Relationship between left atrial spontaneous echo contrast and the features of middle cerebral artery territory in nonvalvular atrial fibrillation.

We investigated the relationship between left atrial spontaneous echo contrast (SEC) and cerebrovascular features in nonvalvular atrial fibrillation (NVAF). Few reports have been published to compare cardiac and cerebrovascular imaging in patients with NVAF. Forty-four patients with NVAF were studied using transesophageal echocardiography and non-invasive imaging including magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and transcranial color Doppler imaging (TCD) in the middle cerebral artery (MCA) territory. The symptomatic severity was divided into asymptomatic, transient ischemic attack (TIA), and stroke. The severity of the MRI findings was divided into normal, small, and large infarcts. The severity of the MRA findings was divided into normal, attenuation, and occlusion. MCA was bilaterally scanned and a side-to-side asymmetry ratio of pulsatility index (PI) was measured. The severity of SEC was divided into normal, SEC, and thrombi. Five patients with other thromboembolic risk or poor results of TCD were excluded. SEC and thrombi were detected in 12 (30%) and in 3 patients (5%), respectively. TIA and stroke were detected in 8 (21%) and in 17 patients (44%), respectively. Small and large infarcts were detected in 9 (23%) and in 18 patients (46%), respectively, on MRI. Attenuation and occlusion were detected in 14 (36%) and in 8 patients (21%), respectively, on MRA. PI ratio was 1.21 +/- 0.25. SEC severity was highly associated with PI ratio and MRA severity in monovariate analysis (P < 0.005), P < 0.01, respectively). SEC severity was highly associated with PI ratio and MRA severity in stepwise multiple regression analysis (P = 0.0001, r = 0.630, n = 39). In patients with NVAF, left atrial SEC was highly related to attenuation or occlusion on MRA and imbalance of cerebral blood flow on TCD in the MCA territory.

MRI of intracranial germ cell tumours.

We reviewed MRI findings in proven intracranial germ cell tumours in 22 cases, 12 of whom received Gd-DTPA. On T1-weighted images, the signal intensity of the tumour parenchyma was moderately low in 19 cases and isointense in 3; on T2-weighted images, it was high in all cases. Regions of different intensity thought to be cysts were found in 17 (77%): 7 of 12 patients with germinoma (58%) and in all other cases. Of the 13 patients with pineal lesions T1-weighted sagittal images showed the aqueduct to be obstructed in 5, stenotic in 7 and normal in 1. Strong contrast enhancement was observed in all 12 cases. Of the 14 patients with suprasellar lesions, 5 were found to have an intrasellar extension, and in 3 of these, the normal pituitary gland, which could be distinguished from the tumour, was displaced anteriorly. Ten patients (45%) had multiple lesions.

Displacement of the normal pituitary gland by sellar and juxtasellar tumours: surgical-MRI correlation and use in differential diagnosis.

We compared the position of the normal pituitary gland as estimated by gadolinium (Gd)-DTPA-enhanced MRI, with its position at surgery in 40 patients with intra- and juxtasellar tumours: 22 pituitary adenomas, 4 craniopharyngiomas, 7 meningiomas, 2 germinomas, and 5 Rathke cleft cysts. In 37 of these, the normal gland showed more intense contrast enhancement than the adjacent tumour, from which it could be differentiated by Gd-DTPA-enhanced MRI, especially in the sagittal plane. The direction of displacement of the normal pituitary gland correlated well with tumour type, so that its position proved helpful in the differential diagnosis. The normal gland was typically displaced superiorly by pituitary adenomas, inferiorly by craniopharyngiomas, and anteriorly by germinomas. It showed variable displacement by Rathke cleft cysts, and was not usually displaced by meningiomas.

MRI of pituitary adenomas: the position of the normal pituitary gland.

The position of the normal pituitary gland, assessed using gadolinium - enhanced MRI was compared with the position found at surgery for pituitary adenoma in 25 patients. The tumours were five microadenomas and 20 macroadenomas. Using T1-weighted imaging, the anterior lobe could be differentiated on the sagittal image in five patients (20%) and on the coronal image in four (16%). The high intensity of the posterior lobe could be differentiated using T1-weighted sagittal imaging in 13 patients (52%). The normal pituitary gland, which enhanced more strongly than tumour, could be differentiated using Gd-DTPA-enhanced MRI on the sagittal images in 22 cases (88%) and on the coronal image in 17 (68%). In seven patients, the normal pituitary gland surrounded the tumour; it was displaced superiorly in 14 cases and superioposterorly in two but in no case was it displaced anteriorly or downwards.

