Letter to the Editor: Knosp Grades 2–3 nonfunctioning pituitary adenomas

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TO THE EDITOR: We read with pleasure the article by Dallapiazza et al.1 that reports on a retrospective analysis of a concurrent series of 99 patients with nonfunctioning pituitary adenomas treated by a well-experienced and renowned surgical group (Dallapiazza R, Bond AE, Grober Y, et al: Retrospective analysis of a concurrent series of microscopic versus endoscopic transsphenoidal surgeries for Knosp Grades 0–2 nonfunctioning pituitary macroadenomas at a single institution. J Neurosurg 121:511–517, September 2014). This study evaluated patients with Knosp Grades 0–2 tumors to compare the results of two different surgical techniques. Fifty-six patients underwent a fully endoscopic transsphenoidal resection, whereas 43 underwent a transsphenoidal microscopic resection. No statistical differences were noticed between the two groups in terms of extent of resection and endocrinological complications. For patients with Knosp Grades 0 and 1 macroadenomas, results similar to those previously reported by us2 were demonstrated. Therefore, both studies confirm the assumption that for an experienced neurosurgeon, no differences exist in terms of the extent of resection for clearly noninvasive pituitary adenoma. For Knosp Grade 2 nonfunctioning pituitary adenoma, however, the situation is more complex. We agree with Dallapiazza et al. that Knosp Grade 2 adenomas are not invasive and that there are doubts regarding true invasion of the cavernous sinus in many tumors classified as Knosp Grade 3 adenomas. According to our experience,2 gross-total resection (GTR) was achieved in 88% and 67% of endoscopically treated Knosp Grades 2 and 3 cases, respectively, compared with 47.8% and 16.7% of cases treated with microscopic surgery. Note that we did not perform an endoscopic transcavernous approach in these tumors and that the good rate of GTR in this patient subgroup was entirely attributable to the extensive opening of the sellar floor, a clear advantage of the endoscopic technique.

The study conducted by Dallapiazza et al. showed no statistically significant correlation between the endoscopic and microsurgical techniques for each subgroup of Knosp grade tumor in relation to the probability of achieving a GTR. This result could be partly due to the fact that their study was restricted to tumors of Knosp Grades 0–2. In our series, however, we compared results between the surgical techniques in all subgroups of Knosp grading. The endoscopic technique was clearly superior to microsurgery in the Knosp Grades 2–3 subgroups whereby the laterosellar extension determined the quality of resection and thus the cure rate for nonfunctioning adenomas. The endoscopic procedure allows a panoramic view from one internal carotid artery to the contralateral one, and thus permitting a more extensive resection than that allowed by the purely microscopic approach (which is restricted primarily to the midline for direct vision). Furthermore, an improved laterosellar view is obtained with the use of 30° and 45° endoscopes.

One major difference between the Dallapiazza and colleagues study and ours is the fact that their series was concurrent while ours was consecutive and that their study was conducted in a short period of time with results originating from the same surgeon. Although surgeon experience could influence the result, the study period for the microsurgical technique in our series did not include the learning curve for the senior surgeon, whereas the learning curve for the endoscopic technique was included. This bias may only negatively impact the endoscopic technique. Our study also showed superior results for the upper part of the adenoma, and the height of the tumor was a factor of paramount importance for the tumor remnant. In our experience, the endoscopic approach allowed better access to the suprasellar or even subfrontal extensions.

Dallapiazza et al. do not comment on the improvement of preoperative endocrine deficits following surgery. Our study showed significant improvement in postoperative endocrine deficits following the endoscopic technique (56%) compared with the improvements attained following microsurgery (25%). Finally, we found that the incidence of CSF leaks was higher with the endoscopic technique but that this was subsequently overcome by the surgeon's increased experience with this technique.

Actually, these two papers feature retrospective studies with small sample sizes that may affect statistical results in both directions and prevent any definitive conclusions. However, it seems reasonable to assume that for small tumors without lateral extensions, no difference has to be expected. If a difference between the two techniques exists, it should probably be expected for a high-grade tumor volume in which endoscopy has a clear advantage in increasing surgical access through extended approaches. The contrasting results of these two studies underline the need for larger, well-designed multicenter studies to decide on the value of either operative technique in determining the quality of resection in Knosp Grades 2–3 groups.

