Phase II evaluation of interferon-alpha-2a for progressive or recurrent craniopharyngiomas

OBJECT: Craniopharyngiomas originate from the same cells as squamous cell skin carcinoma, which can be treated successfully with interferon-alpha (IFNalpha)-2a. The authors evaluated the activity and toxicity of systemic IFN in young patients with craniopharyngiomas. METHODS: Fifteen patients between the ages of 4.2 and 19.8 years who had progressive or recurrent craniopharyngiomas were enrolled in this study. Nine of these patients had never received external-beam radiation therapy. Therapy consisted of 8,000,000 U/m2 IFNalpha-2a administered daily for 16 weeks (induction phase) followed by the same dose three times per week for an additional 32 weeks (maintenance phase). Of the 12 patients who could be evaluated, radiological studies demonstrated a response to treatment in three with predominantly cystic tumors (one minor response, one partial response, and one complete response); one of these patients also showed improvement in visual fields. The size of the cystic component of the tumors often increased temporarily during the first several months of therapy. Three patients met the criteria for progressive disease during therapy. The median time to progression was 25 months. The need for radiation therapy in patients treated with IFN was delayed for 18 to 35 months (median 25 months) in six patients. All patients developed transient flulike symptoms shortly after receiving the first dose of IFN. Other toxicities (predominantly hepatic, neurological, and cutaneous) were seen in nine (60%) of the 15 patients during the first 8 weeks of treatment but resolved after temporary discontinuation and/or dose reduction. CONCLUSIONS: Interferon-alpha-2a is active against some childhood craniopharyngiomas; its toxicity precludes administration of high daily doses, and the optimum dose level and schedule remain to be defined.     

Stereotaxic intracavitary irradiation for cystic craniopharyngiomas

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.     

Stereotactic intracavitary therapy of recurrent cystic craniopharyngioma by instillation of 90yttrium

Six consecutively presenting patients with craniopharyngiomas, (F:M = 4.2; mean age: 35.2 years, range 17-58) histologically proven by one or more previous operations, and with recurrence of a wholly or predominantly cystic nature, were treated by 90yttrium (90Y) radioisotope instillation into the cyst. Five patients had undergone external beam radiotherapy and the remaining patient had concomitant stereotactic radiosurgery to a co-existing solid component. Seven cysts in six patients have been treated. Five cysts, previously requiring repeated aspiration at intervals of 2-20 weeks have required no further surgical intervention following 90Y treatment (FU mean 3.5 years, range 1.2-7), although two of these required a second 90Y treatment. No patient developed a visual field defect or evidence of hypothalamic dysfunction. One patient died within a month of treatment from complications related to a solid recurrence. One patient developed a large solid/cystic recurrence at 4 months and died shortly thereafter from an unrelated cause. We summarize results from other series that have demonstrated the efficacy of this technique, usually as primary therapy, but this is the first series to demonstrate its usefulness as salvage therapy. The prospect of survival with good quality of life can be offered to patients with multiply recurrent disease who have exhausted all conventional means of treatment. In our experience intracavitary 90Y is a safe and highly effective means of controlling cystic recurrence in refractory craniopharyngioma. Some patients require more than one treatment.     

Brain tumors with cysts treated with Gamma Knife radiosurgery: is microsurgery indicated?

Cysts, which are not uncommonly associated with brain tumors, may be responsible for neurological dysfunction. Stereotactic aspiration of such lesions can lead to clinical improvement, but cyst recurrence is common and multiple aspirations may be necessary. Thirteen cases of brain tumors with cystic components were treated by radiosurgery with follow-up of 5-29 months (median 14 months). The tumor diagnoses were three cystic craniopharyngiomas, two brain stem cystic astrocytomas, two cystic cerebellar astrocytomas, one cerebellar hemangioblastoma, one ganglioglioma, one fourth ventricle tumor, one cerebellopontine angle pilocytic astrocytoma, one metastasis from lung cancer and one glioblastoma. The dose at the tumor margin ranged between 10 and 20.5 Gy (mean 15.5 Gy) and the maximum dose ranged between 18 and 45 Gy (mean 32.3 Gy). In 11 of these cases the cystic component recurred in spite of a decrease in the size of the solid tumor component. An Ommaya reservoir was inserted in six cases, stereotactic aspiration was performed in two cases, microsurgery was undertaken in two cases after 2-8 months (mean 4.8 months) and one patient refused further treatment. Multiple aspirations through the Ommaya reservoir were performed in the outpatients on the two patients who required them. It may be appropriate to be cautious in advising radiosurgery for intracranial tumors with a significant cystic component. Microsurgery if possible may be preferable in this situation.     

