Pharmaceutical equivalent 5-aminolevulinic acid fluorescence guided resection of central nervous system tumors: feasibility, safeness and cost-benefit considerations.

PURPOSE: 5-aminolevulinic acid (5-ALA) fluorescence-guided resection (FGR) has been an essential tool in the 'standard of care' of malignant gliomas. Over the last two decades, its indications have been extended to other neoplasms, such as metastases and meningiomas. However, its availability and cost-benefit still pose a challenge for widespread use. The present article reports a retrospective series of 707 cases of central nervous system (CNS) tumors submitted to FGR with pharmacological equivalent 5-ALA and discusses financial implications, feasibility and safeness. METHODS: From December 2015 to February 2024, a retrospective single institution series of 707 cases of 5-ALA FGR were analyzed. Age, gender, 5-ALA dosage, intraoperative fluorescence finding, diagnosis and adverse effects were recorded. Financial impact in the surgical treatment cost were also reported. RESULTS: there was an additional cost estimated in $300 dollars for each case, increasing from 2,37 to 3,28% of the total hospitalization cost. There were 19 (2,69%) cases of asymptomatic photosensitive reaction and 2 (0,28%) cases of photosensitive reaction requiring symptomatic treatment. 1 (0,14%) patient had a cutaneous rash sustained for up to 10 days. No other complications related to the method were evident. In 3 (0,42%) cases of patients with intracranial hypertension, there was vomiting after administration. CONCLUSION: FGR with pharmacological equivalent 5-ALA can be considered safe and efficient and incorporates a small increase in hospital expenses. It constitutes a reliable solution in avoiding prohibitive costs worldwide, especially in countries where commercial 5-ALA is unavailable.

Pediatric Neurosurgical Capacity for the Care of Children With CNS Tumors Worldwide: A Cross-Sectional Assessment.

PURPOSE: Efforts to address inequities in the treatment of pediatric CNS tumors and the burden of childhood cancer globally have prompted the designation of low-grade glioma as one of six index cancers for the World Health Organization Global Initiative for Childhood Cancer. Understanding the importance of neurosurgical interventions and evaluating pediatric neurosurgical capacity may identify critical interventions to improve outcomes for children with low-grade glioma and other CNS tumors. METHODS: An online, cross-sectional survey assessing pediatric neurosurgical practice and capacity was distributed to members of the International Society of Pediatric Neurosurgery. The survey included 36 items covering domains including patient volume, available infrastructure, scope of practice, case distribution, and multidisciplinary care. RESULTS: Responses from 196 individuals from 61 countries, spanning all WHO regions, were included. Ninety-six (49.0%) were from high-income countries, 57 (29.1%) were from upper-middle-income countries, 42 (21.4%) were from lower-middle-income countries (LMICs), and 1 was (0.5%) from a low-income country. Most respondents had a catchment population of ≥ 1 million and indicated the availability of basic neurosurgical resources such as a dedicated neurosurgical operating theater and surgical microscope. The presence of a neurosurgical intensive care unit, inpatient rehabilitation services, and infection monitoring showed similar availability across country groups. Quantitative scoring of 13 infrastructure and service items established that fewer resources were available in low-income countries/LMICs and upper-middle-income countries compared with high-income countries. The volume of pediatric CNS tumor cases and case distribution did not vary according to World Bank country groups. CONCLUSION: This study provides a comprehensive evaluation of pediatric neurosurgical capacity across the globe, establishing variability of resources on the basis of the country income level. Our findings suggest that pediatric neurosurgeons in LMICs may benefit from key neurosurgical instrumentation and increased support for multidisciplinary brain tumor programs and childhood cancer research efforts.

A new study protocol for in-vivo assessment of tumor diagnosis and microscopic tumor infiltration at the resection cavity in central nervous system tumors by a new miniature confocal endomicroscope (CONVIVO system).

