Key-words:
Craniopharyngioma - extent of resection - outcome
Introduction
Craniopharyngiomas (cranio = skull, pharynx = throat, and oma = tumor) are benign,
slow-growing, locally invasive intracranial tumors that can generate considerable
morbidity, and recurrences are often difficult to manage. Reliable morphologic criteria
for accurately predicting the clinical outcome of these tumors are lacking. It has
challenged the neurosurgeon and his skills for many years. These tumors have a very
intricate relation with the hypothalamus, pituitary stalk, and optic apparatus, which
have caused excessive problems regarding optimal management. In spite of its recognition
in the late 1800's, no clear consensus is reached with regard to its treatment. Philosophy
of treatment is not only different among different surgeons but also in the span of
a surgeons career. Computerized tomography (CT) and magnetic resonance imaging (MRI)
are the investigations of choice, but today, the best imaging tool is MRI. Many people
with craniopharyngioma go on to live uncompromised or relatively uncompromised lives.
This is not always the outcome. Early detection and better therapeutic techniques
are still required and must remain a priority. Total tumor removal is still the ideal
form of treatment but should be attempted in situations when all the important adjacent
structures can be safeguarded. Total tumor removal should be confirmed by a 3 month's
postoperative CT scan and residual tumor should be treated with radiation therapy.
Conservative removal of tumor is done when the cerebrovascular structures are at danger
during surgery. The aim is to evacuate the distended cyst, excise as much as is absolutely
safe and decompress the optic apparatus and hypothalamus. Residual tumor is irradiated.
Karavitaki et al.[[1]] reported the 10 years survival rates of 77% to 100% after partial resection and
subsequent radiotherapy and 81.3%–100% after radiologically confirmed total removal.
Data on the treatment option with the most favorable impact on survival are not consistent.
Most studies [[1]],[[2]] suggest that postsurgical follow-up should be planned in 1–2 weeks for all patients
and radiotherapy should start radiation within 3 weeks of surgery. Patients should
be seen every 3 months for the first postsurgical year, every 6 months in the 2nd
year, and 3rd years and yearly thereafter and should have a brain MRI/CT scan for
comparison with previous films. In King George Hospital (KGH), no study has been done
specifically to determine the incidence, management, and outcome of various treatment
modalities on craniopharyngiomas, hence this study aims to generate useful data to
improve the management of these patients.
Methodology
Study design
This is a descriptive hospital-based retrospective and prospective study to enable
the researcher to get the required sample size due to the few number of patients.
Study setting
The study was conducted at the neurosurgery clinic, neurosurgical ward and histological
results were retrieved at the pathology department and patients' files were retrieved
from the records departments.
Study population
The cases treated from January 2014 to January 2018 at the above-mentioned units with
a diagnosis of craniopharyngioma were recruited to the study and cases were followed
for the duration of 3 and 6 months after treatment. Records of retrospective clients
were retrieved and great effort used to follow-up and interview patients taking part
in the study. The Karnofsky score, visual and motor deficits on admission; 1 week,
3 months, and 6 months postoperatively were recorded. Assistance of the ophthalmologists
was required to assess visual acuity.
Where N * Sample number
P * Prevalence of craniopharyngiomas among patients admitted with brain tumors (2%)
Z – Standard errors from the mean corresponding to 95% confidence interval
d = margin of error (absolute precision) (5%)
a = level of significance
The sample size was 41 patients.
Inclusion/exclusion criteria
-
Inclusion criteria
-
Exclusion criteria
Data collection procedure
The information was collected using a data collection sheet (questionnaire). The same
questionnaire was used for both the retrospective and prospective parts of the study.
Demographic data including the age and sex were collected. The presenting symptoms,
signs, and investigations done including laboratory and radiological prior to intervention
and comorbidity factors such as hypertension, diabetes, and others were recorded.
Preoperative care, treatment modalities, and complications after treatment were documented.
Scoring of retrospective clients as per the Karnofsky and Lansky Scores was determined
from the patient's file before admission, postoperatively and findings recorded in
the file during the follow-up visits were used, and every effort was attempted to
follow-up the patients at the neurosurgical clinic. The contacts recorded in the file
were sought if the patients would have absconded to attend the follow-up clinics.
Scoring of prospective patients as per the Karnofsky score was determined by the researcher
on admission, 1-week and 3-months postoperatively, and the patients were followed
up for a maximum period of 6 months.
