Introduction
High-grade gliomas (HGG) are malignant central nervous system (CNS) tumors that present with rapid progression and portend a poor prognosis. They are divided into grade 3 and grade 4 tumors based on histological and genetic findings. They compose 25% of all CNS tumors seen in adults. The standard of care for HGG is maximal safe resection followed by radiation therapy with concomitant and adjuvant chemotherapy. Reference Hottinger, Abdullah and Stupp1 Multiple studies have demonstrated a clear benefit of near total and gross total resection compared with subtotal or partial resection. Reference Han, Liang, Cheng, Yang and Zhao2,Reference Jusue-Torres, Lee, Germanwala, Burns and Parney3
While most patients with gliomas undergo surgery during regular workday hours, occasionally, the surgery may occur after hours in an emergency setting. This could be due to operating room constraints, acute neurological worsening in the patient requiring rapid intervention or other logistical reasons. The significant importance of the extent of resection for these lesions, along with certain challenges of performing an operation after hours, raises questions with regard to the efficacy. Reference Han, Liang, Cheng, Yang and Zhao2–Reference Schneider, Hirani and Hambridge6
There is ample literature that suggests there are increased rates of morbidity and mortality in patients presenting in the evening or the weekend, a term coined as the “weekend effect,” which has become evident in other surgical specialties such as spine surgery, vascular surgery, transplant surgery and general surgery. Reference Fechner, Pezold, Hauser, Gerhardt and Müller7–Reference Galyfos, Sigala, Bazigos and Filis10 The evidence in cranial neurosurgery is conflicting, with some studies supporting this effect Reference Crowley, Yeoh, Stukenborg, Ionescu, Kassell and Dumont4–Reference Schneider, Hirani and Hambridge6 while others refuting it. Reference Goertz, Kabbasch and Pflaeging11,Reference Qadri, Sproule, Girling, West, Cappellani and Chowdhury12 A study from Texas Children’s Hospital investigated the effect of weekend and after-hours surgery on the morbidity and mortality rates in pediatric neurosurgery. Reference Desai, Gonda and Ryan5 They found that pediatric patients undergoing weekday after hours or weekend surgery were more likely to experience complications. Contrarily, a study from the University Hospital of Cologne in Germany examined the impact of the weekend effect on outcomes after clipping of ruptured intracranial aneurysms. Reference Goertz, Kabbasch and Pflaeging11 They found that overnight clipping was not independently associated with poor outcomes. In neurosurgery, factors such as surgeon fatigue, operating room staffing and reduced availability of neurosurgery residents/staff during on-call hours may be contributors to the “weekend effect.” Reference Desai, Gonda and Ryan5,Reference Olson, Drage and Auger13–Reference Bourne, Walcott, Sheth and Coumans16
There is limited research on the impact of this effect on neurosurgical patients undergoing resection for HGG. The primary objective of this study is to evaluate the effect of surgical timing on the outcomes for patients with HGG undergoing resection, with a focus on safety and efficacy.
Methods
We undertook a retrospective review of the neurosurgical database at Vancouver General Hospital. A total of 103 patients presented urgently and underwent surgery for HGG between January 1, 2021, and March 31, 2023. A comprehensive review of clinical records and surgical reports was performed, and patients were categorized into two groups according to the timing of management of their lesion. Group A underwent operative intervention after hours, while Group B underwent operative intervention during regular operating room working hours. The inclusion criteria for Group A were as follows: (1) after hours, (2) emergent presentation and (3) craniotomy for tumor resection. Craniotomies for biopsy only were excluded. For patients in each category, we analyzed the tumor characteristics, clinical presentation, treatment results and complication profile. The following variables were evaluated: the extent of resection, operative time, estimated blood loss, length of stay, intraoperative complications, postoperative complications, reoperation within 30 days, postoperative Eastern Cooperative Oncology Group (ECOG) performance status and 6-month mortality rates.
Surgical timing was characterized according to the standard booking requirements at the institution at which the study was undertaken. After hours (Group A) was defined as >50% of the surgical time between 1630 h and 0659 h or surgery conducted on the weekend. Regular hours (Group B) was defined as Monday through Friday with ≥50% surgical time between 0700 h and 1629 h. Operative room timing from the surgical reports was used to classify skin-to-skin time.
