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Results of surgical management of 319 pituitary adenomas.

Of the 510 patients with pituitary adenoma treated surgically at our hospital in the period 1956-1984 319 were treated by the microsurgical technique, in the period 1973-1984, 235 by transsphenoidal approach and 84 by subfrontal-pterional approach. The transsphenoidal route was used almost exclusively in microadenomas, in intrasellar adenomas, in suprasellar adenomas with midline development, in adenomas invading the sphenoidal sinus and in haemorrhagic adenomas with considerable suprasellar development. In some giant adenomas the transsphenoidal route was used in a first stage operation for debulking the tumour, later removed by transcranial route. The latter route was preferred in large adenomas and especially in adenomas with laterosellar development. In some patients with PRL secreting adenomas post-operative treatment with bromocriptine proved useful when the hormone levels failed to normalize. Post-operative radiotherapy was of value in invasive adenomas and in cases in which tumour removal was not radical.

Adenoma↗

Hormone-active intradural spinal metastasis of a prolactinoma--a case report.

A 44-year-old woman developed acute severe visual field defects and was operated on a macroprolactinoma. Since complete resection of the tumor was not possible, radiotherapy was performed and in addition to hormone replacement therapy, bromocriptine (up to 60 mg daily) was started without however complete normalization of PRL levels. Four years later PRL levels increased to 10(5) microU/ml despite continuation of dopamin agonist (mesulergin) treatment. As shown by ophthalmological examination and computer tomography there were no signs of regrowth of the pituitary tumor. At that time the patient complained of severe lumbar pain and myelography revealed a tumor mass in the spinal cord (L1-L2). Since the spinal tumor was not removable, laminectomy was performed. Histology and immunohistochemistry demonstrated a metastasis of the prolactinoma. Radiotherapy and bromocriptine in extreme doses (140 mg daily) together with an antiestrogen were not able to improve the neurological deficits (paraparesis) and to lower the PRL levels. This case of a metastasis of a prolactinoma after operation, radiotherapy, and dopamin agonist treatment stresses the importance of close surveillance of patients with prolactinomas without PRL normalization during dopamin agonist therapy and shows for the first time the possibility of ectopic PRL production due to an intradural spinal metastasis.

Adenoma↗

Circadian and pulsatile thyrotropin release in treated acromegalics.

We studied the 24-h TSH profiles of 16 treated male acromegalic patients (age range 26-68 yr) in clinical and biochemical remission. Eight had undergone transsphenoidal surgery, the others surgery and pituitary irradiation. Blood samples were taken at 20-min intervals; circadian rhythms were established by cosinor analysis, pulsatile release with the Cluster programme. All patients, except one irradiated subject, were euthyroid. TSH reserve was diminished preoperatively in 7 subjects and at the time of the profile study in 10 subjects, one of whom was biochemically hypothyroid. A significant circadian rhythm was present in 14 subjects and absent in the hypothyroid patient. The acrophase occurred at 2.46 +/- 0.51 h in nonirradiated patients and at 3.37 +/- 0.38 h in irradiated patients (NS). About 10 TSH pulses/24 h (range 6-13) were detected; there was no significant difference between irradiated and non-irradiated patients. With cross-correlation techniques synchronous release of TSH and PRL was demonstrated in 7 out of 8 nonirradiated patients in contrast to only 2 of the irradiated patients. This study demonstrates a qualitatively normal TSH secretion pattern for treated acromegalic patients, but the absolute TSH levels are clearly low compared with published data on normal subjects. The present findings can be explained by a diminished TSH cell mass; in addition radiation therapy causes a disturbance at the hypothalamic level, as indicated by the loss of synchronism between TSH and PRL release.

Acromegaly↗

[Prolactin producing hypophyseal carcinoma. Case report of an extremely rare metastatic tumor].

A 59-year-old male patient was transnasally operated on because of a pituitary adenoma with hypopituitarism. A second operation and X-ray therapy followed a half year later due to recurrent tumor. Both neoplasmas were classified as sparsely granulated prolactin cell adenomas. Immunohistochemical studies revealed strong immunoreactivity for prolactin and FSH in the tumor cells of both the pituitary adenoma and the recurrent tumor. Two years later the prolactin plasma levels were extremely elevated. A tumor in the liver was identified. Biopsy revealed a solid endocrine tumor containing prolactin by immunohistology. Due to structural and immunohistological similarities this tumor could be identified as a metastasis of the pituitary tumor. After 5 months of therapy the patient died from thrombembolism. Post-mortem studies confirmed the diagnosis of a metastasizing prolactin-secreting pituitary carcinoma. Only six similar cases have been reported in the literature. Our case report confirms the experience with 35 definite pituitary carcinomas reparted in the current literature: malignant pituitary tumors develop after pituitary surgery and can be identified not from the pituitary tumor, but only from its metastases.