Observation and Results
Incidence
The study assessed 41 patients who had been managed as cases of craniopharyngiomas
from 2014 to 2018. Twenty-nine (71%) of the study participants were assessed prospectively
and 12 (29%) were assessed retrospectively, over the study period of 2014–2018. There
were 577 tumors treated at KGH, of which 41 (7.17%) were craniopharyngiomas. [[Figure 1]] shows the proportion of brain tumors that were cases of craniopharyngioma treated
at KGH over the period.
Figure 1: Proportion of tumors that were craniopharyngiomas treated at King George Hospital
between 2014 and 2018
Demographics
There were 20 (48.8%) male and 21 (51.2%) female among the study participants. The
mean age was 18.3 years with a mode of 5 and a standard deviation of 15.9 years. The
youngest was <1 year and the oldest was 59 years. As shown in [[Table 1]], craniopharyngioma was the most common in the age group (5–14 years [51.2%]).
Table 1: Demographics
As shown in [[Figure 2]], the craniopharyngioma was more common in the younger population than in the older
one.
Figure 2: Age distribution
Presenting complaints
Thirty-seven patients 90%) had headache, 32 patients (78%) had visual disturbances,
23 patients (56%) had vomiting, and 10 patients (24%) had convulsions. Six patients
(15%) had memory and sleep disorders and 3 patients of those >15 years (12.5%) had
amenorrhea/sexual dysfunction, as shown in [[Figure 3]].
Figure 3: Presenting complaints
Physical examination findings
Six patients with oculomotor deficit, 3 patients (7%) had abducens nerve palsy, and
1 patient (2%) had vestibule cochlear nerve disorder, Twenty patients had decreased
visual acuity and ten patients were totally blind as shown in [[Figure 4]].
Figure 4: Clinical presentation
Laboratory investigations
As shown in [[Table 2]], 4 out of 15 (26.7%), 2 out of 5 (40%), and 11 out of 21 (52.4%) had normal prolactin,
growth hormone, and cortisol levels, respectively. Nine out of 15 (60.0%) patients
had hyperprolactinemia and 13.3% had hypoprolactinemia, while three out of five patients
(60%) had low growth hormone levels. Ten out of 21 patients (47.6%) had hypocortisolemia
as shown in [[Table 2]].
Table 2: Laboratory investigations- hormonal profile
Treatment
Forty-one patients were done CT-scanning and MRI. Twenty-six (63.4%) and 15 patients
(36.6%) had suprasellar and sellar with suprasellar extension on radiological imaging,
respectively, as shown in [[Figure 5]].
Figure 5: Radiological location of tumor
Forty-one patients were done craniotomies. Twenty-three (57.5%) of the patients had
surgery alone and seventeen (42.5%) underwent radiotherapy in addition to surgery.
Thirty-seven (91.0%), three (7.5%), and one (2.5%) of the patients had partial excision/decompression,
biopsy-only, and complete excision, respectively as show in [[Figure 6]], during craniotomy and 23 (57.5%), underwent additional surgical procedures (ventriculoperitoneal
shunt) to relieve hydrocephalus. Six patients had two craniotomies done due to confirmed
tumor recurrence on follow-up.
Figure 6: Type of procedure
Complications after surgical treatment
Forty-one patients were done craniotomies; no intraoperative death was reported. Thirteen
patients (32.5%), seven (17.5%), nine (22.5%), seven (17.5%), and five (12.5%) had
residual neurological deficits, diabetes insipidus, seizures, deteriorating neurological
status, and hydrocephalus, respectively, after surgical intervention. Postoperative
infections (meningitis, wound sepsis, and pneumonia) occurred in seven patients (17.5%)
during the follow-up period. Three patients (7.25%) had meningitis, one patient (2.0%)
developed a wound infection, and three patients (7.25%) developed pneumonia.
Outcome
Overall outcome
Seventeen (41.4%) patients were dead, 23 (56.0%) had a good and moderate performance
and 1 (2.4%) had a poor performance after surgery or surgery combined with radiotherapy
upon 6 months of follow-up as shown in [[Figure 7]].
Figure 7: Outcome in relation to all type of treatment
Outcome in relation to type of treatment
12 out of 23 (52.1%) of patients were dead, 11 (47.8%) had a good and moderate performance,
and none had a poor performance after 6 months of follow-up following surgical intervention
alone and 4 out of 17 (17.6%) patients were dead, 12 (76.5%) had a good and moderate
performance, and one (5.9%) had a poor performance after 6 months of follow-up following
combined surgical and radiotherapy interventions.
Outcome in relation to type of surgery
As shown in [[Figure 8]], outcome was more favorable in patients done biopsy only with 67% being alive at
6 months, whereas 44% of those done partial excision/decompression [[Figure 9]] and [[Figure 10]] being alive at 6 months, outcome was worse in the patient done complete excision.
