Patterns of care and survival of Chinese glioblastoma patients in the temozolomide era: a Hong Kong population-level analysis over a 14-year period.

Background: The aim of this study is to address the paucity of epidemiological data regarding the characteristics, treatment patterns and survival outcomes of Chinese glioblastoma patients. Methods: This was a population-level study of Hong Kong adult (>18 years) Chinese patients with newly diagnosed histologically confirmed glioblastoma between 2006 and 2019. The age standardized incidence rate (ASIR), patient-, tumor- treatment-related characteristics, overall survival (OS) as well as its predictors were determined. Results: One thousand and ten patients with a median follow-up of 10.0 months were reviewed. The ASIR of glioblastoma was 1.0 per 100 000 population with no significant change during the study period. The mean age was 57 + 14 years. The median OS was 10.6 months (IQR: 5.2-18.4). Independent predictors for survival were: Karnofsky performance score >80 (adjusted OR: 0.8; 95% CI: 0.6-0.9), IDH-1 mutant (aOR: 0.7; 95% CI: 0.5-0.9) or MGMT methylated (aOR: 0.7; 95% CI: 0.5-0.8) glioblastomas, gross total resection (aOR: 0.8; 95% CI: 0.5-0.8) and temozolomide chemoradiotherapy (aOR 0.4; 95% CI: 0.3-0.6). Despite the significant increased administration of temozolomide chemoradiotherapy from 39% (127/326) of patients in 2006-2010 to 63% (227/356) in 2015-2019 (P-value < .001), median OS did not improve (2006-2010: 10.3 months vs 2015-2019: 11.8 months) (OR: 1.1; 95% CI: 0.9-1.3). Conclusions: The incidence of glioblastoma in the Chinese general population is low. We charted the development of neuro-oncological care of glioblastoma patients in Hong Kong during the temozolomide era. Although there was an increased adoption of temozolomide chemoradiotherapy, a corresponding improvement in survival was not observed.

Meningioma associated with Gorlin's syndrome.

Gorlin's syndrome or naevoid basal cell carcinoma syndrome is a rare autosominal dominant condition characterised by a variety of congenital anomalies and various malignancies. The chief manifestations include multiple basal cell naevi, mandibular cysts, plantar and palmar pits, vertebral and rib abnormalities and intracranial calcifications. We report a patient with Gorlin's syndrome associated with meningioma treated at our institution. The clinical and radiological features together with the management strategies of this unusual disease entity are discussed.

Copy number variation analysis based on AluScan sequences.

BACKGROUND: AluScan combines inter-Alu PCR using multiple Alu-based primers with opposite orientations and next-generation sequencing to capture a huge number of Alu-proximal genomic sequences for investigation. Its requirement of only sub-microgram quantities of DNA facilitates the examination of large numbers of samples. However, the special features of AluScan data rendered difficult the calling of copy number variation (CNV) directly using the calling algorithms designed for whole genome sequencing (WGS) or exome sequencing. RESULTS: In this study, an AluScanCNV package has been assembled for efficient CNV calling from AluScan sequencing data employing a Geary-Hinkley transformation (GHT) of read-depth ratios between either paired test-control samples, or between test samples and a reference template constructed from reference samples, to call the localized CNVs, followed by use of a GISTIC-like algorithm to identify recurrent CNVs and circular binary segmentation (CBS) to reveal large extended CNVs. To evaluate the utility of CNVs called from AluScan data, the AluScans from 23 non-cancer and 38 cancer genomes were analyzed in this study. The glioma samples analyzed yielded the familiar extended copy-number losses on chromosomes 1p and 9. Also, the recurrent somatic CNVs identified from liver cancer samples were similar to those reported for liver cancer WGS with respect to a striking enrichment of copy-number gains in chromosomes 1q and 8q. When localized or recurrent CNV-features capable of distinguishing between liver and non-liver cancer samples were selected by correlation-based machine learning, a highly accurate separation of the liver and non-liver cancer classes was attained. CONCLUSIONS: The results obtained from non-cancer and cancerous tissues indicated that the AluScanCNV package can be employed to call localized, recurrent and extended CNVs from AluScan sequences. Moreover, both the localized and recurrent CNVs identified by this method could be subjected to machine-learning selection to yield distinguishing CNV-features that were capable of separating between liver cancers and other types of cancers. Since the method is applicable to any human DNA sample with or without the availability of a paired control, it can also be employed to analyze the constitutional CNVs of individuals.

AluScan: a method for genome-wide scanning of sequence and structure variations in the human genome.

