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|Year : 2012 | Volume
| Issue : 2 | Page : 185-190
Surgery for recurrent malignant gliomas: Feasibility and perioperative outcomes
Aliasgar V Moiyadi, Prakash M Shetty
Department of Surgical Oncology, Neurosurgery Services, Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre, Mumbai, India
|Date of Submission||26-Nov-2011|
|Date of Decision||22-Jan-2012|
|Date of Acceptance||04-Mar-2012|
|Date of Web Publication||19-May-2012|
Aliasgar V Moiyadi
Department of Surgical Oncology, Neurosurgical Services, Room 48, Main Building, Tata Memorial Hospital, E Borges Road, Parel, Mumbai 400012
Source of Support: None, Conflict of Interest: None
Background: Surgery for recurrent gliomas is often undertaken in select cases. Equivocal oncological outcomes of such surgeries are responsible for much of the controversy surrounding its role. Adding to the dilemma is the perceived increased morbidity associated with redo surgeries. Lack of studies and absence of uniformity in reporting outcomes is partly responsible for this. We evaluated our perioperative outcomes in recurrent malignant gliomas with the aim of documenting these objectively. Materials and Methods: A consecutive prospectively maintained database was queried for all redo surgeries in malignant gliomas performed at our referral neuro-oncology center. Demographic, clinical, surgical, and perioperative details were retrieved. Perioperative outcomes were objectively categorized as neurological (major/minor, transient/prolonged), regional, and systemic complications, along with overall morbidity and mortality. A similar analysis was performed for all craniotomies for intra-axial tumors. Results: Forty-one surgeries for recurrent malignant gliomas (from a database of 196 craniotomies for all intra-axial tumors) were evaluated. Neurological worsening occurred in 22.2% (12.2% major), whereas 44% showed improvement in the pre-existing deficits. Besides, regional and systemic complications occurred in 14.2% and 4.8%, respectively. Overall morbidity was 29.3% (major in 14.6%) and mortality was 2.4%. Though not significant on multivariate analysis, prior treatment was an important predictor of increased regional complications. Conclusions: Neurological morbidity after surgery for recurrent gliomas is acceptable. Surgery also provides a high chance of restoration of neurological function. Though regional complications can be significant and need to be given cognizance when reporting perioperative outcomes, they are not alarmingly high. Careful case selection can ensure optimization of these outcomes.
Keywords: Complications, morbidity, perioperative outcomes, recurrent gliomas, second craniotomy
|How to cite this article:|
Moiyadi AV, Shetty PM. Surgery for recurrent malignant gliomas: Feasibility and perioperative outcomes. Neurol India 2012;60:185-90
The results reported in this study were presented at the 13th EANS (European Association of Neurosurgery) Congress, Rome, 9-14 Oct 2011.
| » Introduction|| |
Malignant gliomas (which include anaplastic astrocytomas and glioblastomas) have a poor prognosis with recurrences being inevitable. At the time of recurrence, choice of therapies is extremely limited.  Surgery is occasionally offered in selected cases. No clear-cut guidelines exist as to selection of cases for redo surgery, though most neurosurgeons would agree that younger patients with good performance status having localized disease and a longer disease-free interval would be good candidates. , The dilemma (often biased by undue pessimism) arises mainly from the perceived futility (in terms of oncological outcomes) of redo surgery as well as the apparently higher surgical morbidity of operating a previously treated case. Literature too is inadequate in these regards. The efficacy of any treatment modality for cancers needs to be assessed dually - one of course being the oncological efficacy (measured in terms of survival) which is a long-term outcome, and the other being the immediate procedural efficacy (for surgery, this is measured as the perioperative morbidity/benefit) which is a short-term measure. Both are very important measures of the efficacy. For reoperations for malignant gliomas, the oncological efficacy of surgery alone is unlikely to be established in clinical trials (most existing reports are retrospective studies which do not provide a reliable level of evidence and often have heterogeneous population as well as variable adjunctive therapies in addition to the surgery itself). However, perioperative outcomes can be prospectively documented in an objective manner. This will not only provide documentary evidence of procedural efficacy, but will also serve as a yardstick for uniform comparison across studies undertaken to assess the long-term oncological outcomes. Our center is a tertiary care oncological center with a dedicated neuro-oncological practice. We see a large number of recurrent cases, many of whom are offered surgery after a joint tumor board discussion. The aim of this study was to assess the 30-day perioperative outcomes in these patients with malignant gliomas who underwent surgery at our center at the time of recurrence.