Baseline characteristics were collected for all patients. This included age, sex, presenting neurological status (Karnofsky performance status [KPS], neurological deficits), tumor grade, tumor size, tumor volume, tumor location and recurrence status. The tumor volume was approximated by the formula (CC × TR × AP/2), where craniocaudal (CC), transverse (TR) and anteroposterior (AP) dimensions were analyzed. Reference Mascitelli, Yoon, Cole, Kim and Lawton17 Eloquent tumor location was defined as including the following areas: sensorimotor cortex, internal capsule, basal ganglia, language centers, visual pathways, corpus callosum, thalamus, brainstem, deep cerebellar nuclei and cerebellar peduncles. Reference Mascitelli, Yoon, Cole, Kim and Lawton17,Reference Sawaya, Hammoud and Schoppa18
Patients in Group A were matched to Group B (matched pairs). Patients were first isolated based on procedure type, tumor grade and recurrence status. Patients were then grouped based on age and tumor size, and statistical analysis was performed to ensure there were no differences between them for discrete variables (p < 0.05).
The use of surgical adjuncts was recorded for all procedures. Surgical adjuncts included neuronavigation, 5-aminolevulinic acid (5-ALA), intraoperative neurophysiological monitoring and intraoperative ultrasound. Our center does not have access to intraoperative MRI. Additionally, cases completed by staff surgeons with training in neurosurgical oncology were recorded.
The extent of resection was divided into three groups: gross total resection (GTR), near total resection (NTR) and partial resection (PR), based on postoperative imaging evaluated by a neuro-radiologist and confirmed by the senior neurosurgeon (SM). GTR was defined as no enhancing residual lesion on postoperative CT scan or MRI. NTR was defined as residual limited to resection margins (residual volume < 5%), while PR was defined as significant residual (residual volume ≥ 5%).
Complications were determined via detailed chart review and separated into intraoperative and postoperative periods. Intraoperative complications were defined as vascular injury, the requirement for postoperative mechanical ventilation, intraoperative seizures and the surgeon’s decision to abort the operation due to safety concerns. Postoperative complications included infection, wound dehiscence, postoperative hemorrhage, new neurological deficits, seizures, venous thrombosis, pulmonary embolism, myocardial infarction, stroke and death during admission. Length of stay was defined as time from surgery to day of discharge from hospital. The ECOG performance status was determined at the standard 6-week follow-up visit with oncology.
Patients were stratified into the regular-hours and after-hours groups based on their surgical time. Numerical variables were expressed as mean or median and standard deviation and tested for Gaussian distribution using the Shapiro–Wilk test. Groups were compared using two-tailed unpaired Student’s t-test (Gaussian distribution) or Mann–Whitney U test (non-Gaussian distribution). Categorical variables were expressed as percentages and analyzed using the Chi-square test. Significance was set to p < 0.05.
Results
A total of 19 patients met our inclusion criteria for Group A and were matched to 19 patients in Group B. There were 10 patients who underwent evening procedures (1630 h–0659 h on Monday to Friday), 7 patients who underwent weekend procedures and 2 patients who underwent surgery on a weekend evening (1630 h–0659 h on the weekend). Two patients in Group A underwent a procedure that began prior to 1630 h. There was no significant difference in baseline patient characteristics (84.2% patients vs. 73.7% male patients; p = 0.426, mean age 57.7 vs. 60.2 years; p = 0.535), neurological status on presentation (mean presenting KPS 81.5 vs. 77.9; p = 0.578, frequency of neurological deficits 57.9% vs. 63.2%; p = 0.740), maximal tumor size (4.55 vs. 4.85 cm; p = 0.524), tumor volume (36.5 vs. 48.6 cm Reference Jusue-Torres, Lee, Germanwala, Burns and Parney3 ; p = 0.352) or frequency of eloquent tumor location (52.6% vs. 47.4%; p = 0.746) in Group A vs. Group B, respectively (Table 1). There was no difference in the number of cases completed by an oncology fellowship-trained neurosurgeon between the two groups (47.4% vs. 31.6%; p = 0.319) (Table 1). There was also no significant difference in the frequency of surgical adjunct use in Group A versus B (84.3% vs. 68.4%; p = 0.252) (Table 2). Group B utilized intraoperative monitoring in two patients (10.6%), while there was no use of intraoperative monitoring in Group A.
Table 1. Baseline patient and tumor characteristics
Table 2. Comparison of surgical adjunct usage
There was no significant difference in the rate of GTR between Group A and Group B (26.3% vs. 10.5%; p = 0.2093). There were no intraoperative complications in either group and no difference in the frequency of postoperative complications between the two groups (21.1% vs. 21.1%; p = 1.0). The death rate within 6 months was 10.5% and 15.8% in Group A and Group B, respectively (p = 0.6315). These outcomes are listed in Table 3.
Table 3. Comparison of outcomes in after-hours group and the regular-hours group (categorical variables)
Estimated blood loss (milliliters) was lower in Group A (123.7 vs. 205.3 mL; p = 0.0278). The operative time (minutes) trended toward being lower in Group A (136.9 vs. 174.3 min; p = 0.0643). Additionally, the length of stay trended toward being longer in Group A (5 vs. 3 days; p = 0.0601). There was no significant difference in ECOG score at 6-week follow-up between the two groups (1 vs. 1; p = 0.395) (Table 4).
