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Louis J. Kim, Oliver Bozinov, Judy Huang, and Giuseppe Lanzino

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Ulrich Sure, Sandra Freman, Oliver Bozinov, Ludwig Benes, Adrian M. Siegel, and Helmut Bertalanffy

Object. Cerebral cavernous malformations (CCMs) have previously been considered as congenital and biologically static malformations. On the other hand, the potential for growth and de novo generation of CCMs have also been reported. It is therefore important to study the proliferative and neoangiogenetic capacity of these lesions.

Methods. The authors studied the surgical specimens of 56 CCMs (23 deep and 33 superficial) obtained from adult patients. The proliferative activity of the endothelium and the neoangiogenetic capacity of these lesions were considered through immunohistochemical anaylsis of proliferating cell nuclear antigen (PCNA), MIB-1, Flk-1, vascular endothelial growth factor (VEGF), hypoxia-inducible factor (HIF)-1α, and endoglin antibodies.

Positive immunostaining of endothelial cells occurred in 86% of patients for PCNA and in 38% of the cases for MIB-1. The expression of Flk-1 was observed in the endothelium of 71% of the cases, for VEGF in 41%, for HIF-1α in 48.1%, and for endoglin in 63.6% of the cases. The correlation of immunohistochemical and clinical data indicated that VEGF was expressed in significantly less deep-seated lesions when compared with superficial CCMs. Neither the expression of the proliferative markers nor the expression of the angiogenetic antibodies correlated with patient age at surgery, sex, or the number of recent prior hemorrhagic episodes in the patients.

Conclusions. The CCMs from adult patients are active lesions exhibiting endothelial proliferation and neoangiogenesis. According to the data in this study, neoangiogenesis is more prominent in superficial CCMs than in deep-seated CCMs and is not associated with recent prior hemorrhages.

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Anne-Katrin Hickmann, Andrea Ferrari, Oliver Bozinov, Martin N. Stienen, and Carsten Ostendorp

OBJECTIVE

Restrictions on working time and healthcare expenditures, as well as increasing subspecialization with caseload requirements per surgeon and increased quality-of-care expectations, provide limited opportunities for surgical residents to be trained in the operating room. Yet, surgical training requires goal-oriented and focused practice. As a result, training simulators are increasingly utilized. The authors designed a two-step blended course consisting of a personalized adaptive electronic learning (e-learning) module followed by simulator training. This paper reports on course development and the evaluation by the first participants.

METHODS

Adaptive e-learning was curated by learning engineers based on theoretical information provided by clinicians (subject matter experts). A lumbar spine model for image-guided spinal injections was used for the simulator training. Residents were assigned to the e-learning module first; after its completion, they participated in the simulator training. Performance data were recorded for each participant’s e-learning module, which was necessary to personalize the learning experience to each individual’s knowledge and needs. Simulator training was organized in small groups with a 1-to-4 instructor-to-participant ratio. Structured assessments were undertaken, adapted from the Student Evaluation of Educational Quality.

RESULTS

The adaptive e-learning module was curated, reviewed, and approved within 10 weeks. Eight participants have taken the course to date. The overall rating of the course is very good (4.8/5). Adaptive e-learning is well received compared with other e-learning types (8/10), but scores lower regarding usefulness, efficiency, and fun compared with the simulator training, despite improved conscious competency (32.6% ± 15.1%) and decreased subconscious incompetency (22.8% ± 10.2%). The subjective skill level improved by 20%. Asked about the estimated impact of the course, participants indicated that they had either learned something new that they plan to use in their practice (71.4%) or felt reassured in their practice (28.6%).

CONCLUSIONS

The development of a blended training course combining adaptive e-learning and simulator training in a rapid manner is feasible and leads to improved skills. Simulator training is rated more valuable by surgical trainees than theoretical e-learning; the impact of this type of training on patient care needs to be further investigated.

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Pascal O. Zinn, Oliver Bozinov, Jan-Karl Burkhardt, Robert Reisch, M. Gazi Yaşargil, and Helmut Bertalanffy

Mechanical obstruction is a severe complication of ventricular catheter use. Its incidence was shown to be high in the 1960s and 1970s, with up to 41% of the catheters becoming obstructed within 10 years after surgery. The authors present what is to their knowledge the first reported case of a patient with failure of a Torkildsen shunt after 50 years of functioning. A 60-year-old woman presented with increasing gait ataxia, decline in cognitive functions (including short-term memory loss), and slight urinary incontinence. The diagnosis of hydrocephalus and thus malfunction of the Torkildsen shunt implanted 50 years previously was confirmed by MR images, which revealed a prominent triventricular hydrocephalus. The patient subsequently underwent endoscopic third ventriculostomy (ETV), the current surgical treatment of choice, resulting in total resolution of her neurological symptoms and amelioration of cerebral tissue distension. Decrease in ventricle dilation and success of the ETV were confirmed on postoperative follow-up MR images.

