phosphorus-radioisotopes and Pituitary-Neoplasms

Craniopharyngiomas are the most common benign histological tumours to involve the hypothalamo-pituitary region in childhood. Cystic craniopharyngiomas account for more than 90% of the tumours. The optimal treatment of cystic craniopharyngioma remains controversial. Radical resection is the treatment of choice in patients with favourable tumour localisation. When the tumour localisation is unfavourable, a gross-total or partial resection followed by radiotherapy is the main treatment option in adults. However, it presents a risk of morbidity, especially for children. Intracystic bleomycin has been utilised potentially to delay the use of radiotherapy or radical resection, to decrease morbidity. This review is the second update of a previously published Cochrane review.. To assess the benefits and harmful effects of intracystic bleomycin in children from birth to 18 years with cystic craniopharyngioma when compared to placebo (no treatment), surgical treatment (with or without adjuvant radiotherapy) or other intracystic treatments.. We searched the electronic databases CENTRAL (2016, Issue 1), MEDLINE/PubMed (from 1966 to February 2016) and EMBASE/Ovid (from 1980 to February 2016) with pre-specified terms. In addition, we searched the reference lists of relevant articles and reviews, conference proceedings (International Society for Paediatric Oncology 2005-2015) and ongoing trial databases (Register of the National Institute of Health and International Standard Randomised Controlled Trial Number (ISRCTN) register) in February 2016.. Randomised controlled trials (RCTs), quasi-randomised trials or controlled clinical trials (CCTs) comparing intracystic bleomycin and other treatments for cystic craniopharyngiomas in children (from birth to 18 years).. Two review authors independently performed the study selection, data extraction and 'Risk of bias' assessment. We used risk ratio (RR) for binary data and mean difference (MD) for continuous data. If one of the treatment groups experienced no events and there was only one study available for the outcome, we used the Fischer's exact test. We performed analysis according to the guidelines in the Cochrane Handbook for Systematic reviews of Interventions.. We could not identify any studies in which the only difference between the treatment groups was the use of intracystic bleomycin. We did identify a RCT comparing intracystic bleomycin with intracystic phosphorus(32) ((32)P) (seven children). In this update we identified no additional studies. The included study had a high risk of bias. Survival could not be evaluated. There was no clear evidence of a difference between the treatment groups in cyst reduction (MD -0.15, 95% confidence interval (CI) -0.69 to 0.39, P value = 0.59, very low quality of evidence), neurological status (Fisher's exact P value = 0.429, very low quality of evidence), third nerve paralysis (Fischer's exact P value = 1.00, very low quality of evidence), fever (RR 2.92, 95% CI 0.73 to 11.70, P value = 0.13, very low quality of evidence) or total adverse effects (RR 1.75, 95% CI 0.68 to 4.53, P value = 0.25, very low quality of evidence). There was a significant difference in favour of the (32)P group for the occurrence of headache and vomiting (Fischer's exact P value = 0.029, very low quality of evidence for both outcomes).. Since we identified no RCTs, quasi-randomised trials or CCTs of the treatment of cystic craniopharyngiomas in children in which only the use of intracystic bleomycin differed between the treatment groups, no definitive conclusions could be made about the effects of intracystic bleomycin in these patients. Only one low-power RCT comparing intracystic bleomycin with intracystic (32)P treatment was available, but no definitive conclusions can be made about the effectiveness of these agents in children with cystic craniopharyngiomas. Based on the currently available evidence, we are not able to give recommendations for the use of intracystic bleomycin in the treatment of cystic craniopharyngiomas in children. High-quality RCTs are needed.

Topics: Antibiotics, Antineoplastic; Bleomycin; Child; Craniopharyngioma; Cysts; Humans; Injections, Intralesional; Phosphorus Radioisotopes; Pituitary Neoplasms; Randomized Controlled Trials as Topic

Craniopharyngiomas are the commonest benign histological tumours to involve the hypothalamo-pituitary region in childhood. Cystic craniopharyngiomas comprise more than 90% of the tumours. The optimal treatment of cystic craniopharyngioma remains controversial. Radical resection is the treatment of choice in patients with favourable tumour localisation. When the tumour localisation is unfavourable, a gross-total or partial resection followed by radiotherapy is the main treatment option in adults. However, it presents a risk of morbidity, especially for children. Intracystic bleomycin has been utilised potentially to delay the use of radiotherapy or radical resection, to decrease morbidity. This review is an update of a previously published Cochrane review.. To assess the benefits and harmful effects of intracystic bleomycin in children from birth to 18 years with cystic craniopharyngioma when compared to placebo (no treatment), surgical treatment (with or without adjuvant radiotherapy) or some other intracyctic treatments.. We searched the electronic databases CENTRAL (2014, Issue 1), MEDLINE/PubMed (from 1966 to March 2014) and EMBASE/Ovid (from 1980 to March 2014) with pre-specified terms. In addition, we searched the reference lists of relevant articles and reviews, conference proceedings (International Society for Paediatric Oncology 2005-2013) and ongoing trial databases (Register of the National Institute of Health and International Standard Randomised Controlled Trial Number (ISRCTN) register) in May 2014.. Randomised controlled trials (RCTs), quasi-randomised trials or controlled clinical trials (CCTs) comparing intracystic bleomycin and other treatments for cystic craniopharyngiomas in children (from birth to 18 years).. Two review authors independently performed the data extraction and 'Risk of bias' assessment. We used risk ratio (RR) for binary data and mean difference (MD) for continuous data. We planned that if one of the treatment groups experienced no events and there was only one study available for the outcome, we would use the Fischer's exact test.. We could not identify any studies in which the only difference between the treatment groups was the use of intracystic bleomycin. We did identify a RCT comparing intracystic bleomycin with intracystic phosphorus(32) ((32)P) (n = 7 children). The trial had a high risk of bias. Survival could not be evaluated. There was no evidence of a significant difference between the treatment groups in cyst reduction (MD -0.15, 95% confidence interval (CI) -0.69 to 0.39, P value = 0.59), neurological status (Fisher's exact P value = 0.429), 3rd nerve paralysis (Fischer's exact P value = 1.00), fever (RR 2.92, 95% CI 0.73 to 11.70, P value = 0.13) or total adverse effects (RR 1.75, 95% CI 0.68 to 4.53, P value = 0.25). There was a significant difference in favour of the (32)P group for the occurrence of headache and vomiting (Fischer's exact P value = 0.029 for both outcomes).. Since we identified no RCTs, quasi-randomised trials or CCTs of the treatment of cystic craniopharyngiomas in children in which only the use of intracystic bleomycin differed between the treatment groups, no definitive conclusions could be made about the effects of intracystic bleomycin in these patients. Only one low-power RCT comparing intracystic bleomycin with intracystic (32)P treatment was available, but no definitive conclusions can be made about the effectiveness of these agents in children with cystic craniopharyngiomas. Based on the currently available evidence, we are not able to give recommendations for the use of intracystic bleomycin in the treatment of cystic craniopharyngiomas in children. High-quality RCTs are needed.

Topics: Antibiotics, Antineoplastic; Bleomycin; Child; Craniopharyngioma; Humans; Injections, Intralesional; Phosphorus Radioisotopes; Pituitary Neoplasms; Randomized Controlled Trials as Topic

Although microsurgery remains the first-line treatment, gross total resection of cystic craniopharyngeomas (CP) is associated with significant morbidity and mortality and the addition of external irradiation to subtotal resection proves to achieve similar tumor control. However, concern regarding long-term morbidity associated with external irradiation in children still remains. With this retrospective analysis, the authors emphasize intracavitary brachytherapy using phosphorus-32 (P-32) as a treatment option for children with cystic CP.. Between 1992 and 2009, 17 children (median age 15.4 years; range 7-18 years) with cystic CP underwent intracavitary brachytherapy using P-32. Eleven patients were treated for recurrent tumor cysts; 6 patients were treated primarily. MR imaging revealed solitary cysts in 7 patients; 10 patients had mixed solid-cystic lesions (median tumor volume 11.1 ml; range 0.5-78.9 ml). The median follow-up time was 61.9 months (range 16.9-196.6 months).. Local cyst control could be achieved in 14 patients (82 %). Three patients showed progression of the treated cystic formation (in-field progression) after a median time of 8.3 months (range 5.3-10.3 months), which led to subsequent interventions. The development of new, defined cysts and progression of solid tumor parts (out-of-field progression) occurred in 5 patients and led to additional interventions in 4 cases. There was neither surgery-related permanent morbidity nor mortality in this study. The overall progression-free survival was 75, 63, and 52 % after 1, 3, and 5 years, respectively.. Intracavitary brachytherapy using P-32 represents a safe and effective treatment option for children harboring cystic CP, even as primary treatment. However, P-32 does not clearly affect growth of solid tumor parts or the development of new cystic formations.