Rathke cleft cysts: correlation of enhanced MR and surgical findings.

PURPOSE: To describe the gadolinium-enhanced MR findings of Rathke cleft cyst correlate them with the surgical findings, and define those preoperative findings that differentiate this lesion from other sellar and juxtasellar tumors. METHODS: We studied 18 patients who were diagnosed as having Rathke cleft cyst pathologically. These patients were imaged with T1- and T2-weighted coronal and sagittal spin-echo sequences. Fifteen of these patients received gadopentetate dimeglumine. RESULTS: In eight patients, the cyst showed low intensity on T1-weighted images and high intensity on T2-weighted images. At surgery, the cyst fluid was cerebrospinal fluid-like or light brown in five patients, motor oil-like in one patient, and milky in two patients. In 10 patients, cysts showed isointensity to high intensity on T1-weighted images and had various intensity on T2-weighted images. All 10 contained milky fluid. In three patients the intensity of fluid was heterogeneous. A waxy nodule was found in two patients. The position of the normal pituitary gland confirmed by surgery in all cases coincided with enhancement on MR imaging. The variable position of the normal pituitary gland was clearly identified in the sagittal images. The cyst walls showed no enhancement by gadopentetate dimeglumine. CONCLUSIONS: Because Rathke cleft cysts show variable intensities on MR, the diagnosis is often difficult when based on MR signal intensity values alone. MR imaging with gadopentetate dimeglumine does assist in the diagnosis of Rathke cleft cysts. Diagnostic clues include the lack of cyst wall enhancement and displacement of the normal pituitary gland.

Intracranial germ-cell tumor with synchronous lesions in the pineal and suprasellar regions: report of six cases and review of the literature.

The features of intracranial germ-cell tumor with synchronous lesions in the pineal and suprasellar regions (GCTSPS) in six patients were investigated. GCTSPS accounted for 12.8% of all germ-cell tumors (GCT) in our brain tumor study group. In all cases, the initial symptoms were attributable to the suprasellar lesion, and symptoms due to the pineal GCT developed only after admission. Five of the six cases were histologically diagnosed as germinoma. In all cases, tumors of both regions disappeared after irradiation, resulting in no recurrence for an average of 55.3 months. Our experience and reports in the literature suggest that GCTSPS is highly sensitive to radiation in most cases, although some reports indicated that recurrence is frequent after radiation therapy alone. It is suggested that histological diagnosis in one of the GCTSPS lesions is undertaken to make a plan for the following treatment.

Cytocidal effects of bromocriptine, somatostatin analog, and heat on growth hormone-secreting pituitary adenoma in vitro.

The effects of bromocriptine (BC), a somatostatin analog (SMS), and heat on the secretion of growth hormone (GH) and prolactin (PRL), and on the morphologic features of human GH-secreting pituitary adenoma were studied in vitro. The treatment with BC, SMS, or heat (41.5 degrees C and 42.5 degrees C) markedly suppressed the secretion of GH and PRL from the adenoma cells and reduced the number of cells immunoreactive with GH or PRL. The combined treatment with BC and heat induced a marked reduction in the number of GH and PRL cells consistent with the effect on the secretion of GH and PRL. These results suggest that BC, SMS, and heat treatments produced the cytotoxic effects on pituitary adenoma cells, and that the simultaneous treatment of BC and heat enhanced this effect.

[Pineocytomas; clinicopathological evaluation of 4 cases].

Clinicopathological evaluation of pineocytoma was performed in 4 patients. The subjects, 2 males and 2 females, ranged in age from 17 to 40. All the patients were clinically found to have the symptom of increased intracranial pressure on a monthly basis, but none of them were found to have dorsal midbrain dysfunction symptoms such as Parinaud's sign or Argyll Robertson pupil. Diagnostic imaging produced heterogeneous pictures indicating calcifications and cyst in 2 patients and homogeneous pictures of the tumor parenchyma in the other 2 patients. Histologically, the former cases were found to have many pineal-sand-like calcifications. Median sagittal MR images demonstrated expansive growth of pineocytoma. Quadrigeminal plates which kept their shapes were observed in 2 patients. Craniotomy was performed in all cases, removing the tumor totally in 2 patients. Radiation therapy was given to 3 patients, resulting in complete remission, but radiosensitivity varied according to cases. During the follow-up period of 12 to 42 months, one patient died of peritonitis caused by shunt infection. No recurrence of the tumor was seen in any of the patients. The incidence of pineocytoma was very low. Further evaluation of the tumor involving many cases is advisable.