Biliary cystadenoma of the liver

Hepatobiliary cystadenoma is an uncommon lesion that is difficult to diagnose preoperatively. Here we report a 34-year-old woman who presented with enlargement of a cyst that had been observed for the previous 6 months. Diagnostic imaging revealed a 7-cm diameter cystic mass with irregular multiple septation in her liver. All laboratory test results were normal except for serum carbohydrate antigen (CA) 19-9 (62.5 U/ml). Because of the malignant potential and the history of enlargement, a complete surgical excision was performed. The patient was discharged after a good recovery; 2 months after surgery her serum CA19-9 level had returned to normal (32.9 U/ml). Regardless of the diagnostic modalities used, cystadenoma and cystadenocarcinoma cannot be differentiated with accuracy. Therefore complete surgical resection is the recommended therapy. Received for publication on Nov. 25, 1997; accepted on April 6, 1998     

Combined treatment with stereotactic intracavitary irradiation and gamma knife surgery for craniopharyngiomas.

OBJECT: To evaluate the effectiveness of the combined treatment of stereotactic intracavitary irradiation and Gamma Knife surgery on craniopharyngiomas. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Prenatal diagnosis of a large, cervical, intraspinal, neurenteric cyst and postnatal outcome

Neurenteric cysts are rare congenital anomalies derived from the notochord and located in front of the spinal column, mostly at the cervical level. They consist of an intraspinal cystic component that is connected to a mediastinal or thoracic cyst. A case of a cervical, intraspinal, neurenteric cyst, diagnosed at 28 weeks of gestation and operated on at 3 and half months after birth, is reported. Herein, we discuss important features of this case including its rare occurrence, intrauterine diagnosis, and early surgical intervention. In conclusion, the nature of prenatal intradural cysts should be fully evaluated and differentiated between neurenteric cyst and other types of cysts with fetal ultrasonography. Therefore, it is essential to be aware of this potential cyst in fetal ultrasonography in utero. Neurenteric cyst should be considered in the differential diagnosis of cervical intradural cystic lesions. In infants, successful surgery provides a cure in patients with cervical neurenteric cysts.     

Surgical management of the recurrence and regrowth of craniopharyngiomas

OBJECT: The authors performed a retrospective analysis of a consecutive series of craniopharyngiomas and their recurrences, which were managed with surgery alone. METHODS: In the past 20 years, 37 consecutive patients with craniopharyngiomas underwent surgery without adjuvant radiotherapy. During that period there was a consistent strategy that surgical management was the first choice of treatment whenever possible. Of these 37 patients, 11 experienced tumor recurrence (29.7%) during the mean follow-up period of 11.1 years. Of these 11 patients, seven experienced recurrence after neuroimaging-confirmed total removal, and four patients experienced recurrence after partial or incomplete removal. In these 11 patients, surgical removal was performed 17 times. Using a proper surgical approach (mainly a basal interhemispheric approach) and meticulous microsurgical techniques, total removal of the recurrent tumor was achieved in nine surgeries (52.9). The mortality and morbidity rates associated with these 17 surgeries were 0% and 9.1%, respectively. In most cases, visual function was preserved or improved and intellectual performance was also preserved. CONCLUSIONS: Recurrence of craniopharyngioma can be safely managed by using meticulous contemporary microsurgical techniques without additional radiotherapy. The role of surgery and adjuvant radiotherapy for craniopharyngiomas may vary in the future, depending on innovations in treatment and technology. Nevertheless, surgery can be still a major therapeutic option in the management of recurrent craniopharyngiomas.     

