showing a greater propensity for dissemination (p = 0.049). No significant associations were found with age, tumour volume, symptom duration, functional status, WHO grade, hydrocephalus, radiological characteristics, or neurological deficits (all p > 0.05). CSF cytology was available for 47 patients, of whom 10 (21.3%) had positive results. All positive cytology cases had corresponding MRI-confirmed metastases, and no additional metastases were identified by CSF cytology alone. No significant differences were observed in overall or progression-free survival.

Drop metastases occurred in approximately 8/75 (10.7%) of patients and were detected more frequently with whole-neuroaxis MRI. Routine whole-neuroaxis MRI at initial staging may improve early detection of CSF dissemination and guide treatment planning.

The RCT was registered retrospectively at The Pan African Clinical Trials Registry (PACTR) (Trial #: PACTR202208886771106 Date of Approval: 15/08/2022). Link: https://pactr.samrc.ac.za/Search.aspx.

TCNS tumours in children under three years pose unique challenges, especially in resource-limited settings. The objective of this study was to evaluate the demographics, management challenges, and outcomes of these children at Pakistan's largest public-sector paediatric referral centre.

This prospective observational cohort study included all children under three years presenting with CNS tumours at The Children's Hospital Lahore, from January 2023 to December 2025. No formal sample size was calculated. Non-probability consecutive sampling technique was used Written informed consent was obtained from the parents/legal guardians of all participating children. The study was approved by the Institutional Review Board/Ethics Committee of CHL/UCHS, Data were analyzed using descriptive statistics (SPSS v26).

A total of 115 children with radiologically suspected CNS tumours were included (mean age 1.92±0.90 years; male: female ratio being 1.4:1). The median monthly household income was USD 90,(IQR 58) and 27(24%) travelled >600 km for treatment. Median diagnostic delay was 2.0 months (IQR 1.0-4.0); 49(43%) were diagnosed within one month, while healthcare- and patient-related delays accounted for 24(21%) and 42(36%) of cases, respectively. Vomiting (n=41, 36%), focal neurological deficits (n=24, 21%), and motor regression (n=8, 7%) were the most common presenting features. Consanguinity was present in 42 (36%) patients. Tumours were infratentorial (n=56, 49%), supratentorial (n=53, 46%), or spinal (n=6, 5%), with the cerebellum the most common primary site in 48 (42%). Only 38 (33%) patients received definitive treatment (surgery and/or chemotherapy), while the remainder did not receive any tumour-directed therapy. Low-grade glioma was the most common diagnosis in 11(9.5% ) followed by embryonal tumours in 9(7.8%), ependymoma in 8(6.9%), choroid plexus tumours in 6( 5.2%), and highgrade glioma/DIPG in 3(2.6%) each. Median time to treatment initiation was 0.9 months (IQR 0.5-2.0). Median overall survival in treated vs untreated patients was 13.0 vs. 2.5 months (log-rank χ²=8.13, p=0.004). Overall survival was in 25 (22%) patients,45(39%) were lost to follow-up, while 45(39%) patients died, including 17 postoperative deaths (50% of surgically treated patients) and 28 deaths from progressive disease while awaiting surgery. Survivors had a median Lansky score of 100 (IQR 80-100).

Despite relatively early diagnosis and referral, limited access to definitive treatment and substantial surgical mortality resulted in high loss to follow-up and poor survival. However, survivors achieved excellent functional outcomes.

Atypical ductal hyperplasia (ADH) remains one of the few benign breast lesions for which surgical excision is routinely recommended because of the risk of underlying carcinoma, most commonly ductal carcinoma in situ (DCIS). However, increasing interest in active surveillance has emerged alongside broader trends toward surgical de-escalation and ongoing prospective trials evaluating observation for low-risk DCIS. In this commentary, we review the challenges of identifying patients with ADH at sufficiently low risk of upgrade and summarize emerging outcome data supporting active monitoring. We discuss the target trial emulation study by Rangel and colleagues, evaluating active monitoring versus surgical excision for selected patients with ADH, as well as novel tools that may further support this approach. Together, these developments suggest a growing role for individualized management strategies in ADH. See related article by Rangel et al., p. 577.

Head and neck cancers and their treatments result in functional, nutritional, and psychosocial sequelae that remain insufficiently integrated into conventional oncological follow-up. Systematic integration of standardized functional assessments and Patient-Reported Outcome Measures facilitates early identification of patients' needs, promoting more personalized multidisciplinary approaches. This article reviews the rationale for longitudinal follow-up in head and neck cancer patients, its clinical relevance, actual recommended tools for functional assessment, and practical aspects of its implementation. The experience developed at the HUG illustrates the feasibility of this approach and its potential to improve care coordination, optimize supportive care, and establish a prospective clinical database to support future research.