Comparative Analysis of Endoscope Obscuration With Utilization of an Endonasal Access Guide for Endonasal Skull Base Surgery.

BACKGROUND AND OBJECTIVES: In endoscopic endonasal approaches (EEAs) for skull base pathologies, endoscope view obscuration remains a persistent, time-consuming, and distracting issue for surgeons and may result in increased operative time. The endonasal access guide (EAG) has been demonstrated as a possible adjunct to minimize these events. However, to date, there have been no comparative studies performed and the potential time savings by using EAGs have yet to be quantified. This cohort study aimed to determine the operative efficiency benefits of the EAG in EEA operations. METHODS: Analysis of EEA operative videos from an EAG cohort (n = 20) and a control cohort (n = 20) was performed, assessing 12-minute segments in the first, middle, and last third of each operation. The first segment in each cohort was selected before EAG placement, serving as an internal control. Every endoscope lens soiling instance was counted (measured as cleaning actions per minute), timed (obscuration time %), and identified as a withdrawal, irrigation, or other cleaning action. Perioperative variables including skull base repair and postoperative cerebrospinal fluid leakage were assessed. RESULTS: Within the EAG cohort, obscuration time was reduced in the middle and last third compared with the first third (3.73% [CI: 2.39-5.07] vs 12.97% [CI: 10.24-15.70], P < .001; 4.19% [CI: 2.83-5.55] vs 12.97% [CI: 10.24-15.70], P < .001) and cleaning actions were also significantly reduced by EAG (0.69/min [CI: 0.39-0.99] vs 1.67/min [CI: 1.34-2.00], P = .001; 0.66/min [CI: 0.35-0.97] vs 1.67/min [CI: 1.34-2.00], P < .001). Between the control and EAG cohorts, there was no significant difference between obscuration time and cleaning actions in the first third (9.33% vs 12.97%, P = .086; 1.34/min vs 1.67/min, P = .151) or in the middle third (6.24% vs 3.73%, P = .140; 0.80/min vs 0.69/min, P = .335), but there was a significant difference in the last third (9.25% [CI: 6.95-11.55] vs 4.19% [CI: 2.83-5.55], P < .001; 0.95/min [CI: 0.73-1.17] vs 0.66/min [CI: 0.35-0.97], P = .018). CONCLUSION: EAG significantly reduces lens obscurations and cleaning events, particularly during the intradural portion of operations. This technology may offer a greater time-saving impact with patients undergoing long EEA operations.

Response to OKN-007 and NAC in a Patient with Unilateral Hearing Loss and Chronic Tinnitus from Vestibular Schwannoma.

BACKGROUND: Tinnitus is the perception of sound in the absence of external acoustic stimulation. Being one of the most common diseases of the ear, it has a global prevalence ranging from 4.1 to 37.2%. To date, it has been difficult to treat tinnitus as its pathophysiology is poorly understood and there are limited treatment options. OBJECTIVE: To investigate the effect of OKN-007 (also known as HPN-07), a nitrone-based investigational drug, in combination with oral N-acetylcycsteine (NAC), for the treatment of hearing loss and chronic tinnitus under an individual expanded access protocol. PATIENT CASE: We report the case of a patient who presented with left-sided ear fullness, mild tinnitus, and mild high frequency sensorineural hearing loss with 100% word recognition. A large enhancing mass seen on MRI revealed a vestibular schwannoma. He underwent subtotal resection of the tumor resulting in a moderate-to-profound sensorineural hearing loss and catastrophic tinnitus. The patient was treated with intravenous OKN-007 at 60 mg/kg dosed three times per week and oral NAC 2500 mg twice daily. RESULTS: Post-treatment audiometric testing revealed an average of 16.66 dB in hearing threshold improvement in three frequencies (125, 250 and 500 Hz) with residual hearing in the affected left ear. His tinnitus loudness matching improved from 90 dB to 19 dB post-treatment. His Tinnitus Handicap Inventory improved from 86/100 (Catastrophic) to 40/100 (Moderate). He also experienced improvements in sleep, concentration, hearing, and emotional well-being, and reported significantly decreased levels of tinnitusrelated distress. CONCLUSIONS: This case report highlights the feasibility and therapeutic potential of the combination of OKN-007 and NAC in treating hearing loss and tinnitus that warrants further investigation.

Critical appraisal of minimally invasive keyhole surgery for intracranial meningioma in a large case series.

