Craniopharyngioma: treatment by conservative surgery and radiation therapy.RD Nagpal
Dept of Neurosurgery, KEM Hospital, Parel, Bombay, Maharashtra.
Benign neoplasms are curable only when excised. This applies even to craniopharyngiomas. The proximity of craniopharyngiomas to the hypothalamus and neurovascular structures makes total excision difficult to achieve. Over the last 3-4 decades, it has become increasingly obvious that craniopharyngiomas respond to radiation therapy. Early, unhappy results with major excisions have prompted us to adopt a policy of conservative surgery and radiation therapy to the residual tumour. Preliminary results suggest a good outcome in 35 of the 63 patients so treated from 1981. Details of the study are presented.
Keywords: Adolescent, Adult, Aged, Child, Combined Modality Therapy, Craniopharyngioma, complications,radiography,radiotherapy,surgery,Female, Follow-Up Studies, Human, Male, Middle Age, Pituitary Neoplasms, complications,radiography,radiotherapy,surgery,Tomography, X-Ray Computed,
Until the report by Carpenter et al half a century ago, craniopharyngiomas were considered radio resistant. Though X-rays did not destroy the tumour, they killed the lining epithelial cells of the cysts. Only after Kramer et al  (1961) report, radiation therapy came to be accepted as beneficial in treatment of craniopharyngiomas. Subsequent reports,,,, have supported this finding. On the other hand, surgical refinements, use of the microscope and availability of better imaging techniques have encouraged attempts at a total excision,,. Even after apparent 'total' removals a large number of recurrences have been reported. The surgeon's judgement will determine whether an attempt at total removal is worth the risk of possible operative mortality and functional impairment of the patient. 'Total' excision has therefore given way to radical 'safe' excision. At times during surgery this 'safe' limit is inadvertently crossed and the result is devastating. This happens due to the intimate relation of the mass to the optic apparatus, carotid arteries, perforators and the all important hypothalamus. The problem is compounded by the tendency of the neoplasm to spread beneath and behind the chiasm. Partial or subtotal excision by itself is rarely satisfactory and the patients soon present with symptomatic recurrences,. Asymptomatic survival rates for patients after surgery and radiation treatment are better than those after operation alone. Baskin and Wilson have recently reported a 91 percent remission rate in 74 patients treated by radical subtotal removal and radiation therapy and with an operative mortality of only 3 percent. Over the years these facts have made us adopt an approach of conservative 'safe' surgical excision followed by radiation treatment in the management of these neoplasms. The surgery involves evacuation and drainage of the cystic portion, excision of enough tumour to decompress the optic nerves and hypothalamus and insertion of a shunt to control hydrocephalus, if present. In some patients, under favourable conditions a more radical excision has been attempted.
The case records of 63 patients treated between 1981 and 1988 were retrieved. The year 1981 was chosen as the starting point of the study, because this is when the computerised scanner became available to our patients. Two patients (1735/83, 362/85) had earlier operations performed elsewhere. The first of these in fact had undergone two operations followed by quick return of symptoms, and the computed scan showed reformation of the cyst. The rest of the patients were primarily treated by us. The surgery was largely carried out by two surgeons with a few cases being done by an additional two surgeons. Past experience and some fatal outcomes had dampened the enthusiasm for radical surgery. By design, the slightest hazard during surgery dictated a conservative excision. Males constituted 43 patients and females, 20 patients. The largest number of patients (25) resented in the second decade; 19 during the first decade, 7 in the third decade, 6 in the fourth, 4 in the fifth and 1 each in the sixth and seventh decades.
The most common symptoms headache and vomiting were present in 48 patients. Diminished vision was seen in 44 patients. Seizures affected 14 patients. Of these, 12 patients had generalised convulsions, 1 focal fits and the last tonic fits. Symptoms suggestive of diabetes insipidus were present in 7 patients. Obesity and stunted growth was noted in 3 patients each. A large number of symptoms were seen occasionally. These were obesity (3), stunted growth (3), ataxia (2), abnormal behaviour (4), speech impairment (1), drowsiness or excessive sleep (3), memory impairment (1), decreased libido (1), impotence (1), galactorrhoea (1) and amenorrhoea (7). In 1 patient, the amenorrhoea was secondary and in 6 it was primary. In 5 patients, hemiparesis was an additional symptom.
