Unique volatile metabolite signature of sinonasal inverted papilloma detectable in plasma and nasal secretions.

BACKGROUND: Sinonasal inverted papilloma (SNIP) is a benign neoplasm with aggressive features, including a high recurrence rate and a propensity for malignant transformation. Accurate diagnosis with complete resection and the need for close long-term surveillance is widely accepted as standard management. In this study, we investigate whether SNIP produces a unique volatile metabolite signature, which may ultimately lead to a novel approach to diagnose and monitor SNIP. METHODS: Whole blood and nasal secretions from patients with SNIP and healthy age-, sex-, and smoking-status-matched controls, were collected. There were 56 blood samples and 42 nasal secretion samples collected. The volatile metabolite signature of SNIP plasma and nasal secretion samples were compared with those of healthy controls using chromatography. RESULTS: Seventy-two volatiles were identified in plasma samples. Multivariate analysis of variance results, even when controlled for smoking status, indicated toluene as a significant univariate result with lower levels of toluene identified in SNIP plasma samples than healthy control plasma samples. A linear discriminant analysis (LDA) model for plasma volatiles correctly classified 23 of 24 SNIP patients and 26 of 27 control patients, with a cross-validation error rate of 6.02%. Sixty-nine volatiles were identified in nasal samples. For nasal secretion samples, no single univariate response was significant. The LDA model correctly classified 21 of 21 SNIP patients and 11 of 12 control patients, with a cross-validation error rate of 6.55%. CONCLUSION: This study suggests that SNIP produces a unique, detectable volatile metabolite signature. With further investigation, this can have dramatic clinical implications for diagnosis and monitoring. Although most volatile metabolite studies have investigated solid-organ malignancy, this novel study addresses a benign sinonasal neoplasm by using nasal secretions and plasma as an analysis medium, representing the first such study.

Quantitative determination of the optimal temporoparietal fascia flap necessary to repair skull-base defects.

BACKGROUND: The ability to reconstruct large cranial base defects has greatly improved with the development of pedicled vascularized flaps. The temporoparietal fascia flap (TPFF) is a viable alternative to the Hadad-Bassagasteguy nasoseptal flap for large ventral skull-base defects. This study aims to characterize the size of the TPFF necessary for optimal ventral skull-base reconstruction. METHODS: Eleven formaldehyde-fixed cadaveric heads were used to harvest TPFF of varying heights on each side (total = 22). TPFF was passed through the pterygomaxillary fissure (PMF) to the ventral skull base to assess its coverage. For a subgroup of 12 sides, the TPFF was trimmed to determine the minimum height necessary for coverage. RESULTS: The TPFF height was (mean ± standard deviation [SD]) 14.72 ± 1.02 cm (range, 12.5 to 16.5 cm) and width was 8.43 ± 1.05 cm (range, 6 to 10.5 cm). The distance from the TPFF pedicle through the PMF was 5.8 ± 0.5 cm (range, 5 to 6.5 cm). All TPFF flaps provided complete ipsilateral coverage of clival defects, and all but 1 covered the entire clivus. All TPFF flaps, when rotated anteriorly, provided coverage up to the cribriform plate. The minimum TPFF height necessary for complete coverage of cribriform defects and ventral defects up to the planum sphenoidale was 12 cm. TPFF height for specimens with and without complete ventral skull-base coverage was significantly different (p < 0.0001). CONCLUSION: The TPFF is a versatile alternative to the nasoseptal flap and a height of at least 12 cm can provide enough coverage for all ventral skull base defects.

Predicting prolonged length of stay after endoscopic transsphenoidal surgery for pituitary adenoma.