BACKGROUND: To complement next-generation sequencing technologies, there is a pressing need for efficient pre-sequencing capture methods with reduced costs and DNA requirement. The Alu family of short interspersed nucleotide elements is the most abundant type of transposable elements in the human genome and a recognized source of genome instability. With over one million Alu elements distributed throughout the genome, they are well positioned to facilitate genome-wide sequence amplification and capture of regions likely to harbor genetic variation hotspots of biological relevance. RESULTS: Here we report on the use of inter-Alu PCR with an enhanced range of amplicons in conjunction with next-generation sequencing to generate an Alu-anchored scan, or 'AluScan', of DNA sequences between Alu transposons, where Alu consensus sequence-based 'H-type' PCR primers that elongate outward from the head of an Alu element are combined with 'T-type' primers elongating from the poly-A containing tail to achieve huge amplicon range. To illustrate the method, glioma DNA was compared with white blood cell control DNA of the same patient by means of AluScan. The over 10 Mb sequences obtained, derived from more than 8,000 genes spread over all the chromosomes, revealed a highly reproducible capture of genomic sequences enriched in genic sequences and cancer candidate gene regions. Requiring only sub-micrograms of sample DNA, the power of AluScan as a discovery tool for genetic variations was demonstrated by the identification of 357 instances of loss of heterozygosity, 341 somatic indels, 274 somatic SNVs, and seven potential somatic SNV hotspots between control and glioma DNA. CONCLUSIONS: AluScan, implemented with just a small number of H-type and T-type inter-Alu PCR primers, provides an effective capture of a diversity of genome-wide sequences for analysis. The method, by enabling an examination of gene-enriched regions containing exons, introns, and intergenic sequences with modest capture and sequencing costs, computation workload and DNA sample requirement is particularly well suited for accelerating the discovery of somatic mutations, as well as analysis of disease-predisposing germline polymorphisms, by making possible the comparative genome-wide scanning of DNA sequences from large human cohorts.

Lhermitte-Duclos disease associated with Cowden syndrome.

Lhermitte-Duclos disease or dysplastic gangliocytoma of the cerebellum, is a rare cerebellar lesion, which can cause mass effects in the posterior fossa. It may occur sporadically, or in association with Cowden syndrome. Cowden syndrome or multiple hamartoma-neoplasia syndrome, is an uncommon autosomal dominant condition characterized by mucocutaneous lesions and systemic malignancies. We report two patients with Lhermitte-Duclos disease and associated Cowden syndrome. The clinical, radiological and histopathological features and management strategies of this rare disease complex are discussed.

Image-guided craniotomy for cerebral metastases: techniques and outcomes.

OBJECTIVE: The purpose of the present study was to analyze the outcomes after craniotomies for brain metastases in a modern series using image-guided technologies either in the regular operating room or in the intraoperative magnetic resonance imaging unit. METHODS: Neurosurgical outcomes were analyzed for 49 patients who underwent 55 image-guided craniotomies for excision of brain metastases during a 5-year period. Tumors were located in critical and noncritical function regions of the brain. A total of 23 craniotomies for tumors in critical brain were performed using intravenous sedation anesthesia; craniotomies for noncritical function brain regions were completed under general anesthesia. The patients were also divided into Radiation Therapy Oncology Group recursive partitioning analysis (RPA) classes on the basis of age, Karnofsky Performance Scale scores, state of primary disease, and presence or absence of extracranial metastases. RESULTS: There was no perioperative mortality. Gross total resection, as verified by postoperative contrast-enhanced computed tomography or magnetic resonance imaging, was achieved in 96% of patients. The median anesthesia time was 4.25 hours, and the median length of hospital stay was 3 days. In 51 symptomatic cases, there was complete resolution of symptoms in 70% (n = 36), improvement in 14% (n = 7), and no change in 12% (n = 6) postoperatively. No patient who was neurologically intact preoperatively deteriorated after surgery, and 93% of patients maintained or improved their functional status. Only two patients (3.6%) with significant preoperative deficits had increased long-term deficits postoperatively. The mean follow-up was 1 year, and the local recurrence rate was 16%. The median survival of the entire group was 16.23 months (17.5 mo in RPA Class I, 22.9 mo in RPA Class II, and 9.8 mo in RPA Class III). CONCLUSION: Gross total resection of brain metastases, including those involving critical function areas, can be safely achieved with a low morbidity rate using contemporary image-guided systems. RPA Class I and II patients with controlled primary disease benefit from aggressive treatment by surgery and radiation.

Intracranial multiple myeloma involving the dura.

Meningeal involvement in multiple myeloma is rare. We report a case in which a patient with a history of multiple myeloma presented with neurological deficit due to meningeal involvement.

Father of neurosurgery in Hong Kong.

Neurosurgery in Hong Kong had its origins as a division of General Surgery and became a subspecialty only 46 years ago with the arrival of Hsiang-Lai Wen. For well over a decade, Wen would be the only neurosurgeon in the colony. His contributions to neurosurgery included the ventriculosuperior sagittal sinus shunt and the application of acupuncture in anesthesia, pain ablation, and drug detoxification. A pilot with the China National Aviation Corporation during World War II, he played an active part in the Allied war effort. As a diplomate of the American Board of Neurological Surgery, Wen sought to improve the standard of neurosurgery in Hong Kong and southern China with the establishment of the Hong Kong Neurosurgical Society in 1981 and the Research Institute of Neurosciences in Guangzhou in 1988. Wen was acknowledged as Hong Kong's "father of neurosurgery," and his work paved the way for the development of modern neurosurgery in the region.

