From pituitary adenoma to pituitary neuroendocrine tumor (PitNET): an International Pituitary Pathology Club proposal.

The classification of neoplasms of adenohypophysial cells is misleading because of the simplistic distinction between adenoma and carcinoma, based solely on metastatic spread and the poor reproducibility and predictive value of the definition of atypical adenomas based on the detection of mitoses or expression of Ki-67 or p53. In addition, the current classification of neoplasms of the anterior pituitary does not accurately reflect the clinical spectrum of behavior. Invasion and regrowth of proliferative lesions and persistence of hormone hypersecretion cause significant morbidity and mortality. We propose a new terminology, pituitary neuroendocrine tumor (PitNET), which is consistent with that used for other neuroendocrine neoplasms and which recognizes the highly variable impact of these tumors on patients.

Pilot trial of sunitinib therapy in patients with von Hippel-Lindau disease.

BACKGROUND: Von Hippel-Lindau (VHL) disease induces vascular neoplasms in multiple organs. We evaluated the safety and efficacy of sunitinib in VHL patients and examined the expression of candidate receptors in archived tissue. METHODS: Patients with VHL were given four cycles of 50 mg sunitinib daily for 28 days, followed by 14 days off. Primary end point was toxicity. Modified RECIST were used for efficacy assessment. We evaluated 20 archival renal cell carcinomas (RCCs) and 20 hemangioblastomas (HBs) for biomarker expression levels using laser-scanning cytometry (LSC). RESULTS: Fifteen patients were treated. Grade 3 toxicity included fatigue in five patients. Dose reductions were needed in 10 patients. Eighteen RCC and 21 HB lesions were evaluable. Six of the RCCs (33%) responded partially, versus none of the HBs (P = 0.014). LSC revealed that mean levels of phosphorylated vascular endothelial growth factor receptor-2 were lower in HB than in RCC endothelium (P = 0.003) and mean phosphorylated fibroblast growth factor receptor substrate-2 (pFRS2) levels were higher in HB (P = 0.003). CONCLUSIONS: Sunitinib treatment in VHL patients showed acceptable toxicity. Significant response was observed in RCC but not in HB. Greater expression of pFRS2 in HB tissue than in RCC raises the hypothesis that treatment with fibroblast growth factor pathway-blocking agents may benefit patients with HB.

High prevalence of normal tests assessing hypercortisolism in subjects with mild and episodic Cushing's syndrome suggests that the paradigm for diagnosis and exclusion of Cushing's syndrome requires multiple testing.

Many Endocrinologists believe that a single determination of eucortisolism or a single demonstration of appropriate suppression to dexamethasone excluded Cushing's syndrome, except in what was previously thought to be the rare patient with episodic or periodic Cushing's syndrome. We hypothesize that episodic Cushing's syndrome is relatively common and a single test assessing hypercortisolism may not be sufficient to accurately rule out or diagnose Cushing's syndrome and retrospectively examined the number of normal and abnormal tests assessing hypercortisolism performed on multiple occasions in 66 patients found to have mild and/or episodic Cushing's syndrome compared to a similar group of 54 patients evaluated for, but determined not to have Cushing's syndrome. We found that 65 of the 66 patients with Cushing's syndrome had at least one normal test of cortisol status and most patients had several normal tests. The probability of having Cushing's syndrome when one test was negative was 92% for 23:00 h salivary cortisol, 88% for 24-h UFC, 86% for 24-h 17OHS, and 54% for nighttime plasma cortisol. These results demonstrated that episodic hypercortisolism is highly prevalent in subjects with mild Cushing's syndrome and no single test was effective in conclusively diagnosing or excluding the condition. Rather, the paradigm for the diagnosis should be a careful history and physical examination and in those patients in whom mild Cushing's syndrome/disease is strongly suspected, multiple tests assessing hypercortisolism should be performed on subsequent occasions, especially when the patient is experiencing signs and symptoms of short-term hypercortisolism.