BACKGROUND: Endoscopic transsphenoidal surgery (ETS) for the resection of pituitary adenoma has become more common throughout the past decade. Although most patients have a short postoperative hospitalization, others require a more prolonged stay. We aimed to identify predictors for prolonged hospitalization in the setting of ETS for pituitary adenomas. METHODS: A retrospective chart review as performed on 658 patients undergoing ETS for pituitary adenoma at a single tertiary care academic center from 2005 to 2019. Length of stay (LoS) was defined as date of surgery to date of discharge. Patients with LoS in the top 10th percentile (prolonged LoS [PLS] >4 days, N = 72) were compared with the remainder (standard LoS [SLS], N = 586). RESULTS: The average age was 54 years and 52.5% were male. The mean LoS was 2.1 days vs 7.5 days (SLS vs PLS). On univariate analysis, atrial fibrillation (p = 0.002), hypertension (p = 0.033), partial tumor resection (p < 0.001), apoplexy (p = 0.020), intraoperative cerebrospinal fluid (ioCSF) leak (p = 0.001), nasoseptal flap (p = 0.049), postoperative diabetes insipidus (DI) (p = 0.010), and readmission within 30 days (p = 0.025) were significantly associated with PLS. Preoperative continuous positive airway pressure (CPAP) (odds ratio, 15.144; 95% confidence interval, 2.596-88.346; p = 0.003) and presence of an ioCSF leak (OR, 10.362; 95% CI, 2.143-50.104; p = 0.004) remained significant on multivariable analysis. CONCLUSION: For patients undergoing ETS for pituitary adenomas, an ioCSF leak or preoperative use of CPAP predicted PLS. Additional common reasons for PLS included postoperative CSF leak (10 of 72), management of DI or hypopituitarism (15 of 72), or reoperation due to surgical or medical complications (14 of 72).

Treatment-related morbidity in patients treated for sinonasal malignancy.

BACKGROUND: Sinonasal malignancies are a rare, heterogeneous group of tumors that often present at an advanced stage and require multimodal therapy. The presence of high-grade toxicity and sinonasal complications after treatment can negatively impact quality of life. In this study we aim to describe posttreatment morbidity in patients with sinonasal malignancy. METHODS: A retrospective analysis of all patients treated for sinonasal malignancy was conducted from 2005 to 2018 at a tertiary referral institution. A total of 129 patients met the inclusion criteria. Primary outcomes were treatment details, pathology, posttreatment complications, and radiation toxicity. Fisher's exact test, chi-square test, and Student t test were used for statistical analysis. RESULTS: Mean age was 58.4 (median, 61; range, 19-94) years. After diagnosis, 24 patients had surgery alone, 46 had surgery with radiation alone, 47 had surgery with chemoradiation, and 14 received definitive chemoradiation. Overall, 10.4% (n = 12) of patients had postoperative complications, and 21.0% (n = 22) had high-grade (grade 3-5) radiation toxicity. After radiation, 20% (n = 21) of patients had chronic sinusitis requiring functional endoscopic sinus surgery and 20% (n = 21) had symptomatic nasal obstruction requiring operative debridement. CONCLUSION: Sinonasal complications, including nasal obstruction and chronic sinusitis, occur frequently after definitive treatment of sinonasal malignancy and should be addressed when considering quality of life in survivors. These complications occur more frequently in patients who undergo chemoradiation as opposed to surgery alone.

Rate of rhinosinusitis and sinus surgery following a minimally destructive approach to endoscopic transsphenoidal hypophysectomy.

BACKGROUND: There remains considerable variation in the extent of sinonasal preservation during the approach for endoscopic transsphenoidal hypophysectomy (TSH). We advocate for a minimally destructive approach utilizing turbinate lateralization, small posterior septectomy, no ethmoidectomy, and preservation of nasoseptal flap (NSF) pedicles bilaterally. Due to these factors, this approach may affect the rates of postoperative rhinosinusitis. The objective of this study is to define the rates of postoperative rhinosinusitis in patients undergoing this approach. METHODS: Single institution, retrospective chart review of patients undergoing TSH from 2005 to 2018. RESULTS: A total of 415 patients were identified and 14% developed an episode of postoperative rhinosinusitis within 3 months. These patients were significantly more likely to have had a history of recurrent acute or chronic rhinosinusitis. Most cases were sphenoethmoidal sinusitis managed with 1 to 2 courses of antibiotics. Of patients with postoperative rhinosinusitis, most did not undergo NSF. Average follow-up was 38 months. Six patients (1.4%) underwent post-TSH functional endoscopic sinus surgery (FESS). Average time from TSH to FESS was 26.3 months. Two of these patients had a history of prior chronic rhinosinusitis without polyposis. Two patients underwent revision TSH for recurrent tumor as the primary indication for surgery at time of FESS. Twenty-two-item Sino-Nasal Outcome Test (SNOT-22) scores generally increased immediately postoperatively, but frequently decreased below preoperative level by the time of last follow-up, regardless of whether patients developed rhinosinusitis. CONCLUSION: Sinonasal preservation during TSH is associated with a low rate of postoperative rhinosinusitis requiring FESS and excellent long-term patient reported outcomes. We continue to advocate for sinonasal preservation during pituitary surgery.