Effect of long-term treatment with somatostatin analogue (SMS 201-995) on pituitary tumor shrinkage in acromegaly--report of two cases.

The effect of long-term somatostatin analogue (SMS 201-995) treatment in two acromegalic patients is reported. Continuous tumor shrinkage was observed even after 129 and 139 weeks of treatment with 600 micrograms of SMS 201-995 daily. A huge and firm adenoma underwent shrinkage during treatment with SMS 201-995. No serious side effect appeared during 160 weeks of treatment. SMS 201-995 has a longterm tumor shrinkage effect and improves endocrinopathies.

Microprolactinoma invading the cavernous sinus--report of three cases.

Three cases of microprolactinoma with cavernous sinus invasion on magnetic resonance imaging are reported. High-resolution computed tomographic scans did not demonstrate the cavernous sinus involvement. Magnetic resonance imaging is indispensable to detect cavernous sinus invasion before treatment (transsphenoidal surgery or bromocriptine treatment) of a microprolactinoma.

[A case of sellar germinoma which was misdiagnosed as pituitary adenoma].

The authors reported a rare case of sellar germinoma which was misdiagnosed as nonfunctioning pituitary adenoma. A 32-year-old woman was admitted to our hospital because of amenorrhea and disturbance of left visual acuity. She had become amenorrhagic after her second delivery two years before. Neurological examination revealed she was normal except for diminished left visual acuity (Rt. = 1.2, Lt. = 0.5). The general condition was good. Urine volume and its specific gravity were within normal range. Endocrinological examination showed hyperprolactinemia (PRL 72 ng/ml) accompanied with impairment of GH, TSH, LH and FSH's reserve. Basal levels and reserve of the blood cortisol were normal. AFP and hCG were within normal range. CT scan revealed a homogenously enhanced intrasellar tumor which had a suprasellar portion (vertical length: 15 mm). T1 weighted MRI revealed low intensity tumor, and T2 weighted image revealed high intensity tumor. Sagittal MR image with gadolinium enhancement showed the pituitary gland anterior to the tumor. Transsphenoidal removal was performed. The histological diagnosis was pure germinoma. After the operation, the intracranial and spinal disseminations were disclosed. Complete neuraxis irradiation resulted in the complete remission of the tumor. Sellar germinoma without diabetes insipidus is considered to be very difficult to diagnose preoperatively. However, the authors proposed that anterior shift of the pituitary gland in sagittal MR image may be a clue to the diagnosis of sellar germinoma.

[Long-term surgical results of microprolactinomas].

Sixty three patients with microprolactinoma were studied by long-term follow-up after surgical cure. Postoperative normalization of prolactin (PRL) was seen in 38 (60%) of the total 63 cases, and hyperprolactinemia recurred in 5 (13%) during the follow-up period. Spontaneous restoration of menstruation occurred in 45 (71%), and, in 41 (65%), regular menstrual cycle as continuing at the time of the last follow-up. 34 (72%) of 47 patients who wanted children became pregnant, and 31 of these had a subsequent successful delivery. Clinical cure by surgical treatment alone, followed by spontaneous restoration of menstruation and continuation of regular cycle during the follow-up period after pregnancy and delivery was seen in 41 (65%) of the total cases. From these results, it was concluded that transsphenoidal surgery should be the treatment of first choice for microprolactinoma when complete cure is required.

Influence of pregnancy on the serum prolactin level following prolactinoma surgery.