Exophytic ependymomas of the spinal cord.

Intramedullary ependymomas of the spinal cord with exophytic components are rare outside the filum or conus region. Two cases of combined intradural intramedullary and extramedullary ependymomas of the spinal cord are presented. At operation, the tumours proved to be primarily intramedullary but had a contiguous exophytic component that extruded either through a defect in the ventral pia to encase the anterior spinal artery in one patient, or through the dorsal root entry zone in the second patient. When removing intramedullary spinal tumours with an exophytic component, separate removal of the intramedullary and extramedullary components is recommended, rather than en bloc resection, to prevent possible injury to the vascular supply of the spinal cord.

Growth hormone and insulin-like growth factor-I: effects on the growth of glioma cell lines.

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are known to be mitogens for many types of neoplasms. To investigate their role in tumors of glial origin, in vitro and in vivo experiments were performed with a panel of immortalized glioma cell lines (D54, SNB-19, U87, U251 and U373). Initial analysis for mRNA expression demonstrated the following: GH receptor (5/5 cell lines positive), IGF-I (0/5), IGF-II (0/5), IGF-I receptor (5/5), IGF-II receptor (2/5). Thus, each cell line expressed the necessary receptors to respond to GH and the IGFs but there was no autocrine IGF production by the tumors themselves. IGF-I stimulated mitogenesis as measured by [(3)H]thymidine uptake experiments in U251 and U373 cells. However, when these two IGF-responsive cell lines were xenografted into mice, tumor development and growth rates were not significantly different in GH-deficient animals (despite having IGF-I serum concentrations only 31% of normal). Because our studies were performed in immunocompromised animals, GH or IGF effects on immune surveillance, known to be important from some syngeneic glioma models, would not be likely to contribute to our findings. Nevertheless, these studies are important because they demonstrate that the growth of glioma cell lines in an in vivo environment can remain robust in a GH/IGF-I-deficient setting, even if in vitro experiments indicate that IGF-I is mitogenic.

Adenocarcinoma of the salivary gland metastatic to the pituitary gland: case report.

OBJECTIVE AND IMPORTANCE: A case of metastasis to the pituitary gland from a ductal adenocarcinoma of the salivary gland is presented. Metastasis to this site is rare, and a salivary gland source has never previously been described. CLINICAL PRESENTATION: This patient presented with hypopituitarism, including diabetes insipidus. INTERVENTION: A craniotomy was performed to alleviate visual loss. The histological features of the sellar tumor were identical to those of a tumor removed from the parotid gland 18 months earlier. CONCLUSION: Although intrasellar tumors originating from embryonic rests of salivary gland tissue have been reported, metastasis from a malignant neoplasm arising within a true salivary gland is also possible and should not be excluded from consideration for patients in whom a salivary gland-like tumor is discovered in the sella turcica.

Surgical resection of calvarial metastases overlying dural sinuses.