Topics: Adolescent; Brachytherapy; Central Nervous System Cysts; Child; Craniopharyngioma; Female; Humans; Male; Phosphorus Radioisotopes; Pituitary Neoplasms; Radiopharmaceuticals; Radiosurgery; Retrospective Studies; Treatment Outcome

The aim of the study was to evaluate the effect of phosphorus-32 colloid ([(32)P]) intracavitary irradiation on the treatment of patients with cystic craniopharyngiomas.. Twenty patients with predominantly cystic craniopharyngiomas were admitted from 1981 to 2006. Eleven patients had [(32)P] intracavitary irradiation by stereotactic injection or Ommaya cyst instillation as the primary treatment, and the remaining nine had the same internal irradiation as an adjuvant treatment after tumor resection. A calculated irradiation dose of 400 approximately 500 Gy per once was delivered to the cyst wall.. The patients were followed up ranging from 36 to 336 months; no operative morbidity or mortality was found from [(32)P] intracavitary irradiation. Fourteen patients (70%) had tumor progression and required further two to four times intracavitary irradiation. All 20 cases achieved tumor shrinkage or stabilization with effective outcome 3-6 months after the last [(32)P] therapy. For patients with cystic craniopharyngioma, [(32)P] administration by stereotactic injection or Ommaya cyst instillation is a safe and helpful option, which could improve the life quality, prolong the life span, and enhance the survival rate of cystic craniopharyngioma patients.

Topics: Brachytherapy; Child; Child, Preschool; Craniopharyngioma; Cysts; Female; Humans; Male; Phosphorus Radioisotopes; Pituitary Neoplasms; Stereotaxic Techniques; Suction; Tomography, Emission-Computed, Single-Photon

To investigate the antitumor effect of bleomycin on craniopharyngiomas.. A series of cystic craniopharyngiomas were randomly divided into three groups: (A) intracystic chemotherapy with bleomycin; (B) intracystic chemo-radiotherapy with bleomycin and (32)P; (C) intracystic radiotherapy with (32)P and 0.9% saline. The agents were injected into the cysts through stereotactically inserted silicone tubes. Follow-up was done for a minimum of 6 months. Outcome was based on a comparison of the volume of cysts before treatment and at follow-up. The index and lactate dehydrogenase (LD) of the cystic fluids, blood and cerebrospinal fluids and the endocrine function of these patients were determined before and after therapy.. 19 patients finished the whole therapeutic course: 5 from group A, 9 from group B and 5 from group C. Four tumors in group A were polycystic, and the drug was selectively injected into the largest cyst. At follow-up, the volumes of the cysts in groups A and B regressed from 92 to 0%, while the drug-free cysts enlarged. In group B, 6 cysts almost disappeared and another 3 regressed from 78 to 57%. In group C, one cyst progressed and the others shrank by different degrees, but none disappeared completely or nearly. All patients in groups A and B had fever of different degrees, which resolved spontaneously in 8-24 h. The complications in group B included hyponatremia in 1 patient, and both adephagia obesity and cerebral infarction in 2 patients (1 of whom died after 6 months). Apart from the oculomotor paralysis occurring in 1 patient, the remainder of group C had no other severe complications. Blood chemistry, liver, kidney, pituitary and endocrinal functions changed little during the course in all these 19 patients. LD and its isoenzymes from the cystic fluids, CSF and serum showed no marked change after bleomycin injection.. Bleomycin injected into cysts of craniopharyngiomas causes the tumor to shrink. When (32)P is added, the therapeutic effect seems better than treatment with either (32)P or bleomycin alone. Blood chemistry, liver, kidney and endocrine functions change little irrespective of the therapy applied. However, the combination of chemotherapy and radiotherapy may severely disturb both serum electrolytes and endocrine function. LD and its isoenzymes in the cystic fluids, CSF and serum may not change after bleomycin treatment.

Topics: Adolescent; Adult; Bleomycin; Chi-Square Distribution; Child; Child, Preschool; Craniopharyngioma; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neuronavigation; Phosphorus Radioisotopes; Pituitary Neoplasms; Radiosurgery

Interstitial brachytherapy based on phosphorus-32 (P-32) has an established role as a minimally invasive treatment modality for patients with cystic craniopharyngioma. However, reporting on long-term outcomes with toxicity profiles for large cohorts is lacking in the literature. The purpose of this study is therefore to evaluate the long-term visual, endocrinal, and neurocognitive functions in what is the largest patient series having received this treatment to date.. We retrospectively evaluated 90 patients with cystic craniopharyngiomas who were treated with stereotactic intracavitary brachytherapy between 1998 and 2010. Colloidal activity of injected radioisotope P-32 was based on an even distribution within the tumor. After treatment, patients were followed-up for a minimum of 5 years and over a mean of 121 months (60-192 months) to assess radiographic and clinical responses.. The 90 patients included in our study cohort underwent a total of 108 stereotactic surgical procedures for 129 craniopharyngioma-related cysts. Of the included tumors, 65 (72.2%) were associated with a single cyst, 15 (16.7%) were associated with 2 cysts, and 10 (11.1%) tumors had developed septations with 3 to 4 cysts. Stereotactic cyst puncture and content aspiration were used to drain a mean cyst fluid volume of 21.4 mL (1.0-55.0 mL). Each cyst was then instilled for interstitial brachytherapy with colloidal P-32 solution. Based on radiographic follow-up assessments, 56 cysts (43.4%) showed resolution and/or nonrecurrence, which was classified as a complete response to treatment; 47 cysts (36.4%) showed a partial response; and 5 cysts (3.9%) displayed a stable appearance. Treatment resulted in immediate and clinically significant vision improvement in 54 of 63 (86%) symptomatic patients, and this improvement was maintained. Progression-free survival rates at 5 and 10 years were 95.5% and 84.4%, respectively.. P-32-based interstitial brachytherapy can play an effective role in managing patients with cystic craniopharyngiomas. It can be considered a valid alternative to surgery in select patients with a favorable toxicity profile and long-term clinical outcomes.

Topics: Brachytherapy; Craniopharyngioma; Cysts; Humans; Phosphorus Radioisotopes; Pituitary Neoplasms; Retrospective Studies

To investigate the relationship of the expression of vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor-2 (VEGFR-2) and imaging features with the therapeutic efficacy of Phosphorus-32 colloid interstitial radiotherapy in recurrent craniopharyngioma.Thirty-two patients with recurrent craniopharyngioma underwent phosphorus-32 colloid interstitial radiotherapy. The tumor imaging features were classified into 4 types according to the thickness of the cyst wall and signals of the cyst contents as shown by computed tomography (CT) and magnetic resonance imaging (MRI) images. Protein expressions of VEGF and VEGFR-2 in craniopharyngioma tissues were evaluated with immunohistochemistry before radiotherapy. The tumor radiosensitivity was determined at 12 months after the interstitial radiotherapy.VEGF mainly expressed in the tumor cytoplasm, and VEGFR-2 expressed either in vascular endothelial cells or in tumor endothelial cells. VEGF/VEGFR-2 expressions varied significantly in cases sensitive or insensitive to the radiotherapy (VEGF: P = .028; VEGFR-2: P = .017). Tumor imaging features were associated with the therapeutic efficacy of interstitial radiotherapy (P = .000). VEGF expression had no association with the imaging features of tumors (P = .226), but VEGFR-2 expression was associated with the imaging features of tumors (P = .008).Our results confirmed the association among imaging features, VEGFR-2 expressions, and tumor radiosensitivity in craniopharyngiomas. Imaging features and VEGFR-2 expressions may add useful data to the radiosensitive assessment of craniopharyngiomas.