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Carlo Serra, Jan-Karl Burkhardt, Giuseppe Esposito, Oliver Bozinov, Athina Pangalu, Antonios Valavanis, David Holzmann, Christoph Schmid, and Luca Regli

OBJECTIVE

The aim of this study was to quantitatively assess the role of intraoperative high-field 3-T MRI (3T-iMRI) in improving the gross-total resection (GTR) rate and the extent of resection (EOR) in endoscopic transsphenoidal surgery (TSS) for pituitary adenomas.

METHODS

Radiological and clinical data from a prospective database were retrospectively analyzed. Volumetric measurements of adenoma volumes pre-, intraoperatively, and 3 months postoperatively were performed in a consecutive series of patients who had undergone endoscopic TSS. The quantitative contribution of 3T-iMRI was measured as a percentage of the additional rate of GTR and of the EOR achieved after 3T-iMRI.

RESULTS

The cohort consisted of 50 patients (51 operations) harboring 33 nonfunctioning and 18 functioning pituitary adenomas. Mean adenoma diameter and volume were 21.1 mm (range 5–47 mm) and 5.23 cm3 (range 0.09–22.14 cm3), respectively. According to Knosp's classification, 10 cases were Grade 0; 8, Grade 1; 17, Grade 2; 12, Grade 3; and 4, Grade 4. Gross-total resection was the surgical goal (targeted [t]GTR) in 34 of 51 operations and was initially achieved in 16 (47%) of 34 at 3T-iMRI and in 30 (88%) of 34 cases after further resection. In this subgroup, the EOR increased from 91% at 3T-iMRI to 99% at the 3-month MRI (p < 0.05). In the 17 cases in which subtotal resection (STR) had been planned (tSTR), the EOR increased from 79% to 86% (p < 0.05) and GTR could be achieved in 1 case. Intrasellar remnants were present in 20 of 51 procedures at 3T-iMRI and in only 5 (10%) of 51 procedures after further resection (median volume 0.15 cm3). Overall, the use of 3T-iMRI led to further resection in 27 (53%) of 51 procedures and permitted GTR in 15 (56%) of these 27 procedures; thus, the GTR rate in the entire cohort increased from 31% (16 of 51) to 61% (31 of 51) and the EOR increased from 87% to 95% (p < 0.05).

CONCLUSIONS

The use of high-definition 3T-iMRI allowed precise visualization and quantification of adenoma remnant volume. It helped to increase GTR and EOR rates in both tGTR and tSTR patient groups. Moreover, it helped to achieve low rates of intrasellar remnants. These data support the use of 3T-iMRI to achieve maximal, safe adenoma resection.

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Jan-Karl Burkhardt, Pascal O. Zinn, Muriel Graenicher, Alejandro Santillan, Oliver Bozinov, Ekkehard M. Kasper, and Niklaus Krayenbühl

Object

Some patients develop communicating hydrocephalus after meningioma surgery, and this can develop into a serious clinical condition. However, this has rarely been addressed in the literature. Therefore, the authors sought to determine predictive patient variables for the occurrence of postoperative hydrocephalus following skull base meningioma surgery.

Methods

For this purpose, the authors retrospectively analyzed all patients who underwent resection of intracranial meningiomas between 1998 and 2009 at the Department of Neurosurgery, University Hospital Zurich, Switzerland. Of 594 patients with meningioma, 227 (38%) had a lesion located at the skull base, and thus were included for analysis. The following patient variables were examined: demographic data (age and sex); tumor number (solitary vs multiple); tumor side and localization within the skull base region (anterior, medial, posterior); infiltration of the cavernous sinus; compression of the optic channel/optic nerve; tumor volume; preoperative embolization (yes/no); duration of surgery; Simpson grade of resection; histopathological features (WHO grade); number of surgeries (single vs multiple); preoperative embolization; duration of hospital stay; tumor recurrence; use of an artificial dural substitute; postoperative infection rate; and clinical outcome (Glasgow Outcome Scale score at discharge and at 3 months, and vital status at last follow-up). Hierarchical clustering, factor analysis, and stepwise regression models revealed a ranking list for the top predictive variables for the occurrence of postoperative hydrocephalus.

Results

A total of 35 patients (5.9%) of the cohort of 594 developed communicating postoperative hydrocephalus, with no patient manifesting obstructive hydrocephalus. Of these 35 patients, 18 had a meningioma located at the skull base (18 [7.9%] of 227), in contrast to 17 patients with meningiomas in other locations (17 [4.6%] of 367). The following patient variables correlated with the occurrence of hydrocephalus, as defined by factor analysis: age, duration of surgery, duration of hospital stay, tumor volume, postoperative infection, and preoperative embolization. A stepwise regression analysis of the latter variables identified 2 variables as significantly predictive: age (p = 0.0012) and duration of surgery (p = 0.0013).

