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Jeffrey H. Wisoff, John A. Jane Jr., Warren Selman and Rudolf Fahlbusch

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Rudolf Fahlbusch and Venelin M. Gerganov

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Bernd M. Hofmann, Anke Höllig, Christian Strauss, Rolf Buslei, Michael Buchfelder and Rudolf Fahlbusch

Object

The authors report surgical and endocrinological results of a series of 73 cases of craniopharyngioma that they treated surgically since 1997 to demonstrate their change in treatment strategy and its effect on outcome compared with a previous series and results reported in the literature.

Methods

A total of 73 patients underwent surgery for craniopharyngiomas between May 1997 and January 2005. In patients with poor clinical or neuropsychological condition, even following pretreatment, only stereotactic cyst aspiration took place (8 cases). In the remaining patients, gross-total resection (GTR) was intended and appeared to be possible. The most frequent approaches were subfrontal (27 cases) and transsphenoidal (26 cases); in some cases, a multistep approach was used. The rate of GTR, complications, and functional outcome (comparing pre- and postoperative endocrine and neuropsychological testing) were evaluated. The mean duration of follow-up was 25.2 months.

Results

Gross-total resection was achieved in 88.5% of cases in which a transsphenoidal approach was used and 79.5% of those in which a transcranial approach was used (85.2% of those in which a subfrontal approach was used and 72.7% of those in which a frontolateral approach was used). In the total series, GTR was achieved in 83.1% of cases (vs 49.3% in the authors' former series). The complication rate was 13.8% without any mortality. New endocrine deficits were observed more frequently in patients treated with transcranial approaches over the years (16.3%–66.7% vs 2.6%–50.0%) but were less frequent after transsphenoidal approaches (5.2%–19.2% vs 2.9%–45.7%).

Conclusions

Open surgery with intended total resection remains the treatment of choice in most patients. Initial stereotactic cyst aspiration or medical pretreatment to improve the patients' condition and adequate choice of surgical approach(es) are essential to achieve that goal. Nevertheless, a moderate increase in endocrinological deficits has to be accepted. The authors recommend using radiotherapy only in cases in which there are tumor remnants or disease progression after surgery.

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Venelin Gerganov, Hussam Metwali, Amir Samii, Rudolf Fahlbusch and Madjid Samii

Object

An extensive craniopharyngioma is a tumor that extends into multiple compartments (subarachnoid spaces) and attains a size larger than 4 cm. A wide spectrum of approaches and strategies has been used for resection of such craniopharyngiomas. In this report the authors focused on the feasibility and efficacy of microsurgical resection of extensive craniopharyngiomas using a frontolateral approach.

Methods

A retrospective analysis was performed on 16 patients with extensive craniopharyngiomas who underwent operations using a frontolateral approach at one institution. The preoperative and postoperative clinical and radiological data, as well as the operative videos, were reviewed. The main focus of the review was the extent of radical tumor removal, early postoperative outcome, and approach-related complications.

Results

Gross-total resection of craniopharyngioma was achieved in 14 (87.5%) of 16 cases. Early after surgery (within 3 months), 1 patient showed improvement in hormonal status, while in the remaining 15 patients it worsened. No major neurological morbidity was observed. Two patients experienced temporary psychotic disorders. Visual function improved in 6 patients and remained unchanged in 9. One patient experienced a new bitemporal hemianopsia. Three patients with features of short-term memory disturbances at presentation did show improvement after surgery. There were no deaths or significant approach-related morbidity in this patient series. Only 1 patient required revision surgery for a CSF leak.

Conclusions

The safe and simple frontolateral approach provides adequate access even to extensive craniopharyngiomas and enables their complete removal with a reasonable morbidity and approach-related complication rate.

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Sven Berkmann, Sven Schlaffer, Christopher Nimsky, Rudolf Fahlbusch and Michael Buchfelder

Object

The loss of anatomical landmarks, frequently invasive tumor growth, and tissue changes make transsphenoidal reoperation of nonfunctioning pituitary adenomas (NFAs) challenging. The use of intraoperative MRI (iMRI) may lead to improved results. The goal of this retrospective study was to evaluate the impact of iMRI on transsphenoidal reoperations for NFA.

