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Andrew S. Little, Paul A. Gardner, Juan C. Fernandez-Miranda, Michael R. Chicoine, Garni Barkhoudarian, Daniel M. Prevedello, Kevin C. J. Yuen, Daniel F. Kelly and for the TRANSSPHER Study Group

OBJECTIVE

Recovery from preexisting hypopituitarism after transsphenoidal surgery for pituitary adenoma is an important outcome to investigate. Furthermore, pituitary function has not been thoroughly evaluated after fully endoscopic surgery, and benchmark outcomes have not been clearly established. Here, the authors characterize pituitary gland outcomes with a focus on gland recovery following endoscopic transsphenoidal removal of clinically nonfunctioning adenomas.

METHODS

This multicenter prospective study was conducted at 6 US pituitary centers among adult patients with nonfunctioning pituitary macroadenomas who had undergone endoscopic endonasal pituitary surgery. Pituitary gland function was evaluated 6 months after surgery.

RESULTS

The 177 enrolled patients underwent fully endoscopic transsphenoidal surgery; 169 (95.5%) of them were available for follow-up. Ninety-five (56.2%) of the 169 patients had had a preoperative deficiency in at least one hormone axis, and 20/95 (21.1%) experienced recovery in at least one axis at the 6-month follow-up. Patients with adrenal insufficiency were more likely to recover (10/34 [29.4%]) than were those with hypothyroidism (8/72 [11.1%]) or male hypogonadism (5/50 [10.0%]). At the 6-month follow-up, 14/145 (9.7%) patients had developed at least one new deficiency. The study did not identify any predictors of gland recovery (p ≥ 0.20). Permanent diabetes insipidus was observed in 4/166 (2.4%) patients. Predictors of new gland dysfunction included a larger tumor size (p = 0.009) and Knosp grade 3 and 4 (p = 0.051).

CONCLUSIONS

Fully endoscopic pituitary surgery resulted in improvement of pituitary gland function in a substantial minority of patients. The deficiency from which patients were most likely to recover was adrenal insufficiency. Overall rates of postoperative permanent diabetes insipidus were low. This study provides multicenter benchmark neuroendocrine clinical outcome data for the endoscopic technique.

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Andrew S. Little, Daniel F. Kelly, William L. White, Paul A. Gardner, Juan C. Fernandez-Miranda, Michael R. Chicoine, Garni Barkhoudarian, James P. Chandler, Daniel M. Prevedello, Brandon D. Liebelt, John Sfondouris, Marc R. Mayberg and for the TRANSSPHER Study Group

OBJECTIVE

Many surgeons have adopted fully endoscopic over microscopic transsphenoidal surgery for nonfunctioning pituitary tumors, although no high-quality evidence demonstrates superior patient outcomes with endoscopic surgery. The goal of this analysis was to compare these techniques in a prospective multicenter controlled study.

METHODS

Extent of tumor resection was compared after endoscopic or microscopic transsphenoidal surgery in adults with nonfunctioning adenomas. The primary end point was gross-total tumor resection determined by postoperative MRI. Secondary end points included volumetric extent of tumor resection, pituitary hormone outcomes, and standard quality measures.

RESULTS

Seven pituitary centers and 15 surgeons participated in the study. Of the 530 patients screened, 260 were enrolled (82 who underwent microscopic procedures, 177 who underwent endoscopic procedures, and 1 who cancelled surgery) between February 2015 and June 2017. Surgeons who used the microscopic technique were more experienced than the surgeons who used the endoscopic technique in terms of years in practice and number of transsphenoidal surgeries performed (p < 0.001). Gross-total resection was achieved in 80.0% (60/75) of microscopic surgery patients and 83.7% (139/166) of endoscopic surgery patients (p = 0.47, OR 0.8, 95% CI 0.4–1.6). Volumetric extent of resection, length of stay, surgery-related deaths, and unplanned readmission rates were similar between groups (p > 0.2). New hormone deficiency was present at 6 months in 28.4% (19/67) of the microscopic surgery patients and 9.7% (14/145) of the endoscopic surgery patients (p < 0.001, OR 3.7, 95% CI 1.7–7.7). Microscopic surgery cases were significantly shorter in duration than endoscopic surgery cases (p < 0.001).

CONCLUSIONS

Experienced surgeons who performed microscopic surgery and less experienced surgeons who performed endoscopic surgery achieved similar extents of tumor resection and quality outcomes in patients with nonfunctioning pituitary adenomas. The endoscopic technique may be associated with lower rates of postoperative pituitary gland dysfunction. This study generally supports the transition to endoscopic pituitary surgery when the procedure is performed by proficient surgeons, although both techniques yield overall acceptable surgical outcomes.