Adenosine-induced transient hypotension for carotid artery injury during endoscopic skull-base surgery: case report and review of the literature.

BACKGROUND: As the management of ventral skull-base pathology has transitioned from open to endonasal treatment, there has been an increased focus on the prevention and endoscopic endonasal management of internal carotid artery (ICA) and major vascular injury. The use of adenosine to induce transient hypotension or flow arrest has been previously described during intracranial aneurysm surgery; however, there have been no reports of the technique being used during endonasal skull-base surgery to achieve hemostasis following major vascular injury. METHODS: Case report (n = 1) and literature review. RESULTS: A 25-year-old female underwent attempted endoscopic endonasal resection of an advanced right-sided chondrosarcoma. During resection of the tumor, brisk arterial bleeding was encountered consistent with focal injury to the right cavernous ICA. Stable vascular hemostasis could not be achieved with tamponade. An intravenous bolus dose of adenosine was administered to induce a transient decrease in systemic blood pressure and facilitate placement of the muscle patch over the direct site of vascular injury. The patient subsequently underwent endovascular deconstruction of the right ICA. CONCLUSION: This is the first reported use of adenosine to induce transient hypotension for a major vascular injury sustained during endonasal skull-base surgery. Based on well-established safety data from neurosurgical application, adenosine has the potential to be used as a safe and effective adjunctive technique in similar endonasal circumstances and may represent an additional tool in the armamentarium of the skull-base surgeon. Surgeons should consider having adenosine available when a risk of ICA injury is anticipated.

Evaluation of cranial base repair techniques utilizing a novel cadaveric CPAP model.

BACKGROUND: Although recent guidelines for obstructive sleep apnea recommend early postoperative use of continuous positive airway pressure (CPAP) after endonasal skull base surgery, the time of initiation of CPAP is unclear. In this study we used a novel, previously validated cadaveric model to analyze the pressures delivered to the cranial base and evaluate the effectiveness of various repair techniques to withstand positive pressure. METHODS: Skull base defects were surgically created in 3 fresh human cadaver heads and repaired using 3 commonly used repair techniques: (1) Surgicel™ onlay; (2) dural substitute underlay with dural sealant onlay; and (3) dural substitute underlay with nasoseptal flap onlay with dural sealant. Pressure microsensors were placed in the sphenoid sinus and sella, both proximal and distal to the repair, respectively. The effectiveness of each repair technique against various CPAP pressure settings (5-20 cm H2 O) was analyzed. RESULTS: Approximately 79%-95% of positive pressure administered reached the sphenoid sinus. Sellar pressure levels varied significantly across the 3 repair techniques and were lowest after the third technique. "Breach" points (CPAP settings at which sellar repair was violated) were lowest for the first group. All 3 specimens showed a breach after the first repair technique. For the second repair technique, only a single breach was created in 1 specimen at 20 cm H2 O. No breaches were created in the third group. CONCLUSION: Different skull base repair techniques have varying ability to withstand CPAP. Both second and third repair techniques performed in a nearly similar fashion with regard to their ability to withstand positive pressure ventilation.

A cadaveric model for measuring sinonasal continuous positive airway pressure-a proof-of-concept study.

BACKGROUND: Obstructive sleep apnea is a common respiratory disorder that can have negative effects on health and quality of life. Positive pressure therapy (CPAP) is the primary treatment. There is a lack of consensus on the risk of postoperative CPAP after endoscopic sinus or skull base surgery. We present a proof-of-concept cadaver model for measuring sinonasal pressure delivered by CPAP. METHODS: Three fresh cadaver heads were prepared by removing the calvaria and brain. Sphenoidotomies were made and sellar bone was removed. Pressure sensors were placed in the midnasal cavity, sphenoid sinus, and sella. CPAP was applied and the delivered pressure was recorded at increasing levels of positive pressure. Paired t tests and intraclass correlation coefficients were used to analyze results. RESULTS: Increases in positive pressure led to increased pressure recordings for all locations. Nasal cavity pressure was, on average, 81% of delivered CPAP. Pressure was highest in the sphenoid sinus. The effect of middle turbinate medialization on intrasphenoid pressure was not statistically significant in 2 heads. Intrasellar pressure was 80% of delivered CPAP with lateralized turbinates and 84% with medialized turbinates. Pressure recordings demonstrated excellent reliability for all locations. All heads developed non-sellar-based cranial base leaks at higher pressures. Cribriform region leaks were successfully sealed with DuraSeal®. CONCLUSION: Our proof-of-concept cadaver model represents a novel approach to measure pressures delivered to the nasal cavity and anterior skull base by CPAP. With further study, it may have broader clinical application to guide the safe postoperative use of CPAP in this population.

