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Jan Coburger, Jens Engelke, Angelika Scheuerle, Dietmar R. Thal, Michal Hlavac, Christian Rainer Wirtz and Ralph König

Object

High-grade gliomas (HGGs) and metastasis (MET) are the most common intracranial lesions in neurosurgical routine. Both of them show an invasive growth pattern extending into neural tissue beyond the margins of contrast enhancement on MRI. These “undetected” areas might be the origin of early tumor recurrence. The aim of the present study was to evaluate whether 5-aminolevulinic acid (5-ALA) fluorescence provides an additional benefit in detection of invasive tumor compared with intraoperative MRI (iMRI).

Methods

The authors prospectively enrolled 45 patients harboring contrast-enhancing lesions, in whom gross-total resection was intended. All patients had surgery in which iMRI and 5-ALA–guided resection were used following a specific protocol. First, a typical white light tumor resection was performed. Then, spatial location of residual fluorescence was marked. After that, an iMRI was performed and residual uptake of contrast was marked. Navigated biopsy samples were taken from all marked areas and from additional sites according to the surgeon's judgment. Cross tables and receiver operating characteristic curves were calculated, assessing performance of the imaging methods for tumor detection alone and for combined detection of infiltration zone and solid tumor (pathological tissue). Also, correlations of histopathological findings with imaging results were tested using Spearman rho.

Results

Thirty-four patients with HGGs and 11 with METs were enrolled. Three patients harboring a MET showed no 5-ALA enhancement and were excluded; 127 histopathological samples were harvested in the remaining patients. In HGG, sensitivity for tumor detection was significantly higher (p < 0.001) in 5-ALA (0.85) than in iMRI (0.41). Specificity was significantly lower (p < 0.001) in 5-ALA (0.43) than in iMRI (0.70). For detection of pathological tissue, 5-ALA significantly exceeded iMRI in specificity (0.80 vs 0.60) and sensitivity (0.91 vs 0.66) (p < 0.001). Imaging results of iMRI and 5-ALA did not correlate significantly; only 5-ALA showed a significant correlation with final histopathological diagnosis of the specimen and with typical histopathological features of HGGs. In METs, sensitivity and specificity for tumor detection were equal in 5-ALA and iMRI. Both techniques showed high values for sensitivity (0.75) and specificity (0.80). The odds ratio for detection of tumor tissue was 12 for both techniques. Concerning pathological tissue, no statistically significant difference was found either. Imaging results of iMRI and 5-ALA correlated significantly (p < 0.022), as with final histopathological diagnosis in METs.

Conclusions

In METs, due to the rate of nonenhancing lesions, the authors found no additional benefit of 5-ALA compared with iMRI. In HGG, imaging results of 5-ALA and iMRI are significantly different at the border zone; 5-ALA has a higher sensitivity and a lower specificity for tumor detection than Gd-DTPA–enhanced iMRI. For detection of infiltrating tumor at the border of the resection cavity, 5-ALA is superior to Gd-DTPA–enhanced iMRI concerning both sensitivity and specificity. Thus, use of 5-ALA in addition to iMRI might be beneficial to maximize extent of resection. Clinical synergistic effects will be evaluated in a prospective randomized trial.

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Jan Coburger, Ralph König, Klaus Seitz, Ute Bäzner, Christian Rainer Wirtz and Michal Hlavac

Object

Intraoperative MRI (iMRI) provides updated information for neuronavigational purposes and assessments on the status of resection during transsphenoidal surgery (TSS). The high-field technique additionally provides information about vascular structures at risk and precise information about extrasellar residual tumor, making it readily available during the procedure. The imaging, however, extends the duration of surgery. To evaluate the benefit of this technique, the authors conducted a retrospective study to compare postoperative outcome and residual tumor in patients who underwent conventional microsurgical TSS with and without iMRI.

Methods

A total of 143 patients were assessed. A cohort of 67 patients who had undergone surgery before introduction of iMRI was compared with 76 patients who had undergone surgery since iMRI became routine in TSS at the authors' institution. Residual tumor, complications, hormone dependency, biochemical remission rates, and improvement of vision were assessed at 6-month follow-up. A volumetric evaluation of residual tumor was performed in cases of parasellar tumor extension.

Results

The majority of patients in both groups suffered from nonfunctioning pituitary adenomas. At the 6-month follow-up assessment, vision improved in 31% of patients who underwent iMRI-assisted surgery versus 23% in the conventional group. One instance of postoperative intrasellar bleeding was found in the conventional group. No major complications were found in the iMRI group. Minor complications were seen in 9% of patients in the iMRI group and in 5% of those in the conventional group. No differences between groups were found for hormone dependency and biochemical remission rates. Time of surgery was significantly lower in the conventional treatment group. Overall a residual tumor was found after surgery in 35% of the iMRI group, and 41% of the conventional surgery group harbored a residual tumor. Total resection was achieved as intended significantly more often in the iMRI group (91%) than in the conventional group (73%) (p < 0.034). Patients with a planned subtotal resection showed higher mean volumes of residual tumor in the conventional group. There was a significantly lower incidence of intrasellar tumor remnants in the iMRI group than in the conventional group. Progression-free survival after 30 months was higher according to Kaplan-Meier analysis with the use of iMRI, but a statistically significant difference could not be shown.