Figure 8: Outcome in relation to the type of surgery
Figure 9: Retrochiasmatic cyst decompression
Figure 10: Partial decompression of tumor
Discussion
In a study at KNH by Mahindu,[[2]] the relative incidence of craniopharyngioma was reported as 5.8%. In this study,
the relative incidence is 7.1% which is different with the incidence reported by Cushing
[[3]] and Ruberti [[4]] of 4.4%–4.6%. The majority of the patients in this study were mainly from the East
and West Godavari probably due to the proximity to KGH. If the statistics from the
rest of the country were considered, the results could have been different. There
was no gender difference in the study participant. Mcdonald et al.[[5]] reported in their study that there is no variation by gender or race and Shin et
al.[[6]] reported the same findings. Hoffman et al.[[7]] from the hospital for sick children in Toronto in a study of total excision of
craniopharyngioma in 50 children noted that the tumor was more common in boys than
girls (56%, 44%), and this is supported by Nagpal [[8]] and Baskin and Wilson [[9]] (68%, 32%) and (54%, 36%), respectively. The age at diagnosis varies widely and
cases have been reported in fetuses and in the elderly. It may occur at any age but
most commonly presents in childhood or adolescence. A bimodal distribution by age
with peak incidence rates in children (aged 5–14 years) and among older adults (aged
65–74) was noted.[[1]] Fahlbusch et al.[[10]] in Europe also noted a bimodal distribution with peak incidence at 15–20 years
and another at 50–55 years. In this study, the tumor tends to occur in the young age
groups of 0–14 years and 15–24 years. There is no bimodal distribution noted in this
study. Kendall-Taylor et al.[[11]] reported the peak age at onset as 15–20 years.
The most common presenting symptoms were headache (90%) and visual disturbances (78%),
which correspond to findings in other literature of headache (55%–86%) and visual
disturbances (37%–68%). Honegger et al.[[12]] showed visual compromise in 75.0% of patients compared with 78.0% in this study.
Baskin and Wilson[[9]] found that considering the pediatric and adult population together, on physical
examination, 72% of patients have visual defects which correspond to the findings
in this study, whereby 78% of the patients had visual defects. Nagpal [[8]] found that the common presenting symptoms were headache and vomiting (48/63, 76%)
and diminished vision (44/63, 70%) which corresponds to findings in this study. Other
studies have reported the same.[[9]],[[13]],[[14]],[[15]] Amenorrhea/sexual dysfunction occurred in 3 out of 24 (12.5%) patients >15 years
which concurs with findings reported by Nagpal [[8]] of 8 out of 63 (13%) patients. Jennifer et al.[[16]] found that most adult patients with craniopharyngioma present with amenorrhea (64%),
impotence, or diminished libido (45%). In this study, hyperprolactinemia (60%) low
growth hormone levels (60%), and hypocortisolism (47.6%) occurred in the tested population.
In patients done hormonal tests, deficiency was found in 60% of patients compared
to 39%–43% in the literature. Hypocortisolism occurred in 47.69% of tested patients
in this study which is also comparable to 50% in other studies.[[16]] This is due to the close anatomical relationship of the tumor with the pituitary
and hypothalamus leading to compression of these structures and thus various hormonal
deficiencies.
CT and MRI are the examinations of choice. Although today MRI is the imaging tool
of choice, almost all patients were done CT scanning. Most craniopharyngioma lesions
were suprasellar 63.4% and only 36.6% were sellar with suprasellar extension. Craniopharyngioma
lesions are located predominantly in the suprasellar area. Ten percentage of craniopharyngioma
lesions are purely suprasellar in a study by Jennifer et al.,[[16]] and this is supported by Nagpal [[8]] who reported suprasellar lesions/suprasellar extensions in 78% and only 1.6% of
craniopharyngiomas were entirely intrasellar. This is related to development of the
pituitary gland and the development of craniopharyngioma from the Rathke's cleft and
craniopharyngeal duct remnants. Craniopharyngiomas are considered to be most effectively
treated by a total excision.[[17]],[[18]],[[19]],[[20]],[[21]] This is beset with many problems due to the close relationship of the tumors to
the optic apparatus, carotid arteries, and the hypothalamus.[[19]] Some tumors infiltrate into the hypothalamus,[[22]] limited space between the chiasma, and the need to exert constant traction on the
tumor during excision. In this study, complete excision was achieved in 1 out of 41
(2.5%), partial excision/decompression in 37 out of 41 (91.0%), and biopsy only in
3 out of 41 (7.5%). In a study by Nagpal,[[8]] biopsy and aspiration of cyst were done in 21 out of 58 patients (36%), partial
and subtotal excision in 35 out of 58 (61%), and total excision in two patients (3%)
which differs from the findings of this study. There is more tendency toward biopsy
and aspiration of cyst in the Nagpal study.[[8]] This illustrates the difficulty in surgical management of this condition.
