Neurosurgery residency program in Yogyakarta, Indonesia: improving neurosurgical care distribution to reduce inequality.

OBJECTIVE: Educating future neurosurgeons is of paramount importance, and there are many aspects that must be addressed within the process. One of the essential issues is the disproportion in neurosurgical care, especially in low- and middle-income countries (LMICs). As stated in their report "Global Surgery 2030," The Lancet Commission on Global Surgery has emphasized that the availability of adequate neurosurgical care does not match the burden of neurosurgical disease. A strong partnership with the local and national government is very desirable to improve the way everyone addresses this issue. In addition, international collaborative effort is absolutely essential for the transfer of knowledge and technology from a developed country to an LMIC. This paper shows what the authors have done in Yogyakarta to build an educational model that helps to improve neurosurgical care distribution in Indonesia and reduce the inequity between provinces. METHODS: The authors gathered data about the number of neurosurgical procedures that were performed in the sister hospital by using data collected by their residents. Information about the distribution of neurosurgeons in Indonesia was adapted from the Indonesian Society of Neurological Surgeons. RESULTS: The data show that there remains a huge disparity in terms of distribution of neurosurgeons in Indonesia. To tackle the issue, the authors have been able to develop a model of collaboration that can be applied not only to the educational purpose but also for establishing neurosurgical services throughout Indonesia. Currently they have signed a memorandum of understanding with four sister hospitals, while an agreement with one sister hospital has come to an end. There were more than 400 neurosurgical procedures, ranging from infection to trauma, treated by the authors' team posted outside of Yogyakarta. CONCLUSIONS: Indonesia has a high level of inequality in neurological surgery care. This model of collaboration, which focuses on the development of healthcare providers, universities, and related stakeholders, might be essential in reducing such a disparity. By using this model, the authors hope they can be involved in achieving the vision of The Lancet Commission on Global Surgery, which is "universal access to safe, affordable surgical and anesthesia care when needed."

Dual manifestations: spinal and cerebellar hemangioblastomas indicative of von Hippel-Lindau syndrome.

Hemangioblastomas are rare, benign, and highly vascular tumors of the central nervous system, often associated with von Hippel-Lindau (VHL) syndrome, an autosomal dominant disorder characterized by multiple tumors. We present a case of a 32-year-old male with progressive headaches, visual disturbances, and motor deficits, who was diagnosed with multiple hemangioblastomas in the cervical-thoracic spinal cord and bilateral cerebellum through MRI. Surgical resection and histopathological biopsy confirmed the diagnosis. This case highlights the critical role of MRI in diagnosing and managing VHL-associated hemangioblastomas and underscores the importance of regular imaging for early detection and intervention of new or recurring tumors, optimizing patient outcomes.

Diagnostic Accuracy of Immunohistochemistry in Detecting MGMT Methylation Status in Patients with Glioma.

BACKGROUND: The O6-methylguanine-DNA methyltransferase (MGMT) gene prevents mismatch in DNA replication and transcription by repairing mutagenic DNA lesions. MGMT is a predictor biomarker of chemotherapy in high-grade and low-grade gliomas based on high-risk clinical conditions. It also can be used for therapeutic decisions to predict hypermutation in recurrence in newly diagnosed low-grade gliomas. The gold standard  examination for the methylation is Polymerase Chain Reaction (PCR). However, this technique is not widely available in Indonesia for daily practice. Thus, an uncomplicated and simpler method such as immunohistochemistry (IHC) is needed as an alternative examination. This study aimed to predict the diagnostic accuracy of immunohistochemistry (IHC) in detecting the methylation status of O6-methylguanine-DNA methyltransferase (MGMT) in glioma. METHODS: This research was a cross-sectional study using formalin-fixed paraffin embedded (FFPE) tissue samples of glioma patients, dating between October 2017 until March 2021. Diagnosis of glioma was established based on clinical, radiological, and histopathological findings. MGMT methylation status was investigated using the IHC and PCR techniques. Diagnostic value of IHC was analyzed, with PCR as a gold standard method. Optimum threshold to determine positivity of IHC was determined by the Area Under the Curve (AUC) on Receiver Operating Characteristics (ROC) curve and Youden index. RESULTS: Among 75 samples examined, 29 (38.7%) patients were methylated. IHC detected MGMT methylation with sensitivity of 86.2%, specificity of 63.0%, positive predictive value of 59.5%, negative predictive value of 87.9% and accuracy of 72.0%. The AUC was 0.746, indicating moderate diagnostic value. Optimum positivity threshold of the IHC examination based on Youden Index was 10%. CONCLUSION: IHC examination can be used to detect MGMT methylation status of glioma patients in limited resources setting, where PCR technique is not available.

Neurosurgery Services in Dr. Sardjito General Hospital, Yogyakarta, Indonesia, During the COVID-19 Pandemic: Experience from a Developing Country.