Pleomorphic xanthoastrocytoma: report of two cases and review of the prognostic factors.

Pleomorphic xanthoastrocytoma (PXA) is a superficially located, rare glial tumour first described in 1979. It affects young patients, who often present with seizures. The tumour has a relatively favourable prognosis, but 15-20% progress to malignancy. We describe two cases of PXA, both with benign features at presentation, one of which underwent anaplastic transformation. Surgery remains the mainstay of treatment. Factors influencing clinical outcome include extent of resection, and histological features such as mitotic index, necrosis and lymphocytic infiltration. The roles of radiotherapy and chemotherapy remain undefined. We advocate lifelong follow-up and establishment of a central registry in order to further the understanding of this infrequently encountered tumour.

Image-guided craniotomy for cerebral metastases: techniques and outcomes.

OBJECTIVE: The purpose of the present study was to analyze the outcomes after craniotomies for brain metastases in a modern series using image-guided technologies either in the regular operating room or in the intraoperative magnetic resonance imaging unit. METHODS: Neurosurgical outcomes were analyzed for 49 patients who underwent 55 image-guided craniotomies for excision of brain metastases during a 5-year period. Tumors were located in critical and noncritical function regions of the brain. A total of 23 craniotomies for tumors in critical brain were performed using intravenous sedation anesthesia; craniotomies for noncritical function brain regions were completed under general anesthesia. The patients were also divided into Radiation Therapy Oncology Group recursive partitioning analysis (RPA) classes on the basis of age, Karnofsky Performance Scale scores, state of primary disease, and presence or absence of extracranial metastases. RESULTS: There was no perioperative mortality. Gross total resection, as verified by postoperative contrast-enhanced computed tomography or magnetic resonance imaging, was achieved in 96% of patients. The median anesthesia time was 4.25 hours, and the median length of hospital stay was 3 days. In 51 symptomatic cases, there was complete resolution of symptoms in 70% (n = 36), improvement in 14% (n = 7), and no change in 12% (n = 6) postoperatively. No patient who was neurologically intact preoperatively deteriorated after surgery, and 93% of patients maintained or improved their functional status. Only two patients (3.6%) with significant preoperative deficits had increased long-term deficits postoperatively. The mean follow-up was 1 year, and the local recurrence rate was 16%. The median survival of the entire group was 16.23 months (17.5 mo in RPA Class I, 22.9 mo in RPA Class II, and 9.8 mo in RPA Class III). CONCLUSION: Gross total resection of brain metastases, including those involving critical function areas, can be safely achieved with a low morbidity rate using contemporary image-guided systems. RPA Class I and II patients with controlled primary disease benefit from aggressive treatment by surgery and radiation.

Sir Victor Horsley (1857-1916): pioneer of neurological surgery.

Immortalized in surgical history for the introduction of "antiseptic wax," Sir Victor Horsley played a pivotal role in shaping the face of standard neurosurgical practice. His contributions include the first laminectomy for spinal neoplasm, the first carotid ligation for cerebral aneurysm, the curved skin flap, the transcranial approach to the pituitary gland, intradural division of the trigeminal nerve root for trigeminal neuralgia, and surface marking of the cerebral cortex. A tireless scientist, he was a significant player in discovering the cure for myxedema, the eradication of rabies from England, and the invention of the Horsley-Clarke stereotactic frame. As a pathologist, Horsley performed research on bacteria and edema and founded the Journal of Pathology. Horsley's kindness, humility, and generous spirit endeared him to patients, colleagues, and students. Born to privilege, he was nonetheless dedicated to improving the lot of the common man and directed his efforts toward the suffrage of women, medical reform, and free health care for the working class. Knighted in 1902 for his many contributions to medicine, Sir Victor met an untimely death during World War I from heat stroke at the age of 59. An iconoclast of keen intellect, unlimited energy, and consummate skill, his life and work justify his epitaph as a "pioneer of neurological surgery."

Extramedullary haemopoiesis in thalassemia intermedia presenting as paraplegia.

Extramedullary haemopoiesis causing spinal cord compression is a rare manifestation of thalassemia. We describe a 17 year old male with thalassemia intermedia who presented with progressive paraplegia and sphincter disturbance. Magnetic resonance imaging revealed an epidural lesion extending from T5 to T8 compressing the spinal cord. The patient recovered completely after surgical decompression with postoperative radiation therapy. Histological examination of the lesion confirmed the diagnosis of extramedullary haemopoiesis. Clinical awareness of this phenomenon with early treatment is essential for optimizing the neurological outcome.