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Edward F. Chang, Gabriel Zada, Sang Kim, Kathleen R. Lamborn, Alfredo Quinones-Hinojosa, J. Blake Tyrrell, Charles B. Wilson and Sandeep Kunwar


Long-term outcomes following surgery for nonfunctional pituitary adenomas (NFPAs) are unclear. The role of adjuvant radiation therapy is therefore controversial because it is associated with higher tumor control but also carries known long-term morbidity. The authors' aim was to determine predictors of recurrence and overall survival and to define patient subgroups that may benefit from radiotherapy.


The authors performed a retrospective cohort analysis of 663 patients who underwent surgery between 1975 and 1995 for treatment of primary NFPAs. The main outcome measures were disease progression after surgery, defined by clinical and/or imaging criteria, and all-cause mortality.


Over a median clinical follow-up of 8.4 years, there were 64 (9.7%) recurrences after treatment, with a median time to recurrence of 5.6 years. The 5-, 10-, and 15-year recurrence-free probabilities were 0.93, 0.87, and 0.81, respectively. Multivariate Cox proportional hazard regression analysis identified the following predictors as associated with increased recurrence: cavernous sinus invasion (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.5–6.4; p < 0.001) and subtotal resection (STR) without radiotherapy (HR 3.6, 95% CI 1.4–14; p = 0.01). Using time-to-event estimates to adjust for differences in follow-up between groups, radiotherapy was found to reduce tumor recurrence in only those patients who received an STR (p < 0.001, log-rank test) but not gross-total resection (GTR; p = 0.63, log-rank test). Median follow-up for overall survival was 14.0 years. The 5-, 10-, 15- and 20-year overall survival estimates were 0.91, 0.81, 0.69, and 0.55, respectively. Within the study cohort and in age- and sex-adjusted comparison with the general US population, increased relative mortality was observed in patients who underwent radiotherapy or STR.


Cavernous sinus invasion is an important prognostic variable for long-term control of NFPAs. Radiotherapy results in long-term tumor control for patients who undergo STR but does not affect recurrence rates and may increase the risk of death after GTR. Given the risks associated with radiotherapy, there is no role for its routine application in patients who have undergone GTR of their NFPA. In all patients, long-term monitoring is required.

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James E. Boggan, J. Blake Tyrrell and Charles B. Wilson

✓ The development of transsphenoidal microsurgery and the refinement of endocrinological and radiological diagnostic procedures have afforded therapeutic options appropriate to the individual case in patients with hypercortisolism. The present series of 100 cases is derived from 104 patients with the diagnosis of Cushing's disease who underwent transsphenoidal pituitary exploration between 1974 and 1981. Excluding four patients in whom the pituitary gland was not exposed because of intraoperative technical difficulties, an overall cure rate of 78% was achieved. Among 71 patients with tumors confined to the sella turcica, 87% had correction of their hypercortisolism, 11% represented therapeutic failures, and one patient had tumor recurrence. In contrast, among 25 patients with extrasellar extension, correction of hypercortisolism was achieved in only 48%, 40% failed to respond, and 12% of the patients had recurrence. Four patients who failed to respond to total hypophysectomy have ectopic sources of adenocorticotropic hormone.

The results indicate that transsphenoidal microsurgical exploration for a basophilic adenoma is the procedure of choice in adults and children with Cushing's disease. The diagnostic and surgical approach to these tumors, as well as pitfalls in the transsphenoidal treatment of Cushing's disease, are discussed.

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Sang U Hoi, Charles B. Wilson and J. Blake Tyrrell

✓ From July, 1970, to March, 1975, 62 transsphenoidal operations were performed on 61 acromegalic patients (39 males, 22 females). Of these patients, 58 presented with symptoms of hypersecretion of human growth hormone (HGH), with relatively infrequent local effects. Each patient was evaluated neuroradiologically, and each tumor was classified as an enclosed or an invasive adenoma, with or without suprasellar extension. Anterior pituitary function was also evaluated for each patient, pre- and postoperatively. During the transsphenoidal procedure, selective gross total removal of the adenomatous tissue was attempted, and was successful in 53 patients; selective subtotal tumor removal was performed in eight patients.

In 38 patients who had not undergone prior therapy, a selective total excision was achieved in 36; of these, 30 patients were considered cured, on the basis of relief of clinical symptoms and reduction of the serum HGH level to below 10 mg/ml. There was no significant difference in cure rates between the enclosed and the invasive adenomas, and no cures were achieved by any procedure short of selective total tumor removal. In these latter cases, postoperative irradiation was employed. Eighteen patients had received prior therapy in the forms of cryohypophysectomy (eight cases), cryohypophysectomy and irradiation (two cases), craniotomy (two cases), craniotomy and irradiation (two cases), and irradiation alone (four cases). The treatment results in this group were less favorable. In the entire series of 62 operations, complications occurred in eight patients in the form of cerebrospinal fluid leak, meningitis, sinusitis, nasal-oral fistula, transient diabetes insipidus (six cases), and carotid and cavernous injuries. In the group of 43 previously untreated patients, endocrine complications occurred in five, of which only three have permanent deficits. In the previously treated 18 patients, one developed compromised pituitary function from the transsphenoidal procedure. In the entire series, there was no surgical mortality, although two patients died of surgically unrelated causes.