Papilloedema (25 patients), bilateral optic atrophy (15 patients) and unilateral atrophy (3 patients) were the abnormal fundoscopic findings. The vision was bilaterally impaired in 27 patients and unilaterally in 9 patients. Five patients were completely blind. Perimetry revealed bitemporal hemianopia in 3 patients, homonymous in 3 and a concentric field defect in 3 patients. Unilateral field defects consisting of either temporal or nasal field defects were seen in an additional 7 patients. In 3 of these 7 patients the other eye was already blind. In 14 patients there was evidence of stunted physical growth, while secondary sex characters were absent in 12 patients. Obesity was obvious in 2 patients. At the time of admission 9 patients were drowsy. Sixth nerve paralysis was noted in 5 patients. Seventh nerve weakness was found in 4 patients. Cerebellar signs mainly in the form of ataxia were seen in 4 patients. I n 2 patients increased tone and brisk reflexes were found and in 1 patient marked restlessness was seen.
After a clinical evaluation, 61 patients had skull X-rays done. Evidence of raised intracranial pressure was obvious in 37 patients; presellar and intrasellar calcification was seen in 32 patients and sellar enlargement was noted in 29 patients. Air studies had been done in some of the earlier patients as computed scanning was not easily available. In 5 patients ventriculography was done, pneumoencephaiograpy in 2 patients and an inadvertent tumour air cystogram in 1 patient. Preoperative computed tomography was possible in only 50 of the 63 patients. In the earlier days angiography was carried out in 19 patients in the hope that the information about vessel displacement would help during surgery. Since this hope was belied, angiography was abandoned.
On the basis of the imaging, particularly computed scanning, only 1 tumour was entirely intrasellar. Suprasellar extension of a varying degree was found in 49 tumours. This extension varied from a small extension to a large one, obliterating the third ventricle and causing hydrocephalus. Frontal extension of the tumour was seen in 5 patients, temporal extension in 6 patients and the tumour was widespread (suprasellar, frontal, temporal, retrosellar and into the cerebellopontine angle) in 3 patients. On the basis of computed scanning in 50 patients, the tumour was partly cystic and partly solid in 36 patients, completely cystic in 5 patients and wholly solid in 9 patients.
Before surgery on the tumour, 30 of the 40 patients with hydrocephalus, underwent ventriculo-atrial shunts. It was felt in all these patients, that the hydrocphalus contributed significantly to the raised intracranial pressure. Surgery was not carried out in 5 patients for varying reasons. In 3 patients, there wasn't enough time to carry out surgery, as these patients died within hours of admission. One patient preferred to have the operation done elsewhere. This patient has not been seen again. Another patient was subjected to radiation therapy without surgery because the clinical and radiological features craniopharyngioma. Also on the scan, the mass was densely calcified, precluding any useful excision. Four years later the patient underwent evacuation of the posterior fossa extension of the cystic recurrence.
The approach to the tumour was dictated by the direction of its spread. The approach was subfrontal in 30 patients, pterional in 11, transsphenoidal in 12, subtemporal in 3, transcallosal in 4 and retromastoid posterior fossa approach in 1. In this last patient, a shunt was followed by direct radiation treatment in 1985. In 1989, he returned with cerebellar signs. A repeat computed scan showed a large cystic extension into both cerebellopontine angle cisterns. In 7 patients, multiple operations had to be performed. The first patient (1017/83) underwent two operations by the pterional route and another by the subtemporal route in an attempt to excise a large solid tumour compressing the midbrain and hypothalamus. The relatives took him away in a seriously ill state after the third operation. The second (1735/83) of these patients had undergone two previous attempts at excision elsewhere. The third (3621/85) patient had also had a subfrontal operation on a heavily calcified tumour. Unsuccessful surgery led to another unsuccessful attempt by the transsphenoidal route. The fourth patient (1151/85) needed a repeat operation, 6 months after the first due to deteriorating vision from reaccumulation of the cyst. An additional two patients (2260/84, 1266/88) first underwent a trans-sphenoidal approach due to the mistaken preoperative impression of a large subdiaphragmatic intrasellar extension. Failure to achieve useful excision necessitated a subfrontal approach. At this operation only a partial excision was possible in these two patients. The last patient (313/88) needed a second operation within 3 weeks of the first due to the development of a pituitary abscess. This was evacuated by the trans-sphenoidal route. Another patient (319/83) had to have the shunt removed 4 years later as it had extruded at the distal end.
