A single centre's experience of managing spheno-orbital meningiomas: lessons for recurrent tumour surgery.

BACKGROUND: Spheno-orbital meningiomas are complex tumours involving the sphenoid wing and orbit. Various surgical strategies are available but treatment remains challenging and patients often require more than one surgical procedure. This study evaluated whether smaller surgical approaches and newer reconstructive methods impacted the surgical and clinical outcomes of patients undergoing repeat surgery. METHODS: We retrospectively analysed the medical records of consecutive patients who underwent surgery for a spheno-orbital meningioma at a single tertiary centre between 2005 and 2016. We recorded procedural details and analysed complications, postoperative visual status and patient-reported cosmetic outcome. RESULTS: Thirty-four procedures were performed in 31 patients (M:F 12:22, median age 49 years) including 19 (56%) primary operations and 15 (44%) repeat procedures. Seven patients (20.5%) had a pterional craniotomy, 19 (56%) had a standard orbitozygomatic craniotomy and 8 (23.5%) underwent a modified mini-orbitozygomatic craniotomy. Calvarial reconstruction was required in 19 cases with a variety of techniques used including titanium mesh (63%), PEEK (26%) and split calvarial bone graft (5%). Total tumour resection (Simpson grade I-II) was significantly higher in patients undergoing primary surgery compared with those having repeat surgery (41% and 0%, respectively; p = 0.0036). Complications occurred in 14 cases (41%). Proptosis improved in all patients and visual acuity improved or remained stable in 93% of patients. Cosmetic outcome measures were obtained for 18 patients (1 = very poor; 5 = excellent): 1-2, 0%; 3, 33%; 4, 28%; 5, 39%. Tumour recurrence requiring further surgery occurred in four patients (12%). There was no significant difference in clinical outcomes between patients undergoing primary or repeat surgery. CONCLUSION: Spheno-orbital meningiomas are highly complex tumours. Surgical approaches should be tailored to the patient but good clinical and cosmetic outcomes may be achieved with a smaller craniotomy and custom-made implants, irrespective of whether the operation is the patient's first procedure.

Delayed presentation of late-onset cerebrospinal fluid rhinorrhoea following dopamine agonist therapy for giant prolactinoma.

UNLABELLED: Therapeutic shrinkage of prolactinomas with dopamine agonists achieves clinical benefit but can expose fistulae that have arisen as a result of bony erosion of the sella floor and anterior skull base by the invasive tumour, resulting in the potential development of cerebrospinal fluid (CSF) rhinorrhoea, meningitis, and rarely pneumocephalus. Onset of symptoms is typically within 4 months of commencing therapy. The management is typically surgical repair via an endoscopic transnasal transsphenoidal approach. A 23-year-old man presented to the Emergency Department with acute left limb weakness and intermittent headaches. Visual fields were full to confrontation. Immediate computed tomography and subsequent magnetic resonance imaging (MRI), demonstrated a 5 cm lobular/cystic mass invading the right cavernous sinus, displacing and compressing the midbrain, with destruction of the bony sella. He was referred to the regional pituitary multidisciplinary team (MDT). Serum prolactin was 159 455 mIU/l (7514.37 ng/ml) (normal ranges 100-410 mIU/l (4.72-19.34 ng/ml)). Cabergoline was commenced causing dramatic reduction in tumour size and resolution of neurological symptoms. Further dose titrations were required as the prolactin level plateaued and significant residual tumour remained. After 13 months of treatment, he developed continuous daily rhinorrhea, and on presenting to his general practitioner was referred to an otolaryngologist. When next seen in the routine regional pituitary clinic six-months later he was admitted for urgent surgical repair. Histology confirmed a prolactinoma with a low proliferation index of 2% (Ki-67 antibody). In view of partial cabergoline resistance he completed a course of conventional radiotherapy. Nine months after treatment the serum prolactin had fallen to 621 mIU/l, and 12 months after an MRI showed reduced tumour volume. LEARNING POINTS: CSF rhinorrhoea occurred 13 months after the initiation of cabergoline, suggesting a need for vigilance throughout therapy.Dedicated bony imaging should be reviewed early in the patient pathway to assess the potential risk of CSF rhinorrhoea after initiation of dopamine agonist therapy.There was a significant delay before this complication was brought to the attention of the regional pituitary MDT, with associated risk whilst left untreated. This demonstrates a need for patients and healthcare professionals to be educated about early recognition and management of this complication to facilitate timely and appropriate referral to the MDT for specialist advice and management. We changed our nurse-led patient education programme as a result of this case.An excellent therapeutic response was achieved with conventional radiotherapy after limited surgery having developed partial cabergoline resistance and CSF rhinorrhoea.