Methods

Between September 2002 and July 2012, 109 patients underwent reoperations in which 111 transsphenoidal procedures were performed and are represented in this study. A 1.5-T Magnetom Sonata Maestro Class scanner (Siemens) was used for iMRI. Follow-up iMRI scans were acquired if gross-total resection (GTR) was suspected or if no further removal seemed possible.

Results

Surgery was performed for tumor persistence and regrowth in 26 (23%) and 85 (77%) patients, respectively. On the initial iMRI scans, GTR was confirmed in 19 (17%) patients. Remnants were located as follows: 65 in the cavernous sinus (71%), 35 in the suprasellar space (38%), 9 in the retrosellar space (10%). Additional resection was possible in 62 (67%) patients, resulting in a significant volume reduction and increased GTR rate (49%). The GTR rates of invasive tumors on initial iMRI and postoperative MRI (poMRI) were 7% and 25%, respectively. Additional remnant resection was possible in 64% of the patients. Noninvasive tumors were shown to be totally resected on the initial iMRI in 31% of cases. After additional resection for 69% of the procedures, the GTR rate on poMRI was 75%. Transcranial surgery to resect tumor remnants was indicated in 5 (5%), and radiotherapy was performed in 29 (27%) patients. After GTR, no recurrence was detected during a mean follow-up of 2.2 ± 2.1 years.

Conclusions

The use of iMRI in transsphenoidal reoperations for NFA leads to significantly higher GTR rates. It thus prevents additional operations and reduces the number of tumor remnants. The complication rates do not exceed the incidences reported in the literature for primary transsphenoidal surgery. If complete tumor resection is not possible, iMRI guidance can facilitate tumor volume reduction.

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Rudolf Fahlbusch and Amir Samii

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Rudolf Fahlbusch, Alexandra Golby, Francesco Prada and Gabriel Zada

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Hussam Metwali, Venelin Gerganov and Rudolf Fahlbusch

OBJECT

Preservation of the pituitary stalk and its vasculature is a key step in good postoperative endocrinological outcome in patients with craniopharyngiomas. In this article, the authors describe the surgical technique of medial optic nerve mobilization for better inspection and preservation of the pituitary stalk.

METHODS

This operative technique has been applied in 3 patients. Following tumor exposure via a frontolateral approach, the pituitary stalk could be seen partially hidden under the optic nerve and the optic chiasm. The subchiasmatic and opticocarotid spaces were narrow, and tumor dissection from the pituitary stalk under direct vision was not possible. The optic canal was therefore unroofed, the falciform ligament was incised, and the lateral part of the tuberculum sellae was drilled medial to the optic nerve. The optic nerve could be mobilized medially to widen the opticocarotid triangle, which enhanced visualization of and access to the pituitary stalk.

RESULTS

By using the optic nerve mobilization technique, the tumor could be removed completely, and the pituitary stalk and its vasculature were preserved in all patients. In 2 patients, vision improved after surgery, while in 1 patient it remained normal, as it was before surgery. The hormonal status remained normal after surgery in 2 patients. In the patient with preoperative hormonal deficiencies, improvement occurred early after surgery and hormonal levels were normal after 3 months. No approach-related complications occurred.

CONCLUSIONS

This early experience shows that this technique is safe and could be used as a complementary step during microsurgery of craniopharyngiomas. It allows for tumor dissection from the pituitary stalk under direct vision. The pituitary stalk can thus be preserved without jeopardizing the optic nerve.

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Mohamadreza Hajiabadi, Madjid Samii and Rudolf Fahlbusch

OBJECT

Visual impairments are the most common objective manifestations of suprasellar lesions. Diffusion tensor imaging (DTI) is a noninvasive MRI modality that depicts the subcortical white matter tracts in vivo. In this study the authors tested the value of visual pathway tractography in comparison with visual field and visual acuity analyses.