The extent of the tumour excision depended on the findings at surgery and to a lesser extent on the preoperative computed scans. Any danger of injury to the visual apparatus, hypothalamus and vessels (specially the perforators) precluded a major excision. If the surgeon erred, it was towards a conservative excision. In 21 patients, the lesion was biopsied with aspiration of the cyst if present. Usually a silastic tube was led out from the collapsed cyst into the subdural space in an attempt to preempt refilling of the cyst. In predominantly solid tumours, an attempt to excise at least enough to decompress the visual apparatus and hypothalamus was made. Such a partial excision was achieved in 23 patients. Whenever felt safe, a subtotal or total excision was attempted. Subtotal excision was possible in 12 patients and a total excision was achieved in only 2 patients. One (1049/88) of the 2 patients believed to have the tumour excised totally, expired and post-mortem examination showed a large tumour residue. The other patient (1412/82) remains well and the scan continues to show no evidence of recurrent tumour.
Radiation treatment was administered as soon as possible after surgery. A dose of 5000 rads from a 60 co source, in a daily dose of 150-200 rads, over a period of 30-35 days was administered. None of the patients suffered any complications from radiotherapy. A total of 42 patients received radiation therapy. There were 12 patients who did not receive radiation therapy as they expired soon after admission or after surgery. Whether the remaining 9 patients received radiation treatment, is not known. This is because the patients are referred for this treatment to a neighbouring cancer institute and these patients never returned for a follow-up.
The follow-up period varied from less than 1 year to more than 5 years. Five patients never returned for a follow-up examination; 12 patients returned for an evaluation within less than a year; 18 returned between 1 and 3 years, 10 between 3 and 5 years and 5 over 5 years later.
The condition of 36 patients was considered to have been improved. This consisted of either normalization of the raised intracranial pressure, stabilisation or improvement of vision, partial or complete reversal of neurological deficit like hemiparesis and/or attainment of secondary sexual characters. In 5 patients, the condition remained unchanged post-operatively. The condition of 8 patients was worse after surgery. This was either as a complication of surgery or due to tumour progression. Of the 8 patients who worsened after surgery, in 2, the vision deteriorated as a consequence of surgery; in 5, vision deteriorated due to tumour progression and in 1, it deteriorated due to a post-operative pituitary abscess. One of these 8 patients in addition, had post-operative hemiplegia; in 1 patient raised intracranial pressure persisted and 1 patient developed post-operative diabetes insipidus. Twelve patients died and 1 is presumed dead as his condition at discharge was very poor. Three of these patients died within hours of being admitted disallowing even radiological confirmation of the diagnosis. Diabetic ketoacidosis 2 years after biopsy and radiation therapy was the cause of death in another patient. In 1 patient, the cause of death was a drug allergy in the post-operative period. Pyogenic meningitis was responsible for death in 2 patients. In 1 of these, it was related to shunt infection and in the other to surgery on the tumour. Five of these 12 patients had varying degrees of residual tumour and raised intracranial pressure on post-mortern examination. Of the 12 patients who expired, 4 were either very drowsy or unconscious before surgery. Looked at in another way 4 of the 9 pre-operatively drowsy patients expired and another discharged in a very poor state is presumed dead. At the time of the final evaluation of the 51 living patients, 38 were independent, 9 were partially dependent, 3 were dependent and the fate of 1 is not known.
Since a large number of patients had pre-operative visual compromise, the results were assessed in terms of visual improvement. In 17 patients the vision improved, in 15 it remained unchanged, in 11 it was worse and in 6 patients the vision was normal prior to surgery. One patient preferred to have her treated elsewhere. In 1 of the 11 patients, vision worsened immediately after surgery. Worsening was due to direct or indirect (vascular) injury to the optic apparatus in 6 patients and in 1 it was due to pressure from a post-operative pituitary abscess. In the remaining 4 patients vision deteriorated over a period of time due to tumour progression. In the 6 patients in whom operative trauma is presumed, radical excisions were attempted.
The intracranial pressure was pre-operatively normal in 15 patients. In 42 patients, it was normalised after insertion of shunt and/or excision of the tumour. In 2 patients the raised intracranial pressure persisted and in 3 it increased. Of these 5 patients, 3 expired and 2 were discharged in a very ill state. The outcome in 1 patient who sought treatment elsewhere is not known.
In 5 of the 7 amenorrhoeic patients, amenorrhoea persisted, and the situation in 2 is unknown. Of the 12 patients with absence of secondary sexual characters, 9 did not regain them after treatment and in 3 the treatment has been only recently completed.
