Angelo Bollati

Emergent decompressive craniectomy in patients with fixed dilated pupils due to cerebral venous and dural sinus thrombosis: report of three cases.

OBJECTIVE AND IMPORTANCE Cerebral venous and dural sinus thrombosis is a rare cause of stroke. Although morbidity and mortality have greatly decreased in recent years as a result of early diagnosis and timely medical treatment, when coma occurs the prognosis remains poor. We evaluated whether emergent decompressive craniectomy has a role in the treatment of patients with brain herniation from dural sinus thrombosis and hemorrhagic infarct. CLINICAL PRESENTATION Three patients developed large hemorrhagic infarct with coma and bilaterally fixed and dilated pupils resulting from aseptic dural sinus thrombosis. INTERVENTION Two patients underwent emergent surgical decompression as soon as brain herniation developed, and these patients had complete functional recovery. One underwent delayed surgical decompression and remained severely disabled. CONCLUSION Our results provide preliminary evidence that emergent decompressive craniectomy is effective in patients with brain herniation from dural sinus thrombosis, provided that the clinical onset is recent. We therefore recommend consideration of this aggressive surgical technique for such patients, who may survive with good outcomes.

Differential Inhibition of Growth Hormone Secretion by Analogs Selective for Somatostatin Receptor Subtypes 2 and 5 in Human Growth-Hormone-Secreting Adenoma Cells in vitro

Somatostatin (SRIH), a cyclic tetradecapeptide hormone originally isolated from mammalian hypothalamus, is a potent suppressor of pituitary growth hormone (GH) secretion. SRIH acts through a family of G-protein-coupled membrane receptors containing seven transmembrane domains. Five genes encoding distinct SRIH receptor (SSTR) subtypes have so far been cloned in human and other species and termed SSTR1–5. In human somatotrophe pituitary adenomas GH secretion is controlled by both SSTR2 and SSTR5. However, in clinical practice only somatostatin analogs selective for SSTR2 (octreotide and lanreotide) are available. This may explain why clinical and in vitro responses to these analogs in acromegaly are only partial. In this study, we investigated the inhibitory effect of two new SRIH analogs with high selectivity for SSTR2 (NC-4-28B) and SSTR5 (BIM-23268) and compared it to that of native somatostatin (SRIH-14) on a large number of GH-secreting adenomas obtained by transphenoidal neurosurgery. Tissues from 16 adenomas were enzymatically dispersed and plated in 24-well dishes at 50,000 cells/well. After 3 days, groups of three wells were incubated for 4 h with medium alone, SRIH-14 or analogs NC-4-28B or BIM-23268, at the concentrations of 0.01, 0.1 and 1 µM. Our results show that 9 out of 16 adenomas were responsive (GH suppression: 20–40% vs. control, p < 0.05) to SRIH. In this group only 4 adenomas showed similar responses to both selective analogs, with 2 nonresponders (expression of other SRIH receptor subtypes) and 2 responders (concomitant expression of SSTR2 and SSTR5) to both analogs. GH release was selectively inhibited by NC-4-28B in 3 adenomas and by BIM-23268 in the remaining 2 adenomas, suggesting predominant expression of SSTR2 and SSTR5, respectively. SRIH failed to inhibit GH release in 7 adenomas (43%). Interestingly, in that group a better inhibitory effect was obtained with BIM-23268 (5 out of 7 adenomas) than with NC-4-28B, suggesting expression of a few SSTR5 receptors only, or of both SSTR2 and SSTR5, respectively. We conclude that the availability of somatostatin analogs selective for SSTR5 will enhance the treatment potency and spectrum in acromegaly.

