Citations

BackgroundThe impact of failed cerebrospinal fluid leak (CSF) leak repair in endoscopic skull base surgery has not been adequately studied.MethodsIn this investigation we reviewed patients who had undergone endoscopic skull base surgery between 2002 and 2014 at 7 international centers. Demographic variables, comorbidities, tumor characteristics, and repair techniques were evaluated to determine association with successful repair of CSF leak. Postoperative complications and length of stay were compared among groups.ResultsData were collected on 2097 patients who were divided into 3 groups: (1) those with no intraoperative leak (n = 1533); (2) those with successful repair of their intraoperative leak (n = 452); and (3) those with failed repair (n = 112). Compared with successful repair, failed repair was associated with an increased risk of intracranial infection (odds ratio [OR], 5.6; 95% confidence interval [CI], 5.3‐13.15), pneumocephalus (OR, 16; 95% CI, 5.8‐44.4), 30‐day readmission (OR, 8.4; 95% CI, 5.3‐13.5), reoperation (OR, 115.4; 95% CI, 56.3‐236.8), and prolonged hospital stay (14.9 vs 7.0 days, p < 0.01). Outcomes in patients who had successful repairs of intraoperative leaks were similar to those who never had leakage. Intraoperative use of pedicled nasoseptal flaps was associated with successful repair (OR, 0.60; 95% CI, 0.34‐0.92).ConclusionIntraoperative CSF leaks are a frequent and expected occurrence during endoscopic skull base surgery. Failed CSF leak repair has a significant impact on patient outcomes, with increased rates of postoperative pneumocephalus, intracranial infections, reoperation, deep vein thrombosis, readmission, and prolonged hospital stay. Recognition and repair of intraoperative CSF leaks reduces postoperative complications. Use of pedicled nasoseptal flaps improves outcomes in reconstructing defects at higher risk for postoperative leak.

BackgroundIn patients undergoing transnasal endoscopic sellar surgery, an analysis of risk factors and predictors of intraoperative and postoperative cerebrospinal fluid leak (CSF) would provide important prognostic information.MethodsA retrospective review of patients undergoing endoscopic sellar surgery for pituitary adenomas or craniopharyngiomas between 2002 and 2014 at 7 international centers was performed. Demographic, comorbidity, and tumor characteristics were evaluated to determine the associations between intraoperative and postoperative CSF leaks. Correlations between reconstructive and CSF diversion techniques were associated with postoperative CSF leak rates. Odds ratios (OR) were identified using a multivariate logistic regression model.ResultsData were collected on 1108 pituitary adenomas and 53 craniopharyngiomas. Overall, 30.1% of patients had an intraoperative leak and 5.9% had a postoperative leak. Preoperative factors associated with increased intraoperative leaks were mild liver disease, craniopharyngioma, and extension into the anterior cranial fossa. In patients with intraoperative CSF leaks, postoperative leaks occurred in 10.3%, with a higher postoperative leak rate in craniopharyngiomas (20.8% vs 5.1% in pituitary adenomas). Once an intraoperative leak occurred, craniopharyngioma (OR = 4.255, p = 0.010) and higher body mass index (BMI) predicted postoperative leak (OR = 1.055, p = 0.010). In patients with an intraoperative leak, the use of septal flaps reduced the occurrence of postoperative leak (OR = 0.431, p = 0.027). Rigid reconstruction and CSF diversion techniques did not impact postoperative leak rates.ConclusionIntraoperative CSF leaks can occur during endoscopic sellar surgery, especially in larger tumors or craniopharyngiomas. Once an intraoperative leak occurs, risk factors for postoperative leaks include craniopharyngiomas and higher BMI. Use of septal flaps decreases this risk.