Ossified adamantinous type craniopharyngiomas

Summary Thirteen patients admitted to hospital mainly with visual disturbances (100%), retarded growth (39%) and diabetes insipidus (23%) were all diagnosed as ossified adamantinous craniopharyngioma. Tumour size was found to be large in all patients. Localization displayed a heterogenous dissemination; 8% intra-suprasellar, 69% suprasellar-extraventricular, 15% extra-intraventricular, and 8% in the suprasellar region extending bilaterally to the frontal and temporal lobes.During the early postoperative period, four patients died with hypothalamic deterioration. Three patients underwent a second operation in view of recurrence, and one died from an infection. Thus, the postoperative survival rate was 62%. All the patients who survived continued to have visual disturbances, but only one deteriorated. Five patients exhibited diabetes insipidus during the post-operative period, among them 4 after surgical intervention and 5 patients displayed panhypothyroidism, three of them after surgery.Consequently, it is confirmed by the present review that craniopharyngiomas still offer a potential dilemma in their management. Difficulties caused by adhesion or invasion of ossified craniopharyngiomas and thus the increase in morbidity and mortality during surgical intervention and in the postoperative period are discussed.     

Management of tumor bed cysts after chemotherapeutic wafer implantation. Report of four cases

Adjuvant use of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) wafers with surgical resection is becoming common for the treatment of malignant gliomas. Cyst formation in the tumor resection cavity is a recently described complication associated with the use of BCNU wafers. There is currently no report in which successful management of this complication without additional surgical intervention is described. The authors describe four patients in whom postoperative cysts developed in the tumor resection cavity after placement of BCNU wafers. These include a 38-year-old man with a left frontoparietal tumor, a 48-year-old man with a right frontal lobe tumor, a 78-year-old man with a left parietooccipital tumor, and a 61-year-old woman with a left frontotemporal tumor. Histopathological studies of biopsy samples revealed malignant glioma in each patient. All four patients had unremarkable perioperative courses, were discharged within 3 to 8 days of surgery, and subsequently returned with acute neurological deterioration. Follow-up magnetic resonance (MR) imaging demonstrated cyst formation with significant mass effect at the previous resection site. Three patients were treated with high-dose dexamethasone and returned to their neurological baseline over an 8-day period. The fourth patient improved after surgical drainage and biopsy sampling of the cyst, which revealed no evidence of infection or recurrent tumor, but again sought medical care 2 weeks later with cyst recurrence necessitating high-dose steroid therapy. On MR images at least a 30% reduction in cyst size was demonstrated in all four patients, each of whom remained clinically stable at 2, 6, 6, and 4 months of follow-up review. Neurosurgeons should be aware of the potential for postoperative cyst formation accompanied by clinically significant mass effect after BCNU wafer implantation, as well as the potential for successful nonsurgical management leading to clinical and radiological improvement.     

Conservative management of large ovarian cysts in children: the value of serial pelvic ultrasonography.

BACKGROUND. The management of large ovarian cysts in children is controversial and complicated by a poorly understood natural history. The purpose of this study was to determine the course of sonographically detected large ovarian cysts in a pediatric population. METHODS. All pelvic ultrasonograms in which an ovarian cyst was detected during a 6-year period were reviewed. Large cysts were defined as those of more than 5 cm in any dimension or a volume of more than 13 cc. Clinical data and follow-up was derived from either the hospital chart or by telephone interview. RESULTS: Large ovarian cysts were detected in 92 of 191 patients (48.2%). The average age was 14.9 years (range, 3 to 22 years). Eight patients were premenarchal. In 23 patients, surgery was performed, with findings of neoplasm in 10. In patients managed without surgery and with follow-up, 46 of 51 cysts (90%) decreased in size or completely resolved. Both complex and simple cysts resolved. CONCLUSIONS. Most large ovarian cysts in children (simple or complex) may be safely followed with serial pelvic ultrasonography, because most cysts will either decrease in size or resolve. Neither the character of the cyst nor the size reliably predicted clinical outcome. The decision for surgical intervention should not be based solely on ultrasonographic characteristics, but other factors such as severe symptoms, complications associated with the large mass, other evidence suggestive of neoplasm, ovarian source in doubt, or whether the cyst fails to resolve or decrease in size on follow-up ultrasonography.     