| » Materials and Methods|| |
This was a retrospective analysis of prospectively maintained data. The study was approved by the institutional review board. The neurosurgical service has been maintaining a prospective database of all craniotomies performed recording demographic, clinical, radiological, operative, and perioperative outcomes. This database was queried for all craniotomies performed for recurrent malignant gliomas between January 2007 and December 2010. At our center, we have a neuro-oncology working group comprising neurosurgeons, radiation and medical oncologists, neuropathologists, and neuroradiologists working closely together. Patients were selected for surgery after discussion in the joint neuro-oncology tumor board meeting. Standard microneurosurgical principles were followed. Intraoperative ultrasound was used whenever deemed required. No other intraoperative adjuncts (navigation, intraoperative monitoring) were available in this time period. Awake craniotomy with clinical monitoring was utilized in select cases. A uniform policy of antibiotic prophylaxis (single-dose perioperative 2 nd or 3 rd generation cephalosporin) was applied. All patients were operated under perioperative cover of corticosteroids (dexamethasone) which was tapered postoperatively. Antiepileptic medications were used in all patients perioperatively. Nonpharmacological deep venous thrombosis prophylaxis in the form of intermittent pneumatic compression devices and thrombo-elastic devices (stockings) was utilized with pharmacological prophylaxis (heparin or low-molecular weight heparins) reserved for patients with anticipated prolonged recumbence. The extent of resection was measured based on the surgeon's intraoperative impression along with a postoperative (day 1) contrast-enhanced computer tomography (CT) scan.
The outcome measures assessed included immediate postoperative (first 24 h) neurological status, neurological status at discharge, regional complications, systemic complications, overall morbidity, and perioperative mortality. The neurological status at each time point (documented by a formal routine neurological examination) was recorded as same, improved, or worse, as compared to the immediately previous assessment. It was further categorized as per severity into minor (minimal alteration of function) or major (significant alteration in function), as well as in terms of duration as transient (completely or significantly reversible by the time of discharge) or prolonged (minimal or no improvement till the time of discharge). Regional complications included presence of significant operative site hematoma, worsening or new-onset seizures, as well as wound-related complications [which included wound collection, gape, leak, and surgical site infection defined as per the Center for Disease Control (CDC) criteria].  The systemic complications included all other complications such as (but not limited to) metabolic disturbances, hemodynamic complications, systemic infections, and coagulopathy. The overall morbidity (per procedure, as one patient could have had more than one of the earlier mentioned complications) as well as mortality (at the time of discharge) was also recorded.
This analysis was also performed for all patients undergoing craniotomies for intra-axial tumors (n = 196) at our center during the same time period (2007-2009) and has been previously reported.  The analysis of risk factors was performed in this overall cohort only, and previous treatment was one of the risk factors analyzed.
| » Results|| |
A total of 38 patients with recurrent malignant gliomas were operated during the study period. Three of the patients underwent a repeat surgery for a second recurrence again at our center. For assessing procedural morbidity, we considered each surgery as a separate case and hence a total of 41 surgeries for recurrent malignant gliomas. Patients with recurrent malignant gliomas with no previous radiotherapy were excluded from this group. The median age was 38 years [Table 1] identical to the median age of the overall craniotomy group. There was a male preponderance (35 of the 41). Outcomes: 18 had a very good (>70), 21 had a moderate (60-70), and only 2 had a poor (<60) Karnofsky score (KPS). The presenting features included raised intracranial pressure (28), progressive neurological deficits (29), and seizures (20). In general, surgery was indicated due to progressive symptoms in all except one patient who had asymptomatic radiological progression. The disease-free interval ranged from 2 to 97 months (median 22 months). In addition to radiotherapy, 17 patients had received prior chemotherapy. The extent of resection achieved was gross total in 32%, near total (>90%) in 36%, subtotal (50-90%) in 27%, and partial in 5%. Final histology revealed glioblastoma in 31 cases, anaplastic astrocytoma/oligodendroglioma/oligoastrocytoma in 9 cases, and treatment-related changes in 1 case.