Conclusions

The use of high-field iMRI leads to a significantly higher rate of complete resection. In parasellar tumors a lower residual volume and a significantly lower rate of intrasellar tumor remnants were shown with the technique. So far, long-term follow-up is limited for iMRI. However, after 2 years Kaplan-Meier analyses show a distinctly higher progression-free survival in the iMRI group. No significant benefit of iMRI was found for biochemical remission rates and improvement of vision. Even though the surgical time was longer with the adjunct use of iMRI, it did not increase the complication rate significantly. The authors therefore recommend routine use of high-field iMRI for pituitary surgery, if this technique is available at the particular center.

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Bernd Markus Hofmann, Michal Hlavac, Ramon Martinez, Michael Buchfelder, Otto Albrecht Müller and Rudolf Fahlbusch

Object

The aim of this paper was to demonstrate the long-term results following microsurgery in a single surgeon's continuous series of patients with Cushing disease (CD), to assess the influence of changes in surgical procedures, and to compare the results with those of other treatment modalities. In particular, preoperative diagnosis, tumor size, results of histological examination, and complications were considered.

Methods

Between 1971 and 2004, 426 patients suffering from newly diagnosed CD underwent primary surgery. Pre-operative measures included clinical examination, endocrinological workup (testing of the hypothalamic-pituitary-adrenal axis, and 2- and 8-mg dexamethasone overnight suppression tests), sellar imaging (polytomography, computed tomography, and magnetic resonance [MR] imaging), and in patients with negative results on imaging studies, inferior petrosal sinus sampling. Follow-up examinations consisting of endocrinological workup, and imaging took place 1 week and 3 months after surgery and then at yearly intervals.

Results

During microsurgery as first treatment, the adenoma finding rate was 86.6%. After selective adenomectomy, the remission rate was 75.9%, and this rate showed no improvement over the years. The best results were achieved in microadenomas confirmed on MR imaging or histopathological investigation. The recurrence rate (15%) and the complication rate (5.9%) declined over the years. If no adenoma was found, exploration of the sella turcica was performed in 45.6%, hypophysectomy in 3.5%, and hemihypophysectomy in 50.9% of these patients, leading to an early remission in 37.9%. In case of persistence or recurrence, further treatment (repeated operation, adrenalectomy, radio-therapy, or medical treatment) was used to control the disease.

Conclusions

Microsurgery remains the treatment of first choice in CD, even though no improvement in remission rates was observed over the years, because complication or remission rates for other treatment options are comparable or worse.

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Andrej Pala, Fadi Awad, Michael Braun, Michal Hlavac, Arthur Wunderlich, Bernd Schmitz, Christian Rainer Wirtz and Jan Coburger

OBJECTIVE

The gold standard for evaluation of ventriculoperitoneal (VP) shunt position, dislocation, or disconnection is conventional radiography. Yet, assessment with this modality can be challenging because of low image quality and can result in repetitive radiation exposure with high fluctuation in the radiation dose. Recently, CT-based radiation doses have been significantly reduced by using low-dose protocols. Thus, whole-body low-dose CT (LDCT) has become applicable for routine use in VP shunt evaluation. The authors here compared image quality and approximate radiation dose between radiography and LDCT in patients with implanted VP shunt systems.

METHODS

Ventriculoperitoneal shunt systems have been investigated with LDCT scanning at the authors’ department since 2015. A consecutive series of 57 patients (70 investigations) treated between 2015 and 2016 was retrospectively assessed. A historical patient cohort that had been evaluated with radiography was compared with the LDCT patients in terms of radiation dose and image quality. Three independent observers evaluated projection of the valve pressure level and correct intraperitoneal position, as well as complete shunt projection, using a Likert-type scale of 1–5, where 1 indicated “not assessable” and 5 meant “assessable with high accuracy.” Descriptive statistics and the Mann-Whitney U-test were used for analysis.

RESULTS

Twenty-seven radiographs (38.6%) and 43 LDCT scans (61.4%) were analyzed. The median dose-length product (DLP) of the LDCT scans was 100 mGy·cm (range 59.9–183 mGy·cm). The median total dose-area product (DAP) of the radiographic images was 3177 mGy·cm2 (range 641–13,833 mGy·cm2). The estimated effective dose (EED) was significantly lower with the LDCT scan (p < 0.001). The median EED was 4.93 and 1.90 mSv for radiographs and LDCT, respectively. Significantly better identification of the abdominal position of the distal shunt catheter was achieved with LDCT (p < 0.001). Simultaneously, significantly improved visualization of the entire shunt system was realized with this technique (p < 0.001). On the contrary, identification of the valve settings was significantly worse with LDCT (p < 0.001).

CONCLUSIONS

Whole-body LDCT scanning allows good visualization of the distal catheter after VP shunt placement. Despite the fact that only a rough estimation of effective doses is possible in a direct comparison of LDCT and radiography, the data showed that shunt assessment via LDCT does not lead to greater radiation exposure. Thus, especially in difficult anatomical conditions, as in patients who have undergone multiple intraabdominal surgeries, have a high BMI, or are immobile, the use of LDCT shunt evaluation has high clinical value. Further data are needed to determine the value of LDCT for the evaluation of complications or radiation dose in pediatric patients.