Combined Modality Therapy↗

Craniopharyngiomas in children: Turkey experience.

OBJECTIVES: Craniopharyngiomas are the most frequently encountered suprasellar tumors in children. Although they have a benign histology, total resection without morbidity is very difficult. METHODS: We aimed to review the results of pediatric craniopharyngioma patients treated in eight institutions in Turkey. There were 51 boys and 36 girls, ranging in age from 20 months to 18 years (mean 10.2 years). The most frequent symptom was headache, followed by visual disturbances. Hydrocephalus was seen most frequently in tumors greater than 4 cm in size (P=0.002). Hydrocephalus was associated with the decreased gross total resection (P=0.043). The recurrence (28%) was significantly higher in patients with subtotal and partial tumor removal (P=0.010). Bad outcome was significantly associated with tumor dimension (P=0.039); the greater the tumor dimension, the worse the outcome. Outcome was significantly better in patients older than 10 years (P=0.032). Gender, tumor type and location, presence of hydrocephalus and calcification, histological type of craniopharyngioma, and surgical approach did not have a significant effect on the outcome. CONCLUSIONS: The treatment should be individualized and a multidisciplinary approach should be used. The goal of surgery should be gross total removal without mortality and with acceptable morbidity.

Adolescent↗

Radical resection of craniopharyngioma.

INTRODUCTION: The best management of craniopharyngioma in children remains a controversial topic among neurosurgeons. The two treatments for craniopharyngioma most commonly discussed in the literature are primary total resection and limited resection followed by radiotherapy. Without ignoring the challenging behavior of these tumors, we strongly believe that the first approach in a child with a craniopharyngioma is to attempt total removal. Trying to remove a craniopharyngioma that has been treated previously with other methods is, in our experience, much more dangerous because of adherences of the tumor to vascular and neural structures. MATERIAL AND METHODS: Between 1988 and 2004, we operated on 153 patients with craniapharyngioma (40% female and 60% male), whose ages at the time of surgery ranged from 15 days to 21 years (mean 10.5 years). Eighty-seven percent of the patients were found to have some visual disturbance and 42% endocrinological alterations. Fifty-four percent of the patients presented hydrocephalus, but only 18% had shunting. Gross total removal was attempted in all patients. Among the 153 patients, the tumor was prechiasmatic in 35 and retrochiasmatic in 112; in ten, these were considered giant forms, and eight had a posterior fossa extension. We performed 84 single and 69 combined approaches. RESULTS: We achieved total removal in 69% of our patients. None of our patients regarded as having undergone total tumor resection disclosed recurrence after a follow-up of 1-16 years. Radiation therapy was administered in children with subtotal removal. All children underwent total removal, but only 62% of those who underwent subtotal removal had good outcomes. After surgery, endocrinological status worsened in almost all patients, but visual status improved markedly. CONCLUSIONS: The treatment of choice in craniopharyngioma in childhood is total resection in order to avoid radiation therapy and recurrence. When total resection is not possible, subtotal resection plus radiation therapy is the alternative.

Adolescent↗

Childhood craniopharyngioma: Vancouver experience.

OBJECTIVE: To present our institution's experience in the management of childhood craniopharyngioma since 1982. METHODS: We retrospectively reviewed the records of all children diagnosed with craniopharyngioma at our children's hospital from its opening in 1982 through to 2003. One neuroradiologist systematically reviewed the neuroimaging. Kaplan-Meier curves were used to analyze the progression-free survival and the overall survival from the time of the first definitive intervention. CONCLUSIONS: Most children diagnosed with craniopharyngioma are long-term survivors. Survivors suffer from multiple deficits in the long term. A conservative surgical and radiotherapeutic approach and avoiding interventions that are known to cause severe morbidity may minimize these. The use of intracystic bleomycin is a strategy that allows the delay of more aggressive therapies in select patients.

Adolescent↗

Craniopharyngioma: a personal (Boston) experience.