BACKGROUND: Meningioma surgery has evolved over the last 20 years with increased use of minimally invasive approaches including the endoscopic endonasal route and endoscope-assisted and gravity-assisted transcranial approaches. As the "keyhole" concept remains controversial, we present detailed outcomes in a cohort series. METHODS: Retrospective analysis was done for all patients undergoing meningioma removal at a tertiary brain tumor referral center from 2008-2021. Keyhole approaches were defined as: use of a minimally invasive "retractorless" approach for a given meningioma in which a traditional larger approach is often used instead. The surgical goal was maximal safe removal including conservative (subtotal) removal for some invasive locations. Primary outcomes were resection rates, complications, length of stay and Karnofsky Performance Scale (KPS). Secondary outcomes were endoscopy use, perioperative treatments, tumor control and acute MRI FLAIR/T2 changes to assess for brain manipulation and retraction injury. RESULTS: Of 329 patients, keyhole approaches were utilized in 193(59%) patients (mean age 59±13; 30 (15.5%) had prior surgery) who underwent 213 operations; 205(96%) were skull base location. Approaches included: endoscopic endonasal (n = 74,35%), supraorbital (n = 73,34%), retromastoid (n = 38,18%), mini-pterional (n = 20,9%), suboccipital (n = 4,2%), and contralateral transfalcine (n = 4,2%). Primary outcomes: Gross total/near total (>90%) resection was achieved in 125(59%) (5% for petroclival, cavernous sinus/Meckel's cave, spheno-cavernous locations vs 77% for all other locations). Major complications included: permanent neurological worsening 12(6%), CSF leak 2(1%) meningitis 2(1%). There were no DVTs, PEs, MIs or 30-day mortality. Median LOS decreased from 3 to 2 days in the last 2 years; 94% were discharged to home with favorable 90-day KPS in 176(96%) patients. Secondary outcomes: Increased FLAIR/T2 changes were noted on POD#1/2 MRI in 36/213(17%) cases, resolving in all but 11 (5.2%). Endoscopy was used in 87/139(63%) craniotomies, facilitating additional tumor removal in 55%. Tumor progression occurred in 26(13%) patients, mean follow-up 42±36 months. CONCLUSIONS & RELEVANCE: Our experience suggests minimally invasive keyhole transcranial and endoscopic endonasal meningioma removal is associated with comparable resection rates and low complication rates, short hospitalizations and high 90-day performance scores in comparison to prior reports using traditional skull base approaches. Subtotal removal may be appropriate for invasive/adherent meningiomas to avoid neurological deficits and other post-operative complications, although longer follow-up is needed. With careful patient selection and requisite experience, these approaches may be considered reasonable alternatives to traditional transcranial approaches.

Minimally invasive pericranial flap harvest through a supraorbital eyebrow craniotomy: Technical note in salvage skull base reconstruction.

BACKGROUND AND IMPORTANCE: The supraorbital eyebrow craniotomy is a minimally invasive approach that provides access to pathologies of the anterior and middle cranial fossae. Vascularized flaps are preferred when considering reconstructive options, however, small incisions may not provide adequate access to vascularized tissue. We present two cases demonstrating a modified technique for harvesting pericranium through an eyebrow supraorbital craniotomy for reconstruction of large skull base defects. CLINICAL PRESENTATION: The first case is of a 62-year-old woman with an invasive esthesioneuroblastoma. Multiple resections and reconstructions, including a large frontal craniectomy and titanium mesh cranioplasty, resulted in refractory tension pneumocephalus. A supraorbital craniotomy was performed with endoscope-assisted harvesting of a pericranial flap through a coronal plane stab incision for definitive repair. The second case is a 44-year-old woman with a high-grade neuroendocrine tumor transgressing the anterior cranial fossa. Resection was achieved via combined supraorbital eyebrow craniotomy and endoscopic endonasal approach. A multilayered reconstruction including a pericranial flap from above and a nasoseptal flap from below was used to reconstruct the defect. The pericranial flap was again harvested with endoscope assistance through a coronal plane stab incision. Both cases had excellent outcomes with no post-operative cerebrospinal fluid leak. CONCLUSION: Repair of large anterior cranial fossa defects with a vascularized pericranial flap can be performed through a supraorbital eyebrow craniotomy. Utilizing small, strategically placed transverse (coronal plane) incisions behind the hairline allows for the endoscope-assisted harvesting of a highly customized flap. This modified technique increases the flexibility of the minimally invasive supraorbital craniotomy.

Characterization of outcomes and practices utilized in the management of internal carotid artery injury not requiring definitive endovascular management.

BACKGROUND: After internal carotid artery (ICA) injury during endoscopic skull base surgery, the majority of patients undergo ICA embolization or stenting to treat active extravasation or pseudoaneurysm development. However, management practices when embolization or stenting is not required have not been well described. The objective of this study was to determine how patients with ICA injury but no embolization, stenting, or ligation do long-term and ascertain the reconstruction methods utilized. METHODS: Twenty-nine cases of ICA injury were identified in an international multi-institutional retrospective review. Of these, we identified six cases that were not treated with embolization, stenting, or ICA sacrifice. Information was available for five cases. RESULTS: A muscle patch was used in the immediate repair of each case. A nasoseptal flap was used in one case. Prefabricated nasal tampons were used in all cases. Nasal packing was initially left in for a median of 7 days prior to removal. The initial muscle patch was reinforced with a second muscle graft in one case. One case demonstrated ICA bleeding at the time of packing removal and was repacked an additional week. Follow-up for each of these cases was at least 2 years. No cases of subsequent carotid rupture were found and none of these cases ultimately underwent endovascular stenting. Radiation or proton therapy has not been subsequently used in any of these patients. CONCLUSIONS: This study details the reconstruction, lessons learned, and long-term follow-up for five cases of ICA injury not treated with embolization, stenting, or ligation.

