Jean-Pierre Kalala

The hTERT‐protein and Ki‐67 labelling index in recurrent and non‐recurrent meningiomas

Abstract.  Meningiomas are considered as benign neoplasms affecting the coverings of the central nervous system and compromise approximately 20% of all intracranial tumours. However, a number of these tumours recur even after total resection. The aim of this study is to evaluate the prognostic significance for recurrence of the human telomerase catalytic subunit (hTERT) in the cells of meningiomas. The expression of hTERT‐protein can be evaluated by immunohistochemical staining using a monoclonal antibody against hTERT (clone 44F42, NCL‐L‐hTERT). The interdependence between tumour recurrence and cell proliferation in this study is analysed by Ki‐67 immunoreactivity (clone MIB‐1). Archival material from 29 non‐recurrent and 32 recurrent tumours has been evaluated, including specimens from World Health Organization (WHO) stages I (n = 73), II (n = 2) and III (n = 12). Although the tumours were categorized as benign meningiomas following the WHO classification, recurrence in 22 of 50 cases did not correlate with the tumour stage. For hTERT staining, the following results were found for nucleolar and total nuclear staining, respectively: non‐recurrent meningiomas, 2.9% (± 7.7) and 3.0% (± 8.0); recurrent meningiomas at first resection, 16.8% (± 19.7) and 31.6% (± 30.2). Concerning the Ki‐67 labelling index (LI): for the group of non‐recurrent meningiomas, results were 2.1% (± 1.7) and for the recurrent group at first resection, 1.7% (± 2.0). A significant difference was seen for the hTERT staining (P < 0.001) between the non‐recurrent and recurrent meningiomas, whereas no statistical significance was found for Ki‐67. In conclusion hTERT‐positive meningiomas had a high incidence for recurrence. Ki‐67 was a good marker of cell proliferation status of the tumours, but did not correlate with recurrence; thus, hTERT alone seemed to be a potential predictor for recurrence.

18F-fluoromethylcholine (FCho), 18F-fluoroethyltyrosine (FET), and 18F-fluorodeoxyglucose (FDG) for the discrimination between high-grade glioma and radiation necrosis in rats: A PET study

INTRODUCTION Discrimination between (high-grade) brain tumor recurrence and radiation necrosis (RN) remains a diagnostic challenge because both entities have similar imaging characteristics on conventional magnetic resonance imaging (MRI). Metabolic imaging, such as positron emission tomography (PET) could overcome this diagnostic dilemma. In this study, we investigated the potential of 2-[(18)F]-fluoro-2-deoxy-D-glucose ((18)F-FDG), O-(2-[(18)F]-fluoroethyl)-L-tyrosine ((18)F-FET), and [(18)F]-Fluoromethyl-dimethyl-2-hydroxyethylammonium ((18)F-fluoromethylcholine, (18)F-FCho) PET in discriminating high-grade tumor from RN. METHODS We developed a glioblastoma (GB) rat model by inoculating F98 GB cells into the right frontal region. Induction of RN was achieved by irradiating the right frontal region with 60 Gy using three arcs with a beam aperture of 3×3 mm (n=3). Dynamic PET imaging with (18)F-FDG, (18)F-FET, and (18)F-FCho, as well as (18)F-FDG PET at a delayed time interval (240 min postinjection), was acquired. RESULTS MRI revealed contrast-enhancing tumors at 15 days after inoculation (n=4) and contrast-enhancing RN lesions 5-6 months postirradiation (n=3). On (18)F-FDG PET, the mean lesion-to-normal ratio (LNRmean) was significantly higher in GB than in RN (p=0.034). The difference in the LNRmean between tumors and RN was higher on the late (18)F-FDG PET images than on the PET images reconstructed from the last time frame of the dynamic acquisition (this is at a conventional time interval). LNRs obtained from (18)F-FCho PET were not significantly different between GB and RN (p=1.000). On (18)F-FET PET, the LNRmean was significantly higher in GB compared to RN (p=0.034). CONCLUSIONS Unlike (18)F-FCho, (18)F-FDG and (18)F-FET PET were effective in discriminating GB from RN. Interestingly, in the case of (18)F-FDG, delayed PET seems particularly useful. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE Our results suggest that (delayed) (18)F-FDG and (18)F-FET PET can be used to discriminate GB (recurrence) from RN. Confirmation of these results in clinical studies is needed.

Progression of astrocytomas and meningiomas: an evaluation in vitro.

Abstract.  Objectives/Background: In biological terms, progression means that malignancy increases as genetic mutations accumulate leading to increased proliferation and invasion capacity. By verifying the proliferation capacity, human telomerase reverse transcriptase (hTERT) expression and in vitro invasion, in a group of highly malignant glioblastomas, benign meningiomas and astrocytomas, at the initial stage of progression, we have analysed putative progression in vitro for proliferation and telomerase expression. Materials and Methods: The relative proliferation status (visualized with Ki‐67 antibodies) and presence of hTERT protein was analysed in 27 intracranial tumours (6 astrocytomas, 8 glioblastomas and 13 meningiomas) by immunohistochemistry on paraffin‐embedded biopsy tissue, as well as on primary tumour‐derived cell cultures. A confrontation model was used to analyse invasiveness in vitro. Results: The mean proliferation indices were 22.3 (SD = 18.1) for glioblastomas and 2.1 (SD = 1.9) for low‐grade (LG) astrocytomas. The group of benign meningiomas had a labelling index of 2.2 (SD = 2.7). Mean percentages of staining for hTERT varied between 36.5 (SD = 28.4) for glioblastomas and 10.2 (SD = 8.6) for LG astrocytomas. The group of benign meningiomas had a labelling index of 12.4 (SD = 19.2) for hTERT. A significant difference was seen for Ki‐67 (P < 0.05) and hTERT (P < 0.001) in vivo versus in vitro. No difference was seen between the group of invasive and non‐invasive tumour‐derived cell cultures for the histopathological markers Ki‐67 and hTERT (P > 0.05) in vitro. Conclusions: The elevated expression of hTERT and Ki‐67 in vitro provides a potential prognostic tool for early detection of the progression of brain tumours. As tumour cells require telomerase for continued proliferation, the expression of hTERT may mark immortality, leading to indefinite life span. On the other hand, hTERT expression and cell proliferation are not linked directly to invasion in vitro.

