Ultrasound-assisted microsurgery for Cushing's disease.

OBJECTIVE: Localization of microadenomas in Cushing's disease may be difficult as in up to 45% of patients sellar MRI fails to detect a pituitary tumor. Intraoperative transsphenoidal ultrasound may identify microadenomas as hyperechoic structures. We report on the first 18 consecutive cases with intraoperative use of a new device for direct contact high-frequency-ultrasound in patients with Cushing's disease. PATIENTS AND TECHNIQUE: 18 patients (14 female, 4 male, age 24-71 years) with typical endocrinological findings for Cushing's disease were included in the study. One macroadenoma and 13 microadenomas were suspected or identified preoperatively by MRI. In 4 cases, two of them with recurrent disease, sellar MRIs were negative. During transsphenoidal microsurgery an end fire ultrasound-probe (B-mode frequency range 7.5-13 Mhz, field of view 5 mm, penetration 20 mm) was introduced after opening of sellar floor. The pituitary gland was scanned in direct contact to the capsule. RESULTS: In 13 out of 17 cases (77%) with later on proven microadenomas high-frequency-ultrasound identified the tumors as hyperechoic masses, including 3 of the 4 cases with negative preoperative MRI. In 2 cases ultrasound correctly localized the tumor at a site different from MRI finding (MRI false positive). In the macroadenoma, identification of the border between tumor and anterior pituitary gland was not possible. In all 18 patients postoperative early decline of serum cortisol to subnormal levels confirmed remission of hypercortisolism (100%). Other pituitary functions were unaltered in 17 cases (94%). CONCLUSIONS: Intraoperative scanning of the pituitary gland with high-frequency-ultrasound probes may identify intrapituitary anatomy and pathologies even in MRI-negative cases. This may prevent extensive exploration of the gland with the risk of subsequent hypopituitarism.

Assessment of normal perisellar anatomy in 1.5 T T2-weighted MRI and comparison with the anatomic criteria defining cavernous sinus invasion of pituitary adenomas.

OBJECTIVE: The study aimed to evaluate the anatomical relations of sellar and perisellar structures with T2-weighted MRI and to apply criteria for cavernous sinus (CS) invasion by pituitary adenomas to normal sellar anatomy. METHODS: Thin slice (3 mm) coronal T2-weighted MR-images (1.5 Tesla) were obtained in 117 individuals (234 CS) without pituitary disorders (58 females, 59 males; age 17 months to 87 years). In 99 cases data indicating the presence of arterial hypertension (AH) were available, 25 with AH, 74 without AH. RESULTS: The medial wall of the cavernous sinus was detectable in 33% of cases. The inferior rim of the horizontal part of the ICA was located at the level of the sellar floor in 33%, below in 47%, and above in 20%. The mean distance between the both ICAs was 17.8 mm (range, 7-38 mm). The mean distance between the pituitary and the ICA in AH was significantly shorter than in patients without AH (Chi-square, p=0.01). There was contact between the gland and the ICA in 41.5% of the cases. In 16.7% (39 sides) of all 234 SCs investigated, the area of contact between the ICA and the gland was at least 25% of the vessel's circumference. The medial intercarotid line (ICL) was crossed by the pituitary gland in 9% (21 of 234 CS), the central ICL was touched in another 5% (11 of 234 CS), lateral ICL was never reached. There was a weak correlation with age: a more extensive lateral extension of the gland was seen in individuals older than 40 years compared to younger individuals (Chi-square, p=0.03). There was a marked difference in the anatomical findings between both sides in 41.9% of cases. CONCLUSION: Inter- and intra-individual variations of the perisellar anatomy and its relation to the pituitary gland exist, which are partly related to age and AH. This must be remembered when the invasiveness of pituitary adenomas is assessed in MRI.

Surgical and clinical results with the PDN prosthetic disc-nucleus device.

The PDN prosthetic disc-nucleus device has been in use for 6 years, both in clinical trials and through commercial sale. Surgical and clinical data for the device have been collected and analyzed to help determine the strengths and limitations of the implant. The shape of the device has been found to be an important element in predicting surgical success, with wedge and rectangular devices being the most stable. The patient's disc dimensions are also critically important. Data indicate that patients with a disc height of less than 5 mm should be excluded from surgery. Moreover, the anterior-posterior (AP) diameter of the disc endplates must be 37 mm or more in order to properly situate two devices within the disc--patients with a smaller AP diameter should receive only a single device. Body mass and overall patient weight are also good predictors of surgical success. If the patient's body mass index is 30 or greater, then the patient should not receive the implants. Complications related to the PDN implant have included migration of the device and endplate remodeling in some patients. This endplate remodeling has usually been mild, and has occurred in response to the change in load distribution. In a few cases there has been more pronounced remodeling with a loss of disc height. To minimize endplate remodeling, the PDN hydrogel has been reformulated to be softer, absorbing 80% of its weight in water. Subsequent to implementing changes in device design and patient selection, and with the introduction of the ALPA (Anterior-Lateral transPsoatic Approach) technique for implanting the devices, there has been an increase in surgical success with a concomitant reduction in the number of revision surgeries. The current surgical success rate for patients implanted from 1999 through 2001 is 88%. Clinical results are also very encouraging, with marked decreases in Oswestry and visual analog scale pain levels, and disc height also shows improvement and stabilization.