BACKGROUND: Most articles describing the effect of the coronavirus disease 2019 (COVID-19) pandemic on neurosurgical services have been from developed countries. We report our experience in carrying out neurosurgical services at Dr. Sardjito General Hospital, Yogyakarta, Indonesia, during the time of the pandemic. METHODS: To collect information on the effect of the pandemic in Indonesia and Yogyakarta, we gathered data from the Indonesian Ministry of Health's online database for the national data and local government records for the local data (including records of Dr. Sardjito General Hospital Division of Neurosurgery). RESULTS: Compared with other countries, Indonesia has not been severely hit by the impact of COVID-19. To increase our understanding of the natural history of the pandemic, we divided the period into 4 phases: phase 1 (when there were confirmed cases in Indonesia but no cases in Yogyakarta), phase 2 (when the first case in Yogyakarta was detected), phase 3 (when the cumulative cases surpass their peak), and phase 4 (when the pandemic ends). At the time of this writing, we were still in phase 2 and in this phase, we experienced a decrease in the number of emergency surgical procedures, from an average of 4 to 2.4 per week. Moreover, the number of elective operations dropped from an average of 12 to 9 per week. CONCLUSIONS: A pandemic, such as COVID-19, reduces both inpatient and outpatient neurosurgical activities. A comprehensive plan can improve both utilization and safety of the neurosurgical staff.

Comparison of Polymerase Chain Reaction-Restriction Fragment Length Polymorphism, Immunohistochemistry, and DNA Sequencing for the Detection of IDH1 Mutations in Gliomas.

BACKGROUND: IDH1 mutation shows diagnostic, prognostic, and predictive value in gliomas. Direct Sanger sequencing is considered the gold standard to detect IDH1 mutation. However, this technology is not available in most neuropathological centers in developing countries such as Indonesia. Immunohistochemistry (IHC) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) have also been used to detect IDH1 mutation. This study aimed to compare DNA sequencing, IHC, and PCR-RFLP in detecting IDH1 mutations in gliomas. METHODS: Research subjects were recruited from Dr. Sardjito Hospital. Genomic DNA was extracted from fresh or formalin-fixed paraffin-embedded samples of tumor tissue. DNA sequencing, PCR-RFLP and IHC were performed to detect IDH1 mutation. Sensitivity, specificity, and accuracy of PCR-RFLP and IHC were calculated by comparing them to DNA sequencing as the gold standard. RESULTS: Among 61 recruited patients, 13 (21.3%) of them carried a mutation in codon 132 of the IDH1 gene, as shown by DNA sequencing. PCR-RFLP and DNA sequencing have a concordance value of 100%. Meanwhile, the concordance value between IDH1 R132H IHC and DNA sequencing was 96.7%. The sensitivity, specificity, positive predictive values, negative predictive values, and accuracy for PCR-RFLP were all 100%. On the other hand, the sensitivity, specificity, and accuracy of IHC were 92.3%, 97.9%, and 96.7%, respectively. CONCLUSION: This study showed that both PCR-RFLP and IHC have high accuracy in detecting IDH1 mutation. We recommend a combination of PCR-RFLP and IHC to detect IDH1 mutation in resource-limited settings.
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Clinicopathological Features and Prognosis of Indonesian Patients with Gliomas with IDH Mutation: Insights into Its Significance in a Southeast Asian Population.

BACKGROUND: Gliomas remain one of the most common primary brain tumors. Mutations in the isocitrate dehydrogenase (IDH) gene are associated with a distinct set of clinicopathological profiles. However, the distribution and significance of these mutations have never been studied in the Indonesian population. This study aimed to elucidate the association between IDH mutations and clinicopathological as well as prognostic profiles of Indonesian patients with gliomas. METHODS: In total, 106 patients with gliomas were recruited from a tertiary academic medical center in Yogyakarta, Indonesia. Formalin-fixed paraffin-embedded and fresh tissue specimens were obtained and sectioned for hematoxylin-eosin staining and immunohistochemical examinations. Genomic DNA was isolated and analyzed for the presence of IDH mutations using standard polymerase chain reaction and nucleotide sequencing methods. Clinicopathological data were collected from medical records. RESULTS: Although no IDH2 mutation was identified, IDH1 mutations were found in 23 (21.7%) of the patients. Patients with IDH1 mutations tended to have a history of smoking and a shorter interval between onset of symptoms and initial surgical interventions. Frontal lobe involvement, oligodendroglial histology, lower Ki67 expression, WHO grades II and III gliomas, and methylated O6-methylguanine-DNA methyltransferase (MGMT) promoters were significantly associated with the presence of IDH1 mutations. Compared with patients with IDH1-wild-type, patients with IDH1 mutation were observed to have a longer overall survival. CONCLUSIONS: IDH1 mutations are associated with certain clinicopathological and prognostic profiles in Indonesian patients with gliomas. This finding demonstrates the importance of identifying IDH mutations as part of the management of patients with glioma in Indonesia. 
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