Temozolomide in the management of dopamine agonist-resistant prolactinomas.

BACKGROUND: The majority of prolactinomas respond to dopamine agonist therapy, but a proportion are resistant, requiring other treatments including surgery and/or radiotherapy. Temozolomide is an oral chemotherapy agent, which has been used as a salvage therapy to treat aggressive pituitary adenomas and carcinomas, including prolactinomas, unresponsive to all conventional treatment. CASE SERIES: We report three patients where temozolomide was used in the treatment of refractory prolactinomas. Case 1 describes a patient with a highly invasive prolactinoma, resistant to all conventional therapy, which responded dramatically to temozolomide used as a salvage treatment. In case 2, temozolomide was used after incomplete surgical resection to relieve chiasmal compression and avoid chiasm exposure to radiotherapy. In case 3, temozolomide enabled radiotherapy to be deferred in a 16-year old with a resistant prolactinoma. In all three cases, the tumours were negative by immunostaining for methylguanine methyltransferase (MGMT). LITERATURE REVIEW AND DISCUSSION: A review of the published literature reveals 51 reported cases of temozolomide treatment for pituitary tumours, including 20 prolactinomas. Fifteen of the 20 prolactinomas showed a good response to temozolomide. Our analysis demonstrates a strong association between MGMT-negative staining and a good response to temozolomide (OR 9.35, P = 0.0030). Current clinical practice is to use temozolomide as a salvage therapy after all conventional modalities of treatment have failed. We suggest that, in selected cases, consideration should be given to using temozolomide earlier in the treatment algorithm.

The value of interhospital transfer and emergency MRI for suspected cauda equina syndrome: a 2-year retrospective study.

INTRODUCTION: The timing of surgery in cauda equina syndrome due to prolapsed intervertebral disc remains controversial. Assessment of these patients requires magnetic resonance imaging (MRI), which is of limited availability outside normal working hours in the UK. PATIENTS AND METHODS: We reviewed radiological results in all patients undergoing emergency MRI within our unit for suspected cauda equina syndrome over a 2-year period, and all subjects undergoing emergency lumbar discectomy for cauda equina syndrome within the same period. Outcome measures were: proportion of positive findings in symptomatic patients and proportion of patients referred with diagnostic MRI scans undergoing emergency surgery. We also assessed outcomes of patients having surgery for cauda equina syndrome in terms of improvement of pain, sensory and sphincter disturbance. RESULTS: A total of 76 patients were transferred for assessment and 'on-call' MRI; 27 were subsequently operated upon. Only 5 proceeded to emergency discectomy that night (prior to next scheduled list). This may be due to delays in timing--from referral to acceptance, to arrival in the department, to diagnostic scan and to theatre. With the second group of patients, 43 had emergency discectomy for cauda equina syndrome during the study period. Of these, 6 patients had an out-of-hours MRI at our hospital for assessment (one patient living locally). Most surgically treated patients experienced improvement in their pain syndrome, with approximately two-thirds experiencing improvement in sensory and sphincter disturbance. CONCLUSIONS: These data support a policy of advising MRI scan for cauda equina syndrome at the earliest opportunity within the next 24 h in the referring hospital, rather than emergency transfer for diagnostic imaging which has a relatively low yield in terms of patients operated on as an emergency.

Phaeohyphomycosis: an unusual pituitary mass.

A 64-year-old Caucasian woman presented with left eye pain and a transient left oculomotor nerve palsy. Subsequent imaging revealed a mass involving the sphenoid sinus and sella with suprasellar extension. A trans-sphenoidal hypophysectomy was performed. Histopathology showed a fungal infection consistent with phaeohyphomycosis. Development of this lesion is probably attributed to allergic rhinitis and insulin-dependent diabetes mellitus. Intravenous amphotericin and itraconazole treatment resulted in full recovery and the patient remains well at 6-month postoperative follow-up.

Spinal meningioma after treatment for Hodgkin disease. Case report.

Long-term survivors of Hodgkin disease may develop second primary tumors caused by the mutagenic effects of radio- and chemotherapy. The authors describe the case of a 35-year-old woman who presented with an unusual meningioma of the cervical spine 9 years after undergoing combined-modality treatment for Hodgkin disease. To the authors' knowledge, this is the first report of spinal meningioma as a complication of such therapy. Whereas radiation-induced intracranial meningiomas are well described in the literature, treatment-induced meningiomas of the spine have not been widely recognized.

The strange association of pneumosinus dilatans and arachnoid cyst: case report and review of the literature.

