Supratentorial low-grade gliomas. Neuroradiology

The radiologic modality that most likely provides the imaging information needed in a patient suspected of having a brain tumors is magnetic resonance imaging. A brain tumors can be reliably ruled out, if the standard magnetic resonance examination is performed properly and experts interpret the results as negative for tumor. In this paper we will illustrate morphological aspects of low-grade supratentorial neoplasms, including tumors of neuroepithelial tissue, such as low-grade diffuse fibrillary astrocytomas, and circumscribed astrocytic lesions (pilocytic astrocytoma, pleomorphic xantoastrocytoma and subependymal giant cell astrocytoma). Then the main practical applications of functional imaging in neurosurgery will be also debated.     

Haemorrhagic presentation of low-grade glioma in adults

Summary Intracranial bleeding is rare in patients with low-grade gliomas, above all in adult population. We reviewed the literature of such cases and reported another case of a haemorrhagic low-grade glioma in a 54-year-old woman presenting with a left hemiparesis. Computer tomography (CT) images showed a right basal ganglia haemorrhage with no mass effect. Vascular malformations were ruled out by angiography. Eighteen fluoro–fluoro deossiglucosio (18F-FDG) positron emission tomography (PET/CT) showed a large hypometabolic area corresponding to the lesion. We waited for patient’s improvement. Late magnetic resonance images revealed a low-grade glioma at the bleeding site. Tumour was removed and histopathologic examination revealed a WHO grade II mixed glioma. The authors emphazise that this evidence has to be kept in mind since it has important therapeutic implications.     

Supratentorial gliomas: surgical considerations and immediate postoperative results. Gross total resection versus partial resection

Forty-two patients with supratentorial gliomas not involving the basal ganglia (extraganglionic) were studied pre- and postoperatively with computed tomographic (CT) scans to evaluate the effect of the extent of surgical resection on the immediate postoperative results. Thirty-three patients (79%) had malignant astrocytic gliomas (glioblastoma or anaplastic astrocytoma), 4 patients (10%) had well-differentiated astrocytomas, and 5 (12%) had oligodendrogliomas. The median age was 58 years, and the median Karnofsky rating was 70. There was no operative mortality. Six patients (14%) had surgical complications. A gross total resection was defined as the absence of any abnormal enhancement on the postoperative CT scan. A nearly gross total resection had been accomplished when less than 10% of the preoperatively enhancing mass was still seen. A partial resection was indicated by the presence of more than 10% of the enhancing lesion on the postoperative CT scan. A gross total or nearly gross total resection was accomplished in 36 patients (86%), and an improved or stable postoperative neurological status was present in 35 of these patients (97%). In contrast, the rate of neurological morbidity after a partial resection was 40%. Supratentorial extraganglionic gliomas, regardless of their histological type, generally were well-circumscribed lesions except at the level of the ventricular wall, where glioblastomas and anaplastic astrocytomas blended with the subependymal white matter from which they seemed to arise.     

Functional magnetic resonance imaging-guided resection of low-grade gliomas

BACKGROUND: We sought to determine the safety and efficacy of using functional magnetic resonance imaging (fMRI) to guide the resection of low-grade gliomas (LGG). METHODS: From September 1997 to February 2003, fMRI was performed in 16 patients (age, 15-43 years) before an attempted surgical resection of LGG. Functional imaging was used to identify and coregister eloquent cortices pertinent to motor (10), speech (3), motor and speech (2), and short-term memory and speech (1) activation with respect to the tumor using a 1.5-T interventional MRI system. Intraoperatively acquired T(2)-weighted and turbo-fluid attenuated inversion recovery images were used to assess the completeness of surgical resection. RESULTS: Tumors included 10 oligodendrogliomas, 4 astrocytomas, 1 dysembryoplastic neuroepithelial tumor, and 1 pleomorphic xanthoastrocytoma. In every case, the preoperative brain activation study accurately determined the location of neurologic function. After surgery, one patient had a transient hemiparesis and another had a temporary apraxia. Ten patients had radiographically complete resections and 5 with oligodendrogliomas had incomplete resections because of the proximity of their tumors to functional areas. Only one patient with an astrocytoma in the motor strip received postoperative radiation therapy. To date, radiographic tumor progression has not been seen in any patient with either a partial or a complete resection with a median follow-up of 25 months (range, 12-87 months). CONCLUSIONS: Functional MRI was accurate for identifying areas of neurologic function before surgical resection of LGG. Patients with complete radiographic resections or with incompletely resected oligodendrogliomas can be safely followed radiographically after surgery. Radiation therapy was reserved for infiltrating astrocytomas that were not completely resectable.     