|Table 1: Demographic characteristics and surgical details of the patient population|
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New-onset neurological deficits or worsening of pre-existing neurological deficits occurred in 22% cases [Table 2]. Of these, a little over half had major and prolonged neurological deterioration resulting in an overall major neurological morbidity of 12.2%. This was comparable to the overall craniotomy group which had a major neurological morbidity of 11.4%. Importantly though, a larger proportion (44%) of recurrent gliomas showed improvement in neurological deficits as compared to the overall group (28%).
Overall, regional complications occurred in 14.2% cases in the recurrent group [Table 3] as compared to 17.5% in the overall craniotomy group. Wound-related complications accounted for the majority (7.3%) of these complications and included infections and meningitis (4.9% each) besides wound leak and gape in one case each. In addition, one case each of worsening of seizures and significant operative site hematoma (requiring evacuation) were also recorded.
Other complications and overall morbidity
Other (systemic and other) complications occurred in only 4.8% of cases [Table 4]. The overall morbidity was 29.3% (lower than the 38.8% in the overall craniotomy group) [Table 5]. Major significant morbidity comprised half of the overall morbidity (14.6%). There was one death in this group. This was a case of recurrent medial frontal anaplastic oligodendroglioma who developed progressive and fatal superior sagittal sinus thrombosis postoperatively.
Risk factor analysis was not performed on the small cohort of recurrent surgeries. However, various preoperative and intraoperative factors were considered in the overall craniotomy group (196 cases) and have been reported earlier.  Relevant to this report, prior treatment was a significant risk factor for increased regional complications on univariate analysis. However, it did not reach statistical significance on multivariate analysis.
| » Discussion|| |
Our study meticulously documented all the perioperative events in cases operated for recurrent malignant gliomas and compared the results with all craniotomies performed at our center. Standardized perioperative protocols and uniform operative strategy (ours was a single surgeon service till 2010) and prospective maintenance of the database ensured reliability of the data recorded. The median age of this study group was 38 years, a lot younger than that reported in most of western literature. Barker et al. reported younger patients to be more likely to be selected for redo surgery. However, this age (38 years) in our series was identical to the median age of our entire neuro-oncological patient population (reported earlier), and hence cannot be considered a selection bias. Further, our experience and overall registry shows that the median age of patients with gliomas in our country is much younger than in the west (unpublished data). Most of our patients were symptomatic and this could explain the sizeable number with moderate KPS (60-70). Barker et al. also reported that preoperative KPS did not actually influence the outcome.
The present results showed that systematic and meticulous documentation of perioperative events is essential to identify all possible sources of perioperative morbidity (and not just neurological morbidity). Non-neurological morbidity is also a significant component contributing to the overall morbidity and this must be taken into cognizance. The results also showed that the morbidity (neurological, regional, systemic, as well as overall) in recurrent cases was comparable with that in the overall craniotomy group. Surgery for recurrent gliomas need not be associated with an increase in morbidity in properly selected cases. Of course, we cannot comment on the selection criteria for accepting patients for redo surgery in recurrent malignant gliomas as this study was not designed for that. That kind of a study would need a prospective assessment of all cases of recurrent gliomas seen at the clinic and identify the ones which are offered surgery, analyzing various selection criteria.