Topics: Adolescent; Adult; Aged; Brachytherapy; Child; Child, Preschool; Craniopharyngioma; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Recurrence, Local; Phosphorus Radioisotopes; Pituitary Neoplasms; Radiation Tolerance; Retrospective Studies; Tomography, X-Ray Computed; Treatment Outcome; Vascular Endothelial Growth Factor Receptor-2; Vascular Endothelial Growth Factors; Young Adult

OBJECT Radioactive phosphorus-32 (P32) has been used as brachytherapy for craniopharyngiomas with the hope of providing local control of enlarging tumor cysts. Brachytherapy has commonly been used as an adjunct to the standard treatment of surgery and external-beam radiation (EBR). Historically, multimodal treatment, including EBR, has shown tumor control rates as high as 70% at 10 years after treatment. However, EBR is associated with significant long-term risks, including visual deficits, endocrine dysfunction, and cognitive decline. Theoretically, brachytherapy may provide focused local radiation that controls or shrinks a symptomatic cyst without exposing the patient to the risks of EBR. For this study, the authors reviewed their experiences with craniopharyngioma patients treated with P32 brachytherapy as the primary treatment without EBR. The authors reviewed these patients' records to evaluate whether this strategy effectively controls tumor growth, thus avoiding the need for further surgery or EBR. METHODS The authors performed a retrospective review of pediatric patients treated for craniopharyngioma between 1997 and 2004. This was the time period during which the authors' institution had a relatively high use of P32 for treatment of cystic craniopharyngioma. All patients who had surgery and injection of P32 without EBR were identified. The patient records were analyzed for complications, cyst control, need for further surgery, and need for future EBR. RESULTS Thirty-eight patients were treated for craniopharyngioma during the study period. Nine patients (23.7%) were identified who had surgery (resection or biopsy) with P32 brachytherapy but without initial EBR. These 9 patients represented the study group. For 1 patient (11.1%), there was a complication with the brachytherapy procedure. Five patients (55.5%) required subsequent surgery. Seven patients (77.7%) required subsequent EBR for tumor growth. The mean time between the injection of P32 and subsequent treatment was 1.67 ± 1.50 years (mean ± SD). CONCLUSIONS In this small but focused population, P32 treatment provided limited local control for cyst growth. Brachytherapy alone did not reliably avert the need for subsequent surgery or EBR.

Topics: Adolescent; Brachytherapy; Child; Child, Preschool; Craniopharyngioma; Female; Humans; Male; Phosphorus Radioisotopes; Pituitary Neoplasms; Retrospective Studies; Treatment Outcome

The treatment for giant posterior fossa cystic craniopharyngiomas remains an important challenge in neurosurgery. The authors evaluated the effects of treating 20 patients with giant posterior fossa cystic craniopharyngiomas using phosphorus-32 (P-32) interstitial radiotherapy at their hospital.. The patients included 11 boys and 9 girls with an age range of 3 to 168 months. Before treatment, the tumor volumes ranged from 65 to 215 ml. The intracranial pressure was increased in 16 patients, and optic nerve damage had occurred in 18. The patients received P-32 interstitial radiotherapy following stereotactic cyst-fluid aspiration or drainage and were followed up for 7-138 months.. The treatment immediately relieved the intracranial hypertension symptoms in all patients. At the end of follow-up, imaging examinations revealed that the cystic tumors had disappeared, but some residual calcification remained in 12 patients, and had decreased by more than 75% of the initial volume in 8 patients. The damaged optic nerve recovered in 3 cases, improved in 12 cases, remained unchanged in 1 case, and was aggravated in 2 cases. No other severe complications related to surgery or interstitial radiation occurred. During the follow-up period, 7 new cysts appeared in 5 patients who had received additional interstitial radiotherapies with a dose of P-32 that was calculated using the same formula as for the initial treatment. The new tumors then disappeared in 2 patients, significantly shrank in 2 patients, and progressed in 1 patient.. For treating giant posterior fossa cystic craniopharyngiomas, P-32 interstitial radiation after stereotactic cyst-fluid aspiration or drainage can achieve a high tumor control rate and has relatively satisfactory clinical effects and quality of life outcomes with few complications.

Topics: Adolescent; Brachytherapy; Child; Child, Preschool; Craniopharyngioma; Cysts; Drainage; Female; Humans; Infant; Magnetic Resonance Imaging; Male; Phosphorus Radioisotopes; Pituitary Neoplasms; Quality of Life; Stereotaxic Techniques; Treatment Outcome; Tumor Burden

To examine control rates for predominantly cystic craniopharyngiomas treated with intracavitary phosphorus-32 (P-32).. 22 patients with predominantly cystic craniopharyngiomas were treated at Indiana University between October 1997 and December 2006. Nineteen patients with follow-up of at least 6 months were evaluated. The median patient age was 11 years, median cyst volume was 9 ml, a median dose of 300 Gy was prescribed to the cyst wall, and median follow-up was 62 months.. Overall cyst control rate after the initial P-32 treatment was 67%. Complete tumor control after P-32 was 42%. Kaplan-Meier 1-, 3-, and 5-year initial freedom-from-progression rates were 68%, 49%, and 31%, respectively. Following salvage therapy, the Kaplan-Meier 1-, 3-, and 5-year ultimate freedom-from-progression rates were 95%, 95%, and 86%, respectively. All patients were alive at the last follow-up. Visual function was stable or improved in 81% when compared prior to P-32 therapy. Pituitary function remained stable in 74% of patients following P-32 therapy.. Intracystic P-32 can be an effective and tolerable treatment for controlling cystic components of craniopharyngiomas as a primary treatment or after prior therapies, but frequently allows for progression of solid tumor components. Disease progression in the form of solid tumor progression, re-accumulation of cystic fluid, or development of new cysts may require further radiotherapy or surgical intervention for optimal long-term disease control.

Topics: Adolescent; Adult; Brachytherapy; Child; Child, Preschool; Craniopharyngioma; Disease Progression; Female; Humans; Male; Middle Aged; Phosphorus Radioisotopes; Pituitary Neoplasms

In radiation treatments of some types of brain tumors, such as craniopharyngiomas, selection of an appropriate radionuclide is critical. The aim of this work was to calculate distributions of dose rates from (32)P and (186)Re in radiocolloids injected into craniopharyngioma cysts. The calculations were performed with the MCNP4C radiation transport code. Analytical calculations based on the Loevinger formula were also performed for (32)P with the MATLAB software. The results of the two techniques for identical models were compared. The effects of the cyst wall type and of the density of the cyst inner fluid were investigated. The (32)P activities required for providing 200, 250, and 300 Gy to cysts of different sizes were calculated.

Topics: Colloids; Computer Simulation; Craniopharyngioma; Cysts; Humans; Monte Carlo Method; Phosphorus Radioisotopes; Pituitary Neoplasms; Radiation Dosage; Radioisotopes; Rhenium

The neurovascular and anatomic relationships surrounding craniopharyngiomas, and their tending to recur despite any method of primary treatment, has characterized this tumor as an exigent and frustrating clinical entity. Various strategies have been developed to deal with recurrences which include radical re-resection, stereotactic or localized radiotherapy, cyst fenestration, marsupialization or stent placement, and intracavitary therapies such as bleomycin or radionucleotides.. We present a case where the patient had previously experienced a transsphenoidal resection followed by a pterional, microsurgical resection of her craniopharyngioma at an outside hospital. The second recurrence was cystic, and confined to the sella. We elected to proceed with a minimally invasive, transnasal endoscopic approach for the instillation of phosphorus 32 radionucleotide into the cyst. There were no complications, and the patient was discharged home on postoperative day one. At six months, there was no progression of the cyst.. While intracystic adionucleotide therapies have been utilized for primary and secondary treatment of craniopharyngioma, to our knowledge, this is the first report of the delivery of this therapy by an endoscopic transsphenoidal route.

Topics: Adult; Combined Modality Therapy; Craniopharyngioma; Endoscopy; Female; Humans; Minimally Invasive Surgical Procedures; Neoplasm Recurrence, Local; Neurosurgical Procedures; Phosphorus Radioisotopes; Pituitary Neoplasms; Radiotherapy; Treatment Outcome

Cystic craniopharyngiomas are the most frequent intracranial neoplasm of nonglial origin in children. Follow-up data were analyzed to assess the value of intracavitary irradiation with stereotactically applied 32P radioisotopes for the treatment of patients with craniopharyngioma cysts admitted to Shohada Tajrish Hospital, Tehran, Iran, between 1998 and 2005.. Patients with predominantly cystic craniopharyngiomas, who underwent stereotactic intracavitary irradiation, were followed for tumor response and complications. Beta-emitting 32P isotopes were injected into cysts using a computed tomography-guided and computer-assisted three-dimensional stereotactic treatment planning and application system. The cumulative dose to the inner surface of the cyst wall was 250 Gy.. Twenty-two (12 females and 10 males) patients with a mean+/-SD age of 14.0+/-6.6 (range: six to 35) years were studied. The tumor response rate gained with 32P-labeled chromic phosphate was 73% (16 of 22 cysts). The mean+/-SD survival after intracavitary irradiation was 25.4+/-6.8 (95% CI: 12.0 - 38.7) months.. Intracavitary irradiation using 32P is highly effective in the treatment of cystic craniopharyngiomas. In patients with solitary cyst treated exclusively with this method, it has been the only necessary therapy over a long period. It seems reasonable to recommend intracavitary irradiation as the initial treatment for selected patients and as palliative therapy in those with recurrence.

