Masamichi Kurosaki

Surgical Treatment of Clinically Nonsecreting Pituitary Adenomas in Elderly Patients

OBJECTIVEThe goal of this study was to evaluate the efficacy and safety of transsphenoidal pituitary surgery for elderly patients, using improved techniques of the past decade. METHODSWe retrospectively analyzed 32 surgically treated cases of clinically nonsecreting pituitary adenomas in patients more than 70 years of age (mean, 73.9 ± 3.4 yr). These patients were identified in a review of 982 patients with pituitary adenomas who were treated at University Hospital Eppendorf, Hamburg, between January 1991 and November 1999. RESULTSThe mean preoperative duration of symptoms was 1.9 years (2 wk to 11 yr). The chiasmatic syndrome was present for 27 patients (84.4%). All patients underwent transsphenoidal surgery. Seven patients underwent reoperations. Preoperative assessments of anterior pituitary function revealed growth hormone deficiencies for 21 of 27 patients (77.8%), thyroid insufficiencies for 10 of 30 patients (33.3%), and adrenal insufficiencies for 13 of 29 patients (44.8%). Hypogonadism and hyperprolactinemia were observed for 76.7% and 46.9% of the patients, respectively. All tumors were macroadenomas, ranging from 18 to 50 mm (average, 33.6 mm) in size, including 7 enclosed and 25 invasive adenomas. Complete microscopic tumor resection was achieved in 24 cases, and subtotal removal was performed in 8 cases. There were no severe perioperative complications. In the cases involving hyperprolactinemia, serum prolactin levels were normalized for 8 of 11 patients (72.7%). Normal thyroid function was recovered for 1 of 10 patients (10.0%) with preoperative hypothyroidism. However, growth hormone or adrenal insufficiencies persisted for all patients with preoperative insufficiencies. Visual disturbances were improved for 19 of 23 patients (82.6%). All patients recovered well after surgery, with an average hospital stay of 16.3 days. Histological and immunohistochemical studies demonstrated gonadotroph adenomas in 56.7% of cases, null-cell adenomas in 26.7%, and oncocytomas in 13.3%. CONCLUSIONSurgical treatment of nonsecreting pituitary adenomas causing visual disturbances is standard, even for elderly patients. In this series, transsphenoidal surgery was a safe procedure, with minimal morbidity and excellent tolerance. Age alone is not a contraindication for active treatment, particularly with transsphenoidal surgery.

Intrasellar gangliocytomas associated with acromegaly.

The present study was designed to investigate the immunohistochemical characteristics of gangliocytomas associated with growth hormone (GH)-secreting pituitary adenomas. In our surgical collection of 476 GH-secreting adenoma cases, we examined tumor tissue from 6 patients (1.3%). All 6 patients were women, ranging from 29 to 52 years (mean, 40.3±9.5 SD) of age. Among 470 patients with GH-secreting adenomas without gangliocytoma, there were 255 female and 215 male patients. The preponderance of female patients with gangliocytomas was striking. Histological examination of the resected specimens showed areas of ganglion cells and adenomatous cells. Ganglion cell lesions were stained positively for synaptophysin (4 of 4; 100%) and neurofilament (4 of 4; 100%) as well as GH-releasing hormone (5 of 6; 83.3%). Subtypes of GH cell adenomas included 4 cases of sparsely granulated type and 2 cases of mixed GH and prolactin (PRL) cell adenomas. Based on these findings, we hypothesized that the intrasellar gangliocytoma promoted the growth of the pituitary adenoma by chronic overstimulation from excess GH-releasing hormone.