Migration of pump for intrathecal drug delivery into the peritoneal cavity: case report

BACKGROUND We report on a patient in whom a subfascially implanted pump for the intrathecal delivery of baclofen spontaneously migrated into the peritoneal cavity. CASE DESCRIPTION A 54-year-old male patient presented with a refilling problem of a drug pump that had been implanted 16 months earlier subfascially through a right-sided incision 10 cm below the costal margin. Because we were unable to refill the pump even under fluoroscopy, we presumed a backward turning of the pump. At exploration, we found that the deeper part of the pocket had spontaneously eroded and had caused the migration of the pump into the peritoneal cavity. The peritoneum and the abdominal wall were closed and the pump was placed in a subcutaneous pouch. We suppose that the migration of the pump was due to its particular implantation site with the lower extent of the device at or below the level of the linea semilunaris. Below this line, the aponeuroses of all 3 lateral abdominal muscles pass in front of the rectus muscle, leaving only the transversal fascia underneath the rectus, which is not a solid layer. Not considering this anatomical detail may facilitate the inward migration of implanted material. CONCLUSION When creating a pocket for subfascial implantation, a high subcostal incision should be used so that the lower extent of the pocket will still be above the level of the linea semilunaris, hence ensuring a strong fascial layer between the pump and the peritoneum.

Correction: Kinetic Modeling and Graphical Analysis of 18F-Fluoromethylcholine (FCho), 18F-Fluoroethyltyrosine (FET) and 18F-Fluorodeoxyglucose (FDG) PET for the Fiscrimination between High-Grade Glioma and Radiation Necrosis in Rats

Background Discrimination between glioblastoma (GB) and radiation necrosis (RN) post-irradiation remains challenging but has a large impact on further treatment and prognosis. In this study, the uptake mechanisms of 18F-fluorodeoxyglucose (18F-FDG), 18F-fluoroethyltyrosine (18F-FET) and 18F-fluoromethylcholine (18F-FCho) positron emission tomography (PET) tracers were investigated in a F98 GB and RN rat model applying kinetic modeling (KM) and graphical analysis (GA) to clarify our previous results. Methods Dynamic 18F-FDG (GB n = 6 and RN n = 5), 18F-FET (GB n = 5 and RN n = 5) and 18F-FCho PET (GB n = 5 and RN n = 5) were acquired with continuous arterial blood sampling. Arterial input function (AIF) corrections, KM and GA were performed. Results The influx rate (Ki) of 18F-FDG uptake described by a 2-compartmental model (CM) or using Patlak GA, showed more trapping (k3) in GB (0.07 min-1) compared to RN (0.04 min-1) (p = 0.017). K1 of 18F-FET was significantly higher in GB (0.06 ml/ccm/min) compared to RN (0.02 ml/ccm/min), quantified using a 1-CM and Logan GA (p = 0.036). 18F-FCho was rapidly oxidized complicating data interpretation. Using a 1-CM and Logan GA no clear differences were found to discriminate GB from RN. Conclusions Based on our results we concluded that using KM and GA both 18F-FDG and 18F-FET were able to discriminate GB from RN. Using a 2-CM model more trapping of 18F-FDG was found in GB compared to RN. Secondly, the influx of 18F-FET was higher in GB compared to RN using a 1-CM model. Important correlations were found between SUV and kinetic or graphical measures for 18F-FDG and 18F-FET. 18F-FCho PET did not allow discrimination between GB and RN.

Treating Hydrocephalus with Retrograde Ventriculosinus Shunt: Prospective Clinical Study

BACKGROUND Since the 1950s, hydrocephalus has been be treated with cerebrospinal fluid (CSF) shunts, usually to the peritoneal cavity or to the right cardiac atrium. However, because of their siphoning effect, these shunts lead to nonphysiologic CSF drainage, with possible comorbidity and high revision rates. More sophisticated shunt valve systems significantly increase costs and technical complexity and remain unsuccessful in a subgroup of patients. In an attempt to obtain physiologic CSF shunting, many neurosurgical pioneers shunted towards the dural sinuses, taking advantage of the physiologic antisiphoning effect of the internal jugular veins. Despite several promising reports, the ventriculosinus shunts have not yet become standard neurosurgical practice. METHODS In this single-center prospective clinical study, we implanted the retrograde ventriculosinus shunt, as advocated by El-Shafei, in 10 patients. This article reports on our operation technique and long-term outcome, including 4 patients in whom this shunt was implanted as a rescue operation. RESULTS Implantation of a ventriculosinus shunt proved to be feasible, warranting physiologic drainage of CSF. However, in only 3 of 14 patients, functionality of the retrograde ventriculosinus shunt was maintained during more than 6 years of follow-up. In our opinion, these shunts fail because present venous access devices are difficult to implant correctly and become too easily obstructed. After discussion of possible causes of this frequent obstruction, a new dural venous sinus access device is presented. CONCLUSION An easy-to-implant and thrombogenic-resistant dural venous sinus access device needs to be developed before ventriculosinus shunting can become general practice.