CLASSIFICATION OF EVIDENCE Type of question: therapeutic; study design: prospective cohort trial; evidence: class III.

Clinical trial registration no.: NCT02357498 (clinicaltrials.gov)

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Andrew Conger, Fan Zhao, Xiaowen Wang, Amalia Eisenberg, Chester Griffiths, Felice Esposito, Ricardo L. Carrau, Garni Barkhoudarian and Daniel F. Kelly

OBJECTIVE

The authors previously described a graded approach to skull base repair following endonasal microscopic or endoscope-assisted tumor surgery. In this paper they review their experience with skull base reconstruction in the endoscopic era.

METHODS

A retrospective review of a single-institution endonasal endoscopic patient database (April 2010–April 2017) was undertaken. Intraoperative CSF leaks were graded based on size (grade 0 [no leak], 1, 2, or 3), and repair technique was documented across grades. The series was divided into 2 epochs based on implementation of a strict perioperative antibiotic protocol and more liberal use of permanent and/or temporary buttresses; repair failure rates and postoperative meningitis rates were assessed for the 2 epochs and compared.

RESULTS

In total, 551 operations were performed in 509 patients for parasellar pathology, including pituitary adenoma (66%), Rathke’s cleft cyst (7%), meningioma (6%), craniopharyngioma (4%), and other (17%). Extended approaches were used in 41% of cases. There were 9 postoperative CSF leaks (1.6%) and 6 cases of meningitis (1.1%). Postoperative leak rates for all 551 operations by grade 0, 1, 2, and 3 were 0%, 1.9%, 3.1%, and 4.8%, respectively. Fat grafts were used in 33%, 84%, 97%, and 100% of grade 0, 1, 2, and 3 leaks, respectively. Pedicled mucosal flaps (78 total) were used in 2.6% of grade 0–2 leaks (combined) and 79.5% of grade 3 leaks (60 nasoseptal and 6 middle turbinate flaps). Nasoseptal flap usage was highest for craniopharyngioma operations (80%) and lowest for pituitary adenoma operations (2%). Two (3%) nasoseptal flaps failed. Contributing factors for the 9 repair failures were BMI ≥ 30 (7/9), lack of buttress (4/9), grade 3 leak (4/9), and postoperative vomiting (4/9). Comparison of the epochs showed that grade 1–3 repair failures decreased from 6/143 (4.1%) to 3/141 (2.1%) and grade 1–3 meningitis rates decreased from 5 (3.5%) to 1 (0.7%) (p = 0.08). Prophylactic lumbar CSF drainage was used in only 4 cases (< 1%), was associated with a higher meningitis rate in grades 1–3 (25% vs 2%), and was discontinued in 2012. Comparison of the 2 epochs showed increase buttress use in the second, with use of a permanent buttress in grade 1 and 3 leaks increasing from 13% to 55% and 32% to 76%, respectively (p < 0.001), and use of autologous septal/keel bone as a permanent buttress in grade 1, 2, and 3 leaks increasing from 15% to 51% (p < 0.001).

CONCLUSIONS

A graded approach to skull base repair after endonasal surgery remains valid in the endoscopic era. However, the technique has evolved significantly, with further reduction of postoperative CSF leak rates. These data suggest that buttresses are beneficial for repair of most grade 1 and 2 leaks and all grade 3 leaks. Similarly, pedicled flaps appear advantageous for grade 3 leaks, while CSF diversion may be unnecessary and a risk factor for meningitis. High BMI should prompt an aggressive multilayered repair strategy. Achieving repair failure and meningitis rates lower than 1% is a reasonable goal in endoscopic skull base tumor surgery.

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Andrew S. Little, Daniel F. Kelly and Garni Barkhoudarian

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Andrew S. Little, Daniel F. Kelly, John Milligan, Chester Griffiths, Daniel M. Prevedello, Ricardo L. Carrau, Gail Rosseau, Garni Barkhoudarian, Heidi Jahnke, Charlene Chaloner, Kathryn L. Jelinek, Kristina Chapple and William L. White

OBJECT

Despite the widespread adoption of endoscopic transsphenoidal surgery for pituitary adenomas, the sinonasal quality of life (QOL) and health status in patients who have undergone this technique have not been compared with these findings in patients who have undergone the traditional direct uninostril microsurgical technique. In this study, the authors compared the sinonasal QOL and patient-reported health status after use of these 2 surgical techniques.