Post-radiation therapy, computed scanning was possible only in 33 patients. In 40 patients this was not possible due to either financial constraints, lack of follow-up evaluation or death. Of the 23 patients in whom this was possible in 2 patients there was no tumour residue. A large residue was seen in 13 patients, which was predominantly calcified in 7. Since all but 2 of these patients were doing well, no additional surgery was offered. One of these 2 patients whose vision had begun to deteriorate had the cystic portion evacuated again with rapid improvement of vision. The second patient who had undergone radiation therapy to the rock like calcified suprasellar tumour without the benefit of surgery, returned two years later with evidence of raised intracranial pressure and ataxia. Repeat scans showed cystic extensions of the tumours into both cerebellopontine angle cisterns. The cyst was evacuated by a right retromastoid approach. The cyst was partially excised and a tube was left between the cyst and the subarachnoid space. The patient was discharged in an asymptomatic state. In the remaining 8 patients small, partially calcified residues were seen on the scans. More importantly since all these patients were doing well, no additional surgery was offered.
Craniopharyngiomas are considered to be most effectively treated by a total excision,,,,. This is however, beset with many problems, the principal ones being the close relationship of the tumours to the optic apparatus, carotid arteries, its major branches, the vital perforators and the hypothalamus. Some tumours appear to infiltrate into the hypothalamus,,,, and others, wrap themselves inextricably around the suprasellar neurovascular structures. Other daunting factors are the limited space between the usually prefixed chiasm and the need to exert constant traction on the tumour during excision. These are offset to a certain extent by the plane provided by the "glial envelope" between the tumour and the brain, permitting relatively safe dissection in this plane. Despite all the advantages of good imaging, reliable anaesthesia, availability of steroids and use of microsurgical techniques, removal of craniopharyngiomas is associated with significant mortality and morbidity,,,,,,. These take the form of visual deterioration, morbidity from hypothalmic injury, high incidence of diabetes insipidus, syndromes of anterior pituitary deficiency, growth hormone deficits and frontal lobe syndromes due to prolonged retraction during the subfrontal approach. The frequency and graveness of these complications are closely related to the extent of excision carried out. Until radiation therapy was shown to be effective,,,, partial excisions were associated with early symptomatic recurrences. Good results have been reported with radical excision followed by radiation therapy and is recommended by a majority of recent authors,,,,,,.
Past unhappy experiences with radical excision have made us veer towards a conservative excision followed by radiation therapy. The conservative excision in our minds is one in which cysts are surgically evacuated and drained into the subarachnoid space, as much tumour as can be safely removed is excised, the end result being decompression of the optic apparatus and hypothalamus. A radical excision is attempted only when the optic chiasm is displaced postero-superiorly and when no 'blind' tumour excision or traction is necessary, a rare combination of circumstances !
This conservative excision is aided by insertion of a shunt to control the hydrocephalus if present. A similar approach of biopsy and cyst drainage followed by radiation therapy has been recommended by some surgeons,,,,,.
In 21 patients the operation consisted of only a biopsy or was associated with evacuation of a cyst. In 23 patients only a partial excision of the mass was achieved, whereas a subtotal excision was possible in 12 patients and a total excision in only 2. This predominantly conservative approach improved the condition of 36 patients. The state of 5 patients remained unchanged, whereas 8 patients worsened. Radiation treatment was administered to 42 patients and it is believed that it has a major role in control of these tumours. This is dramatically demonstrated in one patient [Figure - 1], [Figure - 2] and [Figure - 3] whose tumour disappeared following biopsy and radiation therapy. On the basis of the above retrospective study the following is proposed:
1. Total tumour removal is the ideal form of treatment. It should be attempted only in situations when all the important adjacent neurovascular structures can be safeguarded. At no stage should traction on the tumour or blind dissection be necessary to remove tumour. Total tumour removal should be confirmed by a 3 month post-operative CT scan. Residual tumour either large and obvious or an enhancing small component needs to be treated further with radiation therapy. Heavily calcified residual tumour should not be radiated, but the patient should have regular clinical and radiological evaluation.
2. Radical or subtotal removal of tumour also follows the above mentioned rules. Residual tumour is treated by radiation therapy.
3. Conservative removal of tumour is resorted to when the neurovascular structures are at danger during surgery. This has been so especially when the chiasm is prefixed and the approach has had to be made through the lamina terminals, or between the optic nerve and carotid artery or lateral to the carotid artery. The aim is to evacuate the distended cyst, excise as much as is absolutely safe and decompress the optic apparatus and hypothalamus. Residual tumour is irradiated.
4. Significant hydrocephalus is controlled with a ventriculoperitioneal or atrial shunt.
[Figure - 1], [Figure - 2], [Figure - 3]