BACKGROUND: The author reports his experience with 79 craniopharyngiomas operated since 1988. The review demonstrates that the biological behavior of these tumors is extremely variable, and that surgical management requires resourcefulness, judgement, and flexibility in the operating room. RESULTS: Tumors will recur after total resection (15% in this series) and after subtotal resection and radiation therapy (22%) and adjuvant treatments of all types, and no treatment guarantees a cure. CONCLUSION: The invasiveness of the tumor leads to difficult-to-treat long-term complications, particularly obesity and behavior disturbances. An extremely long-term follow-up of up to 20 years is necessary in many patients in order to determine the ultimate outcome of treatment.

Behavioral Symptoms↗

A history of the treatment of craniopharyngiomas.

RATIONALE: Nearly 100 years have passed since the first surgical attempt to remove a craniopharyngioma was undertaken, and the management of patients with these tumors continues to both challenge and frustrate those involved with their treatment. METHODS: By constructing a historical framework from past literature on the treatment of craniopharyngioma, the authors have attempted to document the early and important events in the treatment of these tumors in order to add a historical dimension to their current treatment and to engender a more comprehensive understanding of the modern treatment of craniopharyngioma. CONCLUSION: The application of radiotherapeutic techniques to the management of craniopharyngioma would begin to complement the role of surgery, but debate would soon emerge as to what constituted the most appropriate management for craniopharyngioma in children.

Combined Modality Therapy↗

Intracavitary therapeutic options in the management of cystic craniopharyngioma.

BACKGROUND: Craniopharyngioma remains an entity of controversial management due to its critical anatomical relationships and its well-known recurrence tendency. Total resection, although desirable, is not always accomplished, and it is associated with potentially permanent endocrinological and visual deficits. Consequently, this situation has led to the development of new management strategies seeking lesser morbidity. Because a high percentage of these lesions are cystic, bleomycin and radioactive-emitting sources have been postulated as new therapeutic options with promising results. DISCUSSION: The information known to date regarding these substances is summarized and we perform a retrospective review of the clinical trials conducted over the past 30 years with special emphasis on outcome, morbidity, and mortality. Two cases from our institution are presented as examples of multimodality management. CONCLUSION: Overall, these newer options stand out as valid alternatives in the controversial management of these challenging tumors.

Antibiotics, Antineoplastic↗

Prolactin secreting pituitary adenomas: analysis of 429 surgically treated patients, effect of adjuvant treatment modalities and review of the literature.

OBJECTIVE: We performed this retrospective analysis to determine the efficacy of surgery and radiotherapy over hormonal and volumetric control of prolactinomas, many of which had failed during dopa-agonist therapy. In the same analysis, the efficiency of topical bromocriptine application as a preliminary study was compared with standard treatment modalities. MATERIALS AND METHODS: Between 1982-1997, 429 prolactinoma patients who underwent surgery at Hacettepe University Neurosurgery Department and at Bayindir Medical Center were included in this study. All patients were classified according to Hardy's classification scheme and were further divided into 'invasive' and 'non-invasive' groups based on this radiological classification system. The mean follow-up time was 38.4 months. One hundred and thirty five patients had peroperative bromocriptine application into the sellar cavity and these, either receiving radiotherapy (RT) or not, were analysed separately from the other 294 patients. In the early post-operative period, 104 of these patients were given conventional radiotherapy with median dose of 4500 cGy. We focused on the effects of surgery and radiotherapy over volumetric and hormonal tumour control on the basis of invasion characteristics and the early results of topical bromocriptine application in macroprolactinoma patients; and compared our results with the literature. RESULTS: Statistical analysis revealed that radiotherapy was not effective over hormonal and volumetric tumour control for prolactinomas. We did not observe any correlation to dural invasion of the sellar floor, recurrence, and the disease-free survival time. Topical bromocriptine application seemed to improve the volumetric control in 135 selected macroprolactinoma patients but not hormonal response compared with the standard treatment modalities. CONCLUSION: Conventional radiotherapy is not as effective as expected for prolactinomas and should not be preferred considering its adverse effects. Tumoural infiltration of the sellar dura mater is not a prognostic criterion for recurrence expectation and, therefore, should not be a criterion for radiotherapy after surgery. After subtotal removal, postoperative dopa-agonist therapy should be considered even if the patient was intolerant or resistant to previous treatment since surgery seems to improve patients' drug tolerance and cooperation due probably to the lower dose requirement. The early results of topical bromocriptine application seem to improve volumetric tumour control but this should not be accepted as a judgement since we need to wait for later results and to expand the sample size for more reliable interpretation.