Topics: Adolescent; Adult; Brachytherapy; Child; Craniopharyngioma; Cysts; Female; Humans; Male; Phosphorus Radioisotopes; Pituitary Neoplasms; Stereotaxic Techniques; Treatment Outcome

The authors report the results of surgery alone or in combination with radiotherapy in the management of craniopharyngiomas in children.. The authors retrospectively reviewed the outcomes in 31 patients treated for craniopharyngiomas at the Department of Radiation Oncology at Washington University in St. Louis and the St. Louis Children's Hospital. The median age at diagnosis was 8.1 years (range 1.1-21 years). Fourteen patients underwent gross-total resection (GTR) with observation, and 6 patients underwent subtotal resection (STR) with observation. Ten patients underwent STR or cyst aspiration followed by external-beam radiotherapy, and 1 patient underwent cyst aspiration followed by intracystic 32P installation.. The median follow-up for all surviving patients was 78.2 months. Overall survival and local control rates at 10 years were 96 and 58%, respectively. One patient died of the disease, and 12 patients had subsequent recurrences. Of those with recurrences, 6 patients had undergone initial STR with observation and 6 had been treated with GTR and observation. The median time to progression was 17.9 months in the patients who underwent limited resection, and 55 months for those who underwent GTR. There were no recurrences in the patients who received radiotherapy at the time of initial diagnosis.. Radiotherapy delivered as part of the initial management of craniopharyngiomas in children or at the time of recurrence provides effective local control.

Topics: Adolescent; Adult; Brachytherapy; Child; Child, Preschool; Craniopharyngioma; Disease Progression; Disease-Free Survival; Female; Follow-Up Studies; Humans; Infant; Longitudinal Studies; Male; Neoplasm Recurrence, Local; Phosphorus Radioisotopes; Pituitary Neoplasms; Postoperative Complications; Radiopharmaceuticals; Radiotherapy, Adjuvant; Radiotherapy, Conformal; Radiotherapy, High-Energy; Retrospective Studies; Survival Rate; Treatment Outcome

To evaluate the dose distribution outside of a cyst instilled with phosphorous-32 (P-32, an electron emitter with a short effective range of 2-8 mm and average energy of 0.69 MeV, used to treat cystic craniopharyngioma) as a function of cyst size with and without plating (migration and adhesion of P-32 to the cyst surface).. A cystic craniopharyngioma treated with instillation of P-32 was approximated by a sphere of uniformly distributed and plated chromic P-32 colloid. The percent depth dose was calculated along a radial position vector exterior to the sphere with a three-dimensional convolution integral and a dose point kernel.. The percent depth dose variation of surface or volume source external to a family of spheres was plotted. Complex cyst geometry is amenable to evaluation by approximation with simple spheres. Error estimates are calculated for the dose outside of truncated sphere segments. Plating might occur and raise the dose outside the cyst by more than a factor of 5.0. This has the potential to cause damage to adjacent tissues, including the optic chiasm.. Clinicians are faced with a number of treatment options for cystic craniopharyngioma, including intracystic instillation of colloid P-32. Unfortunately, plating might occur and potentially damage adjacent normal tissues. It is recommended that the propensity for a craniopharyngioma to plate be evaluated before full treatment, especially after previous treatment.

Topics: Algorithms; Craniopharyngioma; Cysts; Humans; Phosphorus Radioisotopes; Pituitary Neoplasms; Radiation Dosage; Radiation Injuries; Radiometry

The efficacy of stereotactic intracavitary irradiation with phosphorus-32 ((32)P) for patients with cystic craniopharyngiomas was assessed on the basis of patient survival, tumor control, and visual and endocrinological function before and after treatment. Limited data are available regarding long-term outcomes.. Forty-nine patients were treated with stereotactic (32)P intracavitary irradiation. Of these, 25 had had no prior treatment as the primary treatment, and 24 were treated for residual or recurrent tumor cysts. At the time of (32)P intracavitary irradiation, 34 of the patients were adults, and 15 were children younger than 16 years of age. The mean cyst volume was 13 ml. The radiation dose varied from 189 to 250 Gy to the cyst wall during five half-lives of the isotope (mean, 224 Gy). The mean follow-up periods were 7 years after diagnosis and 4 years after (32)P treatment.. The actuarial survival rates were 90% at 5 years after the diagnosis and 80% at 10 years. The actuarial tumor cyst control rates were 76% at 5 years and 70% at 10 years after the diagnosis. After treatment, 9 (23%) of 40 patients who underwent preoperative and postoperative visual testing were found to have delayed worsening in visual function, 6 as a result of tumor progression and 3 attributed to irradiation. Nineteen patients (48%) had improved visual function. Of 17 patients who had normal preoperative pituitary function or stalk effect, 12 (71%) had preserved and 5 (29%) had worsened visual function. No complications other than visual or endocrinological deterioration occurred in these patients.. For patients with cystic craniopharyngiomas, (32)P intracavitary irradiation proved effective, with a low risk of complications, for the control of tumor cysts but not of solid tumor components.

Topics: Actuarial Analysis; Adolescent; Adult; Aged; Brachytherapy; Child; Child, Preschool; Combined Modality Therapy; Craniopharyngioma; Cysts; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Phosphorus Radioisotopes; Pituitary Neoplasms; Radiotherapy, Adjuvant; Stereotaxic Techniques; Survival Rate

Intraoperative magnetic resonance imaging has been applied to a number of neurosurgical disease processes since the late 1990's. The ability to visualize the operative site in near-real time has added a significant degree of safety to the treatment of lesions such as a cystic craniopharyngioma which can be located in regions of the brain where an untoward consequence can result in significant neurological morbidity. Previous surgical techniques, although often successful, did not allow the neurosurgeon to directly visualize whether the goals of surgery had been met or whether there was an inadvertent complication associated with the surgical approach until after the event had occurred. The safe and accurate instillation of radioactive phosphorus into this cystic tumor resulted in clinical improvement and the maintenance of normal pituitary function for this patient. The extreme accuracy and safety of this surgical technique is demonstrated by the imaging examples provided.

Topics: Craniopharyngioma; Cysts; Humans; Intraoperative Care; Magnetic Resonance Imaging; Male; Optic Chiasm; Phosphorus Radioisotopes; Pituitary Diseases; Pituitary Neoplasms; Suction

The dosimetry for radiocolloid therapy of cystic craniopharyngiomas is investigated. Analytical calculations based on the Loevinger and the Berger formulas for electrons and photons, respectively, are compared with Monte Carlo simulations. The role of the material of which the colloid introduced inside the craniopharyngioma is made of as well as that forming the cyst wall is analyzed. It is found that the analytical approaches provide a very good description of the simulated data in the conditions where they can be applied (i.e., in the case of a uniform and infinite homogeneous medium). However, the consideration of the different materials and interfaces produces a strong reduction of the dose delivered to the cyst wall in relation to that predicted by the Loevinger and the Berger formulas.

Topics: Beta Particles; Brain Neoplasms; Cell Wall; Central Nervous System Cysts; Colloids; Computer Simulation; Craniopharyngioma; Humans; Models, Biological; Models, Statistical; Monte Carlo Method; Phosphorus Radioisotopes; Pituitary Neoplasms; Radioisotopes; Radiometry; Radiopharmaceuticals; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Relative Biological Effectiveness; Reproducibility of Results; Rhenium; Sensitivity and Specificity

The management of craniopharyngiomas has historically been controversial in terms of the extent of initial surgical resection and the use of additional treatments. Various options include radical excision versus a more conservative surgical approach followed by external beam radiation; most recently, intracystic 32P radiation has been used in selected patients.. We reviewed our experience with 25 patients with craniopharyngiomas treated between 1984 and 1999 to assess the effectiveness of external beam radiation and intracystic 32P radiation therapy in preventing progression and recurrence of local disease.. All patients underwent surgery as a component of initial therapy for their histologically-proven craniopharyngiomas. Fifteen patients additionally received external beam radiation. Forty-five percent of patients who underwent incomplete resections followed by external beam radiation required additional therapy. In contrast, 80% of patients who had incomplete resections without post-operative external beam radiation required further treatment. Seven patients had intracystic 32P colloid injections. Neither of the two patients receiving 32P intracystic radiation as part of their initial therapy needed further treatment. Only one of the five patients receiving 32P intracavitary radiation for disease progression following initial therapy required further intervention. Of the remaining four patients, three enjoyed responses to treatment and one had stable disease.. Our observations support the use of external beam radiation for prevention of tumor progression in adults unable to receive a complete surgical resection. Our results additionally suggest that intracystic 32P radiation results in control of cystic components of craniopharyngiomas in the majority of cases.