We studied the influence of pregnancy on the serum prolactin levels after surgery in 35 patients with prolactinomas. Eighteen out of 22 patients with postoperative normalization of the prolactin level were able to achieve repeated spontaneous pregnancies and endocrine cure by surgery alone, but the other 4 had recurrent hyperprolactinemia. Thirteen patients with persistent hyperprolactinemia after surgery achieved one pregnancy with or without bromocriptine treatment, but did not achieve a second one owing to an increase in the prolactin level after delivery. None of the patients with postoperative hyperprolactinemia showed spontaneous normalization of the prolactin level or restoration of menstruation after delivery. In these 13 patients, the mean increase from the postoperative to the post-delivery prolactin level was less for the patients with bromocriptine-induced pregnancy than for those with spontaneous pregnancy. It is concluded that pregnancy did not adversely affect the serum prolactin level in the patients with a normal postoperative level.

[A case of pituitary adenoma with simultaneous secretion of TSH and GH detected by double immunostaining method].

A rare case of simultaneous hypersecretion of thyroid stimulating hormone (TSH) and growth hormone (GH) in a pituitary adenoma is reported. A 59-year-old male complaining of general fatigue, dyspnea on exertion and finger tremor was admitted. Examination on admission, he revealed with hyperthyroidism and hypersecretion of TSH and thyroid hormones. Administration of TRH did not further increase serum TSH level, and administration of T3 also had no effect on TSH secretion. CT scan showed a pituitary macroadenoma 13mm in diameter. MRI demonstrated a homogenously hypointense mass with Gd-DTPA enhancement in the left side of the sella turcica. The entire chromophobic adenoma was removed by trans-sphenoidal surgery. Immunostaining of the specimen showed that the cytoplasm of the adenoma cells was positive for both TSH and GH. Double immunostaining using avidin-biotin-peroxidase complex (ABC) method and immunogold silver staining (IGSS) method, showed that the adenoma cells had been secreting both GH and TSH at the same time. After the adenomectomy, the hyperthyroidism disappeared, and all altered indicators of pituitary function returned to normal.

A case of pituitary adenoma producing both growth hormone (GH) and adrenocorticotropic hormone (ACTH).

The authors report a very rare case of pituitary adenoma producing both GH and ACTH. A 29-year-old female was admitted with obesity, amenorrhea, acromegaly, hirsutism, excessive pigmentation, acne, and diabetes mellitus. Computed tomography revealed an intrasellar tumor 16 mm in height, with a destroyed sellar floor. The blood concentrations of GH, ACTH and cortisol were increased (GH: 92 ng/ml, ACTH: 94 pg/ml, cortisol: 18.3 micrograms/dl). No diurnal variation in the amount of cortisol was observed. The urinary 17-OHCS was suppressed by 8 mg but not by 2 mg of dexamethasone. A subtotal adenomectomy was then performed through the transsphenoidal approach, which led to a sufficient reduction of both blood GH and ACTH (cortisol). Histologically the tumor was an acidophilic pituitary adenoma. Immunoperoxidase staining showed diffuse GH and sporadic ACTH producing cells, but failed to show any cells producing both hormones. The electron micrograms of neoplastic cells showed the ultrastructural characteristics of respective GH and ACTH cells. Another increase in both GH and cortisol, which occurred 19 months after the operation, has been controlled by bromocriptine administration. This case may be the first reported case of a pituitary adenoma producing both GH and ACTH, not accompanied by prolactin (PRL) hypersecretion, which has been fully confirmed endocrinologically and histopathologically.

[Pituitary apoplexy with localized hematoma in the suprasellar region].

The authors report a case of a patient with a pituitary tumor, in which pituitary apoplexy occurred only in the suprasellar part of the tumor. A 26-year-old woman suffered from abrupt worsening of vision and headache. A CT scan showed a dumb-bell-shaped tumor extending to the suprasellar region, in which an irregularly shaped low density area suggesting a liquidized hematoma was seen. The rapid worsening of her symptoms was highly indicative of pituitary apoplexy. The first operation was performed through the transsphenoidal route. There was no evidence of intratumoral hematoma in the intrasellar tumor, which could be removed successfully. However, the suprasellar mass could not be reached because of the hardness of the diaphragma sellae and the presence of a normal pituitary gland. MRI and CT cisternography after this first operation showed a narrow opening of the diaphragma sellae. The second operation using right frontotemporal craniotomy disclosed a suprasellar mass, which consisted of an old hematoma and a necrotic tumor. The tumor was sub-totally removed. The patient's visual acuity improved after the second operation. Although transsphenoidal surgery is the treatment of choice in patients with pituitary apoplexy, the selection of the surgical route should be made only after careful neuroradiological evaluation with regard to the extrasellar extension of the tumor.