METHODS

The study design was a nonblinded prospective cohort study. Adult patients with sellar pathology and planned transsphenoidal surgery were screened at 4 pituitary centers in the US between October 2011 and August 2013. The primary end point of the study was postoperative patient-reported sinonasal QOL as measured by the Anterior Skull Base Nasal Inventory–12 (ASK Nasal-12). Supplementary end points included patient-reported health status estimated by the 8-Item Short Form Health Survey (SF-8) and EuroQol (EQ)-5D-5L instruments, and sinonasal complications. Patients were followed for 6 months after surgery.

RESULTS

A total of 301 patients were screened and 235 were enrolled in the study. Of these, 218 were analyzed (111 microsurgery patients, 107 endoscopic surgery patients). Demographic and tumor characteristics were similar between groups (p ≥ 0.12 for all comparisons). The most common complication in both groups was sinusitis (7% in the microsurgery group, 13% in the endoscopic surgery group; p = 0.15). Patients treated with the endoscopic technique were more likely to have postoperative nasal debridements (p < 0.001). The ASK Nasal-12 and SF-8 scores worsened substantially for both groups at 2 weeks after surgery, but then returned to baseline at 3 months. At 3 months after surgery, patients treated with endoscopy reported statistically better sinonasal QOL compared with patients treated using the microscopic technique (p = 0.02), but there were no significant differences at any of the other postoperative time points.

CONCLUSIONS

This is the first multicenter study to examine the effect of the transsphenoidal surgical technique on sinonasal QOL and health status. The study showed that surgical technique did not significantly impact these patient-reported measures when performed at high-volume centers.

Clinical trial registration no.: NCT01504399 (clinicaltrials.gov).

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John A. Jane Jr.

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Nancy McLaughlin, Amy A. Eisenberg, Pejman Cohan, Charlene B. Chaloner and Daniel F. Kelly

Object

Endoscopy as a visual aid (endoscope assisted) or as the sole visual method (fully endoscopic) is increasingly used in pituitary adenoma surgery. Authors of this study assessed the value of endoscopic visualization for finding and removing residual adenoma after initial microscopic removal.

Methods

Consecutive patients who underwent endoscope-assisted microsurgical removal of pituitary adenoma were included in this study. The utility of the endoscope in finding and removing residual adenoma not visualized by the microscope was noted intraoperatively. After maximal tumor removal under microscopic visualization, surgeries were categorized as to whether additional tumor was removed via endoscopy. Tumor removal and remission rates were also noted. Patients undergoing fully endoscopic tumor removal during this same period were excluded from the study.

Results

Over 3 years, 140 patients (41% women, mean age 50 years) underwent endoscope-assisted adenoma removal of 30 endocrine-active microadenomas and 110 macroadenomas (39 endocrine-active, 71 endocrine-inactive); 16% (23/140) of patients had prior surgery. After initial microscopic removal, endoscopy revealed residual tumor in 40% (56/140) of cases and the additional tumor was removed in 36% (50 cases) of these cases. Endoscopy facilitated additional tumor removal in 54% (36/67) of the adenomas measuring ≥ 2 cm in diameter and in 19% (14/73) of the adenomas smaller than 2 cm in diameter (p < 0.0001); additional tumor removal was achieved in 20% (6/30) of the microadenomas. Residual tumor was typically removed from the suprasellar extension and folds of the collapsed diaphragma sellae or along or within the medial cavernous sinus. Overall, 91% of endocrine-inactive tumors were gross-totally or near-totally removed, and 70% of endocrine-active adenomas had early remission.

Conclusions

After microscope-based tumor removal, endoscopic visualization led to additional adenoma removal in over one-third of patients. The panoramic visualization of the endoscope appears to facilitate more complete tumor removal than is possible with the microscope alone. These findings further emphasize the utility of endoscopic visualization in pituitary adenoma surgery. Longer follow-ups and additional case series are needed to determine if endoscopic adenomectomy translates into higher long-term remission rates.

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Nancy McLaughlin, Alexander Vandergrift, Leo F. Ditzel Filho, Kiarash Shahlaie, Amalia A. Eisenberg, Ricardo L. Carrau, Pejman Cohan and Daniel F. Kelly

Object

Symptomatic sellar arachnoid cysts (ACs) have typically been treated via the transsphenoidal route. After sellar cyst wall fenestration, some authors have advocated cyst wall resection and increasing communication between the AC and suprasellar subarachnoid space (SAS). This study is a report of the authors' experience using a simplified approach to reinforce a defective diaphragma sellae or unseen arachnoid diverticulum by deliberately not enlarging the AC-SAS communication and obliterating the cyst cavity with adipose tissue followed by skull base reconstruction.