BACKGROUND: Confocal laser technology has been recently suggested as a promising method to obtain near real-time intraoperative histological data. We recently demonstrated the accuracy of a newly designed confocal endomiscroscope (CONVIVO) in offering an intraoperative diagnosis during high-grade gliomas (HGGs) removal in an ex vivo study. With this work we aim to perform a standardized, prospective and blinded-to-histological section study for evaluating the potentiality of CONVIVO in offering in-vivo data regarding histological diagnosis and presence of tumor at margins during resection of central nervous system (CNS) tumors. METHODS: This prospective, observational, standardized, blinded-to-histological section, clinical trial was approved by the institutional review board in Carlo Besta Neurologic Institute IRCCS Foundation in Milan and is expected to last 24 months. 75 patients will be included, with at least 53 of them being HGGs based on the statistical sample size calculation. Main objectives will be the assessing of the concordance of tumor diagnoses between CONVIVO images and frozen section at the center of all tumor subtypes and the evaluation of the accuracy of CONVIVO in the identification of tumor tissue at the margins, compared to standard histology. For this purpose, "virtual biopsies" and physical biopsies will be performed directly on patient tumor tissue and surrounding brain parenchima during tumor resection, comparing the results of CONVIVO analysis and frozen and histological sections. RESULTS: Despite promising preliminary data on ex vivo usefulness of CLE machines are emerging in literature, still few studies are available when looking at in vivo potentiality of CONVIVO. At this regard, this study will be the first work where a standardized, prospective, and blinded-to-histological section CONVIVO analysis will be performed in an in-vivo setting in neuro-oncological surgery. CONCLUSIONS: We hypothesize that this new technique may have a role in offering data regarding presence of tumor tissue, eventually giving an intraoperative diagnosis in neuro-oncological surgery, rendering more fluid the decision-making process in the operating room. Furthermore, the result of this study will provide a solid base for further expanding the clinical applications of confocal machines in neurosurgery.

Toward digital histopathological assessment in surgery for central nervous system tumors using stimulated Raman histology.

OBJECTIVE: Intraoperative neuropathological assessment with conventional frozen sections supports the neurosurgeon in optimizing the surgical strategy. However, preparation and review of frozen sections can take as long as 45 minutes. Stimulated Raman histology (SRH) was introduced as a novel technique to provide rapid high-resolution digital images of unprocessed tissue samples directly in the operating room that are comparable to conventional histopathological images. Additionally, SRH images are simultaneously and easily accessible for neuropathological judgment. Recently, the first study showed promising results regarding the accuracy and feasibility of SRH compared with conventional histopathology. Thus, the aim of this study was to compare SRH with conventional H&E images and frozen sections in a large cohort of patients with different suspected central nervous system (CNS) tumors. METHODS: The authors included patients who underwent resection or stereotactic biopsy of suspected CNS neoplasm, including brain and spinal tumors. Intraoperatively, tissue samples were safely collected and SRH analysis was performed directly in the operating room. To enable optimal comparison of SRH with H&E images and frozen sections, the authors created a digital databank that included images obtained with all 3 imaging modalities. Subsequently, 2 neuropathologists investigated the diagnostic accuracy, tumor cellularity, and presence of diagnostic histopathological characteristics (score 0 [not present] through 3 [excellent]) determined with SRH images and compared these data to those of H&E images and frozen sections, if available. RESULTS: In total, 94 patients with various suspected CNS tumors were included, and the application of SRH directly in the operating room was feasible in all cases. The diagnostic accuracy based on SRH images was 99% when compared with the final histopathological diagnosis based on H&E images. Additionally, the same histopathological diagnosis was established in all SRH images (100%) when compared with that of the corresponding frozen sections. Moreover, the authors found a statistically significant correlation in tumor cellularity between SRH images and corresponding H&E images (p < 0.0005 and R = 0.867, Pearson correlation coefficient). Finally, excellent (score 3) or good (2) accordance between diagnostic histopathological characteristics and H&E images was present in 95% of cases. CONCLUSIONS: The results of this retrospective analysis demonstrate the near-perfect diagnostic accuracy and capability of visualizing relevant histopathological characteristics with SRH compared with conventional H&E staining and frozen sections. Therefore, digital SRH histopathology seems especially useful for rapid intraoperative investigation to confirm the presence of diagnostic tumor tissue and the precise tumor entity, as well as to rapidly analyze multiple tissue biopsies from the suspected tumor margin. A real-time analysis comparing SRH images and conventional histological images at the time of surgery should be performed as the next step in future studies.

Avaliação da linguagem em cirurgia de craniotomia com paciente acordado: relato de caso / Language assessment in awake craniotomy: case report

RESUMO O objetivo deste relato foi descrever o caso de um paciente submetido à craniotomia, acordado, para a ressecção neurocirúrgica de um glioma e a avaliação linguística pré-operatória, intraoperatória e pós-operatória. Paciente do gênero masculino, 27 anos, escolaridade nível superior incompleto, apresentando vômitos, confusão mental e crise convulsiva tônico-clônica. Após a avaliação do paciente pela equipe e devidas orientações pré-operatórias, a proposta de excisão da lesão em estado de vigília foi esclarecida e aceita. Ao iniciar o procedimento, os campos foram ajustados para manter as vias aéreas e os olhos acessíveis para mapeamento com estimulação elétrica e avaliação da linguagem no período intraoperatório. Devido à localização do tumor próximo à área motora da fala, foram propostas tarefas para a avaliação da linguagem em quatro momentos: pré-operatório, intraoperatório, pós-operatório imediato e pós-operatório mediato. As habilidades linguísticas testadas nas quatro avaliações foram: compreensão e expressão da linguagem oral, transposição linguística, linguagem associativa, nomeação, discriminação visual, fluência e organização da sintaxe. Com o objetivo de controlar e eliminar o efeito de aprendizagem da testagem, foram solicitadas as mesmas tarefas, porém, com diferentes conteúdos para a testagem das habilidades nas quatro fases. A cirurgia com o paciente acordado permitiu a ressecção completa e segura do tumor, sem prejuízo motor ou linguístico. O engajamento da equipe, a interação interdisciplinar e o planejamento cirúrgico detalhado constituem um pilar para o bom resultado de um procedimento tão complexo e delicado.