Establishment and characterization of human medulloblastoma xenograft line.

A new xenotransplantable tumor line, MED-FU, was derived from a 6-year-old female patient with cerebellar medulloblastoma. This tumor was grown in nude mice as serially transplantable subcutaneous xenografts composed of small round cells with hyperchromatic nuclei and scant cytoplasm. Many rosettes and mitoses were observed. Immunohistochemically, glial fibrillary acidic protein (GFAP), S-100 protein, and neuron specific enolase (NSE) were not detected. The doubling time of the subcutaneous tumors was 6.8 days. Highly concentrated polyamines were detected in the tumor tissue and serum of tumor-bearing mice. This xenotransplanted tumor line, MED-FU, is considered to provide an available experimental model for the study of human medulloblastoma.

Photodynamic therapy for rat pituitary tumor in vitro and in vivo using pheophorbide-a and white light.

This is the first report on the use of photodynamic therapy (PDT) for rat pituitary tumor in vivo. Rat pituitary tumor (GH3) cells were cultured, GH3 tumor was subcutaneously implanted in nude mice, and pheophorbide-a (Ph-a) and white light were prepared. Photocytotoxicity proportional to Ph-a concentration, intensity of irradiation, and incubation time was observed in vitro. Despite the delay in the disappearance of Ph-a from the tumor, Ph-a in the pituitary gland rapidly decreased after intravenous administration in vivo. Through PDT, the tumor grossly disappeared, the plasma levels of rat growth hormone secreted from the tumor also remarkably decreased, and the development of giantism was inhibited. These results indicate that PDT is effective against rat pituitary tumor.

The natural course of growth hormone-secreting pituitary adenomas after surgery alone--clinical significance of the growth hormone response to thyrotropin-releasing hormone and luteinizing hormone-releasing hormone.

The clinical significance of abnormal growth hormone (GH) secretion in response to thyrotropin-releasing hormone (TRH) and luteinizing hormone-releasing hormone (LHRH) was studied in 52 patients with acromegaly due to GH secreting pituitary adenomas treated by trans-sphenoidal microsurgery. The mean period of postoperative follow-up was 4.1 years. In 27 of the 36 patients who had abnormal GH responses to TRH or LHRH before surgery, basal GH levels normalized and abnormal GH responses disappeared immediately after surgery. Among the remaining nine patients, four had normal basal GH levels with abnormal GH responses and five showed persistently abnormal basal GH levels as well as abnormal GH responses. Recurrence requiring retreatment was not observed during follow-up in any of the 31 patients with normal postoperative basal GH levels, regardless of the GH response to TRH or LHRH. All five patients with abnormal basal GH and abnormal GH responses required additional treatment. Among the patients who underwent long-term postoperative TRH and LHRH testing, abnormal GH responses reappeared in three of 19 whose abnormal responses had disappeared immediately after surgery. The abnormal response disappeared spontaneously in two of three patients who had abnormal responses immediately after surgery. In four patients with both abnormal GH responses and abnormal basal GH levels immediately after surgery, abnormal GH responses persisted throughout the follow-up period. In addition, the abnormal GH responses appeared in two of 14 patients who had been nonresponsive before surgery. These results indicate that the postoperative GH response to TRH or to LHRH was not significantly related to the outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Antitumor effect of recombinant human lymphotoxin on a tumor line of human malignant glioma.

We examined the antitumor effect of recombinant human lymphotoxin (rHuLT) on a xenotransplantable human malignant glioma line. Tumor-bearing nude mice were treated with rHuLT for three weeks following four schedules: intratumoral injection of rHuLT 20,000 units once a week, twice a week, intravenous injection once a week and twice a week. The inhibition rate of tumor growth was 98.8%, 99.1%, 92.1% and 98.8%, respectively. Histologically, necrotic lesions were observed in the tumors of all treated mice. Thrombo-obstructive changes of tumor vessels were also seen in the tumors of mice after intravenous injection of rHuLT. None of the mice died as a result of this treatment in spite of significant body weight loss. These results indicate that rHuLT has a strong antitumor effect on a xenotransplantable human malignant glioma line.