METHODS

This prospective study consisted of 25 patients with progressive visual impairment due to suprasellar mass lesions and 6 control patients with normal vision without such lesions. Visual acuity, visual field, and the optic fundus were examined preoperatively and repeated 1 week and 3 months after surgery. Visual pathway DTI tractography was performed preoperatively, intraoperatively immediately after tumor resection, and 1 week and 3 months after surgery.

RESULTS

In the control group, pre- and postoperative visual status were normal and visual pathway tractography revealed fibers crossing the optic chiasm without any alteration. In patients with suprasellar lesions, vision improved in 24 of 25. The mean distance between optic tracts in tractography decreased after tumor resection and detectable fibers crossing the optic chiasm increased from 12% preoperatively to 72% postoperatively 3 months after tumor resection, and undetectable fibers crossing the optic chiasm decreased from 88% preoperatively to 27% postoperatively 3 months after tumor resection. Visual improvement after tumor removal 1 week and 3 months after surgery was significantly correlated with the distance between optic tracts in intraoperative tractography (p < 0.01).

CONCLUSIONS

Visual pathway DTI tractography appears to be a promising adjunct to the standard clinical and paraclinical visual examinations in patients with suprasellar mass lesions. The intraoperative findings, in particular the distance between optic tract fibers, can predict visual outcome after tumor resection. Furthermore, postoperative application of this technique may be useful in following anterior optic pathway recovery.

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Christina Stache, Christiane Bils, Rudolf Fahlbusch, Jörg Flitsch, Michael Buchfelder, Harald Stefanits, Thomas Czech, Udo Gaipl, Benjamin Frey, Rolf Buslei and Annett Hölsken

OBJECTIVE

In this study, the authors investigated the underlying mechanisms responsible for high tumor recurrence rates of adamantinomatous craniopharyngioma (ACP) after radiotherapy and developed new targeted treatment protocols to minimize recurrence. ACPs are characterized by the activation of the receptor tyrosine kinase epidermal growth factor receptor (EGFR), known to mediate radioresistance in various tumor entities. The impact of tyrosine kinase inhibitors (TKIs) gefitinib or CUDC-101 on radiation-induced cell death and associated regulation of survivin gene expression was evaluated.

METHODS

The hypothesis that activated EGFR promotes radioresistance in ACP was investigated in vitro using human primary cell cultures of ACP (n = 10). The effects of radiation (12 Gy) and combined radiochemotherapy on radiosensitivity were assessed via cell death analysis using flow cytometry. Changes in target gene expression were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Survivin, identified in qRT-PCR to be involved in radioresistance of ACP, was manipulated by small interfering RNA (siRNA), followed by proliferation and vitality assays to further clarify its role in ACP biology. Immunohistochemically, survivin expression was assessed in patient tumors used for primary cell cultures.

RESULTS

In primary human ACP cultures, activation of EGFR resulted in significantly reduced cell death levels after radiotherapy. Treatment with TKIs alone and in combination with radiotherapy increased cell death response remarkably, assessed by flow cytometry. CUDC-101 was significantly more effective than gefitinib. The authors identified regulation of survivin expression after therapeutic intervention as the underlying molecular mechanism of radioresistance in ACP. EGFR activation promoting ACP cell survival and proliferation in vitro is consistent with enhanced survivin gene expression shown by qRT-PCR. TKI treatment, as well as the combination with radiotherapy, reduced survivin levels in vitro. Accordingly, ACP showed reduced cell viability and proliferation after survivin downregulation by siRNA.

CONCLUSIONS

These results indicate an impact of EGFR signaling on radioresistance in ACP. Inhibition of EGFR activity by means of TKI treatment acts as a radiosensitizer on ACP tumor cells, leading to increased cell death. Additionally, the results emphasize the antiapoptotic and pro-proliferative role of survivin in ACP biology and its regulation by EGFR signaling. The suppression of survivin by treatment with TKI and combined radiotherapy represents a new promising treatment strategy that will be further assessed in in vivo models of ACP.