Complication avoidance protocols in endoscopic pituitary adenoma surgery: a retrospective cohort study in 514 patients.

PURPOSE: To evaluate the impact of using consistent complication-avoidance protocols in patients undergoing endoscopic pituitary adenoma surgery including techniques for avoiding anosmia, epistaxis, carotid artery injury, hypopituitarism, cerebrospinal fluid leaks and meningitis. METHODS: All patients undergoing endoscopic adenoma resection from 2010 to 2020 were included. Primary outcomes included 90-day complication rates, gland function outcomes, reoperations, readmissions and length of stay. Secondary outcomes were extent of resection, short-term endocrine remission, vision recovery. RESULTS: Of 514 patients, (mean age 51 ± 16 years; 78% macroadenomas, 19% prior surgery) major complications occurred in 18(3.5%) patients, most commonly CSF leak (9, 1.7%) and meningitis (4, 0.8%). In 14 of 18 patients, complications were deemed preventable. Four (0.8%) had complications with permanent sequelae (3 before 2016): one unexplained mortality, one stroke, one oculomotor nerve palsy, one oculoparesis. There were no internal carotid artery injuries, permanent visual worsening or permanent anosmia. New hypopituitarism occurred in 23/485(4.7%). Partial or complete hypopituitarism resolution occurred in 102/193(52.8%) patients. Median LOS was 2 days; 98.3% of patients were discharged home. Comparing 18 patients with major complications versus 496 without, median LOS was 7 versus 2 days, respectively p < 0.001. Readmissions occurred in 6%(31/535), mostly for hyponatremia (18/31). Gross total resection was achieved in 214/312(69%) endocrine-inactive adenomas; biochemical remission was achieved in 148/209(71%) endocrine-active adenomas. Visual field or acuity defects improved in 126/138(91.3%) patients. CONCLUSION: This study suggests that conformance to established protocols for endoscopic pituitary surgery may minimize complications, re-admissions and LOS while enhancing the likelihood of preserving gland function, although there remains opportunity for further improvements.

Endoscopic Endonasal and Supraorbital Removal of Tuberculum Sellae Meningiomas: Anatomic Guides and Operative Nuances for Keyhole Approach Selection.

BACKGROUND: With growing worldwide endoscopy experience, endonasal and supraorbital removal of tuberculum sellae meningiomas (TSM) has increased. OBJECTIVE: To describe anatomic factors for guiding approach selection and outcomes. METHODS: Retrospective analysis of patients undergoing endonasal or supraorbital TSM resection: approach criteria, clinical outcomes, acute magnetic resonance imaging (MRI) fluid-attenuated inversion-recovery (FLAIR)/T2 changes. RESULTS: From 2008 to 2020, 33 patients (mean age 55 ± 11 yr) were identified: 20 (61%) had endonasal and 13 (39%) supraorbital removal. Comparing endonasal and supraorbital approaches, mean tumor volume (3.7 ± 3.5 cm3 vs 7.7 ± 8.5 cm3, P = .07); percent tumor above planum (42% vs 65%, P = .02), and lateral tumor beyond supraclinoid internal carotid arteries (1.4 ± 2.0 mm vs 4.0 ± 3.2 mm, P = .006) were greater for supraorbital route. Sellar depth was greater for endonasal route tumors (12.2 ± 2.6 mm vs 9.3 ± 2.4 mm, P = .003). Endoscopy, used in 10/13(77%) supraorbital cases, was helpful in additional tumor removal in 4/10(40%). Gross total removal and mean volumetric tumor resection were 16/20(80%) and 97.5% by endonasal, and 5/13(39%) and 96% by supraorbital route. Vision improved in 12/17 (71%) endonasal, 6/8 (75%) supraorbital operations, and worsened in 1 (3%) supraorbital case. Endonasal approach with optic canal decompression increased over study period: 15/20 (75%) endonasal patients vs 1/13(8%) supraorbital (P < .001). Postoperative FLAIR/T2 MRI changes occurred in 2/12 supraorbital and 0/20 endonasal cases. CONCLUSION: In our experience, both endonasal and supraorbital routes are safe and effective for TSM removal. Greater tumor extension below planum and medial optic canal invasion favor endonasal route, while larger size and lateral extension favor supraorbital route. Given high frequency of TSM growth into optic canals and better access for medial optic canal tumor removal, endonasal route may be preferred for most TSMs.

Pituitary adenomas in older adults (≥ 65 years): 90-day outcomes and readmissions: a 10-year endoscopic endonasal surgical experience.