Low-grade hemispheric gliomas in adults: a critical review of extent of resection as a factor influencing outcome.

OBJECT: The goal of this study was to perform a critical review of literature pertinent to low-grade gliomas of the cerebral hemisphere in adults and, on the basis of this review, to evaluate systematically the prognostic effect of extent of resection on survival and to determine if treatment-related guidelines could be established for patients in whom these tumors have been newly diagnosed. Quality of evidence for current treatment options, guidelines, and standards as well as methodological limitations were evaluated. METHODS: Several prognostic factors thought to affect outcome in patients with low-grade gliomas include the patient's age and neurological status, tumor volume and histological characteristics, and treatment-related variables such as timing of surgical intervention, extent of resection, postoperative tumor volume, and radiation therapy. Patient age and the histological characteristics of the lesion are generally accepted prognostic factors. Among treatment-related factors, timing and extent of resection are controversial because of the lack of randomized controlled trials addressing these issues and the difficulty in obtaining information from available studies that have methodological limitations. All English-language studies on low-grade gliomas published between January 1970 and April 2000 were reviewed. Thirty studies that included statistical analyses were further evaluated with regard to the prognostic effect of extent of resection. Of these 30 studies, those that included pediatric patients, unless adults were analyzed separately, were excluded from further study because of the favorable outcome associated with the pediatric age group. Also excluded were studies including pilocytic and gemistocytic astrocytomas, because the natural histories of these histological subtypes are significantly different from that of low-grade gliomas. Series in which there were small numbers of patients (< 75) were also excluded. Results for oligodendrogliomas are reported separately. Currently, for patients with low-grade glial tumors located in the cerebral hemisphere, the only management standard based on high-quality evidence is tissue diagnosis. All other treatment methods are practice options supported by evidence that is inconclusive or conflicting. The majority of published series that the authors identified had design-related limitations including a small study size, a small number of events (that is, deaths for survival studies), inclusion of pediatric patients, and/or inclusion of various histological types of tumors with different natural histories. Of the 30 series addressing the issue of timing and extent of surgery, almost all had additional design limitations. Methods used to determine the extent of resection were subjective and qualitative in almost all studies. Only five of the 30 series met the authors' criteria, and these studies are discussed in detail. CONCLUSIONS: Management of low-grade gliomas is controversial and practice parameters are ill defined. This is caused by limited knowledge regarding the natural history of these tumors and the lack of high-quality evidence supporting various treatment options. Although a prospective randomized study seems unlikely, both retrospective matched studies and prospective observational trials will improve the clinician's ability to understand the importance of various prognostic factors.     

Seizure characteristics and control following resection in 332 patients with low-grade gliomas

OBJECT: Seizures play an important role in the clinical presentation and postoperative quality of life of patients who undergo surgical resection of low-grade gliomas (LGGs). The aim of this study was to identify factors that influenced perioperative seizure characteristics and postoperative seizure control. METHODS: The authors performed a retrospective chart review of all cases involving adult patients who underwent initial surgery for LGGs at the University of California, San Francisco between 1997 and 2003. RESULTS: Three hundred and thirty-two cases were included for analysis; 269 (81%) of the 332 patients presented with >or=1 seizures (generalized alone, 33%; complex partial alone, 16%; simple partial alone, 22%; and combination, 29%). Cortical location and oligodendroglioma and oligoastrocytoma subtypes were significantly more likely to be associated with seizures compared with deeper midline locations and astrocytoma, respectively (p=0.017 and 0.001, respectively; multivariate analysis). Of the 269 patients with seizures, 132 (49%) had pharmacoresistant seizures before surgery. In these patients, seizures were more likely to be simple partial and to involve the temporal lobe, and the period from seizure onset to surgery was likely to have been longer (p=0.0005, 0.0089, and 0.006, respectively; multivariate analysis). For the cohort of patients that presented with seizures, 12-month outcome after surgery (Engel class) was as follows: seizure free (I), 67%; rare seizures (II), 17%; meaningful seizure improvement (III), 8%; and no improvement or worsening (IV), 9%. Poor seizure control was more common in patients with longer seizure history (p<0.001) and simple partial seizures (p=0.004). With respect to treatment-related variables, seizure control was far more likely to be achieved after gross-total resection than after subtotal resection/biopsy alone (odds ratio 16, 95% confidence interval 2.2-124, p=0.0064). Seizure recurrence after initial postoperative seizure control was associated with tumor progression (p=0.001). CONCLUSIONS: The majority of patients with LGG present with seizures; in approximately half of these patients, the seizures are pharmacoresistant before surgery. Postoperatively, >90% of these patients are seizure free or have meaningful improvement. A shorter history of seizures and gross-total resection appear to be associated with a favorable prognosis for seizure control.     