Expression of vascular endothelial growth factor in growth hormone-secreting pituitary adenomas: special reference to the octreotide treatment

Abstract Objective: The present study was designed to investigate the localization of VEGF in GH-secreting pituitary adenomas and to evaluate the characteristic differences of VEGF expression in relation to the clinical effect of preoperative treatment with octreotide. Methods: Fifty-six cases of GH-secreting adenomas, which were divided into three groups and three normal pituitary glands, were studied using immunohistochemistry for expression of VEGF. The octreotide group consisted of 33 patients who received the octreotide before the surgery. The bromocriptine group consisted of 11 patients who received bromocriptine orally. The control groups consisted of 12 patients who were not treated with octreotide or bromocriptine pre-operatively. VEGF staining patterns for each specimen were examined under light microscopy and graded in a scale. These findings were correlated with clinical characteristics. Results: VEGF was displayed in a diffuse cytoplasmic pattern in all cases. VEGF staining was strongly seen in the cytoplasm in normal pituitary glands. Moderately positive staining with VEGF appeared in six of 33 (18%) cases of the octreotide group, and in eight of 12 (67%) cases of the control group. In contrast, weakly positive staining was observed in 25 of 33 (76%) cases of the octreotide group, and in three of 12 (25%) cases of the control group. The staining pattern differs statistically between the octreotide and control group, typically in densely granulated GH cell adenomas. Weak staining with VEGF appeared in all ten cases in which the tumor had shrunk. Age, gender, tumor size, tumor invasiveness and adenoma type did not influence VEGF expression. Conclusion: We conclude that octreotide may inhibit the angiogenesis through down-regulation of VEGF.

A non-enzymatic derived arachidonyl peroxide, 8-iso-prostaglandin F2α, in cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage participates in the pathogenesis of delayed cerebral vasospasm

We performed serial measurements of 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha), a non-enzymatic derived arachidonyl peroxide, in the cerebrospinal fluid (CSF) of 34 patients with subarachnoid hemorrhage (SAH). Patients were treated with open or endovascular surgery within 48 h of onset. Delayed cerebral vasospasm was verified by the presence of a low-density area on CT scan indicating focal cerebral infarction occurring after symptomatic delayed vasospasm. Concentrations of 8-iso-PGF2alpha in the CSF of 15 patients exhibiting delayed cerebral vasospasm were compared with those of 19 patients who did not exhibit vasospasm. The concentrations of 8-iso-PGF2alpha in the CSF of patients showing vasospasm were 42.4+/-37.1 pg/ml (mean+/-S.D., n=12) on Days 0-2, 66.4+/-41.0 pg/ml (n=14) on Days 3-5, 118.5+/-89.9 pg/ml (n=15) on Days 6-8, 86.2+/-70.2 pg/ml (n=11) on Days 9-11, 48.8+/-31.8 pg/ml (n=10) on Days 12-14, 27.8+/-20.1 pg/ml (n=7) after Day 20, while the concentrations in patients not showing vasospasm were 24.8+/-12.0 pg/ml (n=18) on Days 0-2, 25.7+/-15.2 pg/ml (n=19) on Days 3-5, 47.5+/-52.3 pg/ml (n=18) on Days 6-8, 56.7+/-72.0 pg/ml (n=13) on Days 9-11, 34.2+/-53.1 pg/ml (n=15) on Days 12-14, 20.1+/-18.2 pg/ml (n=10) after Day 20. CSF concentrations of 8-iso-PGF2alpha on Days 3-5 and Days 6-8 were significantly higher in patients showing vasospasm as compared to patients not showing vasospasm. CSF levels of 8-iso-PGF2alpha in patients showing vasospasm gradually increased in the days after onset of SAH and peaked on Days 6-8. Levels returned to normal after Day 20. These values on Days 3-5, Days 6-8, and Days 9-11 were significantly higher than the value after Day 20. Considering these data and the biological activities of 8-iso-PGF2alpha, such as development of inflammation, membrane perturbation and vasoconstriction, we conclude that 8-iso-PGF2alpha may play a role in delayed cerebral vasospasm after SAH.