Minimizing Septectomy for Endoscopic Transsphenoidal Approaches to the Sellar and Suprasellar Regions: A Cadaveric Morphometric Study.

The purpose of this study was to evaluate the effect of posterior septectomy size on surgical exposure and surgical freedom during the endoscopic transsphenoidal approach to the sella and parasellar region. Dissections were performed on 10 embalmed cadaver heads. Dissections started with wide bilateral sphenoidotomies, lateralization of middle turbinates, and a 5-mm posterior septectomy. The posterior septectomy was increased in 5-mm increments to a maximum of 35 mm, followed by bilateral middle turbinectomies. Surgical exposure was defined as the distance between the ipsilateral and contralateral limit of exposure as allowed by the posterior septum along a midsphenoid horizontal meridian. Surgical freedom was defined as the angle between the ipsilateral and contralateral limit. The mean baseline width of the posterior sphenoid sinus was 29.4 ± 3.7 mm. With a 5-mm septectomy, the mean width of surgical exposure was 21.1 ± 2.8 mm. The surgical exposure increased significantly with progressively larger posterior septectomy until a 20-mm posterior septectomy, after which no further increase in surgical exposure or freedom was obtained. Bilateral lateral opticocarotid recesses were accessible with a 15-mm posterior septectomy. The addition of bilateral middle turbinectomies did not significantly increase lateral exposure within the sphenoid sinus compared with middle turbinate lateralization.

The extended nasoseptal flap for coverage of large cranial base defects.

BACKGROUND: The nasoseptal flap (NSF) is commonly used to repair skull base defects via a transnasal endoscopic approach. The original description of the technique includes 2 parallel incisions that follow the sagittal plane of the septum. We describe a novel modification to the traditional NSF that allows coverage along the posterior wall of the frontal sinus. METHODS: In addition to the 2 sagittal incisions, a third incision is made between these coursing along the maxillary crest from the posterior edge to the midportion of the flap. This provides an extension that can be rotated further anteriorly. We report 4 adult patients with skull base defects too large and anterior to cover with a traditional NSF, on whom we successfully reconstructed with the extended flap. We also performed the technique on six cadaver heads (11 flaps) to provide average measurements of the extension. RESULTS: Our patients were successfully repaired with maintained flap survival. We were able to achieve an average of 1.9 cm, or 26.8%, of additional length on the cadaveric study. CONCLUSION: The relaxing incision described here creates a flap that allows for reconstruction of a larger range of skull base defects.

An evaluation of invasive fungal sinusitis outcomes with subsite analysis and use of frozen section analysis.

BACKGROUND: Invasive fungal sinusitis (IFS) is an aggressive mycosis of the nasal cavity with frequent extension to adjacent structures. Occurring more commonly in immunocompromised individuals, prognosis is typically poor despite aggressive treatment. This study aims to examine postoperative outcomes and survival of a cohort of fungal sinusitis patients at an academic center, as well as identify causes of death in IFS patients. METHODS: This study was a retrospective chart review of patient charts and departmental records, yielding patient demographics, medical and surgical treatments, pathology records, and outcomes data. RESULTS: Twenty-seven patients were identified from departmental records between 1998 and 2014. Twenty-one patients presented with Mucor infections, whereas the remaining 6 patients had Aspergillus. All patients were immunocompromised: diabetes (n = 14) and hematologic malignancy (n = 13). Three patients had multiple causes of immunosuppression. Most commonly involved subsites were the maxillary, ethmoid, and sphenoid sinuses. Nasal septum involvement was independently associated with mortality (p < 0.01). Overall mortality was 57.7% within 1 year, although 66.7% of fatalities occurred within 1 month of diagnosis. CONCLUSION: Overall survival for IFS remains poor. Widespread disease and nasal septum involvement were associated with a negative clinical course. Early identification and aggressive surgical and antifungal therapy is warranted. Even despite intense therapy, comorbid conditions and drug toxicity increase mortality and complicate the clinical course.