References

  • 1

    Dallapiazza RBond AEGrober YLouis RGPayne SCOldfield EH: Retrospective analysis of a concurrent series of microscopic versus endoscopic transsphenoidal surgeries for Knosp Grades 0–2 nonfunctioning pituitary macroadenomas at a single institution. J Neurosurg 121:5115172014

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  • 2

    Messerer MDe Battista JCRaverot GKassis SDubourg JLapras V: Evidence of improved surgical outcome following endoscopy for nonfunctioning pituitary adenoma removal. Neurosurg Focus 30:4E112011

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Response

We thank Dr. Messerer and colleagues for their comments on our study in which we compare the surgical outcomes of microscopic and endoscopic transsphenoidal surgery for Knosp Grades 0–2 nonfunctioning pituitary macroadenomas. Messerer et al. previously compared microscopic and endoscopic surgery for nonfunctioning pituitary macroadenomas in consecutive patients.3 The results of our study and those of Messerer et al. are similar for Knosp Grades 0 and 1 adenomas. In contrast to our results, however, they found significant improvement in the rate of GTR and endocrinological recovery in the group that underwent endoscopic surgery rather than microscopic surgery for Knosp Grade 2 (and 3) adenomas. From their results, they concluded that endoscopic surgery is superior for laterally extending adenomas.

The aim of our study was to compare the results of microscopic and endoscopic surgery for a group of patients without significant lateral extension or cavernous sinus invasion. We were interested to know if there were differences in outcomes for the adenomas for which GTR was expected. Although the original report by Knosp et al. described a high rate of cavernous sinus invasion for adenomas that crossed the midline of the intracavernous segment of the internal carotid artery (ICA) but did not cross the lateral tangential line of the ICA (Knosp Grade 2),2 we found that a significant portion of Knosp Grade 2 growth hormone (GH)–secreting adenomas do not invade the cavernous sinus and are surgically curable.1,6 For Knosp Grade 3 GH-secreting adenomas, there is a much lower remission rate using either method because of lateral cavernous sinus invasion.1,6 We believe that it is inappropriate to combine Knosp Grades 2 and 3 tumors together. Instead, Knosp Grade 3 tumors are more properly grouped with Knosp Grade 4 tumors. In designing our study under discussion, we included only patients with Knosp Grades 0–2 adenomas and excluded those with adenomas that had a high likelihood of cavernous sinus invasion. We concluded that the microscopic and endoscopic techniques provide similar outcomes for patients who do not have cavernous sinus invasion beyond the medial cavernous sinus. For patients in whom GTR is expected, the endoscope and microscope perform equally well.

In our experience, the sublabial, microscopic transsphenoidal approach provides a midline surgical corridor that can expose the sella from cavernous sinus to cavernous sinus, and the sellar floor to sellar tuberculum for extended approaches. This allows full surgical exploration of the sella, medial cavernous sinus walls, and suprasellar space. In our study, there was a 76% rate of GTR of Knosp Grade 2 adenomas using the microscopic approach, as compared with 47.8% in the study by Messerer et al.3 Notably, in Messerer and colleagues' study, a tumor remnant after microscopic surgery was found in the suprasellar space in nearly 25% (10 of 41) of cases and within the sella in more than 25% (11 of 41) of cases. Tumor remnants in the cavernous sinus accounted for the remaining approximately 50% (20 of 41) of cases. Although we did not report the location of adenoma remnants in our study, most residual adenomas, whether after the microscopic or endoscopic method, were located laterally in the region of the cavernous sinus and not within the sella or suprasellar space.

For invasive Knosp Grade 3 adenomas in the lateral aspect of the cavernous sinus, the expanded view afforded by the endoscope can lead to a greater degree of adenoma resection under direct visualization. However, with tumor lying in the medial portion of the cavernous sinus, the microscope can be used to successfully remove invading tumor, as can the endoscope, and either method can be used when it is appropriate. On the other hand, when adenomas invade the cavernous sinus beyond the medial wall, it is highly unlikely that complete resection can be achieved because of microscopic residual tumor.4 Notably, one must consider the surgical goals when assessing the quality of resection. In our opinion, for nonfunctioning pituitary macroadenomas, the goals of surgery are to decompress the optic apparatus, preserve pituitary function, remove as much tumor as can be safely removed, and avoid neurological or surgical complications. In the case of noninvasive adenomas, these goals can be achieved while performing a complete resection. For noninvasive tumors, however, a “quality resection” does not necessitate aggressively de-bulking the lateral portion of adenomas invading the cavernous sinus.

In their study, Messerer et al.3 stated that improved visualization with the endoscopic approach allows for identification of the compressed anterior pituitary gland that is “never seen during microscopic surgery,” leading to better postoperative pituitary function. During microscopic and endoscopic pituitary surgery, by using the histological capsule of the tumor as a surgical capsule, we routinely identify and preserve the compressed anterior pituitary gland during dissection. There was a very low rate of endocrinological deficiency using both methods in our study, which is comparable to the results reported by Messerer et al.