Bromocriptine↗

Results of surgery in 114 patients with prolactin-secreting pituitary adenomas.

The clinical features and prolactin levels of 114 patients, including five men, who had prolactin-secreting adenomas are presented. The rates of resolution of amenorrhea and galactorrhea following surgery were calculated. Fifteen women became pregnant following surgery. Therapeutic failure tended to occur in patients who had higher preoperative serum prolactin levels and those in whom total tumor resection was not achieved. Although clinical anomographic changes preceded elevation of prolactin values in two cases and, in one case, clinical indications and an elevated prolactin value preceded tomographic changes. The morbidity encountered with the procedure was minimal and there were no deaths.

Adenoma↗

Progressive late delayed postirradiation encephalopathy with Klüver-Bucy syndrome. Serial MRI and clinico-pathological studies.

The first pathologically documented case of progressive late delayed postirradiation encephalopathy in a 37-year-old man with Klüver-Bucy syndrome (KBS) is reported here. The pathological findings and clinical course of KBS with recurrent stroke-like episodes and partial epilepsy within a 7-year period following a 'safe dose' radiation therapy for pituitary tumor are presented. Serial magnetic resonance imaging shows, at different stages of the disease, a pontine infarct, enlarged temporal lobes with serpentine hyperintense signal at cortical gyri on T2-weighted and proton density MRI, and progressive brain calcification which appears hyperintense on T1-weighted images and hypointense on T2-weighted images.

Adenoma, Acidophil↗

Evaluation of the effect of radiotherapy for pituitary tumours on cognitive function and quality of life.

AIMS: Pituitary tumours are often treated with radiotherapy, which can cause cognitive impairment when given in high doses. It is assumed that current regimens do not cause damage, but this has not been established. The aim was to determine whether radiotherapy given to people with pituitary tumours was associated with cognitive impairment and reduced quality of life. MATERIAL AND METHODS: We retrospectively compared two outcome groups (patients with pituitary tumours who had undergone radiotherapy and surgery and patients with pituitary tumours who had surgery alone), and carried out standardised tests of cognitive function and quality of life. RESULTS: The data suggested that patients with pituitary tumours treated with surgery, with or without radiotherapy, had cognitive impairment compared with the normal population. Patients receiving radiotherapy performed significantly worse than those receiving only surgery on the Stroop test, a measure of executive function. They also scored significantly lower on the Physical Health composite of the SF36, although this difference was no longer significant when account was taken of baseline differences between the groups. There were no significant differences in other cognitive functions, mood, general well-being or the Mental Health Composite of the SF36. CONCLUSIONS: Patients treated for pituitary disease may have cognitive impairment. A decrease in cognitive function was found regardless of treatment type. The decrease seemed to be greater in the radiotherapy group and was mainly on executive function. This impairment of executive function could affect daily life. Further prospective studies are required to assess the effect of pituitary disease on cognitive function and the safety of radiotherapy.

Adult↗

Pituitary tumors and pregnancy.

This paper contains a review of the natural history of pituitary tumors in nonpregnant and pregnant patients. Data were drawn from previously published reports and from responses to a questionnaire and were analyzed by life-table techniques. Follow-up of 62 nonpregnant patients with untreated pituitary tumors with and without visual field changes revealed a median time to treatment of 15 1/2 years and similar, relatively constant hazard functions. In 91 pregnancies occurring in 73 women with previously untreated pituitary tumors, ovulation had occurred spontaneously in 9 per cent, headache occurred in 23 per cent, and visual disturbances in 25 per cent with 61 per cent remaining asymptomatic. In those patients who developed symptoms, median time to headache was 10 weeks and to visual disturbance, 14 weeks. The hazard functions were relatively constant and similar. The relative risk of developing symptoms is independent of whether or not the first or second pregnancy occurred in the presence of the pituitary tumor. Of the pregnant patients with previously untreated pituitary tumors, 30 per cent required surgery or radiation therapy. Median time to treatment was 19 weeks. None of the 69 pregnant women without pituitary therapy had permanent sequelae. Only four patients who underwent surgery or received radiation treatment developed permanent symptoms and none was serious. In 78 pregnancies occurring in 73 women with previously treated pituitary tumors, headache occurred in 4 per cent and visual disturbances in 5 per cent. Only one patient required therapy. Treatment during pregnancy results in significantly increased prematurity rates but unchanged abortion and perinatal mortality rates. Small pituitary tumors do not constitute a contraindication to either induction of ovulation or pregnancy.

Abortion, Spontaneous↗