BACKGROUND: The authors present the case of a 71-year-old man with dramatic pneumosinus dilatans adjacent to a large, symptomatic, fronto-temporal arachnoid cyst. METHOD: The literature on pneumosinus dilatans and its association with arachnoid cyst is reviewed. FINDINGS: Pneumosinus dilatans may be either idiopathic, a reaction to an adjacent meningioma, or an 'ex-vacuo' response to cerebral volume loss and intracranial hypotension. It is also found with large arachnoid cysts and is probably under-recognised in this context. The co-existence of an expansile intradural lesion with changes in the skull base that tend to reduce the intracranial volume is puzzling, and has not yet been fully explained. Differences in the relative timing of paranasal sinus and arachnoid cyst growth, and the 'temporal agenesis' theory of arachnoid cyst formation have been proposed but do not account for all the features of this unusual association. INTERPRETATION: Pneumosinus dilatans is a useful and under-recognised indicator of the presence and chronicity of a variety of intracranial pathologies. Its association with arachnoid cyst is paradoxical, and a new explanation is offered as to how this may arise.

Depression of glutathione content, elevation of CYP2E1-dependent activation, and the principal determinant of the fasting-mediated enhancement of 1,3-dichloro-2-propanol hepatotoxicity in the rat.

The influence of fasting (18 hours) on the hepatotoxicity of 1,3-dichloro-2-propanol (1,3-DCP) and on various hepatic parameters has been assessed in the rat. Fasting produced an enhancement of the hepatotoxicity which was associated with alterations in a variety of hepatic parameters when measured relative to protein content, most notably glutathione (GSH) levels (decrease) and CYP2E1-mediated enzyme activity (increase), two parameters previously identified as being important determinants to the toxicity. Fasting also decreased the liver weight normalized to body weight. When this was taken into account, total liver CYP2E1-mediated enzyme activity was not significantly altered whereas the total liver GSH level was markedly reduced following fasting. These results imply that the reduction in hepatic GSH is the principal determinant of the enhanced susceptibility to 1,3-DCP hepatotoxicity following fasting.

Up-regulation of microsphere transport across the follicle-associated epithelium of Peyer's patch by exposure to Streptococcus pneumoniae R36a.

Transport of antigens through the follicle-associated epithelium (FAE) of Peyer's patch (PP) is the critical first step in the induction of mucosal immune responses. We have previously described that short-term exposure to Streptococcus pneumoniae R36a induced dramatic morphological alterations of the FAE in rabbit PP. These results prompted us to investigate whether the pneumococci-induced modifications were accompanied by enhanced ability of the FAE to transport antigens. We addressed this problem by evaluating the ability of the FAE to bind, internalize, and transport fluorescent polystyrene microparticles, highly specific to rabbit M cells, after exposure to S. pneumoniae. Quantitative study revealed a marked increase in the number of microspheres in PP tissues exposed to S. pneumoniae compared to tissues exposed to either phosphate-buffered saline or Escherichia coli DH5alpha as controls. No sign of bacterially induced damage to the epithelial barrier was observed. Further confocal microscopy analysis of the FAE surface showed that a significant increase in the number of cells that showed both morphological and functional features of M cells took place within pneumococci-treated PP tissues. These data provide the first direct evidence that the FAE-specific antigen sampling function may be manipulated to improve antigen and drug delivery to the intestinal immune system.

Quantitative outcome and radiographic comparisons between laminectomy and laminotomy in the treatment of acquired lumbar stenosis.

OBJECTIVE: The objective of this study was to conduct a comparative quantitative analysis of outcomes, radiographic findings, and magnetic resonance imaging results after laminectomy or laminotomy was performed for patients with lumbar stenosis. Such as analysis had not previously been conducted. METHODS: Twenty-six patients with no exclusion criteria who were treated surgically for acquired stenosis at the Division of Neurological Surgery at The Ohio State University from 1990 to 1993 were studied retrospectively. At follow-up examinations, each patient completed a detailed questionnaire that included visual analog scales, functional assessments, and the medical outcome study short form health survey, SF-36. Each patient underwent plain static and dynamic radiography that detailed vertebral body sagittal listhesis and rotation and magnetic resonance imaging that evaluated dural sac compression. RESULTS: The mean follow-up duration was 36.7 months. Good outcome was defined by the presence of three criteria: no greater than mild leg pain (Grades 0-4), the ability to walk more than one block without developing lower extremity pain, and the ability to walk without assistance devices. Fifty-eight percent of the patients who had undergone laminectomies and 50% of the patients who had undergone laminotomies had good outcomes. All were judged to have had adequate decompression. The average maximum postoperative listhesis was 17.3 +/- 9.9% in the laminectomy group and 17.6 +/- 12.5% in the laminotomy group. In contrast to some previous studies, pre- or postoperative listhesis was not statistically related to outcome in either group. Patients in each poor outcome category seemed to have worse comorbid medical conditions than did patients in the good outcome category. The SF-36 measurements of poor functioning because of health factors and bodily pain correlated somewhat with poor outcomes in the patients who had undergone laminectomies. In patients who had undergone laminotomies, the only statistically significant finding among the outcome groups was the effect of poor emotional health on activity for the patients with poor outcomes. CONCLUSION: This study indicates that laminotomy can adequately decompress lumbar canal stenosis, that laminectomy and laminotomy have the same degree of postoperative listhesis, and that the quantitative outcome of any treatment for lumbar stenosis is dependent not only on surgical factors but also on comorbid physical and psychological factors.