BackgroundChronic invasive fungal sinusitis (CIFS) is a rare subtype of mycotic diseases involving the paranasal sinuses. It is characterized by a slow onset and invasive organisms with non‐granulomatous inflammation seen on histopathology. Historically, treatment has involved radical surgical resection. The purpose of this study was to describe the presentation, comorbidities, and role of more conservative treatment options.MethodsThis is a multi‐institutional retrospective case series of 6 patients with CIFS over 15 years. Patients’ medical comorbidities, imaging results, operative procedures, pathological findings including organisms identified, antimicrobial medications used, and outcomes were reviewed.ResultsThe mean time from onset of symptoms to diagnosis was 6 months. Cultures and fungal PCR identified Aspergillus species in every case. All 6 patients were found to have systemic comorbidities, with many being diabetic. Imaging findings ranged from thickening of sinus mucosa to invasion of the orbit and skull base. Treatment included long‐term antifungal therapy and conservative endoscopic surgery in all but 1 patient, who had an open approach. Every patient was free of invasive fungal disease at last follow‐up, with a range of 1 to 27 months.ConclusionCIFS is an insidious disease often with months between symptom onset and diagnosis. It is differentiated from chronic granulomatous invasive fungal sinusitis (CGIFS) by a lack of granulomas on histopathology and an association with diabetes mellitus. Endoscopic debridement combined with long‐term oral voriconazole was an effective treatment strategy in this series.

Background Giant frontal mucoceles, characterized by significant intracranial and/or intraorbital extension, can present with significant neurologic symptoms. Although typical mucoceles are managed endoscopically, giant mucoceles are often treated with an open or combined approach due to various concerns, including frontal lobe displacement, size, and rapid decompression of the intracranial component. The impact of significant intracranial extension on outcomes is not well described. Objective This review studied key neurologic considerations in the management of giant frontal sinus mucoceles and analyzed outcomes of different management strategies. Methods Systematic literature review by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Results Thirty-two articles, which represented 85 cases, met inclusion criteria. Neurologic symptoms on presentation ranged from headache (24.7%) and vision loss (12.9%) to extremity weakness (1.2%), frontal lobe syndrome (2.4%), and seizures (4.7%). Twenty-eight patients were treated endoscopically (34.1%), and 54 (65.9%) were treated with an external approach. Twenty-five of the open procedures included a craniotomy. Indications for the open approach included subdural empyema, enucleation, or large anterior table defects. Perioperative antibiotics were not consistently used. No perioperative seizures were reported with any approach. There were six cerebrospinal fluid leaks, all in the patients who underwent open procedures. The overall recurrence rate was 3.5%, with no recurrences reported in patients treated with an open approach. Follow-up ranged from 1 week to 8 years. Conclusions Giant frontal mucoceles often present with various neurologic symptoms. Both open and endoscopic techniques offer excellent results. Endoscopic management is effective and preferred, except in special circumstances. An interdisciplinary team approach should be used to optimize surgical planning.

Background: In the initial PARTNER trial (Placement of Aortic Transcatheter Valves) of transcatheter aortic valve replacement for high-risk (HR) and inoperable patients, mortality at 1 year was 24% in HR and 31% in inoperable patients. A recent report of the 30-day outcomes with the low-profile SAPIEN 3 transcatheter aortic valve replacement system demonstrated very low rates of adverse events, but little is known about the longer-term outcomes with this device. Methods: Between October 2013 and September 2014, 583 HR (65%) or inoperable (35%) patients were treated via the transfemoral (84%) or transapical/transaortic (16%) access route at 29 US sites. Major clinical events at 1 year were adjudicated by an independent clinical events committee, and echocardiographic results were analyzed by a core laboratory. Results: Baseline characteristics included age of 83 years, 42% female, and median Society of Thoracic Surgeons score of 8.4%. At the 1-year follow-up, survival (all-cause) was 85.6% for all patients, 87.3% in the HR subgroup, and 82.3% in the inoperable subgroup. Survival free of all-cause and cardiovascular mortality in the transfemoral patients from the HR cohort was 87.7% and 93.3%, respectively. There was no severe paravalvular leak. Moderate paravalvular leak (2.7%) was associated with an increase in mortality at 1 year, whereas mild paravalvular leak had no significant association with mortality. Symptomatic improvement as assessed by the percentage of patients in New York Heart Association class III and IV (90.1% to 7.7% at 1 year; P <0.0001) and by Kansas City Cardiomyopathy Questionnaire overall summary score (improved from 46.9 to 72.4; P <0.0001) was marked. Multivariable predictors of 1-year mortality included alternative access, Society of Thoracic Surgeons score, and disabling stroke. Conclusions: In this large, adjudicated registry of SAPIEN 3 HR and inoperable patients, the very low rates of important complications resulted in a strikingly low mortality rate at 1 year. Between 30 and 365 days, the incidence of moderate paravalvular aortic regurgitation did not increase, and no association between mild paravalvular leak and 1-year mortality was observed, although a small increase in disabling stroke occurred. These results, which likely reflect device iteration and procedural evolution, support the use of transcatheter aortic valve replacement as the preferred therapy in HR and inoperable patients with aortic stenosis. Clinical Trial Registration : URL: http://www.clinicaltrials.gov . Unique identifier: NCT01314313.