Dissecting the neurological morbidity in our study, we realized that overall neurological worsening was slightly more in the recurrent group than in all craniotomies, but these deficits were more often transient, with eventual major neurological morbidity in the two groups being the same. On the other hand, it was noted that the rates of postoperative improvement were higher in the recurrent group (44% vs. 28%). This may be because of selection bias in recurrent gliomas where it could be possible that only cases with a better chance of symptomatic improvement are chosen for surgery. Moreover, involvement of eloquent areas may result in not selecting patients for surgery in the recurrent setting and may further bias the results. It has been reported that response to an empirical course of steroids is a useful predictor of likelihood of symptomatic relief and could act as a surrogate marker for selecting patients for surgical debulking.  Though we did not objectively document this fact, we admit that we utilize this principle regularly in selecting and counseling patients for surgery. Nonetheless, this result underlines the benefit of surgery in selected cases, a benefit which may be lost if surgery is never offered to them. Moreover, of the neurological deficits encountered postoperatively, a large proportion had shown an improving trend at the time of discharge [Table 2]. Another assessment at a later point of time may have shown a further reduction in the neurological morbidity (which is what a lot of studies report). It is well known that transient deficits may be high in the immediate postoperative period. Though recording of all such transient deficits may overemphasize the morbidity, it is probably important when counseling patients preoperatively to project an accurate and realistic estimate of the likely postoperative course.
Another important component of the perioperative morbidity is regional complications. Surgeons are often apprehensive about wound-related complications in the recurrent setting, but surprisingly few studies actually include them in reporting postoperative morbidity. ,, Further, surgical site infections are often the only regional complications reported. Often, however, wound breakdown (without infection) can also significantly prolong postoperative recovery and delay subsequent oncological therapy. Our results showed that regional complications were comparable in the recurrent and overall group. In the overall group, when we analyzed the various factors predisposing to regional complications, previous treatment did show statistical significance on univariate analysis, but failed to show significance on multivariate analysis.  So, regional (and specifically wound-related) complications may not really be more frequent in recurrent cases. Overall, the cumulative morbidity was comparable in the recurrent and overall groups [Table 5].
A review of literature reveals that most studies assessing the role of surgery focus more on the oncological outcomes than perioperative outcomes. , This holds true for first craniotomies as well as second (recurrent) craniotomies. As far as recurrent gliomas are concerned, the reported morbidity is variable, ranging from 0 to 54% for neurological worsening and from 7 to 45% in improvement rates. ,,,,, Further, different studies either report only certain aspects of morbidity, with the majority focusing on neurological morbidity, or utilize differing endpoints for measuring the morbidity. Reported regional and systemic complications range from 0 to 25% and from 0 to 5.5%, respectively. ,,, This variability in reporting outcomes precludes a valid comparison across the various studies. A uniform and objective measure of morbidity was reported by the Glioma Outcome Project (GOP) in 2003.  The GOP study prospectively recorded morbidity of first and second craniotomies across various centers in North America. We adopted the same measures of outcome in this study, and hence chose to compare our results with the GOP data. Moreover, the GOP study centers included many community center hospitals where levels of care and practices are more representative of general routine services provided (as opposed to strictly controlled conditions in the setting of clinical trials). [Table 6] shows the GOP study data vis-à-vis the results presently reported. This study reported neurological, regional, systemic, and overall morbidity as 18%, 13%, 8.7%, and 32.5%, respectively. Our results compare favorably to the GOP study data in all aspects. The GOP study did not classify neurological outcomes as major or minor, and this may be a subjective interpretation in our study. That study reported no significant differences in complication rates between first and second craniotomies, a finding confirmed in our results too.
Surgery for recurrent malignant gliomas is possible with accepted morbidity. Potential regional and systemic complications, though infrequent, must be factored into the overall morbidity whenever reporting or discussing with the patients. Moreover, it is able to provide significant symptomatic relief in a large group of these cases. The decision to operate, however, needs to be judiciously taken with close interaction and inputs from neurosurgeons (vis-à-vis the perioperative outcomes) and oncologists (regarding the long-term prognosis).
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]
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