OBJECTIVE: Few reports have addressed the surgical management of cranial metastases that overlie or invade the dural venous sinuses. To examine the role of surgery in the treatment of dural sinus calvarial metastases, we reviewed retrospectively 13 patients who were treated with surgery at the University of Texas M.D. Anderson Cancer Center between 1993 and 1999. We compared them with 14 patients who had calvarial metastases that did not involve a venous sinus. METHODS: Clinical charts, radiological studies, pathological findings, and operative reports were analyzed retrospectively. RESULTS: The median age of patients with dural sinus calvarial metastases was 54 years. Nine patients were men and four were women. Renal cell carcinoma and sarcoma were the most common primary tumors. Similar features were noted in the 14 patients with nonsinus calvarial metastases. Of the 13 dural sinus calvarial metastases, 11 involved the superior sagittal sinus, and 2 involved the transverse sinus. In nine patients, the involved sinus was resected, and in four patients, the sinus was reconstituted after tumor removal. Nine patients in the dural sinus calvarial metastases group received en bloc resection, and four received piecemeal resection. No operative deaths occurred. The overall median actuarial survival was 16.5 months. The survival times of the two groups were comparable. In the group with dural sinus calvarial metastases, transient postoperative neurological deficits occurred in two patients (15%), and a permanent deficit occurred in one patient (8%). No patients in the group with nonsinus calvarial metastases experienced deficits after resection. Compared with piecemeal resection, en bloc resection was associated with significantly less blood loss. CONCLUSION: Complete extirpation of calvarial metastases that overlie or invade a dural sinus can be achieved with only slightly more morbidity than complete removal of calvarial metastases that are located away from the sinuses. En bloc resection is as safe as piecemeal resection and is more effective in limiting operative blood loss. The overall recurrence and survival rates of patients with dural sinus calvarial metastases are similar to those of patients with calvarial metastases that do not involve the sinuses. Therefore, involvement of a dural venous sinus should not discourage resection of calvarial metastases. In carefully selected cancer patients, surgery provides effective palliation of symptomatic calvarial metastases that overlie or invade the venous sinuses.

Simultaneous anterior-posterior approach to the thoracic and lumbar spine for the radical resection of tumors followed by reconstruction and stabilization.

OBJECT: Thoracic or lumbar spine malignant tumors involving both the anterior and posterior columns represent a complex surgical problem. The authors review the results of treating patients with these lesions in whom surgery was performed via a simultaneous anterior-posterior approach. METHODS: The hospital records of 26 patients who underwent surgery via simultaneous combined approach for thoracic and lumbar spinal tumors at our institution from July 1994 to March 2000 were reviewed. Surgery was performed with the patients in the lateral decubitus position for the procedure. The technical details are reported. The mean survival determined by Kaplan-Meier analysis was 43.4 months for the 15 patients with primary malignant tumors and 22.5 months for the 11 patients with metastatic spinal disease. At 1 month after surgery, 23 (96%) of 24 patients who complained of pain preoperatively reported improvements (p < 0.001, Wilcoxon signed-rank test), and eight (62%) of 13 patients with preoperative neurological deficits were functionally improved (p = 0.01). There were nine major complications, five minor complications, and no deaths within 30 days of surgery. Two patients (8%) later underwent surgery for recurrent tumor. CONCLUSIONS: The simultaneous anterior-posterior approach is a safe and feasible alternative for the exposure tumors of the thoracic and lumbar spine that involve both the anterior and posterior columns. Advantages of the approach include direct visualization of adjacent neurovascular structures, the ability to achieve complete resection of lesions involving all three columns simultaneously (optimizing hemostasis), and the ability to perform excellent dorsal and ventral stabilization in one operative session.

Antitumor activity of the growth hormone receptor antagonist pegvisomant against human meningiomas in nude mice.