INTRODUCTION: Longer lifespan and newer imaging protocols have led to more older adults being diagnosed with pituitary adenomas. Herein, we describe outcomes of patients ≥ 65 years undergoing endoscopic adenoma removal. To address selection criteria, we also assess a conservatively managed cohort. METHODS: A retrospective analysis of 90-day outcomes of patients undergoing endoscopic pituitary adenomectomy from 2010 to 2019 by a neurosurgical/ENT team was performed. Tumor subtype, cavernous sinus invasion, extent of resection/early remission, endocrinology outcomes, complications, re-operations and readmissions were analyzed. A comparator cohort ≥ 65 years undergoing clinical surveillance without surgery was also analyzed. RESULTS: Of 468 patients operated on for pituitary adenoma, 123 (26%) were ≥ 65 years (range 65-93 years); 106 (86.2%) had endocrine-inactive adenomas; 18 (14.6%) had prior surgery. Of 106 patients with endocrine-inactive adenomas, GTR was achieved in 70/106 (66%). Of 17 patients with endocrine-active adenomas, early biochemical remission was: Cushing's 6/8; acromegaly 1/4; prolactinomas 1/5. Gland function recovery occurred in 28/58 (48.3%) patients with various degrees of preoperative hypopituitarism. New anterior hypopituitarism occurred in 3/110 (2.4%) patients; permanent DI in none. Major complications in 123 patients were: CSF leak 2 (1.6%), meningitis 1 (0.8%), vision decline 1 (0.8%). There were no vascular injuries, operative hematomas, anosmia, deaths, MIs, or thromboembolic events. Median length of stay was 2 days. Readmissions occurred in 14/123 (11.3%) patients, 57% for delayed hyponatremia. Intra-cohort analysis by age (65-69, 70-74, 75-79, ≥ 80 years) revealed no outcome differences. Cavernous sinus invasion (OR 7.7, CI 1.37-44.8; p = 0.02) and redo-surgery (OR 8.5, CI 1.7-42.8; p = 0.009) were negative predictors for GTR/NTR. Of 105 patients evaluated for presumed pituitary adenoma beginning in 2015, 72 (69%) underwent surgery, 8 (7%) had prolactinomas treated with cabergoline and 25 (24%) continue clinical surveillance without surgery, including two on new hormone replacement. CONCLUSION: This study suggests that elderly patients carefully selected for endoscopic adenoma removal can have excellent short-term outcomes including high resection rates, low complication rates and short length of stay. Our experience supports a multidisciplinary approach and the concept of pituitary centers of excellence. Based on our observations, approximately 25% of elderly patients with pituitary adenomas referred for possible surgery can be monitored closely without surgery.

Minimally invasive surgical treatment of intracranial meningiomas in elderly patients (≥ 65 years): outcomes, readmissions, and tumor control.

OBJECTIVE: Increased lifespan has led to more elderly patients being diagnosed with meningiomas. In this study, the authors sought to analyze and compare patients ≥ 65 years old with those < 65 years old who underwent minimally invasive surgery for meningioma. To address surgical selection criteria, the authors also assessed a cohort of patients managed without surgery. METHODS: In a retrospective analysis, consecutive patients with meningiomas who underwent minimally invasive (endonasal, supraorbital, minipterional, transfalcine, or retromastoid) and conventional surgical treatment approaches during the period from 2008 to 2019 were dichotomized into those ≥ 65 and those < 65 years old to compare resection rates, endoscopy use, complications, and length of hospital stay (LOS). A comparator meningioma cohort of patients ≥ 65 years old who were observed without surgery during the period from 2015 to 2019 was also analyzed. RESULTS: Of 291 patients (median age 60 years, 71.5% females, mean follow-up 36 months) undergoing meningioma resection, 118 (40.5%) were aged ≥ 65 years and underwent 126 surgeries, including 20% redo operations, as follows: age 65-69 years, 46 operations; 70-74 years, 40 operations; 75-79 years, 17 operations; and ≥ 80 years, 23 operations. During 2015-2019, of 98 patients referred for meningioma, 67 (68%) had surgery, 1 (1%) had radiosurgery, and 31 (32%) were observed. In the 11-year surgical cohort, comparing 173 patients < 65 years versus 118 patients ≥ 65 years old, there were no significant differences in tumor location, size, or outcomes. Of 126 cases of surgery in 118 elderly patients, the approach was a minimally invasive approach to skull base meningioma (SBM) in 64 cases (51%) as follows: endonasal 18, supraorbital 28, minipterional 6, and retrosigmoid 12. Endoscope-assisted surgery was performed in 59.5% of patients. A conventional approach to SBM was performed in 15 cases (12%) (endoscope-assisted 13.3%), and convexity craniotomy for non-skull base meningioma (NSBM) in 47 cases (37%) (endoscope-assisted 17%). In these three cohorts (minimally invasive SBM, conventional SBM, and NSBM), the gross-total/near-total resection rates were 59.5%, 60%, and 91.5%, respectively, and an improved or stable Karnofsky Performance Status score occurred in 88.6%, 86.7%, and 87.2% of cases, respectively. For these 118 elderly patients, the median LOS was 3 days, and major complications occurred in 10 patients (8%) as follows: stroke 4%, vision decline 3%, systemic complications 0.7%, and wound infection or death 0. Eighty-three percent of patients were discharged home, and readmissions occurred in 5 patients (4%). Meningioma recurrence occurred in 4 patients (3%) and progression in 11 (9%). Multivariate regression analysis showed no significance of American Society of Anesthesiologists physical status score, comorbidities, or age subgroups on outcomes; patients aged ≥ 80 years showed a trend of longer hospitalization. CONCLUSIONS: This analysis suggests that elderly patients with meningiomas, when carefully selected, generally have excellent surgical outcomes and tumor control. When applied appropriately, use of minimally invasive approaches and endoscopy may be helpful in achieving maximal safe resection, reducing complications, and promoting short hospitalizations. Notably, one-third of our elderly meningioma patients referred for possible surgery from 2015 to 2019 were managed nonoperatively.