Topics: Adolescent; Child; Combined Modality Therapy; Craniopharyngioma; Databases, Factual; Female; Humans; Male; Middle Aged; Phosphorus Radioisotopes; Pituitary Neoplasms; Radiotherapy; Treatment Outcome

Intracavitary treatment of solitary cystic craniopharyngiomas with (32)P is an emerging treatment option, especially for pediatric patients. We have treated two patients with solitary cystic craniopharyngiomas using intraoperative MRI (iMRI)-guided catheter placement.. The optical tracking system of the General Electric Signa SP iMRI system was utilized for preoperative planning and intraoperative catheter tracking during insertion. Intraoperative volumetric imaging was then used to confirm final catheter position. Patients were brought back to the iMRI suite approximately 8 weeks later and diluted gadolinium was injected with further MRI to confirm the absence of communication between the cyst lumen and surrounding CSF spaces and for volumetric analysis.. Intraoperative imaging illustrated deformation and changes in the cyst wall during catheter placement and cyst aspiration and confirmed final catheter placement. Images acquired 8 weeks following catheter placement prior to the instillation of (32)P showed decreases in cyst volume of 40 and 85%.. iMRI-guided catheter placement for cystic craniopharyngiomas helps to assure successful catheter placement. Significant decreases in cyst volume occur in the interval between catheter placement and (32)P administration and must be accounted for to prevent overdosing of the radioisotope.

Topics: Adolescent; Brachytherapy; Catheters, Indwelling; Child, Preschool; Combined Modality Therapy; Craniopharyngioma; Female; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Phosphorus Radioisotopes; Pituitary Neoplasms; Radiotherapy, Adjuvant; Stereotaxic Techniques; Suction; Surgery, Computer-Assisted

To evaluate the effectiveness of the combined treatment of stereotactic intracavitary irradiation and Gamma Knife surgery on craniopharyngiomas.. Combined treatment with stereotactic instillation of radioisotopes and Gamma Knife surgery was performed on 46 patients with craniopharyngioma between October 1996 and June 1999. There were 13 solid tumors and 33 mixed solid and cystic tumors.. 38 patients (10 solid and 28 mixed) were followed up from 6 months to two years. The tumor control rate was 90% in solid tumors, 85.7% in mixed tumors, 92.1% in the solid segment and 89.5% in total.. Gamma Knife surgery plays an important role in the treatment of the solid component of craniopharyngiomas and the combination of treatment is a simple, safe and effective method for treatment of craniopharyngiomas, especially for the recurrent mixed solid and cystic tumors.

Topics: Adolescent; Adult; Brachytherapy; Child; Child, Preschool; Combined Modality Therapy; Craniopharyngioma; Craniotomy; Cysts; Female; Follow-Up Studies; Humans; Injections, Intralesional; Male; Microsurgery; Middle Aged; Phosphorus Radioisotopes; Pituitary Neoplasms; Radiopharmaceuticals; Radiosurgery; Radiotherapy, Adjuvant; Treatment Outcome; Vision Disorders

Craniopharyngiomas are benign cystic para-hypophyseal tumors often associated with hypopituitarism and visual-field abnormalities. Their therapy by surgery and external beam radiotherapy is imperfect. The intracavitary instillation of beta-emitting colloid radiopharmaceuticals into the cysts permits the delivery of far higher radiation doses to the cyst lining than is possible by external beam radiotherapy. This technique permits destruction of the lining epithelium with resultant elimination of cyst fluid formation and cyst shrinkage in up to 80% of cases.

Topics: Brachytherapy; Colloids; Craniopharyngioma; Humans; Phosphorus Radioisotopes; Pituitary Neoplasms; Radiotherapy Dosage

Craniopharyngiomas is a kind of intractable tumor in neurosurgery. Since the radical excision is very difficult and occasionally hazardous because of its deep location and close neighbouring to critical cerebral structures, it is necessary to look for a simple and effective method.. Stereotactic intratumour irradiation with instillation of nuclide colloid was performed in 220 patients with craniopharyngiomas (altogether 265 times), of whom, 130 were male and 90 female. Their ages ranged from 5 to 69 years. The syndromes of optic path's impairment were present in all of the patients. CT or MRI scan showed cystic tumour in 125 patients, solid and cystic in 80 and solid in 15. No severe complications and death were related to the operation.. 150 patients were followed up for 2 months to 7 years (average 3.5 years). Tumours disappeared in 92 patients (61.4%), decreased dramatically in 20 (13.4%), decreased less than 50% in 19 (12.6%), and increased in 15 (10%); and there were 4 deaths (2.6%).. Stereotactic intratumour irradiation with instillation of nuclide colloid is effective in the patients with craniopharyngiomas. Beta-emitting isotopes (P-32 and Y-90) are the preferred internal radiation source because of their limited penetration of the energy released and the greater ease of handling. A calculated dose of 20 000 rads to the cyst wall is recommended.

Topics: Adolescent; Adult; Aged; Brachytherapy; Child; Child, Preschool; Craniopharyngioma; Female; Follow-Up Studies; Humans; Male; Middle Aged; Phosphorus Radioisotopes; Pituitary Neoplasms; Stereotaxic Techniques; Yttrium Radioisotopes

Craniopharyngioma, often with cystic diliatation, is difficult to resect radically. Fifty patients with huge craniopharyngioma (diameter of tumor was over 5 cm) treated with intratumoral irradiation of radioactive isotopes (32P and 90Y) through CT-guided Leksell stereotactic system are reported. The patients were 2 to 69 years of age with the disease of 1- to 12-year duration. Of the 50 patients, 21 had recurrent tumor after craniotomy, 29 without surgery operation before. All tumors were confirmed pathologically. The major clinical symptoms were as follows: visual field defect, headache, vomiting, diabetes insipidus, hemiplegia and growth retardation in juvenile cases. There was no death or serious complications following the treatment procedure. Partial response (> 50% reduction of tumor size on CT scanning with improvement of symptoms and signs) rate of the treatment was 82.0% at one month and 62.0% at 2 to 7 years after treatment.

Topics: Adolescent; Adult; Aged; Brachytherapy; Child; Child, Preschool; Craniopharyngioma; Female; Follow-Up Studies; Humans; Male; Middle Aged; Phosphorus Radioisotopes; Pituitary Irradiation; Pituitary Neoplasms; Stereotaxic Techniques; Yttrium Radioisotopes

The management of patients with craniopharyngiomas is often multifaceted and multidisciplinary. The purpose of this study was to examine the results of phosphorus-32 intracavitary irradiation in the treatment of patients with predominately cystic craniopharyngiomas.. Thirty patients with cystic craniopharyngiomas underwent phosphorus-32 intracavitary irradiation at our center between 1981 and 1993. The median patient age was 26 years (range, 3-70 years). Thirteen patients had intracavitary irradiation as the primary surgery for their cystic tumors, whereas 17 patients had adjuvant intracavitary irradiation after microsurgical resection, fractionated radiotherapy, or both. Patients in the adjuvant treatment group were more likely to have preoperative anterior pituitary insufficiency (p = 0.008 Fischer exact test) and diabetes insipidus (p = 0.003 Fischer exact test). The median follow-up was 37 months (mean, 46 months, range, 7-116 months).. Phosphorus-32 intracavitary irradiation resulted in cyst regression in 28 of 32 treated cysts (88%). Ten patients (33%) have had tumor progression requiring further surgical intervention. Three patients (10%) died: two of tumor progression, and one of unrelated causes. Visual acuity and fields improved or remained stable in 63% of the patients. Fifteen patients had residual anterior pituitary function before intracavitary irradiation and 10 (67%) retained their preoperative endocrine status. New-onset diabetes insipidus occurred in 3 of 17 patients (18%) who had normal posterior pituitary function preoperatively. Fourteen of 20 adult patients (70%) continued to perform at their preoperative functional level; 3 of 5 pediatric patients who were age appropriate at the time of treatment continued to develop normally. No difference was noted between primary and adjuvant treatment patients with respect to cyst control, visual deterioration, or endocrine preservation after phosphorus-32 intracavitary irradiation.. The goals of craniopharyngioma management should be tumor control with preservation of visual, endocrine, and cognitive function. Phosphorus-32 intracavitary irradiation is an important option that enhances the likelihood of achieving these goals in patients with primarily cystic craniopharyngiomas.