Impact of extent of resection and adjuvant therapy in diffuse gliomas of the spine

BACKGROUND CONTENTDiffuse gliomas of the spine (DGS)—consisting of intradural intramedullary glioblastoma, astrocytoma, and oligodendroglioma—are exceedingly rare tumors that account for about 2% of primary spinal cord tumors. Much is unknown about their optimal treatment regimen due to a relative lack of clinical outcome data.PURPOSETo provide an updated analysis on treatment and outcomes in DGS.STUDY DESIGN/SETTINGObservational cohort study using The National Cancer Database (NCDB), a multicenter prospectively collected oncology outcomes database. A systematic literature review was also performed to compare the resulting data to previous series.PATIENT SAMPLEPatients with histologically confirmed DGS from 2004 to 2018.OUTCOME MEASURESLong-term overall survival and short-term 30/90-day postsurgical mortality, 30-day readmission, and prolonged hospital length of stay.METHODSImpact of extent of resection and adjuvant therapy on overall survival was evaluated using Kaplan–Meier estimates and multivariable Cox proportional hazards regression. Univariate and multivariate logistic regression was used to analyze covariables and their prognostic impact on short-term surgical outcomes.RESULTSOf the 747 cases that met inclusion criteria, there were 439 astrocytomas, 14 oligodendrogliomas, and 208 glioblastomas. Sixty percent (n=442) of patients received radiation, and 45% (n=324) received chemotherapy. Tumor histology significantly impacted survival; glioblastoma had the poorest survival (median survival time [MS]: 12.3 months), followed by astrocytoma (MS: 70.8 months) and oligodendroglioma (MS: 71.6 months) (p<.001). Gross total resection (GTR) independently conferred a survival benefit in patients with glioblastoma (hazard ratio [HR]: 0.194, p<0.001) and other WHO grade four tumors (HR: 0.223, p=.003). Adjuvant chemotherapy also improved survival in patients with glioblastoma (HR: 0.244, p=.007) and WHO grade four tumors (HR: 0.252, p<.001). Systematic literature review identified 14 prior studies with a combined DGS mortality rate of 1.3%, which is lower than the 4% real-world outcomes calculated from the NCDB. This difference may be explained by selection biases in previously published literature in which only centers with favorable outcomes publish their results.CONCLUSIONSThere remains a paucity of data regarding treatment paradigms and outcomes for DGS. Our analysis, the largest to date, demonstrates that GTR and adjuvant therapy independently improve survival for certain high-grade subgroups of DGS. This best-available data informs optimal management for such patients.     

Surgical treatment for glioma: extent of resection applying functional neurosurgery

Current treatments for gliomas, including surgery, chemotherapy, and radiation therapy, frequently result in unsuccessful outcomes. Studies on glioma resection were reviewed to assess better treatment outcomes applying the newest neurosurgical multimodalities. We reviewed reports of surgical removal of gliomas utilizing functional brain mapping, monitoring, and other functional neurosurgery techniques such as neuronavigation and awake surgery. Attempts to maximize the extent of glioma resection improved survival. A close proximity of the resection to the eloquent areas increased the risk of perioperative neurological deficits. However, those deficits often improved during the postoperative rehabilitation and recovery period when the essential or the compensative eloquent areas remained intact. Pre- and intraoperative application of the latest brain function analysis methods promoted safe elimination of gliomas. These methods are expected to help explore the long-term prognosis of glioma treatment and the mechanism for recovery from functional disabilities.     