Tuberculum Sellae Meningiomas in Pregnancy: 3 Cases Treated in the Second Trimester and Literature Review.

BACKGROUND: Tuberculum sella meningiomas typically present with progressive visual loss. It is also known that meningiomas can become symptomatic during pregnancy. Herein we report on 3 patients who presented with progressive visual decline during pregnancy, prompting urgent surgical removal of their meningiomas. CASE DESCRIPTIONS: From our prospectively collected brain tumor database, all women surgically treated for tuberculum sella meningioma since 2006 were retrospectively reviewed. Clinical presentation, surgical approach, perioperative management, and pathology of pregnant patients were reviewed and compared with those of the nonpregnant cohort. Of 43 women with newly diagnosed tuberculum sella meningioma, 3 (7%) presented in pregnancy with progressive visual loss, 1 in the late first trimester and 2 in the early second trimester. One woman pregnant with twins had a broad-based meningioma and underwent a supraorbital craniotomy and gross total tumor removal in her second trimester. Two women with singleton pregnancies both underwent endoscopic endonasal gross total tumor removal during their second trimesters. All 3 patients had visual recovery, 2 of which were complete, and all went on to have successful uncomplicated deliveries of their children and maintain normal pituitary gland function. CONCLUSIONS: Presentation of tuberculum sella meningioma during pregnancy is uncommon but not rare, accounting for 7% of women in our series. Ideally, surgery is performed in the second trimester, ensuring fetal safety while restoring maternal vision and maintaining pituitary gland function are essential. Depending on tumor size and sellar anatomy, endoscopic endonasal or supraorbital keyhole craniotomy approaches are both viable options.

Assessment of Factors Associated With Internal Carotid Injury in Expanded Endoscopic Endonasal Skull Base Surgery.

Importance: Injury to the internal carotid artery (ICA) during endoscopic endonasal skull base surgery does not typically occur as an isolated circumstance but often is the result of multiple factors. Objective: To assess the factors associated with ICA injury in an effort to reduce its occurrence. Design, Setting, and Participants: This quality improvement study used a multicenter root cause analysis of ICA injuries sustained during endoscopic endonasal skull base surgery performed at 11 tertiary care centers across 4 continents (North America, South America, Europe, and Asia) from January 1, 1993, to December 31, 2018. A fishbone model was built to facilitate the root cause analysis. Patients who underwent an expanded endoscopic endonasal approach that carried a substantial potential risk of an ICA injury were included in the analysis. A questionnaire was completed by surgeons at the centers to assess relevant human, patient, process, technique, instrument, and environmental factors associated with the injury. Main Outcomes and Measures: Root cause analysis of demographic, human, patient, process, technique, instrument, and environmental factors as well as mortality and morbidity data. Results: Twenty-eight cases of ICA injury occurred during 7160 expanded endoscopic endonasal approach procedures (incidence of 0.4%). The mean age of the patients was 49 years, with a female to male predominance ratio of 1.8:1 (18 women to 10 men). Anatomical (23 [82%]), pathological (15 [54%]), and surgical resection (26 [93%]) factors were most frequently reported. The surgeon's mental or physical well-being was reported as inadequate in 4 cases (14%). Suboptimal imaging was reported in 6 cases (21%). The surgeon's experience level was not associated with ICA injury. The ICA injury was associated with use of powered or sharp instruments in 20 cases (71%), and use of new instruments or technology in 7 cases (25%). Two patients (7%) died in the operating room, and 3 (11%) were alive with neurological deficits. Overall, patient-related factors were the most frequently reported risk factors (in 27 of 28 cases [96%]). Factors associated with ICA injury catalyzed a list of preventive recommendations. Conclusions and Relevance: This study found that human factors were associated with intraoperative ICA injuries; however, they were usually accompanied by other deficiencies. These findings suggest that identifying risk factors is crucial for preventing such injuries. Preoperative planning and minimizing the potential for ICA injury also appear to be essential.

Correction to: Rathke's cleft cysts: a 6-year experience of surgery vs. observation with comparative volumetric analysis.