Methods

A retrospective analysis was conducted of patients who underwent an endonasal transsphenoidal obliteration of symptomatic ACs with a fat graft and skull base repair.

Results

Between July 1998 and September 2010, 8 patients with a sellar AC were identified (6 women and 2 men, mean age 57 years). Clinical presentation included headache, pituitary dysfunction, and visual dysfunction (4 patients each group). Maximal cyst diameter averaged 22 mm (range 15–32 mm). In all cases the sellar communication to the SAS was deliberately not enlarged. The endoscope was used for visualization in 8 of 9 procedures. Postoperatively, headache improved in all 4 patients, vision in all 4 patients, and partial resolution of endocrine dysfunction (hyperprolactinemia and/or recurrent hyponatremia) occurred in 3 (75%) of 4 patients. No new endocrinopathy, CSF leak, meningitis, or neurological deficits occurred. Two patients experienced cyst reaccumulation: 1 symptomatic recurrence was treated with reoperation at 43 months postsurgery, and 1 asymptomatic partial recurrence continued to be monitored at 29 months postsurgery.

Conclusions

Sellar ACs can be effectively treated using endonasal fenestration and obliteration with fat with resultant reversal of presenting symptoms in the majority of patients. This simplified technique of AC cavity obliteration without enlarging communication to the SAS has a low risk of CSF leakage, and in most cases appears to effectively disrupt cyst progression, although longer follow-up is required to monitor for cyst recurrence.

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Daniel F. Kelly

✓ Cushing's disease is a serious endocrinopathy that, if left untreated, is associated with significant morbidity and mortality rates. After diagnostic confirmation of Cushing's disease has been made, transsphenoidal adenomectomy is the treatment of choice. When a transsphenoidal adenomectomy is performed at experienced transsphenoidal surgery centers, long-term remission rates average 80% overall, surgical morbidity is low, and the mortality rate is typically less than 1%. In patients with well-defined noninvasive microadenomas, the long-term remission rate averages 90%. For patients in whom primary surgery fails, treatment options such as bilateral adrenalectomy, stereotactic radiotherapy or radiosurgery, total hypophysectomy, or adrenolytic medical therapy need to be carefully considered, ideally in a multidisciplinary setting. The management of Nelson's Syndrome often requires both transsphenoidal surgery and radio-therapy to gain disease control.

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Carlos A. Mattozo, Antonio A. F. De Salles, Ivan A. Klement, Alessandra Gorgulho, David McArthur, Judith M. Ford, Nzhde Agazaryan, Daniel F. Kelly and Michael T. Selch

Object

The authors analyzed the results of stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) for the treatment of recurrent meningiomas that were described at initial resection as showing aggressive, atypical, or malignant features (nonbenign).

Methods

Twenty-five patients who underwent SRS and/or SRT for nonbenign meningiomas between December 1992 and August 2004 were included. Thirteen of these patients underwent treatment for multiple primary or recurrent lesions. In all, 52 tumors were treated. All histological sections were reviewed and reclassified according to World Health Organization (WHO) 2000 guidelines as benign (Grade I), atypical (Grade II), or anaplastic (Grade III) meningiomas. The median follow-up period was 42 months.

Seventeen (68%) of the cases were reclassified as follows: WHO Grade I (five cases), Grade II (11 cases), and Grade III (one case). Malignant progression occurred in eight cases (32%) during the follow-up period; these cases were considered as a separate group. The 3-year progression-free survival (PFS) rates for the Grades I, II, and III, and malignant progression groups were 100, 83, 0, and 11%, respectively (p < 0.001). In the Grade II group, the 3-year PFS rates for patients treated with SRS and SRT were 100 and 33%, respectively (p = 0.1). After initial treatment, 22 new tumors required treatment using SRS or SRT; 17 (77%) of them occurred inside the original resection cavity. Symptomatic edema developed in one patient (4%).

Conclusions

Stereotactic radiation treatment provided effective local control of “aggressive” Grade I and Grade II meningiomas, whereas Grade III lesions were associated with poor outcome. The outcome of cases in the malignant progression group was intermediate between that of the Grade II and Grade III groups, with the lesions showing a tendency toward malignancy.