OBJECT: The authors have previously demonstrated that modulation of the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis can significantly affect meningioma growth in vitro. These studies were performed to evaluate the efficacy of GH receptor blockade in vivo. METHODS: Primary cultures from 15 meningioma tumors obtained in humans were xenografted into athymic mice. Approximately 1.5 million cells from each of the 15 tumors were implanted into the flanks of two female mice, one pair for each tumor. One animal from each of the 15 pairs was then treated with the GH receptor antagonist pegvisomant and the other with vehicle alone for 8 weeks. The tumor volume was measured using digital calipers three times per week. The mean tumor volume at the initiation of injections was 284 +/- 18.8 mm3 in the vehicle group and 291.1 +/- 20 mm3 in the pegvisomant group. After 8 weeks of treatment, the mean volume of tumors in the pegvisomant group was 198.3 +/- 18.9 mm3 compared with 350.1 +/- 23.5 mm3 for the vehicle group (p < 0.001). The serum IGF-I concentration in the vehicle group was 319 +/- 12.9 microg/L compared with 257 +/- 9.7 in the pegvisomant group (p < 0.02). A small but significant decrease was observed in circulating IGF binding protein (IGFBP)-3 levels, whereas slight increases occurred with respect to serum IGFBP-1 and IGFBP-4 levels. In the placebo group the tumor weight was 0.092 +/- 0.01 g compared with 0.057 +/- 0.01 g in the pegvisomant group (p < 0.02). The IGF-I and IGF-II concentrations were measured in the tumors by using a tissue extraction method. These human-specific immunoassays demonstrated that there was no autocrine production of IGF-I in any of the tumors, either in the pegvisomant or vehicle group. The IGF-I levels were highly variable (0-38.2 ng/g tissue) and did not differ significantly between treatment groups. CONCLUSIONS: In an in vivo tumor model, downregulation of the GH/IGF-I axis significantly reduces meningioma growth and, in some instances, causes tumor regression. Because the concentrations of IGF-II in tumor did not vary with pegvisomant treatment and there was no autocrine IGF-I production by the tumors, the mechanism of the antitumor effect is most likely a decrease of IGF-I in the circulation and/or surrounding host tissues. Because the authors have previously demonstrated that the GH receptor is ubiquitously expressed in meningiomas, direct blockade of the GH receptor on the tumors may also be contributing to inhibitory actions.

Use of pedicle screw fixation in the management of malignant spinal disease: experience in 100 consecutive procedures.

OBJECT: Few reports are available on the use of pedicle screw fixation for cancer-related spinal instability. The authors present their experience with pedicle screw fixation in the management of malignant spinal column tumors. METHODS: Records for patients with malignant spinal tumors who underwent pedicle screw fixation at the authors' institution between September 1994 and December 1999 were retrospectively reviewed. RESULTS: Ninety-five patients with malignant spinal tumors underwent 100 surgeries involving pedicle screw fixation: metastatic spinal disease was present in 81 patients, and locally invasive tumors were demonstrated in 14 patients. Indications for surgery were pain (98%) and/or neurological dysfunction (80%). A posterior (48%) or a combined anterior-posterior (52%) approach was performed depending on the extent of tumor and the patient's condition. At the mean follow up of 8.2 months, 43 patients (45%) had died; median survival, as determined by Kaplan-Meier analysis, was 14.8 months. At I month postsurgery, self-reported pain had improved in 87% of cases (p < 0.001), which is a finding substantiated by reductions in analgesic use, and 29 (47%) of 62 patients with preoperative neurological impairments were functionally improved (p < 0.001). Postoperative complications were associated only with preoperative radiation therapy (p = 0.002) and with preexisting serious medical conditions (p = 0.04). In two patients asymptomatic violation of the lateral wall of the pedicle was revealed on postoperative radiography. The 30-day mortality rate was 1%. CONCLUSIONS: For selected patients with malignant spinal tumors, pedicle screw fixation after tumor resection may provide considerable pain relief and restore or preserve ambulation with acceptable rates of morbidity and mortality.

A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival.

OBJECT: The extent of tumor resection that should be undertaken in patients with glioblastoma multiforme (GBM) remains controversial. The purpose of this study was to identify significant independent predictors of survival in these patients and to determine whether the extent of resection was associated with increased survival time. METHODS: The authors retrospectively analyzed 416 consecutive patients with histologically proven GBM who underwent tumor resection at the authors' institution between June 1993 and June 1999. Volumetric data and other tumor characteristics identified on magnetic resonance (MR) imaging were collected prospectively. CONCLUSIONS: Five independent predictors of survival were identified: age, Karnofsky Performance Scale (KPS) score, extent of resection, and the degree of necrosis and enhancement on preoperative MR imaging studies. A significant survival advantage was associated with resection of 98% or more of the tumor volume (median survival 13 months, 95% confidence interval [CI] 11.4-14.6 months), compared with 8.8 months (95% CI 7.4-10.2 months; p < 0.0001) for resections of less than 98%. Using an outcome scale ranging from 0 to 5 based on age, KPS score, and tumor necrosis on MR imaging, we observed significantly longer survival in patients with lower scores (1-3) who underwent aggressive resections, and a trend toward slightly longer survival was found in patients with higher scores (4-5). Gross-total tumor resection is associated with longer survival in patients with GBM, especially when other predictive variables are favorable.