Conclusions

In this study, the incidence of communicating postoperative hydrocephalus was almost twice as high in patients with skull base lesions as in patients with meningiomas in other locations. Patient age, duration of surgery, duration of hospital stay, tumor volume, postoperative infection, and preoperative embolization were associated with the occurrence of hydrocephalus. In the statistical prediction model, patient age and duration of surgery were the most significant predictors of postoperative hydrocephalus after skull base meningioma surgery.

Free access

Sophie S. Wang, Friederike Selge, Martina Sebök, Pierre Scheffler, Yang Yang, Giovanna Brandi, Sebastian Winklhofer, and Oliver Bozinov

OBJECTIVE

Identifying tumor remnants in previously operated tumor lesions remains a challenge. Intraoperative MRI (ioMRI) helps the neurosurgeon to reorient and update image guidance during surgery. The purpose of this study was to analyze whether ioMRI is more efficient in detecting tumor remnants in the surgery of recurrent lesions compared with primary surgery.

METHODS

All consecutive patients undergoing elective intracranial tumor surgery between 2013 and 2018 at the authors’ institution were included in this retrospective cohort study. The cohort was divided into two groups: re-craniotomy and primary craniotomy. In contrast-enhancing tumors, tumor suspicion in ioMRI was defined as contrast enhancement in T1-weighted imaging. In non–contrast-enhancing tumors, tumor suspicion was defined as hypointensity in T1-weighted imaging and hyperintensity in T2-weighted imaging and FLAIR. In cases in which the ioMRI tumor suspicion was a false positive and not confirmed during in situ inspection by the neurosurgeon, the signal was defined as a tumor-imitating ioMRI signal (TIM). Descriptive statistics were performed.

RESULTS

A total of 214 tumor surgeries met the inclusion criteria. The re-craniotomy group included 89 surgeries, and the primary craniotomy group included 123 surgeries. Initial complete resection after ioMRI was less frequent in the re-craniotomy group than in the primary craniotomy group, but this was not a statistically significant difference. Radiological suspicion of tumor remnants in ioMRI was present in 78% of re-craniotomy surgeries and 69% of primary craniotomy surgeries. The incidence of false-positive TIMs was significantly higher in the re-craniotomy group (n = 11, 12%) compared with the primary craniotomy group (n = 5, 4%; p = 0.015), and in contrast-enhancing tumors was related to hemorrhages in situ (n = 9).

CONCLUSIONS

A history of previous surgery in contrast-enhancing tumors made correct identification of tumor remnants in ioMRI more difficult, with a higher rate of false-positive ioMRI signals in the re-craniotomy group. The majority of TIMs were associated with the inability to distinguish contrast enhancement from hyperacute hemorrhage. The addition of a specific sequence in ioMRI to further differentiate both should be investigated in future studies.

Free access

Sophie S. Wang, Friederike Selge, Martina Sebök, Pierre Scheffler, Yang Yang, Giovanna Brandi, Sebastian Winklhofer, and Oliver Bozinov

OBJECTIVE

Identifying tumor remnants in previously operated tumor lesions remains a challenge. Intraoperative MRI (ioMRI) helps the neurosurgeon to reorient and update image guidance during surgery. The purpose of this study was to analyze whether ioMRI is more efficient in detecting tumor remnants in the surgery of recurrent lesions compared with primary surgery.

METHODS

All consecutive patients undergoing elective intracranial tumor surgery between 2013 and 2018 at the authors’ institution were included in this retrospective cohort study. The cohort was divided into two groups: re-craniotomy and primary craniotomy. In contrast-enhancing tumors, tumor suspicion in ioMRI was defined as contrast enhancement in T1-weighted imaging. In non–contrast-enhancing tumors, tumor suspicion was defined as hypointensity in T1-weighted imaging and hyperintensity in T2-weighted imaging and FLAIR. In cases in which the ioMRI tumor suspicion was a false positive and not confirmed during in situ inspection by the neurosurgeon, the signal was defined as a tumor-imitating ioMRI signal (TIM). Descriptive statistics were performed.

RESULTS

A total of 214 tumor surgeries met the inclusion criteria. The re-craniotomy group included 89 surgeries, and the primary craniotomy group included 123 surgeries. Initial complete resection after ioMRI was less frequent in the re-craniotomy group than in the primary craniotomy group, but this was not a statistically significant difference. Radiological suspicion of tumor remnants in ioMRI was present in 78% of re-craniotomy surgeries and 69% of primary craniotomy surgeries. The incidence of false-positive TIMs was significantly higher in the re-craniotomy group (n = 11, 12%) compared with the primary craniotomy group (n = 5, 4%; p = 0.015), and in contrast-enhancing tumors was related to hemorrhages in situ (n = 9).