The original version of this article unfortunately contained errors in legend numbers of Figure 2 caption.

Analysis of Olfaction after Bilateral Nasoseptal Rescue Flap Transsphenoidal Approach with Olfactory Mucosal Preservation.

OBJECTIVE: To ascertain the impact of septal olfactory strip preservation and bilateral rescue flap elevation on the incidence of olfactory dysfunction. STUDY DESIGN: Case series with chart review of patients undergoing endoscopic endonasal skull base surgery (2012-2014). SETTING: Providence Saint John's Health Center and John Wayne Cancer Institute. SUBJECTS AND METHODS: The incidences of postoperative epistaxis, hyposmia, and anosmia were analyzed using the Brief Smell Identification Test (B-SIT), which was completed in 110 of the 165 patients. RESULTS: Seventy-eight patients required extended approaches. Bilateral nasoseptal rescue flaps were elevated in 144 patients (87.3%) and pedicled nasoseptal or middle turbinate flaps in 21 patients (12.7%). The neurovascular pedicles were preserved in all patients, and there were no episodes of postoperative arterial epistaxis. Normal olfaction was noted in 95 patients (86%), with new hyposmia noted in 5 patients (5.5%). Within the rescue flap cohort, new hyposmia occurred in 6.3% (P < .01) of patients, balanced by improvement of olfaction in 43% of patients with preoperative dysfunction (overall pre- and postoperative olfactory function: 85% vs 86%). Patients with pedicled nasoseptal flaps did not have new hyposmia, with a net improvement of olfaction (71% vs 86%, P = .07). No patients experienced new anosmia. There was no difference between flap type within either subgroup. CONCLUSIONS: Superior olfactory strip preservation during elevation of reconstructive flaps preserves olfactory function and maintains adequate surgical exposure. In addition, rescue flaps have significantly diminished the rate of arterial postoperative epistaxis while maintaining the ability to harvest nasoseptal flaps for future reconstruction.

Strategy and Technique of Endonasal Endoscopic Bony Decompression and Selective Tumor Removal in Symptomatic Skull Base Meningiomas of the Cavernous Sinus and Meckel's Cave.

BACKGROUND: Parasellar meningiomas involving the cavernous sinus and Meckel's cave pose a management challenge because of invasion around neurovascular structures and the pituitary gland. The management options range from aggressive resection to focused radiotherapy alone. We present a strategy for these tumors that includes endonasal bony decompression, partial tumor removal, and stereotactic radiotherapy (SRT) in select cases. METHODS: The tumor location, previous treatments, cranial neuropathies, pituitary dysfunction, tumor control rates, use of stereotactic radiosurgery, SRT, and complications were retrospectively evaluated. RESULTS: Twenty patients (age range, 43-81 years; 65% women; 90% with World Health Organization grade I; median follow-up, 57 months; 14 without previous debulking and RT; 6 with previous debulking and RT) underwent endonasal bony decompression and partial tumor removal. The most common tumor locations were cavernous sinus (95%), Meckel's cave (95%), sella (75%), petroclival (60%), and optic canal/orbit (30%). Three patients with large meningiomas underwent staged transcranial and endonasal debulking. Of the 14 patients without previous debulking and RT, 11 had undergone postoperative SRT, with tumor shrinkage in 3 (27%). At the last follow-up examination, for these 14 patients and the 6 patients who had undergone previous surgery and RT, tumor control was 100% and 33% (P < 0.001) and the cranial neuropathies had improved in 57% and 33%, respectively. Major complications occurred in 2 patients: a permanent sixth cranial nerve palsy and cerebrospinal fluid leakage requiring reoperation. CONCLUSIONS: Endonasal bony decompression and selective tumor removal, followed by SRT, appears to be a reasonable treatment option for most previously untreated parasellar meningiomas. For patients who have undergone previous debulking and RT, new targeted treatment strategies are needed.

Rathke's cleft cysts: a 6-year experience of surgery vs. observation with comparative volumetric analysis.