Sperm protein 17 is expressed in human nervous system tumours

BackgroundHuman sperm protein 17 (Sp17) is a highly conserved protein that was originally isolated from a rabbit epididymal sperm membrane and testis membrane pellet. It has recently been included in the cancer/testis (CT) antigen family, and shown to be expressed in multiple myeloma and ovarian cancer. We investigated its immunolocalisation in specimens of nervous system (NS) malignancies, in order to establish its usefulness as a target for tumour-vaccine strategies.MethodsThe expression of Sp17 was assessed by means of a standardised immunohistochemical procedure [(mAb/antigen) MF1/Sp17] in formalin-fixed and paraffin embedded surgical specimens of NS malignancies, including 28 neuroectodermal primary tumours (6 astrocytomas, 16 glioblastoma multiforme, 5 oligodendrogliomas, and 1 ependymoma), 25 meningeal tumours, and five peripheral nerve sheath tumours (4 schwannomas, and 1 neurofibroma),.ResultsA number of neuroectodermal (21%) and meningeal tumours (4%) were found heterogeneously immunopositive for Sp17. None of the peripheral nerve sheath tumours was immunopositive for Sp17. The expression pattern was heterogeneous in all of the positive samples, and did not correlate with the degree of malignancy.ConclusionThe frequency of expression and non-uniform cell distribution of Sp17 suggest that it cannot be used as a unique immunotherapeutic target in NS cancer. However, our results do show the immunolocalisation of Sp17 in a proportion of NS tumour cells, but not in their non-pathological counterparts. The emerging complex function of Sp17 makes further studies necessary to clarify the link between it and immunopositive cells.

Microsurgical anterior cervical disk removal without interbody infusion

A series of 57 patients with root syndromes or compressive myelopathy were operated upon by a modified Cloward technique. No bone grafts were used. The patients were observed for 6 months to 5 years after surgery. Of the 47 patients with radiculopathy, 44 were cured and three complained of minor pains in their arms. Of the 10 patients with myelopathy, three were greatly improved, five were slightly improved, and two remained unchanged. In 100% of these cases, immobilization of the involved interspace occurred within a year. The surgical technique is discussed.

Inhibitory effects of galanin on growth hormone (GH) release in cultured GH-secreting adenoma cells: Comparative study with octreotide, GH-releasing hormone, and thyrotropin-releasing hormone

The aim of the present study was to characterize in a large series (N = 12) of cultured somatotrope adenomas the in vitro effects of the neuropeptide galanin on growth hormone (GH) secretion. This was contrasted with two peptides known to be GH secretagogues (GH-releasing hormone [GHRH] and thyrotropin-releasing hormone [TRH]) and a peptide with a known GH-inhibitory effect (the somatostatin analog octreotide). Groups of three wells were incubated for 4 hours with growth medium alone (control incubation), galanin, GHRH(1-29)NH2, TRH, or octreotide. Galanin and octreotide were applied at concentrations of 0.1, 1, and 10 mumol/L, and GHRH and TRH at concentrations of 0.01, 0.1, and 1 mumol/L. Galanin was able to inhibit GH release in nine of 12 cultured somatotrope adenoma cells. This inhibitory effect was clearly dose-dependent in five adenomas. Overall, the mean GH nadir after galanin was -36.1% in nine responder adenoma cultures versus control wells. Octreotide inhibited GH release in five of eight cultured somatotrope adenoma cells. The mean GH nadir after octreotide was -32.7% in five responder adenoma cultures compared with control wells. GHRH and TRH were able to stimulate GH release, respectively, in seven of 11 and in six of seven cultured somatotrope adenoma cells. The mean GH peaks after either GHRH or TRH in responder adenoma cultures were, respectively, +71.5% and +143.7% compared with levels in the control wells. In conclusion, the consistency and potency of the in vitro GH-inhibitory effect of galanin in a large series of somatotrope adenomas are at least similar to those of the most effective available GH-lowering agent, the somatostatin analog octreotide.

Results of Combined Surgical and Medical Therapy in Patients with Prolactin-secreting Pituitary Macroadenomas

To assess the long term effectiveness of combined sequential surgical and medical therapy in the management of prolactin-secreting pituitary macroadenomas, we followed 21 patients for 46 +/- 6 months (mean +/- SE) after diagnosis (range, 12 to 96 months). All patients underwent operation. Six were also treated with bromocriptine, 7.5 mg/day immediately after operation. A group of 15 patients with tumor sizes similar to those of the first group was followed without medical therapy until signs of regrowth of the neoplasia were evident. No patient of the combined therapy group experienced a recurrence of the disease. On the other hand, only 2 patients of the second group were recurrence-free at the end of follow-up. In the other 13 cases, adjunctive therapy had to be established for clinical and radiological evidence of tumor recurrence 26 +/- 7 months after operation. We conclude that combined sequential surgical and medical therapy may be useful in the management of macroprolactinomas. Our hypothesis must be confirmed by studies that compare patients treated with operation plus bromocriptine with patients treated with bromocriptine alone.