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  • By Author: Laws, Edward R. x
  • By Author: Alden, Tord D. x
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John A. Jane Jr., Daniel M. Prevedello, Tord D. Alden and Edward R. Laws Jr.

Object

The majority of pediatric craniopharyngiomas are treated using a transcranial approach. Although there is an increasing acceptance of transsphenoidal resection in adults, there are few reports describing this approach in the pediatric population. The purpose of this study is to report the outcomes after transsphenoidal surgery in a consecutive series of pediatric patients with craniopharyngiomas treated at a single institution with the goal of gross-total resection (GTR).

Methods

Twenty-three patients with pathologically proven craniopharyngiomas were identified who were 18 years of age or less at the time of surgery. The medical records and imaging studies of the patients were retrospectively reviewed. One patient who was lost to follow-up after surgery was excluded.

Results

Among the 22 patients included in the study, 11 underwent transsphenoidal surgery as the primary procedure and 11 underwent transsphenoidal surgery as a secondary procedure after a previous procedure. All patients had at least some sellar component to their tumor and all had either anterior or posterior pituitary dysfunction at presentation. In the entire cohort, a GTR was achieved in 15 (68%) of 22 patients, a radical subtotal resection in 4 (18%) of 22 patients, a subtotal resection in 1 patient, and a partial resection in 2 patients. The degree of resection was higher in the primary transsphenoidal group. After a mean follow-up of 82 months, 4 patients (18%) experienced recurrence. Recurrence occurred in 13% after GTR compared with 28.5% after all other degrees of resection. Tumor recurred in 9% of the primary transsphenoidal group and in 30% of patients who had undergone other therapies prior to the transsphenoidal operation. No patient who had panhypopituitarism experienced a gain of function postoperatively, 67% developed new panhypopituitarism, and 56% experienced new diabetes insipidus. Vision improved or normalized in 9 (64%) of 14 patients presenting with visual loss. Complications included 1 death 3 weeks postoperatively, 2 CSF leaks, and new obesity in 37%.

Conclusions

Transsphenoidal resection of pediatric craniopharyngiomas results in a high rate of both visual improvement and GTR with a low associated risk of recurrence. The transsphenoidal approach should be considered in selected pediatric patients with craniopharyngioma, especially those with infradiaphragmatic origin.

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Dilantha B. Ellegala, Tord D. Alden, Daniel E. Couture, Mary L. Vance, Nicholas F. Maartens and Edward R. Laws Jr.

Object. Older men with clinically nonfunctioning pituitary tumors have been noted to be anemic, to have hypopituitarism, and to have low serum levels of testosterone. The authors hypothesized that men with pituitary adenomas and hypogonadism have a physiologically related decrease in hematocrit.

Methods. A retrospective analysis was conducted of 216 patients older than 50 years of age who harbored pituitary adenomas. In 100 men serum testosterone levels and a complete blood (cell) count (CBC) were obtained before treatment; a CBC was also acquired in a series of women with pituitary adenomas. Using clinical laboratory standards, anemia was defined as a hematocrit less than 40% in men and less than 35% in women.

Thirty-one (46.3%) of 67 men with low serum concentrations of testosterone were anemic. In men with low levels of testosterone, the average hematocrit was 39.9%, compared with 45.6% for men with normal testosterone levels (p < 0.001). Men with macroadenomas were most likely to have both anemia and a low serum concentration of testosterone. Anemia was associated with a low level of testosterone, adjusting for tumor size (odds ratio 19, 95% confidence interval 4.86–77.03). Of patients with anemia, 84% were men and 16% were women (p < 0.001). The prevalence of anemia in women was low and was not correlated with tumor size. Men receiving testosterone replacement therapy had a significantly higher hematocrit value than men with low or normal testosterone levels.

Conclusions. These findings support a direct relationship between serum testosterone levels and hematopoiesis in men, and demonstrate that hematopoiesis is compromised in men who have low concentrations of testosterone due to a pituitary adenoma.

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Björn P. Meij, Maria-Beatriz S. Lopes, Dilantha B. Ellegala, Tord D. Alden and Edward R. Laws Jr.

Object. Pituitary adenomas are considered benign tumors; however, they may infiltrate surrounding tissues including the dura mater. In this paper the authors analyze the clinical significance of microscopically confirmed dural invasion by comparing a range of variables (age and sex of patients, adenoma type, adenoma size on magnetic resonance [MR] images, remission, residual pituitary disease, recurrence, survival, and disease-free interval after surgery) between patients with noninvasive adenomas and those with invasive ones.