Supratentorial recurrences of gliomas. Results of reoperations on astrocytomas and oligodendrogliomas

Summary On the basis of our previous investigation regarding histological transformation of recurrent astrocytomas and oligodendrogliomas we report the clinical results of reoperations. The present observations deal with 121 cases: grade 1 astrocytomas (45), oligodendrogliomas (12), grade 2 astrocytomas (47), and oligodendrogliomas (17), respectively. In all these a second reoperation was performed in 14 cases. Operative mortality was relatively high, but without significant difference in the two groups of malignancy: 24.5% and 29.6%. Survival times in both groups showed striking individual differences. We achieved post-reoperation survivals exceeding one year in 18 and 14 cases, respectively. The results of second reoperations were generally poor. We find no remarkable differences in survival time following reoperations in primary grade 1 and grade 2 tumours. Similarly, malignant change proved to be not decisive for survival times. On the contrary, most of our patients with unchanged grade 1 astrocytomas, reoperated on after a longer interval, achieved a short second survival only. Prolongation of life expectancy by radiotherapy is doubtful. Irradiation seems to be necessary with malignantly transformed tumours if the patient did not have any treatment before reoperation.     

Evaluation of mithramycin in the treatment of anaplastic gliomas.

A controlled, prospective, randomized study evaluated the use of mithramycin in the treatment of anaplastic glioma compared to a similar group of patients receiving best conventional care. From a total of 116 patients in the study, 96 were within the valid study group. All patients were operated on, had histological confirmation of anaplastic glioma, and received radiotherapy at the discretion of the principal investigator. Fifty-two patients received mithramycin at a dose of 25 mug/kg/day for 21 days, while 44 patients were in the control group. There was no significant difference in the median survival from time of randomization in those receiving mithramycin (21 weeks) as compared to those not receiving mithramycin (26 weeks). There was no significant difference between the two groups in relation to age distribution, sex, location, diagnosis, tumor characteristics, signs or symptoms, or radiotherapy received. Duration of symptoms correlates positively with survival and was also significantly longer in the control group than in the treated group. This, however, did not account for the failure of mithramycin to be found an effective agent. Although the study was not designed to evaluate the efficacy of radiotherapy, patients who were so treated had a significant improvement in survival. The toxic complications of mithramycin included gastrointestinal symptoms, dermatological involvement, anemia, and liver dysfunction, indicating the need for close supervision.     

Navigated three-dimensional intraoperative ultrasound-guided awake resection of low-grade glioma partially infiltrating optic radiation

We report a case of awake resection of temporal low-grade glioma infiltrating the optic radiation (OR). The OR was localized by direct electrical stimulation (DES) and the tumor was delineated by navigated intraoperative 3D ultrasound. Ultrasound artifacts were eliminated by 3D-ultrasound data acquisition with a miniature probe inserted into the resection cavity. A total of 97 % resection was achieved, and small tumor portion involving OR was intentionally left in place. Functional result was partial quadrantanopia instead of more profound visual deficit, which would follow gross-total resection. To our knowledge, DES of OR was reported once; the aforementioned method of ultrasound artifact elimination has not been reported before.     

Synergism between BCNU and irradiation in the treatment of anaplastic gliomas. An in vivo study using the avian sarcoma virus-induced glioma model.

The therapeutic effects of irradiation, BCNU, or combined irradiation and BCNU were studied in the avian sarrcoma virus (ASV)-induced glioma model in rats. Whole-head orthovoltage radiation therapy was given in six equal fractions over 2 weeks, and BCNU was administered intraperitoneally as a single dose of 10 mg/kg. Two series of experiments were performed in order to duplicate the results. In Series I, the median survival times of the experimental groups, in days after randomization were as follows: control group (no treatment), 69; group receiving 200 rads, 84 (p less than 0.05); group receiving BCNU, 80.5 (p less than 0.1); and group receiving 2000 rads + BCNU, 112 (p less than 0.001). In Series 2, the median survival times were: control group, 73.5; group receiving 2300 rads, 85 (p less than 0.01); group receiving BCNU, 92.5 (p less than 0.025); and group receiving 2300 rads + BCNU, 123.5 (p less than 0.001). In both series, combined therapy was significantly better than either radiation or BCNU alone. This is the first time that a synergistic effect of BCNU and irradiation has been reported in an in vivo brain-tumor model and supports the clinical use of this combination in the treatment of malignant gliomas.     

The preoperative use of navigated transcranial magnetic stimulation facilitates early resection of suspected low-grade gliomas in the motor cortex

Background

Resection is recommended for low-grade gliomas, but often it is not performed if the tumor is suspected of invading the primary motor cortex. The study aim is to assess what influence preoperative navigated transcranial magnetic stimulation (nTMS) has on the treatment strategy and clinical outcome for suspected low-grade gliomas in presumed motor eloquent location.