A tactile feedback hexapod operating robot for endoscopic procedures.

This paper describes a test prototype for precision robot-assisted surgery using a hexapod operating robot and a movable operating cockpit for tactile feedback. The objective of the work described is twofold: 1, to evaluate the use of hexapod robots for precisely manipulating endoscopes and surgical instruments in submillimeter surgery; 2, to test a new user interface concept based on tactile feedback. Based on the principle of a flight simulator, the aim is to give the surgeon motion cues in addition to the endoscope image, to assist his spatial orientation. The paper gives a detailed description of the system components and the potential applications.

Time-dependent expression of donor- and host-specific major histocompatibility complex class I and II antigens in allogeneic dopamine-rich macro- and micrografts: comparison of two different grafting protocols.

Neural transplantation, as a therapeutic approach to Parkinson's disease, still requires allogeneic graft material and raises questions of immunosuppression and graft rejection. The present study investigated the time course of major histocompatibility complex (MHC) expression and astrocytic response in allogeneic dopaminergic grafts, comparing two different grafting protocols. Adult 6-hydroxydopamine-lesioned Lewis 1.W rats received intrastriatal cell suspension grafts from the ventral mesencephalon of DA rat fetuses, either as single 1-microliter macrograft via metal cannula or as four micrografts of 250 nl/deposit via a glass capillary. No immunosuppression was administered. Immunohistochemistry was performed at 1, 3, 6, and 12 weeks after grafting, using antibodies against donor- and host-specific MHC class I and II antigen, glial fibrillary acidic protein (GFAP) and tyrosine hydroxylase (TH). Most animals showed good allograft survival up to 12 weeks after transplantation with no signs of rejection. Reinnervation of the lesioned striatum by TH-positive neurites was observed from 3-6 weeks on. Expression of donor-specific MHC class I was comparably low in both allogeneic grafting groups, while host MHC class I and II reaction as well as astrocytic response tended to be higher in the macrografted animals. Donor MHC class II was not observed at any time point. It is concluded that intraparenchymal allografts of fetal mesencephalic cell suspensions can survive well in the rat Parkinson model without immunosuppression for at least 12 weeks, and that the expression of moderate amounts of donor-specific MHC class I antigen does not suffice to initiate a rejection process. In addition, the microtransplantation approach may reduce the level of trauma and subsequent MHC and GFAP expression and may, thereby, minimize the risk of graft rejection.

Mitoxantrone-induced DNA strand breaks in cell-cultures of malignant human astrocytoma and glioblastoma tumors.

In this study mitoxantrone (Mtx) induced DNA strand breaks were measured with the alkaline elution technique in short term cell cultures derived from human gliomas. Glioblastomas or astrocytomas from 5 patients who underwent intracranial surgery were cultured and incubated i h with different concentrations of Mtx (0, 0.01, 0.1 and 1.0 microgram/ml). The alkaline elution method was modified to measure DNA lesions in human gliomas. Mtx induced DNA strand breaks in a dose dependent manner in all cell cultures tested. There was a linear increase of DNA strand break frequency induced by Mtx between 0.01-1.0 microgram/ml. concerning these in vitro data, Mtx might be potentially useful for the treatment of patients with malignant brain tumors.

Chronic compression of the cervical myelon as complication of anterior interbody fusion (AIF): neurological improvement after late anterior decompression. Case report.

Severe neurological deficits directly related to intraoperative injury of the spinal cord and the nerve roots is a rare complication of anterior interbody fusion (AIF) in cervical spondylosis. A case of radiculopathy and Brown-Séquard Syndrome caused by a bone fragment following AIF in which a late anterior decompression and fusion of the cervical spine was performed four years after the initial operation is presented. Immediate relief of the radicular pain, improvement of the spasticity, and better sphincter control could be achieved. Therefore, patients with chronic anterior compression of an incomplete spinal cord injury after AIF may benefit from a late anterior decompression and fusion.

The significance for postoperative hearing of preserving the labyrinth in acoustic neurinoma surgery.