Given the results of our study, we assert that for noninvasive nonfunctioning pituitary macroadenomas for which complete resection is expected, there is no difference in the rate of GTR, postoperative endocrine outcomes, or surgical complications using the microscopic or endoscopic method for resection. Since we consider most Knosp Grade 3 adenomas to be invasive and more appropriately grouped with Knosp Grade 4 adenomas, they were excluded from our study, and thus we cannot compare the results for Knosp Grade 3 adenomas with those reported by Messerer et al.3 Comparing the extent of resection for Knosp Grades 3 and 4 adenomas would be a valuable future study. However, it is noteworthy that the difference in the results between the two studies of Knosp Grades 0–2 tumors was with the use of the microscope in Grade 2 tumors (47.8% GTR in their study vs 76% in ours), a difference that may have been produced by our routine focus on the margin of the pseudocapsule during tumor resection.5

References

  • 1

    Jane JA JrStarke RMElzoghby MAReames DLPayne SCThorner MO: Endoscopic transsphenoidal surgery for acromegaly: remission using modern criteria, complications, and predictors of outcome. J Clin Endocrinol Metab 96:273227402011

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  • 2

    Knosp ESteiner EKitz KMatula C: Pituitary adenomas with invasion of the cavernous sinus space: a magnetic resonance imaging classification compared with surgical findings. Neurosurgery 33:6106181993

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  • 3

    Messerer MDe Battista JCRaverot GKassis SDubourg JLapras V: Evidence of improved surgical outcome following endoscopy for nonfunctioning pituitary adenoma removal. Neurosurg Focus 30:4E112011

    • Search Google Scholar
    • Export Citation
  • 4

    Oldfield EH: Editorial. Management of invasion by pituitary adenomas. J Neurosurg 121:5015042014

  • 5

    Oldfield EHVortmeyer AO: Development of a histological pseudocapsule and its use as a surgical capsule in the excision of pituitary tumors. J Neurosurg 104:7192006

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    • Export Citation
  • 6

    Starke RMRaper DMPayne SCVance MLOldfield EHJane JA Jr: Endoscopic versus microsurgical transsphenoidal surgery for acromegaly: outcomes in a concurrent series of patients using modern criteria for remission. J Clin Endocrinol Metab 98:319031982013

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    • Export Citation

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Article Information

Contributor Notes

INCLUDE WHEN CITING Published online February 13, 2015; DOI: 10.3171/2014.9.JNS141998.DISCLOSURE The authors report no conflict of interest.
Headings
References
  • 1

    Dallapiazza RBond AEGrober YLouis RGPayne SCOldfield EH: Retrospective analysis of a concurrent series of microscopic versus endoscopic transsphenoidal surgeries for Knosp Grades 0–2 nonfunctioning pituitary macroadenomas at a single institution. J Neurosurg 121:5115172014

    • Search Google Scholar
    • Export Citation
  • 2

    Messerer MDe Battista JCRaverot GKassis SDubourg JLapras V: Evidence of improved surgical outcome following endoscopy for nonfunctioning pituitary adenoma removal. Neurosurg Focus 30:4E112011

    • Search Google Scholar
    • Export Citation
  • 1

    Jane JA JrStarke RMElzoghby MAReames DLPayne SCThorner MO: Endoscopic transsphenoidal surgery for acromegaly: remission using modern criteria, complications, and predictors of outcome. J Clin Endocrinol Metab 96:273227402011

    • Search Google Scholar
    • Export Citation
  • 2

    Knosp ESteiner EKitz KMatula C: Pituitary adenomas with invasion of the cavernous sinus space: a magnetic resonance imaging classification compared with surgical findings. Neurosurgery 33:6106181993

    • Search Google Scholar
    • Export Citation
  • 3

    Messerer MDe Battista JCRaverot GKassis SDubourg JLapras V: Evidence of improved surgical outcome following endoscopy for nonfunctioning pituitary adenoma removal. Neurosurg Focus 30:4E112011

    • Search Google Scholar
    • Export Citation
  • 4

    Oldfield EH: Editorial. Management of invasion by pituitary adenomas. J Neurosurg 121:5015042014

  • 5

    Oldfield EHVortmeyer AO: Development of a histological pseudocapsule and its use as a surgical capsule in the excision of pituitary tumors. J Neurosurg 104:7192006

    • Search Google Scholar
    • Export Citation
  • 6

    Starke RMRaper DMPayne SCVance MLOldfield EHJane JA Jr: Endoscopic versus microsurgical transsphenoidal surgery for acromegaly: outcomes in a concurrent series of patients using modern criteria for remission. J Clin Endocrinol Metab 98:319031982013

    • Search Google Scholar
    • Export Citation
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