CONCLUSIONS

A history of previous surgery in contrast-enhancing tumors made correct identification of tumor remnants in ioMRI more difficult, with a higher rate of false-positive ioMRI signals in the re-craniotomy group. The majority of TIMs were associated with the inability to distinguish contrast enhancement from hyperacute hemorrhage. The addition of a specific sequence in ioMRI to further differentiate both should be investigated in future studies.

Free access

Nicolai Maldaner, Marketa Sosnova, Anna M. Zeitlberger, Michal Ziga, Oliver P. Gautschi, Luca Regli, Oliver Bozinov, Astrid Weyerbrock, and Martin N. Stienen

OBJECTIVE

The 6-minute walking test (6WT) and the Timed Up and Go (TUG) test are two of the most commonly applied standardized measures of objective functional impairment that help support clinical decision-making for patients undergoing surgery for degenerative lumbar disorders. This study correlates smartphone-app–based 6WT and TUG results to evaluate their responsiveness.

METHODS

In a prospective study, 49 consecutive patients were assessed preoperatively and 6 weeks postoperatively using the 6WT, the TUG test, and commonly used patient-reported outcome measures. Raw values and standardized z-scores of both objective tests were correlated. An external criterion for treatment success was created based on the Zurich Claudication Questionnaire patient satisfaction subscale. Internal and external responsiveness for both functional tests was evaluated.

RESULTS

The mean preoperative 6WT results improved from 401 m (SD 129 m), z-score −1.65 (SD 1.6) to 495 m (SD 129 m), z-score −0.71 (SD 1.6, p < 0.001). The mean preoperative TUG test results improved from 10.44 seconds (SD 4.37, z-score: −3.22) to 8.47 seconds (SD 3.38, z-score: −1.93, p < 0.001). The 6WT showed a strong negative correlation with TUG test results (r = −66, 95% CI 0.76–0.53, p < 0.001). The 6WT showed higher internal responsiveness (standardized responsive mean = 0.86) compared to the TUG test (standardized responsive mean = 0.67). Evaluation of external responsiveness revealed that the 6WT was capable of differentiating between patients who were satisfied and those who were unsatisfied with their treatment results (area under the curve = 0.70), whereas this was not evident for the TUG test ( area under the curve = 0.53).

CONCLUSIONS

Both tests adequately quantified functional impairment in surgical candidates with degenerative lumbar disorders. The 6WT demonstrated better internal and external responsiveness compared with the TUG test.

Clinical trial registration no.: NCT03977961 (clinicaltrials.gov)

Free access

Nicolai Maldaner, Marketa Sosnova, Anna M. Zeitlberger, Michal Ziga, Oliver P. Gautschi, Luca Regli, Oliver Bozinov, Astrid Weyerbrock, and Martin N. Stienen

OBJECTIVE

The 6-minute walking test (6WT) and the Timed Up and Go (TUG) test are two of the most commonly applied standardized measures of objective functional impairment that help support clinical decision-making for patients undergoing surgery for degenerative lumbar disorders. This study correlates smartphone-app–based 6WT and TUG results to evaluate their responsiveness.

METHODS

In a prospective study, 49 consecutive patients were assessed preoperatively and 6 weeks postoperatively using the 6WT, the TUG test, and commonly used patient-reported outcome measures. Raw values and standardized z-scores of both objective tests were correlated. An external criterion for treatment success was created based on the Zurich Claudication Questionnaire patient satisfaction subscale. Internal and external responsiveness for both functional tests was evaluated.

RESULTS

The mean preoperative 6WT results improved from 401 m (SD 129 m), z-score −1.65 (SD 1.6) to 495 m (SD 129 m), z-score −0.71 (SD 1.6, p < 0.001). The mean preoperative TUG test results improved from 10.44 seconds (SD 4.37, z-score: −3.22) to 8.47 seconds (SD 3.38, z-score: −1.93, p < 0.001). The 6WT showed a strong negative correlation with TUG test results (r = −66, 95% CI 0.76–0.53, p < 0.001). The 6WT showed higher internal responsiveness (standardized responsive mean = 0.86) compared to the TUG test (standardized responsive mean = 0.67). Evaluation of external responsiveness revealed that the 6WT was capable of differentiating between patients who were satisfied and those who were unsatisfied with their treatment results (area under the curve = 0.70), whereas this was not evident for the TUG test ( area under the curve = 0.53).

CONCLUSIONS

Both tests adequately quantified functional impairment in surgical candidates with degenerative lumbar disorders. The 6WT demonstrated better internal and external responsiveness compared with the TUG test.

Clinical trial registration no.: NCT03977961 (clinicaltrials.gov)