Hemangioblastomas and other uncommon intramedullary tumors.

Astrocytoma and ependymoma make up 90% of intramedullary tumors between them. However, a host of less common tumors form the remaining 10%: these include hemangioblastomas, subependymomas, gangliogliomas and other neuronal variants, metastases from extraneural cancers, and a host of other lesions that typically occur intracranially but which present on rare occasions in the intramedullary location. Most neurosurgeons will encounter the unusual tumors of the spinal cord described in this review only a few times during their professional careers, but it is nevertheless important to recognize the distinct radiological and intraoperative features of those for which significant series of patients have been accumulated. Metastases and germinomas aside, the other neoplasms described here are relatively benign in their clinical and histological behavior, and can be meaningfully resected by careful microsurgical technique.

The effects of insulin-like growth factors on tumorigenesis and neoplastic growth.

Several decades of basic and clinical research have demonstrated that there is an association between the insulin-like growth factors (IGFs) and neoplasia. We begin with a brief discussion of the function and regulation of expression of the IGFs, their receptors and the IGF-binding proteins (IGFBPs). A number of investigational interventional strategies targeting the GH or IGFs are then reviewed. Finally, we have assembled the available scientific knowledge about this relationship for each of the major tumor types. The tumors have been grouped together by organ system and for each of the major tumors, various key elements of the relationship between IGFs and tumor growth are discussed. Specifically these include the presence or absence of autocrine IGF-I and IGF-II production; presence or absence of IGF-I and IGF-II receptor expression; the expression and functions of the IGFBPs; in vitro and in vivo experiments involving therapeutic interventions; and available results from clinical trials evaluating the effect of GH/IGF axis down-regulation in various malignancies.

Pituitary carcinoma containing gonadotropins: treatment by radical excision and cytotoxic chemotherapy: case report.

OBJECTIVE AND IMPORTANCE: Pituitary carcinomas are extremely rare. Cases reported in the medical literature in the 20th century included tumors that produced adrenocorticotropic hormone, prolactin, growth hormone, and/or thyrotropin. CLINICAL PRESENTATION: Here we present a 22-year-old woman with a pituitary carcinoma that was immunohistochemically positive for luteinizing hormone and follicle-stimulating hormone at both the primary and metastatic sites. The patient exhibited elevated serum levels of alpha-subunit. INTERVENTION: The patient had experienced failure of previous treatments, including standard surgery and radiotherapy, and presented to us for radical resection of the tumor, with exenteration of the involved cavernous sinus. She was pretreated with cytotoxic chemotherapy and continued to receive this therapy after surgery. CONCLUSION: This is the only documented case of a gonadotropin-staining pituitary carcinoma for which hormone production was proven in both the primary and metastatic tumors. Many benign "nonsecreting" pituitary adenomas actually produce subclinical amounts of gonadotropins, and malignant nonfunctional pituitary neoplasms may do the same.

Fibroblast growth factor receptor-1 alpha-exon exclusion and polypyrimidine tract-binding protein in glioblastoma multiforme tumors.

Neoplastic transformation of glial cells alters inclusion of the alpha exon in human fibroblast growth factor receptor-1 (FGFR-1) mRNA transcripts. Although normal cells predominantly include the alpha exon, this exon is excluded in most glioblastoma cell transcripts, creating a high-affinity receptor form. In this study, we identified polypyrimidine tract-binding protein (PTB) as a regulator of FGFR-1 splicing. PTB interacted in a sequence-specific manner with the ISS-1 regulatory element in the intron upstream of the a exon. PTB expression was also strongly increased in seven malignant glioblastoma multiforme tumors relative to adjacent normal tissue, but not in a low-grade astrocytoma. These results suggest that increased expression of PTB may contribute to glial cell malignancy.