Low-dose diethyldithiocarbamate attenuates the hepatotoxicity of 1,3-dichloro-2-propanol and selectively inhibits CYP2E1 activity in the rat.

The effect of low doses of diethyldithiocarbamate (DEDC) on hepatic cytochrome P450-dependent enzyme activity and 1,3-dichloro-2-propanol (DCP) hepatotoxicity in the rat have been investigated. DEDC at a dose of 5 mg/kg selectively inhibited enzyme markers for CYP2E1 activity, and provided substantial protection against DCP hepatotoxicity. At a higher dose (25 mg/kg), DEDC also inhibited an enzyme marker for CYP1A2 activity and provided complete protection against DCP hepatotoxicity. It is concluded: (a) that DEDC at a dose of 5 mg/kg is a selective CYP2E1 inhibitor in the rat in vivo; and (b) that DCP hepatotoxicity is mediated principally by CYP2E1, with a possible contribution from CYP1A2.

Particle uptake and translocation across epithelial membranes.

Oral delivery of drugs and vaccines has many advantages over other routes of administration. For example, for vaccination, enteric delivery may result in the induction of a mucosal immune response against pathogens which colonise and invade the mucosa. However, the oral delivery of peptide or protein drugs or antigens is beset with problems, such as gastrointestinal breakdown of labile molecules, low level of macromolecular absorption and, for vaccines, the poor immune response usually elicited by orally administered soluble antigens. Investigations are therefore in progress to develop means of increasing intestinal absorption and decreasing digestion of orally administered molecules. Molecules can be incorporated into biodegradable microparticles to reduce the effect of gut secretions and to enable the absorption of bioactive agents in an unaltered form. The uptake of microparticulates through the gut wall is accepted as a true biological phenomenon but the mechanism and route of uptake have not been established. Furthermore, in general, only small numbers of microparticles are translocated across epithelial membranes, possibly making these systems inappropriate for drug or vaccine delivery. This paper reviews particle uptake across the gastrointestinal tract and describes studies carried out to determine whether a humoral response can be elicited following oral administration of an antigen associated with biodegradable poly(DL lactide-coglycolide) microparticles. The use of lipid delivery vehicles to enhance microparticle uptake and the selective transport of microspheres across M cells is also described.

Further studies on the lobar heterogeneity in response to coumarin-mediated hepatotoxicity.

A randomized sampling protocol coupled with quantitative morphometry has been used to evaluate the inter-lobe variation in centrilobular hepatic necrosis in the mouse, and periportal hepatic necrosis in the beta-naphthoflavone-induced rat, both in response to treatment with coumarin. The results of these studies indicate a random inter-lobe variation in xenobiotic-mediated hepatotoxicity.

Meningiomas of the cerebellopontine angle. A report of 41 cases.

A retrospective study of the surgical management of 41 cerebellopontine angle (CPA) meningiomas was performed. All patients were treated by a single surgeon (TTK) over a 25 year period (1967-1992). There were 13 males, 28 females with a median age of 53.5 years. The median follow-up after surgery was 9 years (range 2-20.4 years). Tumours were classified anatomically into six groups (lateral, midpetrosal, petroclival, internal auditory meatal, Meckel's cave and inferior). Only the petroclival tumours posed difficulties with complete resection (achieved in 7 out of 16) and for most of them a transtentorial transpetrous approach was used. In other groups, complete resection was achieved in all patients. There were four recurrences (two mid-petrosal, one petroclival, one internal auditory meatal), three of which had complete macroscopic resection at the initial operation.

Lobar variation of carbon tetrachloride hepatotoxicity in the rat.

The lobar variation in carbon tetrachloride-induced liver damage in the rat has been assessed by use of a systematic random sampling protocol and quantitative morphometry. A random inter-animal lobar variation in severity of damage was apparent, in contrast with the results obtained previously in which sampling bias, small animal numbers, and lack of fully quantitative measurement were apparent. The route of administration (oral vs. i.p.) did not influence these findings.