Long-term Results of Endonasal Endoscopic Transsphenoidal Resection of Nonfunctioning Pituitary Macroadenomas

Abstract BACKGROUND: Several studies report early results of endoscopic endonasal transsphenoidal surgery; however, none discuss long-term outcome measures such as tumor recurrence rates and the need for additional surgical procedures. OBJECTIVE: To discuss the long-term outcomes after endoscopic endonasal transsphenoidal surgery for nonfunctioning pituitary macroadenomas. METHODS: This is a retrospective study. Patients were included only if they had at least 5 years of clinical and imaging follow-up after surgery. RESULTS: Eighty patients met the study criteria. Grossly complete resection was achieved in 71% of patients. Knosp grade 0 to 2 tumors and tumor with volumes <10 cm3 were significantly more likely to have received a grossly complete resection. There were 7 recurrences (12%) in patients who had received grossly complete resections, with a mean time to recurrence of 53 months. Among the 23 patients who had subtotal resections, 11 (61%) progressed radiographically, and 3 (17%) had symptomatic progression. Knosp score, surgical and radiographic evidence of invasion, and preoperative visual deficits were predictive of recurrence in a univariate analysis, but Knosp grade was the only independent predictor in a multivariate analysis. Kaplan-Meier analysis projected a 10-year progression-free survival rate of 80% and 21% for patients with gross total resections and subtotal resections, respectively. CONCLUSION: At the long-term follow-up, 12% of patients had recurrent tumors after grossly complete resection. Recurrent or residual tumors were treated with either repeat surgery or Gamma Knife radiosurgery. Rates of complete resection, postoperative surgical and endocrinological complications, and additional surgical procedures are similar to previously published reports after microscopic transsphenoidal surgery

Delayed contrast extravasation MRI for depicting tumor and non-tumoral tissues in primary and metastatic brain tumors.

The current standard of care for newly diagnosed glioblastoma multiforme (GBM) is resection followed by radiotherapy with concomitant and adjuvant temozolomide. Recent studies suggest that nearly half of the patients with early radiological deterioration post treatment do not suffer from tumor recurrence but from pseudoprogression. Similarly, a significant number of patients with brain metastases suffer from radiation necrosis following radiation treatments. Conventional MRI is currently unable to differentiate tumor progression from treatment-induced effects. The ability to clearly differentiate tumor from non-tumoral tissues is crucial for appropriate patient management. Ten patients with primary brain tumors and 10 patients with brain metastases were scanned by delayed contrast extravasation MRI prior to surgery. Enhancement subtraction maps calculated from high resolution MR images acquired up to 75 min after contrast administration were used for obtaining stereotactic biopsies. Histological assessment was then compared with the pre-surgical calculated maps. In addition, the application of our maps for prediction of progression was studied in a small cohort of 13 newly diagnosed GBM patients undergoing standard chemoradiation and followed up to 19.7 months post therapy. The maps showed two primary enhancement populations: the slow population where contrast clearance from the tissue was slower than contrast accumulation and the fast population where clearance was faster than accumulation. Comparison with histology confirmed the fast population to consist of morphologically active tumor and the slow population to consist of non-tumoral tissues. Our maps demonstrated significant correlation with perfusion-weighted MR data acquired simultaneously, although contradicting examples were shown. Preliminary results suggest that early changes in the fast volumes may serve as a predictor for time to progression. These preliminary results suggest that our high resolution MRI-based delayed enhancement subtraction maps may be applied for clear depiction of tumor and non-tumoral tissues in patients with primary brain tumors and patients with brain metastases

Correlation with time to progression.

<p>The correlation between the late enhancement subtraction maps and time to progression was studied in a small cohort of 13 GBM patients post chemoradiation. Kaplan-Meier curves of time to progression in patients above and below the median of four predictors are shown: Initial fast volume (A), initial enhanced volume (B), initial fast growth rate (C) and initial enhanced growth rate (D). The curves are plotted for each predictor for patients above (black) and below (gray) the median. It can be seen that the initial fast growth rate predictor provides a near-significant difference between the two groups of patients, suggesting this predictor may be a candidate for prediction of time to progression.</p

Newly diagnosed GBM cohort.

<p>List of newly diagnosed GBM patients with post chemoradiation treatment follow-up.</p>*<p>Column #2: Patients were diagnosed with GBM prior to initiation of chemoradiation by histological analysis of either gross tumor resection (GTR), sub-total resection (STR) or stereotactic biopsy samples (STB).</p>*<p>Column #4: Stereotactic samples were taken from locations determined using the late enhancement subtraction maps calculated from the pre-surgical MRIs.</p>*<p>Column #5: In cases where progression was not reached, the duration of follow-up is listed in parenthesis.</p

Enhancing lesion volume.

<p>Contrast-enhanced T1-weighted MRI without (A) and with (B) a mask selecting the enhancing portion of a GBM tumor (patient #4) are shown. The enhancing lesion volume was calculated from the pixels marked pink in (B). Enhancement subtraction maps calculated at 15 min (C) and 75 min (D) demonstrate the contributions of the red/non-tumor and blue/tumor contributions to the enhancing lesion volume.</p

Histological determination of tumor and non-tumoral components – GBM.

<p>Examples of contrast-enhanced T1-weighted MRI (A–C), enhancement subtraction maps calculated from the 2 and 75 min data (D–F) and H&E stained histological samples of a rapidly growing lesion in patient #1 with newly diagnosed GBM undergoing standard chemoradiation are shown. Data was acquired prior to surgery, 6 months after initiation of treatment. Samples were taken from a mixed blue and red region (A, D, arrows), a blue region (B, E, arrows) and a red region (C, F, arrows). Histological analysis reveals mixed regions of tumor and necrosis (G, magnification×200), hypercellular tumor (H, magnification×400) and radiation necrosis (J, magnification×400), respectively.</p

Comparison with rCBV.

<p>Contrast-enhanced T1-weighted MRI (A, D, G), enhancement subtraction maps (B, E, H) and rCBV maps (C, F, I) of patients # 6 (A–C), #3 (D–F) and #26 (G–I) are shown. Patient #6 (GBM) shows a blue rim surrounding the surgery site, representing morphologically active tumor, in agreement with high rCBV values in the corresponding rCBV map. Patient #3 (GBM) is a contradicting example, showing a massive lesion dominated by the blue population in the subtraction maps (confirmed by histology to consist of ∼70% morphologically active tumor), in contrast to low rCBV values in the corresponding rCBV map. Patient #26 (breast cancer brain metastases) shows a thin rim of the blue populations in our maps in agreement with a thin rim of increased rCBV values. The advantages of our vessel function maps over rCBV acquired using DSC in means of high resolution, high sensitivity to contrast and minimum sensitivity to susceptibility artifacts can be seen.</p

Histological determination of tumor and non-tumoral components – brain metastases.

<p>Examples of contrast-enhanced T1-weighted MRI (A), enhancement subtraction map calculated from the 2 and 75 min data (B), macro H&E stained histological sample (C, magnification x20), tumor region from a peripheral region of the sample (D, magnification x400) and radiation necrosis from the central region of the sample (E, magnification x400) of a medial NSCLC brain metastasis of patient #23 (metastasis #1), 1 year post radiosurgery, are shown. The metastasis was resected unblock and marked by the neurosurgeon to enable comparison with the MRI data. H&E staining shows a large central necrotic region surrounded by a rim of morphologically active tumoral tissue, in agreement with the subtraction map. It is also possible to see part of a necrotic blood vessel in the region of radiation necrosis (E) and scattered blood cells in the tissue.</p