Use of long-term intravenous phosphate infusion in the palliative treatment of tumor-induced osteomalacia.

Tumor-induced osteomalacia is characterized by paraneoplastic defects in vitamin D metabolism, proximal renal tubular functions, and phosphate transport. The resulting hypophosphatemia can cause generalized pain and muscle weakness, which significantly affect the quality of life of the patients. Palliative treatment with calcium, vitamin D, and phosphate replacement is indicated for patients in whom the causative tumor cannot be completely resected. In this report we describe a case of tumor-induced osteomalacia in whom adequate oral doses of phosphate could not be used because of gastrointestinal side-effects. Long term (3-6 months) iv phosphate infusion delivered by ambulatory infusion pumps in combination with oral calcium and vitamin D was used successfully to decrease pain and increase muscle strength. Careful monitoring of serum calcium, phosphate, and creatinine levels and reliable microinfusion technology have allowed the long term use of iv phosphate infusion without serious morbidity. This patient received repeated (three times) phosphate infusions over 8 yr, resulting in laboratory and symptomatic improvement after each course. However, this patient did suffer two episodes of central venous catheter-related infection. Because of potentially serious complications, such as severe hypocalcemia, calcified right ventricular thrombi, and nephrocalcinosis, long term iv phosphate infusion should be reserved for patients who cannot tolerate adequate doses of oral phosphate and for whom the benefits outweigh the risks.

Intracranial injection of human meningioma cells in athymic mice: an orthotopic model for meningioma growth.

OBJECT: Although human meningioma cells have been heterotopically implanted in nude mice, introducing these cells into intracranial locations seems more likely to reproduce normal patterns of tumor growth. To provide an orthotopic xenograft model of meningioma, the authors implanted a controlled quantity of meningioma cells at subdural and intracerebral sites in athymic mice. METHODS: Malignant (one tumor), atypical (two tumors), or benign (three tumors) meningiomas were placed into primary cell cultures. Cells (10(6)/10 microl) from these cultures and from an immortalized malignant meningioma cell line, IOMM-Lee, were injected with stereotactic guidance into the frontal white matter or subdural space of athymic mice. Survival curves were plotted for mice receiving tumor cells of each histological type and according to injection site. Other mice were killed at intervals and their heads were sectioned whole. Hematoxylin and eosin staining of these sections revealed the extent of tumor growth. CONCLUSIONS: The median length of survival for mice with malignant, atypical, or benign tumors was 19, 42, or longer than 84 days, respectively. Atypical and malignant tumors were invasive, but did not metastasize extracranially. Malignant tumors uniformly showed leptomeningeal dissemination and those implanted intracerebrally grew locally and spread noncontiguously to the ventricles, choroid plexus, convexities, and skull base. Tumors formed in only 50% of mice injected with benign meningioma cells, whereas injection of more aggressive cells was uniformly successful at tumor production. The three types of human meningiomas grown intracranially in athymic mice maintained their relative positions in the spectrum of malignancy. However, atypical meningiomas became more aggressive after xenografting and acquired malignant features, implying that there had been immune constraint in the original host. Tumor cells injected into brain parenchyma migrated to more optimal environments and grew best there. This model provides insights into the biology of meningiomas and may be useful for testing new therapies.

Pronounced and sustained central hypernoradrenergic function in major depression with melancholic features: relation to hypercortisolism and corticotropin-releasing hormone.