Results of transsphenoidal extirpation of craniopharyngiomas and Rathke's cysts

Fourteen patients undergoing transsphenoidal extirpation of craniopharyngiomas or Rathke's cysts underwent endocrinological evaluation before and after surgery. One patient died during the procedure because of uncontrollable arterial bleeding. The other patients were followed for up to 16 years (average, 8.5 years). One patient had recurrence of tumor 12 years after surgery. Another patient, the only one operated on because of a recurrent craniopharyngioma after previous radiation therapy, died 2 years after the transsphenoidal operation. No patient recovered pituitary functions that had been lost before surgery. One patient, who had an isolated growth hormone deficiency, and another, who had panhypopituitarism with sustained antidiuretic hormone secretion, had no change postoperatively from their preoperative endocrine status. The other 11 patients lost pituitary function and required pharmacological replacement of one to four pituitary hormones.     

Craniopharyngiomas in childhood. A rational approach to treatment.

The authors review 60 children who presented with craniopharyngiomas. Patients were treated by either 1) cyst aspiration followed by deep x-ray therapy (DXT), 2) radical excision, 3) incomplete tumor excision, or 4) incomplete excision followed by DTX. Symptomatic clinical recurrence signified failure of treatment. Of the patients treated by cyst aspiration and DXT, 50% experienced recurrence (mean time after treatment, 4.4 years), while recurrences occurred in 23% undergoing radical excision (mean time, 2.4 years). Symptomatic recurrences occurred in 78% treated by incomplete removal only (mean time, 2.2 years). No recurrences have occurred in seven patients whose incomplete removal was followed by DTX. The authors conclude that radical excision is most likely to produce survival free of recurrence. When radical excision is not possible, DXT appears to provide an additional effect on preventing tumor regrowth. Characteristics of craniopharyngiomas favoring radical excision are also discussed.     

Management of cystic craniopharyngiomas with phosphorus-32 intracavitary irradiation

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.     

CT follow-up studies in postoperative craniopharyngiomas.

Thirty patients with histologically proved craniopharyngiomas were controlled by CT after surgical excisions. Recurrence occurred in 70%. Of these tumours 33% were cystic, 30% were solid, and 12% were calcified. The ventricles were dilated in 67%, and postoperative cavities were found in 33%. The effectiveness of various forms of therapy has been monitored by CT. The purpose of our study is to investigate the value of early and long term CT scanning in craniopharyngiomas after surgical excision.     

Treatment of spinal cord compression by epidural malignancy in childhood

Epidural spinal cord compression by a malignant tumor is a rare occurrence in children. Both the tumors involved and the extent of involvement of the vertebral column are different in children and adults. Often, the epidural tumor in a child is identified before significant spinal canal compromise has occurred, and these children frequently can be managed by radiation therapy and/or chemotherapy. There is a group of children, however, who have severe spinal canal encroachment by a tumor, as evidenced by a near complete or complete block on myelography. In this study, we report a group of patients with severe spinal cord compression, as documented by imaging studies. We compared the results of a decompressive laminectomy and subtotal tumor resection followed by adjuvant therapy with the results obtained with radiation therapy and/or chemotherapy alone. Thirty-three patients met the criteria for inclusion in the study. Twenty-six were treated with a laminectomy and adjuvant therapy, and 7 were treated without surgical intervention. With surgical therapy, 25 of 26 epidurals were either improved or stable, whereas 4 of 7 nonsurgical patients deteriorated. Especially notable was a decrease in pain in the operative patients immediately after their procedure. There was no surgical mortality or morbidity. The results of this study indicate that children with severe spinal cord compression as evidenced by a near complete or complete block on myelography or filling of 50% or more of the spinal canal on magnetic resonance imaging are best treated by a combination of surgical decompression and tumor removal followed by adjuvant therapy.     

Are Facial Nerve Outcomes Worse Following Surgery for Cystic Vestibular Schwannoma?