Topics: Adolescent; Adult; Aged; Brachytherapy; Child; Child, Preschool; Craniopharyngioma; Female; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Male; Microsurgery; Middle Aged; Phosphorus Radioisotopes; Pituitary Gland; Pituitary Neoplasms; Radiotherapy, Adjuvant; Visual Acuity; Visual Fields

The properties of the calcium/calmodulin-dependent protein phosphatase calcineurin and its potential role in stimulus-secretion coupling were examined in AtT20 mouse pituitary corticotrope tumor cells. Protein phosphatase activity was assayed by measuring the liberation of 32P from 32P-casein, adrenocorticotropin secretion was measured by radioimmunoassay. About 60% of the total phosphatase activity was inhibited by 500 nM okadaic acid, suggesting the presence of protein phosphatases 1 and/or 2A. A further 25-30% reduction of phosphatase activity was achieved by chelating free calcium. Addition of the EF-hand protein blocker trifluoperazine or a calcineurin autoinhibitory peptide fragment markedly reduced okadaic acid resistant and calcium-dependent protein phosphatase activity indicating that calcium-dependent 32P release is largely due to calcineurin (protein phosphatase 2B). The remaining 10-15% of total activity was Mg2+ dependent and blocked by NaF, hence possibly due to protein phosphatase 2C. Calcineurin activity was inhibited by the immunosuppressants FK506 and cyclosporin A, either when added to the cell lysates or after preincubation of intact cells with the drugs for 30 min at 37 degrees C. When added to lysates, cyclosporin A inhibited calcium/calmodulin-dependent phosphatase more effectively than FK506. However, when tested on intact cells, FK506 proved 10-fold more potent than cyclosporin A. Both immunosuppressive agents enhanced the calcium-dependent release of adrenocorticotropic hormone into the medium, once more, FK506 was 10-fold more potent than cyclosporin A. Taken together, these data suggest that calcineurin is an inhibitory element in the signal transduction pathway controlling exocytotic secretion in pituitary cells that express voltage-operated calcium channels. This is in direct contrast with leukocytes where voltage-operated calcium channels are not found, and calcineurin is an important element for agonist-induced activation.

Topics: Adrenocorticotropic Hormone; Animals; Calcineurin; Calcium; Calmodulin-Binding Proteins; Cyclosporine; Ethers, Cyclic; Kinetics; Magnesium; Mice; Okadaic Acid; Phosphoprotein Phosphatases; Phosphorus Radioisotopes; Pituitary Neoplasms; Tacrolimus; Trifluoperazine; Tumor Cells, Cultured

Six patients suffering from cystic hypophysoma and one from craniopharyngioma treated with intracavitary radiation by colloidal 32P transnasophenoid injection were studied. After injection, the headache was eliminated and vision improved in all cases, visual field enlarged in 4, and sexuality improved in 5 male cases. All the patients recovered their normal daily life and work in 2-12 year's follow-up period. The conclusion is that the above mentioned therapy is simple, safe and effective.

Topics: Adult; Brachytherapy; Contraindications; Craniopharyngioma; Female; Follow-Up Studies; Humans; Male; Middle Aged; Phosphorus Radioisotopes; Pituitary Neoplasms

DNA from human brain tumor samples was analysed by the 32P-postlabeling technique for the presence of aromatic DNA adducts. Thirteen out of 16 samples showed low levels of adducts at 0.14-3.53 adducts per 10(9) nucleotides. Inter-individual variations in the patterns of these aromatic adducts were observed. On the other hand, none of 5 brain samples from epilepsy patients revealed any evidence of such adducts. The data demonstrated the presence of low level, large molecule aromatic DNA adducts in malignant brain tissues and these adducts may either result from environmental exposure to an undetermined genotoxic agent or from the aging process.

Topics: Adenoma; Adult; Aged; Brain Chemistry; Brain Neoplasms; Carcinogens; Carcinoma, Squamous Cell; Chromatography, Thin Layer; Cytochrome P-450 Enzyme System; DNA Damage; DNA, Neoplasm; Epilepsy; Female; Glioma; Humans; Male; Meningioma; Middle Aged; Neurilemmoma; Phosphorus Radioisotopes; Pituitary Neoplasms; Polycyclic Compounds

The authors report on 40 brain tumor patients treated with CT-guided stereotactic injection of 198Au and 32P. Among the 40 cases were astrocytoma in 23 cases, craniopharyngioma in 9, meningioma in 4, pituitary adenoma in 2, and pinealoma and metastatic carcinoma each in 1 case. The tumors were all located in deep or important areas of the brain which were difficult to deal with by conventional operation. 62 injections of colloidal isotopes were performed, and all were successful. No major adverse effects or complications occurred on follow-up of 6-12 months, 28 patients were improved in their clinical symptoms, and CT scanning showed that the tumor sizes were diminished. The effective rate is 70%.

Topics: Adenoma; Adult; Astrocytoma; Brain Neoplasms; Craniopharyngioma; Female; Gold Radioisotopes; Humans; Male; Meningeal Neoplasms; Meningioma; Phosphorus Radioisotopes; Pinealoma; Pituitary Neoplasms; Radiosurgery; Stereotaxic Techniques; Tomography, X-Ray Computed

From Jan. 1988 to June 1990, 32 patients with huge cystic craniopharyngiomas were treated by CT-guided stereotactic injection of phosphorus-32. Among them, 14 were male and 18 female. Their ranged 3 to 56 years (average 20 years). The history of illness varied from 1 to 8 years (average 2.8 years). All patients were confirmed pathologically, eleven of them had recurrent tumor after craniotomy. The volume of cystic tumor varied from 14 to 126ml (average 32ml). 1.2-5.6mCi (average 2.3mCi) of 32P were injected in each time. 65 injections were successfully performed. There were neither deaths nor serious complications. Follow-up time ranged from 12 to 24 months. The clinical symptoms of these patients were improved in 27 patients and volumes of the tumors were reduced on CT scans. The effective rate was 84.4%. We conclude that this technique is simple, efficient and safe for the treatment of huge cystic craniopharyngiomas.

Topics: Adolescent; Adult; Brachytherapy; Child; Child, Preschool; Craniopharyngioma; Female; Humans; Injections, Intralesional; Male; Middle Aged; Phosphorus Radioisotopes; Pituitary Neoplasms; Stereotaxic Techniques; Tomography, X-Ray Computed

CMP is known to activate phosphatidylinositol (PtdIns)/inositol (Ins) base exchange and has been reported to activate reversal of PtdIns synthase also. Because it is possible that PtdIns synthase acting in the reverse direction, followed by re-incorporation of ambient Ins, could be responsible for base-exchange activity, we characterized these processes in rat pituitary GH3 cells. In permeabilized GH3 cells prelabelled with [3H]Ins and incubated in buffer with LiCl but without added Ins, CMP stimulated rapid accumulation of [3H]Ins and decreases in [3H]PtdIns; the Km for CMP was 1.7 mM. CDP and CTP were less effective, whereas 2'-CMP, 3'-CMP, other nucleoside monophosphates and cytidine did not influence this process. In permeabilized cells prelabelled to isotopic equilibrium with [3H]Ins and [32P]Pi, CMP stimulated decreases in both the 32P and 3H labelling of PtdIns, but did not increase that of [32P]phosphatidic acid. These findings demonstrate that in the absence of added Ins the effect of CMP is not via activation of base exchange nor via a phospholipase D, but by reversal of PtdIns synthase. In permeabilized cells prelabelled with [3H]Ins and [32P]Pi, unlabelled Ins inhibited loss of 32P labelling of PtdIns caused by CMP while markedly stimulating loss of 3H labelling of PtdIns and release of [3H]Ins. These data demonstrate that Ins inhibits reversal of PtdIns synthase, but stimulates base exchange. We conclude that in GH3 cells reversal of PtdIns synthase and PtdIns/Ins base exchange are both stimulated by CMP, but are distinct processes.

Topics: Animals; CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase; Cell Line; Cytidine; Cytidine Diphosphate; Cytidine Monophosphate; Cytidine Triphosphate; Inositol; Kinetics; Magnesium; Membrane Proteins; Phosphorus Radioisotopes; Phosphotransferases; Pituitary Neoplasms; Rats; Transferases (Other Substituted Phosphate Groups); Tritium

Seven patients with cystic craniopharyngiomas were treated with stereotactic instillation of radioactive phosphorus-32 (32P). Five patients had been previously treated with various combinations of surgery and external beam irradiation, whereas two had the 32P instillation at a primary therapy. Visual acuity improved in 13 eyes and remained stable in 1. Visual fields normalized in three patients, improved in two, and remained stable in two. Two patients received single treatments with 32P, whereas five required multiple instillations for recurrent cyst expansion.