Fahlbusch et al.[[10]] in a study of 148 patients undergoing initial surgery, total tumor removal was
accomplished in 45.7% of transcranial and 85.7% of transsphenoidal procedures. Reasons
for incomplete removal were attachment and/or infiltration of the hypothalamus/major
calcifications and attachment to vascular structures. 17 out of 40 patients (42.5%)
received radiotherapy and 23 patients (57.5%) did not receive radiotherapy due to
death in the immediate postoperative period, death at home/other peripheral health
facilities after discharge, and loss to follow-up. In Nagpal study,[[8]] 42 out of 58 (72.4%) patients received radiotherapy, which is higher than the number
of patients who received radiotherapy in this study. Neurosurgical options at first
surgery for craniopharyngioma included subtotal resection with radiotherapy (29%)
Subtotal resection alone (57%) and gross total resection alone (14%) in a study by
Jennifer et al.[[19]]
Thomsett et al.[[23]] in a review of the effect of treatment in 42 patients found that recurrence and
mortality rates as well as neurological outcome of survivors were similar in children
treated by radical excision and those treated by limited excision plus radiotherapy.
The neurologic prognosis was poorest in those children who had limited excision or
drainage without radiotherapy. Additional hypothalamopituitary dysfunction following
treatment was less common in children who had limited excision plus radiotherapy than
in children who had either limited excision or attempted total removal. They concluded
that unless gross total tumor excision can be readily achieved, limited excision plus
radiotherapy appears to be the treatment of choice for craniopharyngioma in childhood.
39% had a moderate and good outcome and 2.4% had a poor outcome at 6 months of follow-up.
Nagpal [[8]] at the time of the final evaluation of the 51 living patients found that 38 (74.5%)
were independent, 9 (17.6%) were partially dependent, and 3 (6%) were dependent. Hoffman
et al.[[22]] at the final evaluation found that of the 46 children followed 64%, 27%, and 9%
had good, moderate, and poor prognosis, respectively, which differs from the findings
of this study.
In this study, the outcome was more favorable in patients <18 years, males, patients
without headache, patients with vomiting, visual disturbances, hyperprolactinemia,
hypoprolactinemia, and hypocortisolism. The outcome was also favorable in patients
with completely suprasellar lesions, intrasellar with suprasellar extension, patients
done biopsy only, partial excision/decompression, and in those who received postoperative
radiotherapy.
Bunin et al.[[24]] in the USA found a 5-year survival rate of 80% and decreased with older age at
diagnosis. Survival is higher among children and has improved in the recent years.
Duff et al.[[25]] found that 73 of 121 patients devaluated had a good outcome of a mean follow-up
period of 10 years. A good outcome was associated with survival at the follow-up examination,
functional vision; a Katz grade of A and a Karnofsky Performance Scale score of at
least 80.
In this study, 7 patients (17.3%) had tumor recurrence after partial excision/biopsy.
This is low in comparison to findings in other studies. This could be due to the high
mortality rate in this study and lack of regular postoperative CT scan/MRI to assist
in early detection of recurrence.
In the study by Shin et al.,[[6]] recurrence rate was 62% and the mean time to recurrence + 24 months. None of the
patients who had gross total resection had a recurrence in contrast to the 67% who
had partial excision. The cumulative rates of recurrence-free survival were 57% at
5 years, 48% at 10 years, and 43% at 20 years. A similar recurrence rate (69%) with
partial removal was found by Fahlbusch et al.[[10]] Recent series reports indicate 81%–91% 10 years recurrence-free survival rate after
subtotal tumor removal followed by radiotherapy with 46%–58% of the survivors living
a normal independent life.[[26]]
Conclusions
We believe that total removal of craniopharyngiomas is possible in selected cases,
and it has been our experience in adults that this cannot often be achieved. A subtotal
removal followed by radiation therapy has been a satisfactory approach in our hands,
and with modern microsurgical techniques as well as with the advantages of modern
radiotherapeutic techniques, this approach has led to remission in approximately 90%
of our patients. While our follow-up period is admittedly short and it will be important
to continue to follow these patients over the next several decades, it appears that
with continuing and careful endocrine replacement therapy and monitoring, these patients
can resume a fully functional life with few limitations.