Among 186 patients with preoperative hearing, a total of 189 acoustic neurinomas were removed through a lateral suboccipital approach with anatomical preservation of the cochlear nerve. Functional hearing was preserved in 92 (49%) of these patients; despite anatomical preservation of the cochlear nerve, deafness was the result in 51% of the series. Many factors have been considered to cause hearing loss in patients whose cochlear nerve was intact after surgery; these include nerve retraction, nerve or cochlear ischemia, overheating and vibration damage to the nerve, and opening of the labyrinth. To evaluate the significance of injury to the labyrinth in postoperative hearing loss, a prospective study was undertaken. High-resolution computerized tomography studies through the inner ear with bone algorithm were performed pre- and postoperatively. The postoperative status of the labyrinth was classified into three patterns: intact, fenestrated, and widely opened. Injury to the labyrinth occurred in 30% of the cases. The most frequently injured labyrinth structures were the crus commune of the posterior and superior semicircular canals (52%), the posterior semicircular canal (23%), the vestibule (21%), and the superior semicircular canal (4%). A statistically significant relationship was found between injury to the labyrinth and deafness, elevated thresholds, and lower discrimination values at pure-tone audiograms and speech audiometry (p < 0.0001). The degree of the injury (comparison between fenestration and wide opening of the labyrinth) was also significantly related to postoperative deafness (p < 0.0001). Disturbance of the inner-ear fluids was considered to be the cause of the hearing loss. In 12 patients labyrinth injury was not associated with deafness. This finding may support the existence of mechanisms of cochlear protection. The homeostatic function of the endolymphatic sac was considered to play an important role in recovery of damaged hearing in these 12 cases.

The MTT assay for chemosensitivity testing of human tumors of the central nervous system. Part I: Evaluation of test-specific variables.

The aim of this study was to optimize the experimental conditions of the MTT assay for primary cultures of human brain tumors. This assay is based on the mitochondrial reduction of MTT-(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) salt to formazan crystals by living cells. Formazan can be quantified spectrophotometrically. This assay measures the antimetabolic and, by using an adequate recovery period for the cells, also the antiproliferative effects of cytotoxic drugs. Our results suggest the following experimental design for its application as an chemosensitivity assay for human brain tumors: 1-h drug exposure followed by a seven days recovery period without drugs. Then tumor cells are incubated 4 hours with 1 mg MTT/ml and final absorbance readings are performed at 550 nm and 630 nm as test and reference wavelengths respectively. In this way, the assay seems to be a reliable and simple method for rapid chemosensitivity testing in human brain tumors.

The MTT assay for chemosensitivity testing of human tumors of the central nervous system. Part II: Evaluation of patient- and drug-specific variables.

In this study we assessed the influence of patient- and drug-specific parameters in the short-term MTT-chemosensitivity assay in 150 primary cell cultures derived from human brain tumors. In 45 patients the MTT assay was directly compared with the CFA (Colony Forming Assay). Resistance was 10-20% higher in the MTT assay than in the CFA, but there was a good agreement in both assays, that more malignant gliomas had a higher in vitro chemosensitivity against ACNU and BCNU. Overall the results demonstrate, that there is no uniform correlation between the in vitro chemosensitivity and the histopathological classification of the tumors, which corresponds well to the clinical situation. On the basis of this study we suggest prospective clinical trials with the MTT assay in human brain tumors.

Intraventricular cavernous angioma. A survey.

Since the availability of CT diagnosis 23 cases of intraventricular cavernous angioma (IVCA) have been published in the literature. Three additional cases have been operated upon in our Department. Based on these 26 cases the clinical data, radiological findings, treatment and outcome of IVCAs are reviewed.

Sensitivity of human malignant intracranial tumors against MCNU in vitro in comparison to ACNU and BCNU.

An in vitro chemosensitivity test was carried out in 50 specimen of human malignant intracranial tumors. Aim of the study was to evaluate the proportion of sensitivity against MCNU (Ranomustine) in comparison to ACNU and BCNU. 47 tests were evaluable. Mean viability of the specimen was 83.3 +/- 18.7%, mean plating efficiency was 0.068 +/- 0.051%. 9/47 settings revealed sensitivity against MCNU in vitro (ACNU: 10/47; BCNU: 16/46). There was no advantage of MCNU concerning age or sex of the patients. Brain metastases seemed to be slightly more frequent sensitive against MCNU than primary brain tumors. Cross resistance between ACNU, BCNU and MCNU was rather high. The results of this in vitro series do not encourage a clinical trial of MCNU as an alternative to the commonly used nitrosoureas.

Enterogenous intraspinal cysts.

The authors have reviewed the literature and recorded the distinguishing features of intraspinal enterogenous cysts. There are no characteristic clinical findings or history associated with this disease. These congenital space-occupying lesions frequently go undiagnosed, and the patient may be treated for many years as a case of multiple sclerosis. The teratogenic "determination period" is decisive for the development of anomalies affecting one, two, or all three of the germinal layers. All of these cysts belong to the same group, and their structure is an expression of the differing determination periods. The various theories about their etiology are discussed. True intraspinal enterogenous cysts are usually found in the cervical region. After careful operative removal, the prognosis is favorable.

Brain stem tumours-diagnosis and surgical treatment.

The diagnosis of brain stem tumours is mainly based on clinical findings and CT examinations: The CT examination including intravenous or intrathecal administration of contrast media together with electronic image-reconstruction greatly influences the indications for direct operation. According to our interpretation, direct surgical treatment is apparently successful under the following circumstances: - in tumours with external growth, which allows a decompression of the tumour without harming the surrounding structures in the brain stem. - in tumours with a marked cystic component, especially if the compressive effect is causing the features and progress of the symptoms.