Topics: Adolescent; Adult; Brachytherapy; Child; Craniopharyngioma; Cysts; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Phosphorus Radioisotopes; Pituitary Neoplasms; Prognosis; Tomography, X-Ray Computed; Visual Acuity; Visual Fields

We have previously identified a group of cytoplasmic phosphoproteins (proteins 1-11) whose phosphorylation could be related, on a pharmacological basis, to the multihormonal regulation of PRL synthesis and release in the anterior pituitary tumor-derived GH cell lines. Phosphoproteins with identical migration properties on two-dimensional electrophoresis gels were also detectable in normal rat anterior pituitary cells in culture. We designed appropriate culture and [32P] phosphate-labeling conditions allowing to analyze the regulation of the phosphorylation of these proteins in normal pituitary cells. TRH, 12-O-tetradecanoylphorbol-13-acetate, and vasoactive intestinal peptide induced the same qualitative changes in phosphorylation of proteins 1-11 in normal as in GH cells. Quantitative differences observed are most likely due to the heterogeneity of primary pituitary cultures. Phosphorylation changes affecting proteins 14-16, not previously detected in GH cells, were also observed with normal anterior pituitary cells. GH cell lines have lost the sensitivity of pituitary lactotrophs for dopamine, an important physiological inhibitor of PRL synthesis and release. In normal anterior pituitary cells in culture, dopamine inhibited also the TRH-stimulated phosphorylation of proteins 1-10, thus strengthening the correlation between phosphorylation of these proteins and multihormonal regulation of pituitary cell functions. Our results indicate: 1) that the same phosphoproteins as in GH cells are related to the multihormonal regulation of nontumoral, normal anterior pituitary cells in culture; 2) that dopamine acts by interfering with the phosphorylation of these proteins. The phosphoproteins described here are therefore likely to be part, in normal anterior pituitary cells and possibly in other cell types, of the intracellular machinery involved in the cascade of transducing events leading from the binding of extracellular signals to the regulation of their target biological functions.

Topics: Animals; Cell Line; Cells, Cultured; Dopamine; Female; Phosphates; Phosphorus Radioisotopes; Phosphorylation; Pituitary Gland, Anterior; Pituitary Neoplasms; Prolactin; Rats; Rats, Inbred Strains; Reference Values; Tetradecanoylphorbol Acetate; Thyrotropin-Releasing Hormone; Vasoactive Intestinal Peptide

Stereotaxic intracavitary irradiation with instillation of phosphorus-32 (32P) colloidal chromic phosphate was performed in nine patients with cystic craniopharyngiomas. Serial neurological, ophthalmological, neuroendocrinological, and radiological examinations were performed before and after treatment. Dosimetry was determined based on a computerized tomography (CT) estimation of tumor volume, and was calculated to provide a tumoricidal dose (200 to 300 Gy) to the cyst wall. The follow-up period ranged from 14 to 45 months (mean 27 months). After treatment, all nine patients showed improvement of symptoms and radiological evidence of cyst regression. Because of an expanding solid component producing recurrent symptoms, one patient required a craniotomy 14 months after isotope instillation. Three of five patients with impaired visual acuity before surgery had significant improvement in acuity after treatment. Preoperative visual field defects in eight patients improved in four after 32P therapy. Of seven patients with preoperative endocrine abnormalities, one individual showed almost complete normalization and another had improvement in endocrine function. Patients who exhibited residual neuroendocrine function before isotope instillation developed no significant deterioration in endocrine status during the follow-up period. The findings suggest that stereotaxic intracavitary irradiation is a safe and effective treatment which should be considered as the initial surgery for cystic craniopharyngiomas.

Topics: Adolescent; Aged; Child, Preschool; Craniopharyngioma; Cysts; Female; Humans; Male; Middle Aged; Phosphorus Radioisotopes; Pituitary Diseases; Pituitary Neoplasms; Radiography; Stereotaxic Techniques; Vision, Ocular

The purpose of the present study was to investigate the effects of activation of different second messenger systems on protein phosphorylation in pituitary corticotrophic tumor cells (AtT-20/D16-16). Using two-dimensional gel analysis of cytosolic extracts from AtT-20 cells, several phosphoproteins exhibited alterations in 32P incorporation in response to stimulation of the cells with either forskolin--an activator of adenylate cyclase--or 12-O-tetradecanoyl phorbol-13-acetate (TPA)--a tumor promoting phorbol ester linked to protein kinase C activation. Alterations in phosphorylation levels were seen for phosphoproteins of the following apparent molecular weights and pIs: 87 kDa (pI 4.4-4.6), 67 kDa (pI 4.7-4.9), 43 kDa (pI 4.8-5.0), 39 kDa (pI 4.9-5.1), 33 kDa (pI 4.8-5.0), 19.5 kDa (pI 5.7-5.9), 19 kDa (pI 5.8-6.0), 16 kDa (pI 5.2-5.4) and 14 kDa (pI 5.1-5.3). For individual phosphoproteins, 32P incorporation varied over time and was also modulated by concentrations of Ca2+ and Mg2+ in the incubation medium. Treatment of the cells with forskolin led to statistically significant changes in the phosphorylation states of the 19.5 and 14 kDa proteins. Treatment of the cells with TPA also produced statistically significant changes in the 19.5 and 14 kDa proteins but, in addition, the 87 kDa, the 39 kDa and the 16 kDa phosphoproteins also exhibited significant changes. Alterations in the phosphorylation states of the 19.5 and the 14 kDa proteins were significantly correlated with alterations in beta-endorphin release from the cells. The primary finding of the present study was that activation of distinct second messenger systems can lead to alterations in the phosphorylation states of both shared and distinct phosphoproteins.

Topics: Adenylyl Cyclases; Animals; beta-Endorphin; Cell Line; Colforsin; Cytosol; Endorphins; Enzyme Activation; Kinetics; Mice; Neoplasm Proteins; Phosphorus Radioisotopes; Phosphorylation; Pituitary Neoplasms; Protein Kinase C; Tetradecanoylphorbol Acetate

Topics: Adenosine Triphosphate; Animals; Cells, Cultured; Chromatography, Thin Layer; Diglycerides; Fatty Acids, Nonesterified; Glycerol; Inositol; Lithium; Phosphates; Phospholipids; Phosphorus Radioisotopes; Pituitary Neoplasms; Radioisotope Dilution Technique; Rats; Thyrotropin-Releasing Hormone; Tritium

A cystic craniopharyngioma in a two-year-old boy recurred six months after surgery and postoperative external-beam radiotherapy. Successful retreatment was accomplished with radioisotope injection of 0.5 mCi of chromic phosphorus P 32 into the intracranial cyst, which delivered approximately 300.00 Gy to the cyst wall. The patient's symptoms were relieved, and he is without evidence of disease or cystic fluid accumulation four years after intracavitary (32)P irradiation.

Topics: Child, Preschool; Craniopharyngioma; Humans; Male; Neoplasm Recurrence, Local; Phosphorus Radioisotopes; Pituitary Neoplasms

Instillation of [32P]chromic phosphate to cystic brain tumors was performed in six patients. Three patients had craniopharyngioma, two had Grade IV astrocytoma and one had Grade II astrocytoma. The cyst volumes ranged from 2 to 44 cc. A calculated dose of 20,000 rad was delivered to the cyst wall. The [32P]chromic phosphate dose given to achieve this dose ranged from 0.11 mCi to 2.5 mCi. Radionuclide leakage was not detected in either the central nervous system or the reticuloendothelial system by bremsstrahlung scanning. Stereotactic instillation was done in some cases, others had indwelling catheters. The frequency of cyst fluid aspiration in the three patients with craniopharyngioma decreased postinstillation. In the two patients with Grade IV astrocytoma, reductions in both the CT documented cyst size as well as the frequency of cyst aspiration were noted. We conclude that [32P]chromic phosphate installation by stereotactic or indwelling catheter method is a safe and helpful procedure in the management of cystic brain tumors.

Topics: Adult; Aged; Brain Neoplasms; Craniopharyngioma; Female; Glioblastoma; Humans; Male; Middle Aged; Phosphorus Radioisotopes; Pituitary Neoplasms

We employed a protein gel blotting procedure to search for nuclear proteins from rat pituitary cells that bind preferentially to the 5'-flanking region of the rat prolactin gene. By gel blots of chromatin proteins from GH3 rat pituitary tumor cells with a 32P-labeled prolactin genomic clone, we detected two major binding proteins with molecular weights of approximately 44,000 and 48,000, designated NP44 and NP48, respectively. Both NP44 and NP48 are minor chromatin proteins which are extracted at low salt concentrations (0.4 M NaCl) and exhibit a range of slightly acidic isoelectric variants. NP44 and NP48 were detected at similar levels in chromatin extracts of GH3 cells, the prolactin-negative GC cell variant of the GH3 cells, and normal rat pituitary tissue. Considerably lower levels of these two proteins were found in chromatin extracts from rat liver and rat C6 glial cells. NP44 and NP48 exhibit DNA sequence specificity, as evidenced by their strong binding to the upstream flanking region of the prolactin gene, but only very weak binding to plasmid DNA, rat prolactin or growth hormone cDNAs, or upstream flanking regions of two other rat genes. By analyzing subclones of a rat prolactin genomic clone, we established that NP44 and NP48 bind to at least two sites, which are located between 0.4 and 2.0 kilobases (region I) and between 2.0 and 4.8 kilobases (region II) upstream of the transcription initiation site. These findings are discussed in the context of a possible functional association between the strong binding of NP44 and NP48 to the prolactin 5'-flanking region and pituitary-specific expression of the prolactin gene.