Methods

This paper reports on all our patients with gliomas in the primary motor cortex that were non-enhancing on MRI, since we began using nTMS (n?=?11). For the comparison group, we identified the 11 most recent such patients just before we started using nTMS.

Results

Exact delineation of motor functional versus non-functional cortical tissue was provided by nTMS in all cases, also within the area of altered FLAIR signal. In 6 out of 11 cases, the nTMS mapping result changed the treatment plan towards early and more extensive resection. Only one nTMS patient had another seizure within the follow-up period, whereas four patients in the comparison group had further seizures. In the nTMS group, 1 of 4 patients with pre-op neurological deficits improved by one year; whereas the comparison group had increased neurological deficits in 3 of the 8 patients not having surgery. The median (range) change of tumor volume from baseline to 1 year was ?83 % (?67 % to ?100 %) in the nTMS group, but +12 % (+40 % to ?56 %) in the comparison group (p?<?0.001).

Conclusions

nTMS provides accurate motor mapping results also in infiltrative gliomas and enables more frequent and more extensive surgical resection of non-enhancing gliomas in or near the primary motor cortex. The substantial differences observed here in neurological and oncological outcomes suggest that further comparative research is warranted.     

Extent of resection and survival in supratentorial infiltrative low-grade gliomas: analysis of and adjustment for treatment bias

Background

Any correlation between the extent of resection and the prognosis of patients with supratentorial infiltrative low-grade gliomas may well be related to biased treatment allocation. Patients with an intrinsically better prognosis may undergo more aggressive resections, and better survival may then be falsely attributed to the surgery rather than the biology of the disease. The present study investigates the potential impact of this type of treatment bias on survival in a series of patients with low-grade gliomas treated at the authors’ institution.

Methods

We conducted a retrospective study of 148 patients with low-grade gliomas undergoing primary treatment at our institution from 1996–2011. Potential prognostic factors were studied in order to identify treatment bias and to adjust survival analyses accordingly.

Results

Eloquence of tumor location proved the most powerful predictor of the extent of resection, i.e., the principal source of treatment bias. Univariate as well as multivariate Cox regression analyses identified the extent of resection and the presence of a preoperative neurodeficit as the most important predictors of overall survival, tumor recurrence and malignant progression. After stratification for eloquence of tumor location in order to correct for treatment bias, Kaplan–Meier estimates showed a consistent association between the degree of resection and improved survival.

Conclusion

Treatment bias was not responsible for the correlation between extent of resection and survival observed in the present series. Our data seem to provide further support for a strategy of maximum safe resections for low-grade gliomas.     

The extent of resection in rectal cancer

The condition of the "tumor field" in cancer of the rectum was studied. The work was performed on 28 preparations of the resected and extirpated rectum as serial paraffin sections in 8 radial directions for a distance of 10 cm from the visible margin of the tumor. The "tumor field" border at the distal direction is not less than 3.5-4 cm with the exophital growth and 4-5 cm with the endophital growth. The "tumor field" contours resemble an ellipse with excentricity in the proximal direction.     

Permanent anosmia and ageusia after resection of a left temporoinsular low-grade glioma: anatomofunctional considerations

Five percent of the general population has olfactory or gustatory disorders, although most do not complain about it. However, in some cases, these symptoms can be disabling and may affect quality of life. Anosmia was reported as a possible complication following head injury and neurosurgical procedures, particularly after the resection of tumors located in the anterior fossa and the treatment of aneurysms in the anterior circulation. Nonetheless, in all of these situations, olfactory dysfunction could be explained by damage to the peripheral olfactory system. Here, the authors report a case of complete anosmia associated with ageusia following awake resection of a low-grade glioma involving the left temporoinsular region, with no recovery during a follow-up of 3 years. The frontal lobe was not retracted, and the olfactory tract was not visualized during surgery; therefore, postoperative anosmia and ageusia are likely explained by damage to the cortex and central pathways responsible for these senses. The authors suggest that the patient might have had a subclinical right hemianosmia before surgery, which is a common condition. After resection of the central structures critical for smell and taste processing in the left hemisphere, the patient could have finally had bilateral and complete olfactory and gustatory loss. This is the first known report of permanent anosmia and ageusia following glioma surgery. Because these symptoms might have been underestimated, more attention should be devoted to olfaction and taste, especially with regard to possible subclinical preoperative deficit.