BACKGROUND: Rathke's cleft cysts (RCCs) are common sellar lesions. Their management remains controversial, particularly when small or asymptomatic. Herein we review a consecutive series of RCC patients managed with surgery or observation. METHODS: All patients with a new diagnosis of presumed RCC, based on MRI, from February 2012-March 2018 were retrospectively divided into observational and surgical cohorts based on an intent-to-treat model. The cohorts were compared for clinical presentation, and cyst volume. The observational cohort was followed for change in cyst size. The surgical cohort was followed for changes in endocrinopathy, visual symptoms, headache and recurrence. RESULTS: Of 90 patients (mean age 36.7 ± 19.4 years; 68% female), 60% (n = 54) were in the observational cohort and 40% (n = 36) in the surgical cohort. Average follow-up was 13 ± 23 months in the observational cohort and 24 ± 19 months in the surgical group. In comparing the cohorts, mean ages were similar with more women in the surgical group (81% vs. 56%, p = 0.04). Most patients in the observational cohort had incidentally-discovered RCCs (n = 50, 88%) as opposed to the surgical cohort (n = 6, 17%). The surgical cohort had higher rates of headache (89% vs 26%, p < 0.001), endocrinopathy (36% vs 0%, p < 0.001), and visual dysfunction (19% vs 0%, p = 0.001). Mean cyst volume and maximal cyst dimensions were greater in the surgical cohort (0.94 ± 0.77 cm3 and 14.2 ± 4.1 mm), compared to the observational cohort (0.1 ± 0.14 cm3 and 6.4 ± 3 mm), (p < 0.001). Among the 53% (n = 30/54) of patients in the observational group with follow-up, 3 (10%) had spontaneous RCC shrinkage, 1 (3%) had modest asymptomatic growth (at 10 months from initial MRI), and 87% had stable cyst size. Of the 36 patients recommended to have surgery, 89% (n = 32) did so. Post-operatively, complete or partial resolution of headache, endocrinopathy and visual dysfunction were documented in 90% (n = 28/30), 75% (n = 10/12), and 100% (n = 7/7), respectively. On follow-up MRI, 8 (22%) patients had some cyst reaccumulation, of whom 3 (8%) were symptomatic and underwent uneventful reoperation. No major complications such as hematoma, CSF leak, new endocrinopathy or visual deficits occurred. CONCLUSION: From this consecutive series, a majority (60%) of RCCs do not appear to warrant surgical intervention and have a low risk of cyst progression. However, surgical cyst removal appears to be indicated and safe for patients with larger, symptomatic RCCs. Simple cyst drainage has a high rate of improvement in pituitary gland function, visual function and headache resolution with low complication rates and symptomatic recurrence risk. These findings stress the importance of careful case selection and potential utility of volumetric assessment for patients with RCCs.

Predominance of triple wild-type and IGF2R mutations in mucosal melanomas.

BACKGROUND: Primary mucosal melanoma (MM) is a rare subtype of melanoma that arises from melanocytes in the mucosa. MM has not been well profiled for mutations and its etiology is not well understood, rendering current treatment strategies unsuccessful. Hence, we investigated mutational landscape for MM to understand its etiology and to clarify mutations that are potentially relevant for MM treatment. METHODS: Forty one MM and 48 cutaneous melanoma (CM) tissues were profiled for mutations using targeted deep next-generation sequencing (NGS) for 89 cancer-related genes. A total of 997 mutations within exons were analyzed for their mutational spectrum and prevalence of mutation, and 685 non-synonymous variants were investigated to identify mutations in individual genes and pathways. PD-L1 expression from 21 MM and 18 CM were assessed by immunohistochemistry. RESULTS: Mutational spectrum analysis revealed a lower frequency of UV-induced DNA damage in MM than in CM (p = 0.001), while tobacco exposure was indicated as a potential etiologic factor for MM. In accordance with low UV damage signatures, MM demonstrated an overall lower number of mutations compared to CM (6.5 mutations/Mb vs 14.8 mutations/Mb, p = 0.001), and less PD-L1 expression (p = 0.003). Compared to CM, which showed frequent mutations in known driver genes (BRAF 50.0%, NRAS 29.2%), MM displayed lower mutation frequencies (BRAF; 12.2%, p < 0.001, NRAS; 17.1%), and was significantly more enriched for triple wild-type (no mutations in BRAF, RAS, or NF1, 70.7% vs 25.0%, p < 0.001), IGF2R mutation (31.7% vs 6.3%, p = 0.002), and KIT mutation (9.8% vs 0%, p = 0.042). Of clinical relevance, presence of DCC mutations was significantly associated with poorer overall survival in MM (log-rank test, p = 0.02). Furthermore, mutational spectrum analysis distinguished primary anorectal MM from CM metastasized to the bowel (spectrum analysis p < 0.001, number of mutations p = 0.002). CONCLUSIONS: These findings demonstrated a potential etiologic factor and driver mutation for MM and strongly suggested that MM initiation or progression involves distinct molecular-mechanisms from CM. This study also identified mutational signatures that are clinically relevant for MM treatment.

Pregnancy-associated Cushing's disease? An exploratory retrospective study.