Table 4. Comparison of outcomes in after-hours group and the regular-hours group (numerical variables)
Discussion
To our knowledge, this is the first study investigating outcomes in patients undergoing craniotomy for resection of HGG after hours. Our study supplements other investigations on this topic in neurosurgery, specifically, the landmark study by Desai et al. on after-hours pediatric neurosurgical procedures demonstrating increased risk of complications Reference Desai, Gonda and Ryan5 , as well as investigations into after-hours aneurysm clipping with similar findings. Reference Goertz, Kabbasch and Pflaeging11
There are several factors that may theoretically lead to worse outcomes for after-hours procedures. Surgeon-specific factors include general mood, cognitive fatigue and sleep deprivation Reference Olson, Drage and Auger13,Reference Wilhelm, Widmann, Durst, Heine and Otto14 although prior work has demonstrated sleep deprivation has little impact on surgeon performance. Reference Sturm, Dawson and Vaughan15,Reference Yaghoubian, Kaji and Ishaque20 After-hours procedures are more likely to involve nursing staff who are not trained or extensively familiar with complex neurosurgical procedures. At our institution specifically, surgical staff for procedures performed on weekends or after hours belong to the general work schedule and may or may not have specialty training in neurosurgical oncology. Furthermore, as with any institution, there are fewer residents and staff neurosurgeons present after hours to assist in technically challenging cases. Although these factors exist, they do not appear to significantly influence outcomes for patients undergoing after-hours glioma surgery.
We did not demonstrate that after-hours surgery was associated with increased morbidity or mortality in our cohort, nor was there a difference in the extent of resection between the two groups. Neurosurgeon surgical expertise and protocol-driven standard of care may override the potential impact of other negative factors related to staffing as discussed above.
The overall complication rate in this study (21.1%) was comparable to rates reported in previously published studies focusing on HGG resections with no significant difference between the two cohorts. Reference Kommers, Ackermans and Ardon21,Reference Graus, Bruna and Pardo22 Lastly, there was no difference in 30-day reoperation rate, 6-month mortality or functional outcomes between the two groups.
Interestingly, after-hours procedures had lower blood loss than those done during regular hours without a statistically significant difference in surgical time. This could be due to reduced learner involvement as neurosurgeons may be less likely to have senior surgical trainees assisting them at our institution. Reference Seicean, Kumar, Seicean, Neuhauser, Selman and Bambakidis23 Additionally, complex resections are deferred to electively scheduled slates, such as those requiring awake language mapping, neurostimulation or other adjuncts such as 5-ALA. Length of stay was longer in after-hours patients, but this did not reach statistical significance and is likely reflective of the overall neurological and medical status of these patients that necessitated urgent surgical intervention.
Limitations
The present study was a retrospective review of the outcomes in a moderate-sized cohort of patients in a single institution with a culture that favors daytime surgery, limiting its generalizability. The availability of surgical staff and access to resources, such as daytime operating room availability and call coverage, introduced a degree of selection bias. Furthermore, recent institutional disruptions such as the COVID-19 pandemic and transition from paper to electronic charting systems limited the data range for our study in attempts to minimize confounding factors.
Tumors within eloquent regions were not all of equal complexity as certain eloquent regions (e.g., motor cortex) require more conservative approaches than others (e.g., sensory cortex, corpus callosum). There are inherent institutional variations in philosophy and approaches to lesions near eloquent brain tissue, where the extent of resection may be guided by individual tolerance for the specific neurological deficits.
Furthermore, considering the impact of extensive resources needed for functional intraoperative monitoring or awake surgeries, these complex cases were performed during regular hours, highlighting that the sample size would be limited in capturing differences in these populations.
Conclusions
HGG patients often have a poor prognosis; thus; achieving maximally safe resection and avoiding complications is key. We demonstrate in our study that patients undergoing craniotomy and tumor resection after hours do not have increased morbidity or mortality, nor is there a meaningful impact on the extent of resection or complication rates. This is likely due to strict adherence to established surgical plans and standardized perioperative care. This study provides additional insight into the consideration of surgical timing in the management of patients undergoing surgical intervention for HGG.
Acknowledgments
None.
Author contributions
KD: data collection, data analysis and interpretation, statistical analysis, drafting article, revising article, reviewing final version.
MR: conception and design, data analysis and interpretation, statistical analysis, revising article, reviewing final version.
MF: conception and design, data analysis and interpretation, statistical analysis, revising article, reviewing final version.
SM: study supervision, conception and design, data analysis and interpretation, statistical analysis, revising article, reviewing final version.
Funding statement
No funding to report.
Competing interests
None.