Pituitary Tumors in the Elderly

The present study was designed to investigate the incidence and immunohistochemical characteristics of pituitary tumors in the elderly. In our surgical collection of 1925 cases, we examined tumor tissue from 15 patients over 80 years of age. Pituitaries obtained at routine autopsies from 692 subjects over 80 years of age were also investigated. Of the 15 surgical cases studied, the majority of patients presented with chiasmatic syndromes, likely caused by macroadenomas. Gonadotroph adenomas were the most frequently diagnosed tumor type, followed by null-cell adenomas and oncocytomas. There is only one case with GH cell adenoma. Among 692 autopsy cases, 79 (11.4%) pituitaries were found to contain adenomas in the anterior lobe. In one pituitary, two separate adenomas were detected, hence the number of adenomas in our material was 80. All autopsy cases were microadenomas except one. The mean diameter of adenomas was 2.2 mm. ACTH cell adenomas were the most frequently diagnosed tumor type, followed by PRL cell adenomas and null cell adenomas. The occurrence of pituitary adenomas discovered after routine autopsy in the elderly was common, although these tumors were not found frequently in surgical cases over 80 years of age. Our immunohistochemical study revealed that many tumors contained one or more than one anterior pituitary hormone, although almost all pituitary adenomas were considered to be clinically inactive in surgical and autopsy cases.

Immunohistochemical localisation of cytokeratins in craniopharyngioma

Summary Background. Although craniopharyngiomas have been examined in several microscopical studies to date, immunohistochemical analysis has not been sufficient. Method. In addition to the routine haematoxylin and eosin staining, 38 cases of intra- and/or supra-sellar craniopharyngioma, including 34 adamatinomatous and 4 squamous papillary types, were studied using immunohistochemistry for expression of four types of cytokeratin. Findings. Histological examination found epithelial cells in 26 of 38 (68.4%) cases. However, cytokeratins were demonstrated in 35 of 38 (92.1%) cases. The remaining 3 cases without demonstration of epithelial cell nests were supposed to be adamantinomatous craniopharyngiomas based on the findings in the stroma. In 31 of 34 adamantinomatous craniopharyngioma cases, the epithelium was detected by immunostaining for cytokeratins. The epithlieum expressed 56 kDa (KL-1) and 40 kDa (cytokeratin 19) cytokeratins with similar staining patterns and intensities. The staining intensity of 54 kDa cytokeratin (cytokeratin 7) was similar to that of the high molecular weight cytokeratin (keratin M-903). However, in many cases (15 of 27), immunoreactivity of cytokeratin 7 was not demonstrated in an outer palisaded basal layer. In all 4 squamous papillary craniopharyngiomas, moderate staining with cytokeratin 7 appeared in the superficial layer, whereas basal or mid-zone epithelial cells were negative for cytokeratin 7. The basal layer stained negatively for KL-1, as well as cytokeratin 7. Interpretation. Immunostaining for cytokeratin is valuable in the investigation of craniopharyngioma, especially when specimens contain only a small or questionable part of epithelium. Most notably, KL-1 or cytokeratin 7 stainings are suitable for analyzing these tumours, with special reference to histological subtypes.

A comparative study of MIB-1 staining indices of gliomas measured by NIH Image analysis program and conventional manual cell counting method

Abstract To evaluate the NIH Image measured MIB-1 staining index (SI) as a useful tool for the determination of proliferative activity of gliomas, MIB-1 immunohistochemistry was performed on paraffin sections to estimate the proliferative activity of 50 gliomas. Five to eight RGB images at 200 magnifications were acquired per sample in a Macintosh computer using a RD-175 digital camera and Adope Photoshop program, followed by conversion of the RGB image to B (blue subtracted) and R (red subtracted) images and finally automatic cell counting of more than 1000 cells per sample by the NIH Image analysis program. The mean MIB-1 staining indices by both NIH count and visually assessed (manual) count respectively were 12.7% ±9.9% (mean ± standard deviation) and 12.6%±9.9% in all gliomas (n = 50), 2.9%± 0.6% and 2.3%± 0.6% in grade I and II astrocytomas (n = 9), 10.7%± 8.9% and 11.1%±9.0% in grade III gliomas (n=17), 16.1%±9.1% and 16.3%±9.1% In glioblastoma multiformes (n = 20), 26.0%±4.9% and 24.5% ± 2.6% in other glial tumors (n = 4). These paired values were assumed to be identical, since the p value obtained by paired t-test in all gliomas was 0.905. We conclude that the MIB-1 staining index measured by NIH Image is reliable and universal. [Neurol Res 2000; 22: 495-500]

Choroid plexus metastasis from papillary thyroid carcinoma presenting with intraventricular hemorrhage: case report.