Both stress-system activation and melancholic depression are characterized by fear, constricted affect, stereotyped thinking, and similar changes in autonomic and neuroendocrine function. Because norepinephrine (NE) and corticotropin-releasing hormone (CRH) can produce these physiological and behavioral changes, we measured the cerebrospinal fluid (CSF) levels each hour for 30 consecutive hours in controls and in patients with melancholic depression. Plasma adrenocorticotropic hormone (ACTH) and cortisol levels were obtained every 30 min. Depressed patients had significantly higher CSF NE and plasma cortisol levels that were increased around the clock. Diurnal variations in CSF NE and plasma cortisol levels were virtually superimposable and positively correlated with each other in both patients and controls. Despite their hypercortisolism, depressed patients had normal levels of plasma ACTH and CSF CRH. However, plasma ACTH and CSF CRH levels in depressed patients were inappropriately high, considering the degree of their hypercortisolism. In contrast to the significant negative correlation between plasma cortisol and CSF CRH levels seen in controls, patients with depression showed no statistical relationship between these parameters. These data indicate that persistent stress-system dysfunction in melancholic depression is independent of the conscious stress of the disorder. These data also suggest mutually reinforcing bidirectional links between a central hypernoradrenergic state and the hyperfunctioning of specific central CRH pathways that each are driven and sustained by hypercortisolism. We postulate that alpha-noradrenergic blockade, CRH antagonists, and treatment with antiglucocorticoids may act at different loci, alone or in combination, in the treatment of major depression with melancholic features.

Quinagolide in the management of prolactinoma.

OBJECTIVE: This study reports a six year experience with quinagolide (CV205-502) in the treatment of 40 patients with hyperprolactinemia or prolactinoma. PATIENTS AND MEASUREMENTS: Forty patients with hyperprolactinemia were treated with quinagolide (CV 205-502, Norprolac) for 2-72 months (mean 31.6 months). The patient's ages ranged from 12 to 53 years and 90% were female. Seventeen had no radiologic evidence of tumor; 11 had microadenomas; and 12 had macroadenomas. RESULTS: All patients had a reduction of the serum prolactin following quinagolide therapy with normalization in 82% with no tumor, 73% with microadenomas, and 67% with macroadenomas. Fifty-five percent of microadenoma and 75% of macroadenoma patients had a decrease in tumor size when assessed by a blinded reviewer. Ten of 38 female patients became pregnant while taking quinagolide. The dosage of quinagolide ranged from 75 to 400 [mgr]g/day with a median dose of 100[mgr]g/day. A comparison of side effects in a subgroup of 35 patients who had taken bromocriptine prior to quinagolide administration showed a greater than 75% reduction in nausea, vomiting, dizziness, and drowsiness during quinagolide administration. CONCLUSIONS: We conclude that quinagolide is a safe and effective long-term alternative to bromocriptine therapy, particularly in those individuals with bromocriptine intolerance.

Brain metastasis from prostate carcinoma: antemortem recognition and outcome after treatment.

BACKGROUND: In patients with prostate carcinoma, brain metastasis has most commonly been reported in autopsy series. Symptomatic brain metastasis from prostate carcinoma has occasionally been detected. METHODS: The authors retrospectively studied a series of 38 patients with antemortem intracerebral metastasis found on review of 7994 patients treated over an 18-year period at the University of Texas M. D. Anderson Cancer Center. RESULTS: The mean time from diagnosis of prostate carcinoma to discovery of brain metastasis was 28 months, with a mean survival of 9.2 months after the discovery of the brain metastasis. The brain metastasis was treated only with whole brain irradiation in 29 patients, with craniotomy and irradiation in 8 patients, and with surgery alone in 1 patient. Small cell carcinomas and primary transitional cell carcinomas of the prostate were much more likely to produce brain metastasis than were adenocarcinomas. Also noted among the overall prostate carcinoma cohort was a second group of 16 patients with prostate carcinoma and brain metastasis that had developed from a second primary tumor, which in all was either lung carcinoma or melanoma. CONCLUSIONS: The occurrence of brain metastasis in prostate carcinoma patients is rare, usually signifies a late stage of the disease, and may in some patients be produced by a tandem extraprostatic tumor.