Background: Needle biopsy has proven to be a potentially adequate method for initial biopsy of many soft-tissue and bone lesions. To help optimize this procedure, this study sought to test the characteristics of several needles, including a steerable needle. Materials and Methods: Five needle types were tested, including a steerable needle. Animal muscle tissue was used for all testing. The following experiments were performed: (1) sample collection with different needle types, (2) histological analysis of needle track, (3) observation of steerable needle characteristics using CT-guidance. Results: Sample collection: The Menghini 21 g and Chiba 22 g needles were graded as excellent for ease of use and integrity of sample. Histologic evaluation showed good specimen preservation with all needle types. Histological analysis of needle track: tracks created by the Menghini 21 g and Spinal 20 g needles both showed no histologically detectable damage to surrounding tissue. Observation of steerable Menghini needle under CT-guidance: needle advanced easily through tissue, even when maximally curved. Small, large, and double curves were feasible to avoid obstacles and reach targets. There was no deflection or change in position of the needle tip when the stylet was removed. Needle withdrawal did not damage surrounding tissue. Conclusions: Compared to the other needles, the steerable needle was found to be durable and easy to use, allowing for precise navigation around vital structures yielding superior integrity of sample tissue.

SummaryBackgroundMatrix metalloproteinase‐9 is a proteolytic enzyme whose expression is increased in ulcerative colitis.AimTo evaluate the safety and efficacy of GS‐5745, a fully humanised anti‐matrix metalloproteinase‐9 monoclonal antibody, in moderately‐to‐severely active ulcerative colitis.MethodsWe randomised 74 patients with ulcerative colitis to treatment with single or multiple ascending intravenous or subcutaneous doses of GS‐5745 or placebo. Multiple‐dose cohorts received either IV infusions (0.3, 1.0, 2.5 or 5.0 mg/kg GS‐5745 or placebo) every 2 weeks (three total IV infusions) or five weekly SC injections (150 mg GS‐5745 or placebo). The primary outcomes were the safety, tolerability and pharmacokinetics of escalating single and multiple doses of GS‐5745. Exploratory analyses in the multiple‐dose cohorts included clinical response (≥3 points or 30% decrease from baseline in Mayo Clinic score and ≥1 point decrease in the rectal bleeding subscore or a rectal bleeding subscore ≤1) and clinical remission (a complete Mayo Clinic score ≤2 with no subscore >1) at Day 36. Biological effects associated with a clinical response to GS‐5745 were explored using histological and molecular approaches.ResultsTwenty‐three of the 42 patients (55%) receiving multiple doses of GS‐5745 had adverse events, compared with 5/8 patients (63%) receiving placebo. GS‐5745 showed target‐mediated drug disposition, approximately dose‐proportional increases in maximum plasma concentration and more than dose‐proportional increases in the area under the plasma drug concentration‐time curve. Clinical response occurred in 18/42 patients (43%) receiving GS‐5745 compared with 1/8 patients (13%) receiving placebo. Clinical remission occurred in 6/42 patients (14%) receiving GS‐5745 and 0/8 (0%) receiving placebo. Patients with a clinical response to GS‐5745 had reductions in matrix metalloproteinase‐9 tissue levels (mean 48.9% decrease from baseline compared with a mean 18.5% increase in nonresponders, P = 0.008) significant improvements in histopathology scores (confirmed with three separate histological disease activity indices), as well as changes in colonic gene expression that were consistent with reduced inflammation.ConclusionThis phase 1 trial provides preliminary evidence for the safety and therapeutic potential of GS‐5745 in the treatment of ulcerative colitis.