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.

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.

The Minimal Clinically Important Difference of the Anterior Skull Base Nasal Inventory-12.

BACKGROUND: The minimal clinically important difference (MCID) is defined as the smallest change in health-related quality of life (QOL) that patients consider meaningful. The MCID is essential for determining clinically significant changes, rather than simply statistically significant changes, in QOL scores. The Anterior Skull Base Nasal Inventory-12 (ASK Nasal-12), a site-specific sinonasal QOL instrument, has emerged as a standard instrument for assessing QOL in patients who have undergone endonasal transsphenoidal surgery. OBJECTIVE: To determine the MCID for the ASK Nasal-12. METHODS: Distribution- and anchor-based methods were used to determine the MCID for the ASK Nasal-12 based on raw data from a multicenter prospective QOL study of 218 patients. RESULTS: Two distribution-based statistical methods, the one-half standard deviation method and the effect-size method, both yielded MCIDs of 0.37 (medium effect). The first anchor-based method, using the 2-wk postoperative overall nasal functioning item as the anchor, yielded an MCID of 0.31. The second anchor-based method, using the 2-wk postoperative Short Form Health Survey 8 bodily pain item as the anchor, yielded an MCID of 0.29. CONCLUSION: The largest MCID obtained for the ASK Nasal-12 using 4 statistical methods 2 wk postoperatively was 0.37. This information provides clinicians with an essential context for determining the clinical significance of changes in QOL scores after interventions. Our results will help clinicians better interpret QOL scores and design future studies that are powered to detect meaningful QOL changes.

Role of Endoscopic Skull Base and Keyhole Surgery for Pituitary and Parasellar Tumors Impacting Vision.

Significant advances over the last 2 decades in imaging technology, instrumentation, anatomical knowledge, and reconstructive techniques have resulted in the endonasal endoscopic approach becoming an integral part of modern skull base surgery. With growing use and greater experience, surgical outcomes continue to incrementally improve across many skull base pathologies, including those tumors that impact vision and ocular motility. The importance of the learning curve and use of a multi-disciplinary approach is critical to maximizing success, minimizing complications, and enhancing quality of life in these patients. Realizing the limits of the endonasal route and reasonable use of transcranial approaches such as the supraorbital eyebrow craniotomy, it may br appropriate to consider nonsurgical therapy including various forms of radiotherapy [corrected] and medical treatment options.

Endonasal Endoscopic Management of Parasellar and Cavernous Sinus Meningiomas.

The management of cavernous sinus and invasive parasellar meningiomas often requires a multimodality treatment approach. Early attempts at complete or near-complete removal of parasellar meningiomas involving the cavernous sinus, Meckel cave, clivus, and sella using anterolateral or lateral skull base approaches were typically unsuccessful and yielded high rates of new cranial neuropathy and other complications. This article presents a strategy of endonasal endoscopic parasellar skull base bony decompression and limited tumor removal followed by stereotactic radiotherapy, stereotactic radiosurgery, or observation. Patient selection, technical nuances, potential complications, and initial outcomes in a small series of patients are discussed.

The expanding role of the endonasal endoscopic approach in pituitary and skull base surgery: A 2014 perspective.

BACKGROUND: The past two decades have been the setting for remarkable advancement in endonasal endoscopic neurosurgery. Refinements in camera definition, surgical instrumentation, navigation, and surgical technique, including the dual surgeon team, have facilitated purely endonasal endoscopic approaches to the majority of the midline skull base that were previously difficult to access through the transsphenoidal microscopic approach. METHODS: This review article looks at many of the articles from 2011 to 2014 citing endonasal endoscopic surgery with regard to approaches and reconstructive techniques, pathologies treated and outcomes, and new technologies under consideration. RESULTS: Refinements in approach and closure techniques have reduced the risk of cerebrospinal fluid leak and infection. This has allowed surgeons to more aggressively treat a variety of pathologies. Four main pathologies with outcomes after treatment were identified for discussion: pituitary adenomas, craniopharyngiomas, anterior skull base meningiomas, and chordomas. Within all four of these tumor types, articles have demonstrated the efficacy, and in certain cases, the advantages over more traditional microscope-based techniques, of the endonasal endoscopic technique. CONCLUSIONS: The endonasal endoscopic approach is a necessary tool in the modern skull base surgeon's armamentarium. Its efficacy for treatment of a wide variety of skull base pathologies has been repeatedly demonstrated. In the experienced surgeon's hands, this technique may offer the advantage of greater tumor removal with reduced overall complications over traditional craniotomies for select tumor pathologies centered near the midline skull base.

Avoidance of postoperative epistaxis and anosmia in endonasal endoscopic skull base surgery: a technical note.

BACKGROUND: Most endoscopic transsphenoidal approaches jeopardize the sphenopalatine artery and septal olfactory strip (SOS), increasing the risk of postoperative anosmia and epistaxis while precluding the ability to raise pedicled nasoseptal flaps (NSF). We describe a bilateral "rescue flap" technique that preserves the mucosa containing the nasal-septal vascular pedicles and the SOS. This approach can reduce the risk of postoperative complications, including epistaxis and anosmia. METHODS: A retrospective analysis was conducted of all patients who underwent endoscopic transsphenoidal surgery with preservation of both sphenopalatine vascular pedicles and SOS. In a recent subset of patients, olfactory assessment was performed. RESULTS: Of 174 consecutive operations performed in 161 patients, bilateral preservation of the sphenopalatine vascular pedicle and SOS was achieved in 139 (80 %) operations, including 31 (22 %) with prior transsphenoidal surgery. Of the remaining 35 operations, 18 had a planned formal NSF and 17 had prior surgery or extensive lesions precluding use of this technique. Of pituitary adenomas, RCCs or sellar arachnoid cysts, 118 (94 %) underwent this approach, including 91 % of patients who had prior surgery. Preoperative olfaction function was maintained in 97 % of patients that were tested. None of the patients had postoperative arterial epistaxis. CONCLUSION: Preservation of bilateral sphenopalatine vascular pedicles and the SOS is feasible in over 90 % of patients undergoing endonasal endoscopic surgery for pituitary adenomas and RCCs. This approach, while not hindering exposure or limiting instrument maneuverability, preserves the nasoseptal vasculature for future NSF use if needed and appears to minimize the risks of postoperative arterial epistaxis and anosmia.