Topics: Animals; Base Sequence; Cell Line; Chromatin; Cloning, Molecular; DNA; Genes; Nucleic Acid Hybridization; Nucleoproteins; Phosphorus Radioisotopes; Pituitary Neoplasms; Prolactin; Protein Binding; Rats

A patient with residual suprasellar cystic neoplasm was treated by direct instillation of the 32P colloid. The incidental bremsstrahlung images on a conventional gamma camera helped to localize the pharmaceutical within and outside of the lesion. Advantages of bremsstrahlung imaging and the dosimetry results of phantom studies carried out are described.

Topics: Craniopharyngioma; Humans; Male; Middle Aged; Phosphorus Radioisotopes; Pituitary Neoplasms; Radiotherapy Dosage; Tomography, Emission-Computed

Ten patients with intracranial cystic tumors underwent stereotactic intracavitary irradiation using 32P colloidal chromic phosphate. Accurate dosimetry (25,000-30,000 rad to the cast wall) was achieved by volume estimation using computed tomography. Between 1 and 15 months after surgery both craniopharyngioma and astrocytoma cysts regressed. Neurological, visual, and endocrinological deficits either stabilized or improved. Intracavitary irradiation should be the primary method of treating solitary cystic tumors of the brain.

Topics: Adolescent; Adult; Aged; Astrocytoma; Brain Neoplasms; Cerebral Ventricle Neoplasms; Child; Child, Preschool; Chromium; Chromium Compounds; Colloids; Craniopharyngioma; Cysts; Female; Humans; Male; Middle Aged; Phosphates; Phosphorus Radioisotopes; Pituitary Neoplasms; Stereotaxic Techniques

Thyrotropin-releasing hormone (TRH) stimulates prolactin production by GH4C1 rat pituitary tumor cells, which possess high-affinity membrane receptors for the peptide. TRH caused up to a 50% increase in the activity of a low-Km GTPase in membranes from GH4C1 cells. The TRH stimulatory effect was maximal at GTP concentrations of 1 microM or lower. TRH caused an increase in GTPase activity of between 0.2 and 20 pmol of GTP hydrolyzed per mg of protein per min, depending on GTP concentration, while TRH binding was 0.3 pmol/mg of protein. TRH did not stimulate GTPase activity in membranes from GH12C1, or GH-Y cells, two pituitary lines lacking TRH receptors. Stimulation of GTPase depended on occupancy of the TRH receptor; half-maximal increases in GTPase activity required 46 nM TRH and 25 nM [N3-methyl-His]TRH, but the TRH free acid was inactive. The apparent Kds of these peptides for receptors were similar when measured under the same conditions. The fact that TRH binding to receptors is regulated by guanyl nucleotides, together with the demonstration of TRH stimulation of low-Km GTPase activity, suggests that the TRH receptor is associated with a guanyl nucleotide regulatory protein in the lactotroph membrane.

Topics: Animals; Cell Line; Cell Membrane; GTP Phosphohydrolases; Guanosine Triphosphate; Kinetics; Phosphoric Monoester Hydrolases; Phosphorus Radioisotopes; Pituitary Neoplasms; Rats; Thyrotropin-Releasing Hormone

Thyrotropin-releasing hormone (TRH) is a tripeptide that rapidly enhances prolactin secretion in clonal, hormone-responsive GH3 rat pituitary cells. In an effort to identify postreceptor mechanisms for TRH, protein phosphorylation studies have been conducted. Our previous studies (Drust, D.S., Sutton, C.A., and Martin, T. F. J. (1982) J. Biol. Chem. 257, 3306-3312; Drust, D.S., and Martin, T. F. J. (1982) J. Biol. Chem. 257, 7566-7573) showed that TRH rapidly (less than 15 s) increased the phosphorylation of at least six cytosolic proteins (41K (Mr = 41,000), several 59K, 65K, 82K, and 97K) and, with a 5- to 10-min latency, increased the phosphorylation of a seventh (80K). Cyclic AMP did not appear to mediate TRH-stimulation of protein phosphorylation; in contrast, Ca2+ translocation and Ca2+-dependent protein phosphorylation accounted for hormone-induced changes in 97K (and possibly 41K) phosphorylation. The studies reported here indicate that lipid (diacylglycerol) accumulation and protein kinase C activation mediate TRH-stimulated phosphorylation of the additional five cytosolic proteins (two 59K, 65K, 80K, and 82K). This conclusion is based on the findings that: 1) phospholipase C treatment, which produces diacylglycerol, mimicked several TRH effects; 2) bombesin, another peptide that induces inositol phosphatide turnover, mimicked several TRH effects; 3) phorbol esters, which were shown to activate GH3 cell protein kinase C directly, produced TRH-like effects; 4) partially purified GH3 cell cytosolic protein kinase C was activated by diacylglycerol; and 5) 59K and 82K proteins were endogenous in vitro substrates for a cytosolic lipid-stimulated protein kinase. We conclude that rapid TRH effects in promoting inositol phosphatide turnover in GH3 cells may be linked to the activation of protein phosphorylation mediated by protein kinase C. These, and previously reported studies, indicate a role for Ca2+ and lipids (diacylglycerol) as dual intracellular messengers for TRH.

Topics: Animals; Cell Line; Cytosol; Diglycerides; Enzyme Activation; Kinetics; Neoplasm Proteins; Phosphoproteins; Phosphorus Radioisotopes; Phosphorylation; Pituitary Neoplasms; Protein Kinase C; Protein Kinases; Rats; Thyrotropin-Releasing Hormone; Type C Phospholipases

Topics: Animals; Cattle; Mice; Molecular Weight; Phosphorus Radioisotopes; Phosphorylation; Pituitary Gland; Pituitary Gland, Anterior; Pituitary Hormones, Anterior; Pituitary Neoplasms; Pro-Opiomelanocortin; Protein Precursors; Rats

The authors report the results of internal irradiation with labeled chromic phosphate (32P) and gold-198 (198Au) colloid in eight cases of cystic craniopharyngiomas. They used a newly developed dosimetric formula, by which the radiation dose at the cyst wall and at any point far from the radioactive source can be calculated. Ten courses of irradiation in eight patients were carried out by injection of either 32P or 198Au colloid into the cyst through an Ommaya drainage system that had been placed at craniotomy. Follow-up studies ranging from 13 to 156 months revealed that all cysts were effectively treated, with elimination of fluid or collapse of the cyst. This was confirmed by Conray cystography and/or computerized tomography. Not only the dose delivered to the wall but also the thickness of the cyst wall and the location of the cyst are important factors in planning internal irradiation. A safe and adequate dose to the cyst wall could range between 9000 to 30,000 rads for craniopharyngioma. This treatment is suitable for large cysts that are thought to be difficult to remove radically, recurrent cysts resistant to previous treatment, or multiple cysts. Internal irradiation may also be applicable in other cystic intracranial tumors if dosimetry is calculated accurately.

Topics: Adolescent; Adult; Child, Preschool; Chromium; Chromium Compounds; Craniopharyngioma; Female; Follow-Up Studies; Gold Colloid, Radioactive; Humans; Male; Methods; Middle Aged; Phosphates; Phosphorus Radioisotopes; Pituitary Neoplasms; Radiotherapy Dosage; Tomography, X-Ray Computed

Topics: Animals; Calcium; Cell Line; Clone Cells; Kinetics; Phosphates; Phosphatidic Acids; Phospholipids; Phosphorus Radioisotopes; Pituitary Neoplasms; Rabbits; Thyrotropin-Releasing Hormone

Topics: Adolescent; Adult; Brachytherapy; Child; Craniopharyngioma; Female; Humans; Phosphorus Radioisotopes; Pituitary Neoplasms

Topics: Craniopharyngioma; Humans; Phosphorus Radioisotopes; Pituitary Neoplasms; Radiometry; Radiotherapy Dosage

Topics: Adenoma, Acidophil; Adenoma, Chromophobe; Follow-Up Studies; Gold Colloid, Radioactive; Humans; Iridium; Phosphorus Radioisotopes; Pituitary Irradiation; Pituitary Neoplasms; Radioisotopes; Stereotaxic Techniques; Time Factors; Vision Disorders; Visual Fields; Yttrium Isotopes

Topics: Brain; Craniopharyngioma; Humans; Injections; Phosphorus; Phosphorus Radioisotopes; Pituitary Neoplasms; Split-Brain Procedure; Stereotaxic Techniques