Surgical management of rhinosinusitis in endoscopic-endonasal skull-base surgery.

BACKGROUND: Endoscopic-endonasal skull base surgery (ESBS) provides an important approach to select pathologies. There remains a paucity of data, however, regarding morbidity in patients undergoing ESBS with comorbid acute rhinosinusitis (ARS), a fungal ball (FB), or chronic rhinosinusitis (CRS). METHODS: A retrospective database review between January 2008 and January 2013 identified 35 patients with concurrent skull-base pathology and refractory ARS, FB, CRS, and CRS with nasal polyposis (CRSP) who underwent endoscopic sinus surgery (ESS) and ESBS. RESULTS: Two of 35 (5.7%) had an FB, 3 of 35 (8.6%) had ARS, 19 of 35 (54.2%) had CRSP, and 11 of 35 (31.4%) had CRS. Five of 35 (14.3%) were staged procedures whereas 30 of 35 (85.7%) underwent concurrent ESS and ESBS. Four patients (80%) who were staged carried diagnoses of an FB and ARS. Two patients in the concurrent group required revision ESS for recurrent polyposis. There were no cases of intraorbital or intracranial infectious complications. CONCLUSION: Management of the paranasal sinuses is paramount to maintain healthy sinonasal function in patients undergoing ESBS. In our experience, most cases of CRS and CRSP can be surgically managed at the time of ESBS without increased risk of intracranial infection. Patients with ARS at the time of surgery or an FB should be staged to avoid postoperative ESBS morbidity.

Perforation of a nasoseptal flap does not increase the rate of postoperative cerebrospinal fluid leak.

BACKGROUND: The nasoseptal flap (NSF) has been shown to be a valuable addition to the reconstructive armamentarium of the endoscopic skull-base surgeon. We aimed to evaluate the rate of postoperative cerebrospinal fluid (CSF) leak after use of a NSF that had a small tear during harvest. METHODS: After Institutional Review Board (IRB) approval, we analyzed our database of patients undergoing skull-base resection. We included all patients who had a NSF reconstruction, septoplasty, and/or spur on preoperative computed tomography (CT) imaging. We then evaluated video of each procedure to determine if a tear occurred in the NSF during harvest. Patient records were reviewed to determine if a postoperative CSF leak occurred. RESULTS: We evaluated video of 21 patients who underwent a skull-base resection, were reconstructed with a NSF, and had either a septoplasty or evidence of a septal spur on CT imaging. Of these 21 cases, 11 small tears occurred during harvest of the NSF flap and none of the patients with a torn NSF had a postoperative CSF leak. CONCLUSION: Our series shows a 0% postoperative CSF leak rate in patients undergoing skull-base reconstruction with a NSF that was torn during harvest. Small tears in the NSF do not seem to affect postoperative CSF leak rates.

The Relationship between Substance Use and HIV Transmission in Peru.

OBJECTIVES: The primary aim of this article is to review literature regarding the relationship between substance use and HIV transmission in Peru. METHODS: Detailed search of published literature completed in PubMed and Google-Scholar and other local Peruvian publications. Mesh words: "Peru"; "substance-related-disorders"; "HIV"; "sexual-behavior" and their combinations. From 3921 articles, 150 were chosen for more careful review and only 26 were used for the review. No date limit was used in this review. RESULTS: Peruvian HIV epidemic is limited to MSM and its prevalence goes up to 33% in certain MSM-subpopulations. Transmission is mainly through sexual contact. Drug use doubled the risk for casual sex, decreased by half the chances of using condoms, increased the number of partners per year and the risk for STD's. Peruvian HIV-positive populations have higher rates drug use and using drugs have been associated with a higher prevalence of being HIV-positive. This may be also true for other populations such as pregnant women in which there is an association between drug use and HIV. CONCLUSIONS: Although the amount of Peruvian research in this area limits the review, there seems to be a relationship between using drugs, having risky-sexual-behaviors and being HIV positive in Peru. HIV-prevention strategies for Peruvians must address the link between sex and substance use.