PURPOSE: In most clinical series of Cushing's disease (CD), over 80% of patients are women, many of whom are of reproductive age. The year following pregnancy may be a common time to develop CD. We sought to establish the incidence of CD onset associated with pregnancy. METHODS: A retrospective review was conducted for patients with biochemically-proven CD. Demographics, clinical history, biochemistry, imaging, pathology, and outcomes were reviewed. Pregnancy-associated CD was defined as symptom onset within 1 year of childbirth. RESULTS: Over 10 years, 77 patients including 64 women (84%), with CD underwent endonasal surgery. Of the 64 women, 64% were of reproductive age (15-45 years) at the time of diagnosis, and 11 (27%) met criteria for pregnancy-associated CD. Of these 11 women, median number of pregnancies prior to onset of CD was 2 (range 1-4) compared to zero (range 0-7) for 30 other women with CD onset during reproductive age (p = 0.0024). With an average follow-up of 47 ± 34 months, sustained surgical remission rates for woman with pregnancy-associated CD, other women of reproductive age, and women not of reproductive age were 91%, 80% and 83%, respectively. The average lag-time from symptom onset to diagnosis for women with pregnancy-associated CD was 4 ± 2 years. CONCLUSIONS: In this exploratory study, over one quarter of women of reproductive age with CD appeared to have symptomatic disease onset within 1 year of childbirth. This relatively high rate of pregnancy-associated CD suggests a possible causal relationship related to the stress of pregnancy and pituitary corticotroph hyperactivity in the peripartum period. This possible association suggests a heightened degree of clinical suspicion and biochemical testing for CD may be warranted after childbirth. Further study of this possible link between pregnancy and CD is warranted.

Imaging-Ambiguous Lesions of Meckel's Cave-Utility of Endoscopic Endonasal Transpterygoid Biopsy.

INTRODUCTION: Meckel's cave is a dural-lined cavity in the middle fossa skull base in which lies the Gasserian ganglion, a potential site for tumors and inflammatory lesions. A variety of lesions can be predominantly isolated to Meckel's cave, including extension from head and neck cancers, other malignant tumors, as well as benign lesions. Clinical presentation and imaging findings are often insufficient to establish a diagnosis. Hence, histologic confirmation is required to determine the appropriate treatment strategy. Several surgical approaches have been used to reach this deep-seated area, often with significant morbidity and prolonged recovery. Given advancements in endoscopy and greater facility with the technique, the endoscopic endonasal approach has been used increasingly to reach lesions in the region. METHODS: A single-institution, retrospective chart review over a 10-year period was performed to identify and describe patients with pathologically differing but imaging-similar lesions with their epicenter in Meckel's cave. RESULTS: Of a total of 21 cases of lesions in Meckel's cave approached by an endoscopic endonasal transpterygoid approach, we present 6 patients with imaging-ambiguous lesions involving Meckel's cave that were biopsied via the extended endoscopic endonasal approach. Among this diverse group, pathology included B-cell lymphoma, squamous cell carcinoma, adenocarcinoma, malignant schwannoma, benign schwannoma, and neurosarcoidosis. CONCLUSIONS: We explore not only the relevance of this approach in the armamentarium of the modern skull-base surgeon but also its limitations and conclude that the endoscopic endonasal approach provides a safe and relatively direct, minimally invasive corridor to many lesions of Meckel's cave.

Evolution of the graded repair of CSF leaks and skull base defects in endonasal endoscopic tumor surgery: trends in repair failure and meningitis rates in 509 patients.

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 2010­April 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 0­2 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 1­3 repair failures decreased from 6/143 (4.1%) to 3/141 (2.1%) and grade 1­3 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 1­3 (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.

A single-center, pilot study evaluating a novel TriHex peptide- and botanical-containing eye treatment compared to baseline.

BACKGROUND: Topical treatments containing tripeptide and hexapeptide (TriHex technology) have been proven to contribute to youthful skin by clearing the extracellular matrix and stimulating collagen and elastin production. OBJECTIVE: Evaluate the efficacy of a novel eye treatment containing TriHex peptides and other synergistic ingredients for the daily treatment of fine lines/crow's feet around the eyes, under eye hollowing, under eye bags, and dark circles. PATIENTS/METHODS: In this study, 10 subjects (9 female and 1 male) aged 30-60 of Fitzpatrick skin type I, II, or III were selected to use an eye treatment containing TriHex peptides and active botanicals (Alastin Restorative Eye Treatment with TriHex Technology™, ALASTIN Skincare, Inc., Carlsbad, CA) twice daily for 12 weeks. Subjects were photographed and evaluated at baseline, week 4, week 8, and week 12 by a board-certified facial plastic surgeon. Using an adjusted Griffiths scale (0 = none, best possible condition and 9 = severe, worst possible condition), subjects were evaluated on severity of fine lines/crow's feet, under eye hollowing, under eye bags, and dark circles at each visit. Subjects completed a "Subject Questionnaire" at week 4, week 8, and week 12 pertaining to the subject's observations and perceived improvement of these measures. RESULTS: Based on the investigator's assessments, overall improvement in periocular skin was noted for all 10 subjects. Over the course of 12 weeks, raw scores significantly decreased indicating reduction of lines/crow's feet (41% improvement), under eye hollowing (29% improvement), under eye bags (48% improvement), and dark circles (39% improvement). Based on the "Subject Questionnaire," all subjects noted overall improvement of the appearance of skin around the eyes. CONCLUSION: Based on the findings of this study, this eye treatment containing TriHex peptides and active botanicals is an effective stand-alone treatment for the rejuvenation of periocular skin. When used twice daily, this product can reduce the appearance of lines/crow's feet, under eye hollowing, under eye bags, and dark circles.