OBJECTIVEMetastases to the choroid plexus from extracranial tumors are rare. Kidney, lung, and colon are the common primary origins of choroid plexus metastases. Choroid plexus metastases from thyroid carcinoma are very rare, with only 2 cases reported thus far. We report the third case of choroid plexus metastasis from thyroid carcinoma. CLINICAL PRESENTATIONA 75-year-old man presented with severe headache, nausea, and vomiting. He had a history of thyroid carcinoma, which had metastasized to the lymph nodes and lung. Computed tomography, magnetic resonance imaging, and magnetic resonance angiography revealed right intraventricular hemorrhage with mild hydrocephalus, without evidence of a bleeding source. The bleeding source was assumed to be the choroid plexus metastasis in the trigone of the right lateral ventricle (following second admission). INTERVENTIONSurgery was performed using a navigation-assisted system. The tumor was entirely removed, including some choroid plexus tissue. A ventriculoperitoneal shunt was also performed to treat the hydrocephalus. Histopathological examination revealed brain metastasis from papillary thyroid carcinoma. Postoperatively, the patient showed good recovery, with nausea and vomiting improved, and gait disturbance diminished. The patient was discharged from the hospital one month later. CONCLUSIONChoroid plexus metastasis from papillary thyroid carcinoma is very rare, and this is the first case of intraventricular hemorrhage reported.

Three-dimensional gradient echo versus spin echo sequence in contrast-enhanced imaging of the pituitary gland at 3 T

INTRODUCTION To clarify whether a three-dimensional-gradient echo (3D-GRE) or spin echo (SE) sequence is more useful for evaluating sellar lesions on contrast-enhanced T1-weighted MR imaging at 3.0Tesla (T). METHODS We retrospectively assessed contrast-enhanced T1-weighted images using 3D-GRE and SE sequences at 3.0T obtained from 33 consecutive patients with clinically suspected sellar lesions. Two experienced neuroradiologists evaluated the images qualitatively in terms of the following criteria: boundary edge of the cavernous sinus and pituitary gland, border of sellar lesions, delineation of the optic nerve and cranial nerves within the cavernous sinus, susceptibility and flow artifacts, and overall image quality. RESULTS At 3.0T, 3D-GRE provided significantly better images than the SE sequence in terms of the border of sellar lesions, delineation of cranial nerves, and overall image quality; there was no significant difference regarding the boundary edge of the cavernous sinus and pituitary gland. In addition, the 3D-GRE sequence showed fewer pulsation artifacts but more susceptibility artifacts. CONCLUSION Our results indicate that 3D-GRE is the more suitable sequence for evaluating sellar lesions on contrast-enhanced T1-weighted imaging at 3.0T.

The Value of Intraoperative Cytology During Transsphenoidal Surgery for ACTH-Secreting Microadenoma

Summary Background. Microsurgical selective adenomectomy is the best established method available for the treatment of Cushings disease. However, this surgical method warrants still more efforts to improve the results in minute microadenomas. In this paper the authors evaluate a method of intraoperative cytological investigations during transsphenoidal surgery. Method. Between January 1997 and September 1999, transsphenoidal surgery was performed in 75 patients with the diagnosis of Cushings disease. Fifty-one cases of proven microadenomas were reviewed. Findings. Of 51 cases, 33 tumors were 3 mm or less in diameter, here after called minute adenomas. In 49 of 51 (96.1%) microadenomas, adenoma tissue was identified by intraoperative cytological techniques. Postoperatively, only 35 of 51 ACTH-secreting microadenomas (68.6%) were confirmed by immunostaining methods. This lower percentage was most probably due to the small amount of tissue obtained. Therefore, in 14 cases (including 12 minute adenomas) the presence of the adenoma was only proven by cytological preparation and clinical outcome. The sensitivity of cytological preparations in cases of confirmed Cushings disease was 100%. Interpretation. The method described here was particularly well suited for the intraoperative discrimination and documentation of minute adenomas. Cytological preparation appears to be effective in improving the adenoma finding rate and the surgical outcome in cases of Cushings disease.