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Kyle C. Wu, Edward R. Laws Jr., and John A. Jane Jr.

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Michael P. Catalino, David M. Meredith, Umberto De Girolami, Sherwin Tavakol, Le Min, and Edward R. Laws Jr.

OBJECTIVE

This study was done to compare corticotroph hyperplasia and histopathologically proven adenomas in patients with Cushing disease by analyzing diagnostic features, surgical management, and clinical outcomes.

METHODS

Patients with suspected pituitary Cushing disease were included in a retrospective cohort study and were excluded if results of pathological analysis of the surgical specimen were nondiagnostic or normal. Cases were reviewed by two experienced neuropathologists. Total lesion removal was used as a dichotomized surgical variable; it was defined as an extracapsular resection (including a rim of normal gland) in patients with an adenoma, and for hyperplasia patients it was defined as removal of the presumed lesion plus a rim of surrounding normal gland. Bivariate and multivariate analyses were performed. Recurrence-free survival was compared between the two groups.

RESULTS

The final cohort consisted of 63 patients (15 with hyperplasia and 48 with adenoma). Normal pituitary acinar architecture was highly variable. Corticotroph hyperplasia was diagnosed based on the presence of expanded acini showing retained reticulin architecture and predominant staining for adrenocorticotropic hormone. Crooke’s hyaline change was seen in 46.7% of specimens, and its frequency was equal in nonlesional tissue of both groups. The two groups differed only by MRI findings (equivocal/diffuse lesion in 46% of hyperplasia and 17% of adenoma; p = 0.03). Diagnostic uncertainty in the hyperplasia group resulted in additional confirmatory testing by 24-hour urinary free cortisol. Total lesion removal was infrequent in patients with hyperplasia compared to those with adenoma (33% vs 65%; p = 0.03). Initial biochemical remission was similar (67% in hyperplasia and 85% in adenoma; p = 0.11). There was no difference in hypothalamic-pituitary-adrenal axis recovery or disease recurrence. The median follow-up was 1.9 years (IQR 0.7–7.6 years) for the hyperplasia group and 1.2 years (IQR 0.4–2.4 years) for the adenoma group. Lack of a discrete lesion and diagnostic uncertainty were the only significant predictors of hyperplasia (sensitivity 53.3%, specificity 97.7%, positive predictive value 88.9%, negative predictive value 85.7%). An adjusted Cox proportional hazards model showed similar recurrence-free survival in the two groups.

CONCLUSIONS

This study suggests an association between biochemically proven Cushing disease and histopathologically proven corticotroph hyperplasia. Imaging and operative findings can be ambiguous, and, compared to typical adenomas with a pseudocapsule, the surgical approach is more nuanced. Nevertheless, if treated appropriately, biochemical outcomes may be similar.

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Michael P. Catalino, David M. Meredith, Umberto De Girolami, Sherwin Tavakol, Le Min, and Edward R. Laws Jr.

OBJECTIVE

This study was done to compare corticotroph hyperplasia and histopathologically proven adenomas in patients with Cushing disease by analyzing diagnostic features, surgical management, and clinical outcomes.

METHODS

Patients with suspected pituitary Cushing disease were included in a retrospective cohort study and were excluded if results of pathological analysis of the surgical specimen were nondiagnostic or normal. Cases were reviewed by two experienced neuropathologists. Total lesion removal was used as a dichotomized surgical variable; it was defined as an extracapsular resection (including a rim of normal gland) in patients with an adenoma, and for hyperplasia patients it was defined as removal of the presumed lesion plus a rim of surrounding normal gland. Bivariate and multivariate analyses were performed. Recurrence-free survival was compared between the two groups.

RESULTS

The final cohort consisted of 63 patients (15 with hyperplasia and 48 with adenoma). Normal pituitary acinar architecture was highly variable. Corticotroph hyperplasia was diagnosed based on the presence of expanded acini showing retained reticulin architecture and predominant staining for adrenocorticotropic hormone. Crooke’s hyaline change was seen in 46.7% of specimens, and its frequency was equal in nonlesional tissue of both groups. The two groups differed only by MRI findings (equivocal/diffuse lesion in 46% of hyperplasia and 17% of adenoma; p = 0.03). Diagnostic uncertainty in the hyperplasia group resulted in additional confirmatory testing by 24-hour urinary free cortisol. Total lesion removal was infrequent in patients with hyperplasia compared to those with adenoma (33% vs 65%; p = 0.03). Initial biochemical remission was similar (67% in hyperplasia and 85% in adenoma; p = 0.11). There was no difference in hypothalamic-pituitary-adrenal axis recovery or disease recurrence. The median follow-up was 1.9 years (IQR 0.7–7.6 years) for the hyperplasia group and 1.2 years (IQR 0.4–2.4 years) for the adenoma group. Lack of a discrete lesion and diagnostic uncertainty were the only significant predictors of hyperplasia (sensitivity 53.3%, specificity 97.7%, positive predictive value 88.9%, negative predictive value 85.7%). An adjusted Cox proportional hazards model showed similar recurrence-free survival in the two groups.