Objectives: This study sought to determine explicitly whether postsurgical facial nerve outcomes for patients with a cystic component to a vestibular schwannoma were significantly different from those with a solid tumor. Design: Seventy patients who underwent translabyrinthine surgery for a cystic vestibular schwannoma between May 1981 and the present, and who had complete records in our database, were identified. These were compared with a group of patients with solid tumors matched to the study group on the following parameters: House-Brackmann grade at presentation, tumor size, surgical approach, age. Setting: Regional tertiary referral center. Participants: Adult patients with vestibular schwannomas. Main Outcome Measures: House-Brackmann score 2 years following surgery. Results: No significant difference was found between the two groups. Conclusions: The perceived difference in outcomes between cystic and solid vestibular schwannomas cannot be demonstrated when confounding factors such as tumor size are taken into account.     

Adenoid cystic carcinoma (cylindroma) and mucoepidermoid carcinoma of the bronchus. Factors affecting survival.

A review was made of the presentation, treatment, and follow-up of 20 patients with adenoid cystic carcinoma and 12 patients with mucoepidermoid carcinoma of the bronchus who were seen at the Mayo Clinic during the 50 year period 1927 through 1977. Three forms of therapy were employed: complete surgical resection, radiation therapy alone, and radiation therapy after endoscopic removal of tumor tissue. Superior results were obtained in the group with adenoid cystic carcinoma, when complete resection was possible. Significant survival and palliation of sepsis was achieved with subtotal resection. The mucoepidermoid carcinomas in this series were classified on the basis of histologic differentiation. Mucoepidermoid carcinoma of Grade 1 was managed by conservative pulmonary resection. Mucoepidermoid carcinoma of Grades 2 and 3 showed a greater propensity for malignancy. Widespread dissemination caused death with unresectable high-grade mucoepidermoid carcinomas of Grades 2 and 3.     

Management of pancreatic pseudocysts

Between 1969 and 1987, 68 patients with pancreatic pseudocysts were treated. The median cyst size was 10 cm (range 2-25 cm). Nine patients were managed conservatively with resolution of the pseudocyst occurring in eight patients. These patients had significantly smaller (median 4 cm) cysts compared with those in both percutaneously and surgically treated patients (P less than 0.01). In 22 patients the pseudocysts (median 9 cm) were punctured percutaneously under ultrasound guidance and the cyst fluid was aspirated or drained through a catheter. Complete resolution occurred in 13 patients after 1-4 (mean 1.8) punctures per patient, regression occurred in six patients after 1-4 (mean 2.0) puncture procedures per patient and three were unchanged. No complications were noted, except that two patients treated percutaneously required additional surgery. Thirty-seven patients were managed surgically (median cyst size 11 cm) with external drainage (12 patients), cystgastrostomy (17 patients), cystduodenostomy (three patients) cystjejunostomy (three patients) and pancreatic resection (two patients). Resolution of the cyst was noted in 29 patients, regression in five and three were unchanged. Five patients required additional surgery. Twelve complications were seen in ten patients (27 per cent), most frequently after external drainage. One patient died after surgical treatment. Mean hospital stay was 13 days among patients treated conservatively and 30 days in both percutaneously and surgically treated patients. Aspiration or catheter drainage of pseudocyst fluid guided by ultrasonography seems a safe and effective treatment of pancreatic pseudocysts and should be considered as initial therapy. If surgery is required cystgastrostomy is preferred.     

Astrocytoma of the cerebellum in children. Apropos of 57 cases

57 children with a cerebellar astrocytoma have been operated on between 1964-1982. Since 1977, CT Scan has led to safer and earlier diagnosis. CT Scan has documented three macroscopical types of cerebellar astrocytomas; a cystic form with a mural nodule enhanced and the wall of the cyst non enhanced, a cystic form with a nodule and the wall of the cyst enhanced, and a massive form. 6 patients were submitted to a ventricular-atrial shunt before direct surgery. All the patients underwent posterior fossa surgery in the sitting position. Removal of the tumor was macroscopically total in 48 patients. Removal is limited to the nodule for cystic form with the wall non enhanced. Removal is extended to the wall of the cyst when it is enhanced. In 9 patients, the CSF pathway was restored at the end of the procedure by cannulation of the Aqueduct with silastic tube. 3 patients died postoperatively (5.2%), 2 others later on (4 and 8 years). 3 patients had a recurrency. In 6 patients, radiation therapy was used after surgery.