Methods. Between 1992 and 1997 dural specimens were obtained in 354 patients with pituitary adenomas who underwent transsphenoidal surgery performed by the senior author (E.R.L.). Dural specimens were examined using routine histological methods and assessed for invasion by pituitary adenoma tissue.

The dura was invaded by the pituitary adenoma in 161 patients (45.5%), and in 192 patients (54.5%) no evidence of dural invasion was found. Dural invasion was present significantly more frequently in the repeated surgery group (69%, 55 patients) than in the primary transsphenoidal surgery group (41%, 291 patients). The mean age of patients undergoing primary transsphenoidal surgery was significantly older in cases of invasive adenomas (50 years) compared with cases of noninvasive adenomas (43 years), and these age differences also correlated with adenoma size. Women tend to develop clinically evident, smaller adenomas at a younger age than men. Of the patients with pituitary adenomas that were 20 mm or smaller, 117 (76%) of 154 were women, whereas of the patients with adenomas that were larger than 20 mm, 74 (54%) of 137 were men. The frequency of dural invasion increased with increasing size of the pituitary adenoma as measured on MR images. In 291 patients who underwent primary pituitary surgery, the frequency of dural invasion according to adenoma size was 24% (≤ 10 mm), 35% (> 10 to ≤ 20 mm), 55% (> 20 to ≤ 40 mm), and 70% (> 40 mm). In patients who underwent primary transsphenoidal surgery, dural invasion was present in more than 50% of those with nonfunctioning adenomas and in 30 to 35% of patients with endocrinologically active adenomas. The mean diameter of the gonadotrophic adenomas and null-cell adenomas was significantly larger than that of each of the endocrinologically active adenomas.

In 58 (20%) of 291 patients who underwent primary pituitary surgery there was residual pituitary disease postsurgery, and 20% of this subset of patients showed clinical improvement to such an extent that no further management was recommended. After pituitary surgery, residual tumor tissue was demonstrable significantly more frequently in patients with invasive adenomas than in those with noninvasive adenomas.

Recurrences after initial remission (cure) of pituitary disease occurred in 18 (8.8%) of 205 patients between 2 and 79 months after primary pituitary surgery (median 25 months). The recurrence rate was not related to dural invasion in a consistent or significant fashion. Seven patients died between 14 and 79 months after pituitary surgery and all had invasive adenomas identified on gross observation at surgery and on microscopy. The survival rate was slightly but significantly decreased for patients with invasive adenomas (91%) compared with patients with noninvasive adenomas (100%) at 6 years postsurgery.

Conclusions. The principal significance of dural invasion by pituitary adenoma is the persistence of tumor tissue after transsphenoidal surgery (incomplete adenomectomy; 20% in primary pituitary tumor resections). The increase in adenoma size with time and the concurrent development of dural invasion are the major factors that determine an incomplete adenomectomy. When the adenoma remains restricted to the sellar compartment or shows only moderate suprasellar extension, dural invasion may not yet have developed and conditions for complete selective adenomectomy are improved.

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Nathan E. Simmons, Tord D. Alden, Michael O. Thorner and Edward R. Laws Jr.

Object. Transsphenoidal surgery remains the optimal treatment for Cushing disease, but the definitions of surgical cure and failure remain debatable. In this study the authors evaluated serum cortisol levels in patients before and after they underwent transsphenoidal surgery to elucidate the patterns of cortisol decrease and the optimal time and criteria for determining surgically induced remission.

Methods. Twenty-seven patients were evaluated throughout an 8-month period. Serum cortisol levels were obtained before surgery and at 6-hour intervals postoperatively. No exogenous steroid medications were administered until after cortisol sampling was discontinued, following diagnosis of remission.

Twenty-one (78%) of 27 cases were labeled initial surgically induced remissions. Twenty-two (81%) of 27 cases were deemed surgically induced remissions at follow-up examination. Following surgery, initial remissions and failures demonstrated divergent patterns of cortisol levels. No patient whose condition was deemed an initial surgically induced remission has experienced definitive relapse of disease since discharge. One patient whose condition was initially deemed a surgical failure, eventually was found to exhibit surgically induced remission without further intervention.

Conclusions. Given such findings, exogenous steroid medications do not appear to be required for patients until after the determination of remission. During the 1st postoperative day, there is a time period during which serum cortisol values significantly differ between the categories of surgically induced remissions and surgical failures. Surgically induced remissions were identified when postoperative values of cortisol were lower than preoperative midnight levels and when absolute values of cortisol were less than 10 µg/dl. In a small proportion of patients remission on a delayed basis may also be demonstrated. These data allow for a simple and rapid determination of postoperative remission in patients undergoing transsphenoidal surgery for Cushing disease.