CONCLUSIONS

This study suggests an association between biochemically proven Cushing disease and histopathologically proven corticotroph hyperplasia. Imaging and operative findings can be ambiguous, and, compared to typical adenomas with a pseudocapsule, the surgical approach is more nuanced. Nevertheless, if treated appropriately, biochemical outcomes may be similar.

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Eric Suero Molina, Michael P. Catalino, and Edward R. Laws

Harvey Cushing is considered the father of neurosurgery, not just for his work within the United States, but also for his global influence through international visitors and trainees. Starting in 1920, the neurosurgical clinic at the Peter Bent Brigham Hospital in Boston, led by Cushing, trained surgeons from all over the globe, many of whom returned home to establish neurosurgical departments and become neurosurgical pioneers themselves. The objective of this vignette is to highlight the importance of Cushing’s international trainees, describe their contributions, and discuss how each had an impact on the development of the practice of neurosurgery worldwide. The authors demonstrate how Cushing provided the impetus for a movement that revolutionized neurology and neurosurgery worldwide. Even today, international cooperation continues to shape the success of our delicate specialty.

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Gabriel Zada, Henry W. S. Schroeder, Andrew S. Little, and Edward R. Laws Jr.

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David J. Cote, Sherry L. Iuliano, Michael P. Catalino, and Edward R. Laws Jr.

OBJECTIVE

Perioperative management of patients with sellar lesions is complex, requiring input from a multidisciplinary team of specialists for ongoing management of both endocrinological and neurosurgical issues. Here, the authors reviewed the experience of a single multidisciplinary center over 10 years to identify key postoperative practices that ensure positive outcomes for patients with sellar lesions who undergo transsphenoidal surgery.

METHODS

The authors performed a retrospective review of all transsphenoidal operations carried out by the senior author at a single center from April 2008 through November 2018. They included only adult patients and recorded perioperative management. They also reviewed the evolution of clinical practices for perioperative care at their institution to identify strategies for ensuring positive patient outcomes, and they reviewed the literature on select related topics.

RESULTS

In total, 1023 operations in 928 patients were reviewed. Of these, 712 operations were for pituitary adenomas (69.6%), and 122 were for Rathke cleft cysts (11.9%). The remainder included operations for craniopharyngiomas (3.6%), arachnoid cysts (1.7%), pituitary tumor apoplexy (1.0%), and other sellar pathologies (12.2%). Among the reviewed operations, the median hospital stay was 3 days (IQR 2–3). Patient management details during the pre-, intra-, and postoperative periods were identified, including both shared characteristics of all patients undergoing transsphenoidal surgery and unique characteristics that are specific to certain lesion types or patient populations.

CONCLUSIONS

Patients with sellar lesions who undergo transsphenoidal surgery require complex, multidisciplinary perioperative care to monitor for common adverse events and to improve outcomes, but there is a dearth of high-quality evidence guiding most perioperative practices. Here, the authors reviewed practices at their institution across more than 1000 transsphenoidal operations that may help ensure successful patient outcomes.

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Michael P. Catalino and Edward R. Laws Jr.

Harvey Cushing overcame tremendous obstacles to his personal and professional development from 1912 to 1919. These trials could have jeopardized the early and necessary formation of the Society of Neurological Surgeons in 1920. War separated young neurosurgeons pursuing the advancement of this “special field,” but Cushing’s principled mentoring of these aspiring surgeons in the midst of this demanding time was unwavering. This historical vignette is a collection of stories composed to highlight certain trainees during this period in his career. It also puts the mentoring relationship into a context that is often encountered today. There is much to learn from those who endure trials of any kind, but there is much more to learn from those, like Cushing, who inspire perseverance in others during their trials.

Free access

Michael P. Catalino and Edward R. Laws Jr.

Harvey Cushing overcame tremendous obstacles to his personal and professional development from 1912 to 1919. These trials could have jeopardized the early and necessary formation of the Society of Neurological Surgeons in 1920. War separated young neurosurgeons pursuing the advancement of this “special field,” but Cushing’s principled mentoring of these aspiring surgeons in the midst of this demanding time was unwavering. This historical vignette is a collection of stories composed to highlight certain trainees during this period in his career. It also puts the mentoring relationship into a context that is often encountered today. There is much to learn from those who endure trials of any kind, but there is much more to learn from those, like Cushing, who inspire perseverance in others during their trials.