ABSTRACT The purpose of this report is to describe the case of a patient who underwent awake craniotomy for neurosurgical resection of a glioma and pre, intra and postoperative linguistic assessment. Male patient, 27 years old, incomplete higher education presenting vomiting, mental confusion and tonic-clonic seizures. After the evaluation of the patient by the team and due preoperative guidance, the proposal of excision of the lesion while awake was clarified and accepted. At the start of the procedure, the fields were adjusted to keep the airway and eyes accessible for mapping with electrical stimulation and intraoperative language assessment. Due to the location of the tumor close to the speech motor area, tasks were proposed for the assessment of language in four moments: preoperative, intraoperative, immediate postoperative and mediate postoperative. The language skills tested in the four assessments were: comprehension and expression of oral language, linguistic transposition, associative language, naming, visual discrimination, fluency and syntax organization. In order to control and eliminate the learning effect of testing, the same tasks were requested, but with different contents for testing skills in the four phases. Surgery with the patient awake allowed the complete and safe resection of the tumor, without motor or linguistic damage to the patient. Team engagement, interdisciplinary interaction and detailed surgical planning constitute the pillar for the good result of such a complex and delicate procedure

The Ebb and Flow of Neurosurgery in a Re-Emerging Sub-Saharan Center. Lessons from 1025 Consecutive Operated Cases and Progress Models. A Prospective Observational Cohort Study.

BACKGROUND: The evolution of neurosurgery in our center comprises 2 active phases separated by a decade-long latent phase. This study evaluates our experience in the renaissance phase using 1025 cases. We identify paradigms that predict progress under existing practice conditions. METHODS: A prospective observational study was undertaken of all freshly operated patients from 2009 to 2016. Ethical approval was obtained from the hospital institutional review board. Data of enrolled patients were acquired and analyzed using SPSS software for Windows version 21. Inferences were evaluated using a 95% level of significance. Major and intermediate cases were included, whereas bedside cases as well as patients operated on elsewhere were excluded. RESULTS: Of 5132 patients treated, 3033 had surgical lesions, 1129 (33.2 ± 2.7% confidence limit [CL]) were operated on, and 1025 satisfied the study criteria. The unmet surgical load (66.1%) was significant (χ2 = 10.9; degree of freedom = 1; P = 0.001). The most common diseases treated were neurotrauma in 438 patients, congenital malformations in 268, and tumors in 170. The mean annual operative rate was 125 ± 5.7 patients (95% CL). Cases showed significant variability using 1-way analysis of variance (F = 13.77; P = 0.03). Residency training was a positive influence on surgeons' operative rate (χ2 = 7.59; P = 0.02). The mean complication rate was 10.3% ± 2.9%, and the mortality was 5.5% ± 1.7%. CONCLUSIONS: We found a large unmet neurosurgical load. To resolve this situation, we recommend an increase in the number of training programs for neurosurgery residency. As neurosurgery units evolve, their progress may be evaluated using the NESCAPE (Neurosurgery Care Phase Evolution) paradigm.

Solitary fibrous tumours and haemangiopericytoma of the meninges. A retrospective study for outcome and prognostic factor assessment.

BACKGROUND: To report on the outcome of patients diagnosed with central nervous system haemangiopericytoma (HPC) or solitary fibrous tumours (SFT) and identify factors that may influence recurrence and survival. MATERIAL AND METHODS: Between January 1977 and December 2016, a retrospective search identified 22 HPCs/SFTs. The patients underwent a total of 40 surgical resections and 63.6% received radiotherapy. Median follow-up was 7.8 years. RESULTS: Six patients (27.3%) were re-operated for tumour recurrence. At the end of the study, 15 patients (68.2%) had no residual tumour on the last imaging. Surgical recurrence-free survival at 5 years was 77.4%, [95% CI: 60.1-99.8]. None of the investigated variables was associated with recurrence. At the end of the study, 5 patients were deceased (22.7%) and only 10 patients (45.5%) had no residual tumour on the last imaging and were alive. Overall survival at 5 years was 95%, [95% CI: 85.9-100]. None of the investigated variables was associated with overall survival. Patients who received radiotherapy demonstrated neither a reduced risk of surgical recurrence (P=0.378) nor a longer overall survival (P=0.405). CONCLUSION: SFTs/HPCs are associated with a significant risk of recurrence that may reduce the survival. Even if we could not demonstrate their benefit in this limited series, we believe that tailored maximal tumour resection on initial surgery is beneficial and that adjuvant RT is useful for tumours displaying grade II or III, even in case of complete removal.

