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Georg Widhalm, Stefan Wolfsberger, Matthias Preusser, Ingeborg Fischer, Adelheid Woehrer, Joerg Wunderer, Johannes A. Hainfellner and Engelbert Knosp

Object

In residual nonfunctioning pituitary adenomas, reliable prognostic parameters indicating probability of tumor progression are needed. The Ki 67 expression/MIB-1 labeling index (LI) is considered to be a promising candidate factor. The aim in the present study was to analyze the clinical usefulness of MIB-1 LI for prognosis of tumor progression.

Methods

The authors studied a cohort of 92 patients with nonfunctioning pituitary adenomas. Based on sequential postoperative MR images, patients were classified as tumor free (51 patients) or as harboring residual tumor (41 individuals). The residual tumor group was further subdivided in groups with stable residual tumors (14 patients) or progressive residual tumors (27 patients). The MIB-1 LI was assessed in tumor specimens obtained in all patients, and statistical comparisons of MIB-1 LI of the various subgroups were performed.

Results

. The authors found no significant difference of MIB-1 LI in the residual tumor group compared with the tumor-free group. However, MIB-1 LI was significantly higher in the progressive residual tumor group, compared with the stable residual tumor group. Additionally, the time period to second surgery was significantly shorter in residual adenomas showing an MIB-1 LI > 3%.

Conclusions

The data indicate that MIB-1 LI in nonfunctioning pituitary adenomas is a clinically useful prognostic parameter indicating probability of progression of postoperative tumor remnants. The MIB-1 LI may be helpful in decisions of postoperative disease management (for example, frequency of radiographic intervals, planning for reoperation, radiotherapy, and/or radiosurgery).

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Georgi Minchev, Gernot Kronreif, Wolfgang Ptacek, Christian Dorfer, Alexander Micko, Svenja Maschke, Federico G. Legnani, Georg Widhalm, Engelbert Knosp and Stefan Wolfsberger

OBJECTIVE

As decisions regarding tumor diagnosis and subsequent treatment are increasingly based on molecular pathology, the frequency of brain biopsies is increasing. Robotic devices overcome limitations of frame-based and frameless techniques in terms of accuracy and usability. The aim of the present study was to present a novel, minimally invasive, robot-guided biopsy technique and compare the results with those of standard burr hole biopsy.

METHODS

A tubular minimally invasive instrument set was custom-designed for the iSYS-1 robot-guided biopsies. Feasibility, accuracy, duration, and outcome were compared in a consecutive series of 66 cases of robot-guided stereotactic biopsies between the minimally invasive (32 patients) and standard (34 patients) procedures.

RESULTS

Application of the minimally invasive instrument set was feasible in all patients. Compared with the standard burr hole technique, accuracy was significantly higher both at entry (median 1.5 mm [range 0.2–3.2 mm] vs 1.7 mm [range 0.8–5.1 mm], p = 0.008) and at target (median 1.5 mm [range 0.4–3.4 mm] vs 2.0 mm [range 0.8–3.9 mm], p = 0.019). The incision-to-suture time was significantly shorter (median 30 minutes [range 15–50 minutes] vs 37.5 minutes [range 25–105 minutes], p < 0.001). The skin incision was significantly shorter (median 16.3 mm [range 12.7–23.4 mm] vs 28.4 mm [range 20–42.2 mm], p = 0.002). A diagnostic tissue sample was obtained in all cases.

CONCLUSIONS

Application of the novel instrument set was feasible in all patients. According to the authors’ data, the minimally invasive robot-guidance procedure can significantly improve accuracy, reduce operating time, and improve the cosmetic result of stereotactic biopsies.

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Georg Widhalm, Jonathan Olson, Jonathan Weller, Jaime Bravo, Seunggu J. Han, Joanna Phillips, Shawn L. Hervey-Jumper, Susan M. Chang, David W. Roberts and Mitchel S. Berger

OBJECTIVE

In patients with suspected diffusely infiltrating low-grade gliomas (LGG), the prognosis is dependent especially on extent of resection and precision of tissue sampling. Unfortunately, visible 5-aminolevulinic acid (5-ALA) fluorescence is usually only present in high-grade gliomas (HGGs), and most LGGs cannot be visualized. Recently, spectroscopic probes were introduced allowing in vivo quantitative analysis of intratumoral 5-ALA–induced protoporphyrin IX (PpIX) accumulation. The aim of this study was to intraoperatively investigate the value of visible 5-ALA fluorescence and quantitative PpIX analysis in suspected diffusely infiltrating LGG.

METHODS

Patients with radiologically suspected diffusely infiltrating LGG were prospectively recruited, and 5-ALA was preoperatively administered. During resection, visual fluorescence and absolute tissue PpIX concentration (CPpIX) measured by a spectroscopic handheld probe were determined in different intratumoral areas. Subsequently, corresponding tissue samples were safely collected for histopathological analysis. Tumor diagnosis was established according to the World Health Organization 2016 criteria. Additionally, the tumor grade and percentage of tumor cells were investigated in each sample.

RESULTS

All together, 69 samples were collected from 22 patients with histopathologically confirmed diffusely infiltrating glioma. Visible fluorescence was detected in focal areas in most HGGs (79%), but in none of the 8 LGGs. The mean CPpIX was significantly higher in fluorescing samples than in nonfluorescing samples (0.693 μg/ml and 0.008 μg/ml, respectively; p < 0.001). A significantly higher mean percentage of tumor cells was found in samples with visible fluorescence compared to samples with no fluorescence (62% and 34%, respectively; p = 0.005), and significant correlation of CPpIX and percentage of tumor cells was found (r = 0.362, p = 0.002). Moreover, high-grade histology was significantly more common in fluorescing samples than in nonfluorescing samples (p = 0.001), whereas no statistically significant difference in mean CPpIX was noted between HGG and LGG samples. Correlation between maximum CPpIX and overall tumor grade was highly significant (p = 0.005). Finally, 14 (40%) of 35 tumor samples with no visible fluorescence and 16 (50%) of 32 LGG samples showed significantly increased CPpIX (cutoff value: 0.005 μg/ml).

CONCLUSIONS

Visible 5-ALA fluorescence is able to detect focal intratumoral areas of malignant transformation, and additional quantitative PpIX analysis is especially useful to visualize mainly LGG tissue that usually remains undetected by conventional fluorescence. Thus, both techniques will support the neurosurgeon in achieving maximal safe resection and increased precision of tissue sampling during surgery for suspected LGG.

Clinical trial registration no.: NCT01116661 (clinicaltrials.gov)

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Oral Presentations

2010 AANS Annual Meeting Philadelphia, Pennsylvania May 1–5, 2010