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Advances in Surgery for Pituitary Tumors
in tumorigenesis in the pituitary in a mouse model, the retinoblastoma Although prolactinomas are the most common sub-type of pituitary
(Rb-1)
+/-
mouse. This will, no doubt, stimulate considerable interest in the tumor in population-based studies, they account for a minority of
study of the cellular originators of human pituitary tumors. patients in surgical series. This is because of the excellent control rates
achieved with the use of the dopamine agonists bromocryptine and
Diagnosis of Pituitary Tumors cabergoline. Two recent studies have added new information on surgical
Accurate surgical planning and prognostication for pituitary tumors rely outcomes in patients with prolactinomas. Kreutzer and colleagues
10
heavily on pre-operative imaging studies, primarily MRI. Invasion of the reported on their experience in 212 patients who underwent resection
cavernous sinus is a recognized indicator of increased aggressiveness of prolactinomas from 1990 to 2005. These included patients who
of the tumor and reduced probability of complete surgical removal. underwent surgery for ‘non-classic indications,’ i.e. cystic tumors and
However, in many cases it can be difficult to differentiate between patients who simply preferred surgery over prolonged medical therapy.
invasion of the cavernous sinus by the tumor and simple compression They found an overall remission rate of 42% for all tumors. However,
of the sinus, even with high-resolution MRI. Yoneoka and colleagues
8
patients with microadenomas and cystic tumors fared much better. This
used a new MRI technique, 3D anisotropy contrast (3DAC) MRI, to report confirms that prolactinomas can be successfully treated with
address this problem. They found that 3DAC MRI identified the surgery in a large number of patients and that those with small tumors
oculomotor and ophthalmic/maxillary nerves in the cavernous sinus in and cystic tumors have a higher probability of long-term tumor and
100% of controls and the trochlear and abducent nerves in 76 and 72% endocrine control. An interesting study from UCSF
11
took advantage of
of cases, respectively. They compared imaging of 33 patients with their large surgical experience that extends back to a time before
pituitary macroadenomas with 25 control subjects. They used tumor medical therapy for prolactinomas was well-established as the first-line
encasement of at least half the circumference of one of the choice of therapy for these tumors. They compared patients who
intracavernous cranial nerves as a criterion for sinus invasion. This was underwent surgery for prolactinoma as the initial treatment with
validated by direct intra-operative observations at the time of tumor patients who had a course of dopamine agonist therapy prior to surgery.
removal. They found 100% correlation between the imaging-based They found that short- and long-term endocrine control rates were
predictions and the operative findings. Although preliminary, these better in patients who had medical therapy prior to surgery. This argues
findings suggest that 3DAC MRI may prove to be a useful addition to pre- against the observation reported by some surgeons that pre-surgical
surgical work-up in patients with pituitary macroadenomas. medical therapy makes prolactinomas harder to remove.
Surgical Techniques and In a related issue, investigators continue to address the concern for
Peri-operative Management possible deleterious effects of the ergot-derived dopamine agonist,
Although pituitary adenomas are most often benign and slow-growing, cabergoline, on heart valve abnormalities in patients with prolactinomas.
they remain a considerable source of morbidity and mortality over a long Two studies demonstrated an increased risk in patients taking pergolide or
time-frame. Uncertainties exist regarding long-term post-operative cure cabergoline for Parkinson’s disease.
12,13
Both drugs were associated with an
and control rates for pituitary tumors, with some centers recommending increased risk for heart valve regurgitation. This is similar to heart valve
post-operative radiation therapy in all patients. A recent retrospective abnormalities seen with other ergot alkaloids and carcinoid tumors and
study from the University of California, San Francisco (UCSF)
9
has appears to be related to activation of the serotonin receptor type 2B
provided excellent long-term outcome data from patients with (5-HT2B). However, the doses of cabergoline used in the Parkinson’s
non-functioning pituitary adenomas treated with surgery and, in some studies were much higher than those typically used in the treatment of
cases, adjuvant radiation therapy. They followed 663 patients treated by prolactinomas. Three recent cross-sectional studies have attempted to
a single surgeon from 1975 to 1995. They compared outcomes for address the issue of safety of carbergoline in the treatment of
patients with surgery alone and those with surgery followed by prolactinomas. Two studies found no increased pevalence of clinically
fractionated radiation therapy. They found overall recurrence-free relevant heart disease in patients treated with cabergoline.
14,15
One study
probabilities of 0.87 at 10 years and 0.81 at 15 years. They found that found an increased prevalence of moderate tricuspid regurgitation on
radiation therapy did not provide any improvement in recurrence-free echocardiography in patients being treated with cabergoline compared
status if a gross total resection of the tumor had been achieved, but it did with newly diagnosed prolactinoma patients and control subjects.
16
improve outcome if a sub-total resection had been performed. They Currently, most centers are continuing to use cabergoline to treat
found that patients with gross total resections and those with sub-total prolactinomas, but many are advocating an increased use of surveillance
resections followed by radiation therapy had similar long-term control echocardiography in these patients and the safe upper limit of cabergoline
rates. However, when comparing long-term mortality rates with those dosage in relatively refractory prolactinomas remains an open issue.
expected from the general population, they found that the patients with
sub-total resections and those who had undergone radiation therapy had Minimally invasive approaches to pituitary tumors continue to generate
increased long-term mortality rates and those with gross total resection widespread enthusiasm in the surgical community. The endonasal,
had mortality rates similar to the general population. This led to the trans-sphenoidal approach offers the advantage of no visible incision,
recommendation that a gross total resection should be the goal of all limited disruption of soft tissue and bony structures, no need for post-
surgeries where it is feasible and radiation therapy should be reserved operative nasal packing, and shorter hospital stays. The minimally
for those patients with known residual or recurrent disease. This study invasive endonasal approach can be used either with direct vision
also documented the importance of long-term follow-up with pituitary through a surgical microscope or as a purely endoscopic procedure. Both
adenomas, as recurrences could occur five to 10 years after treatment. methods have their proponents. Several new clinical series have
US ENDOCRINOLOGY 101
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