Assessment of the treatment approach and survival outcomes in a modern cohort of patients with atypical teratoid rhabdoid tumors using the National Cancer Database.

BACKGROUND: Atypical teratoid rhabdoid tumors (ATRTs) are rare brain tumors that occur primarily in children under the age of 3 years. This report evaluates the treatment approach and survival outcomes in a large cohort of patients treated in the United States. METHODS: Using the National Cancer Database, the analysis included all ATRT patients aged 0 to 18 years who were diagnosed between 2004 and 2012 and had complete treatment data. RESULTS: Three hundred sixty-one ATRT patients were evaluated. The 5-year overall survival (OS) rate was 29.9%, and it was significantly lower for children who were less than 3 years old (5-year OS, 27.7%) versus those who were 3 years old or older (5-year OS, 37.5%; P < .001). The best outcome was seen for patients with localized disease who received trimodality therapy (surgery, chemotherapy, and radiation therapy [RT]) with a 5-year OS rate of 46.8%. The utilization of trimodality therapy significantly increased during the study period (27.7% in 2004-2008 vs 45.1% in 2009-2012; P < .01), largely because of the increased use of RT. In a multivariate analysis, treatment that did not utilize trimodality therapy was associated with significantly worse OS (hazard ratio, 2.52; 95% confidence interval (1.82-3.51). Children aged 0 to 2 years were significantly less likely to receive trimodality therapy because of decreased utilization of RT in this age group. CONCLUSIONS: The use of trimodality therapy significantly increased during the study period and was associated with improved outcomes. For patients with localized disease who received trimodality therapy, the OS rate at 5 years approached 50%. However, further research into the optimal management of children less than 3 years old is needed because of their significantly worse OS in comparison with older children. Cancer 2017;123:682-687. © 2016 American Cancer Society.

The two-week waiting time standard for cancer: a neurosurgical perspective.

The implementation of the two-week wait initiative for cancer referrals in the NHS has had a major impact on outpatient services. A low clinical detection rate among GPs for neurological cancer has resulted in a large number of urgent referrals with a low yield of positive diagnoses. We have devised a strategy for minimizing the impact on outpatient clinics: patients are scanned prior to clinical review and those with normal scans are referred back to the GP without a clinic appointment. Out of 69 referrals of suspected CNS cancer made in 2003, 61 were scanned and six resulted in a positive diagnosis. The equivalent of 10 clinics was saved, and an increased speed of diagnosis and treatment was achieved with no compromise in patient care. Our study illustrates the consequences of the 2-week wait initiative on the neurosurgical service, and proposes an effective and safe solution.

Surgeons' assessment of symptoms suggesting extrathoracic metastases in patients with lung cancer. Canadian Lung Oncology Group.

BACKGROUND: In patients with apparently operable non-small cell lung cancer (NSCLC), clinicians often omit investigation for M disease in asymptomatic patients. Previous investigations have not specified in detail what is meant by "symptomatic," and this could differ between surgeons. We have investigated the extent to which surgeons' criteria differ for presence of symptoms. METHODS: Participating surgeons from seven centers, enrolled patients they judged "asymptomatic" in a randomized trial of investigational strategies for NSCLC. Patients completed a structured questionnaire describing symptoms of the central nervous system (CNS). In 685 patients, we documented CNS symptom recurrence after resectional surgery over 1 year of follow-up. RESULTS: Two centers enrolled only patients without even the mildest symptoms. Three centers took an intermediate approach, occasionally classifying patients with mild symptoms as "asymptomatic" and thus enrolling them in the trial. Two centers classified an appreciable number of patients with minimal symptoms, and occasionally with more than minimal symptoms, as "asymptomatic." Patients with even mild CNS symptoms were more likely to subsequently present with CNS metastases. CONCLUSIONS: Thoracic surgeons differ in their ideas of what may constitute the symptoms of M disease. Patients with structured questionnaire results that suggest symptoms of CNS disease are more likely to have CNS symptom recurrence after resectional surgery.