Evidence of Biofilm and Persister Cell Formation in Revision Rhinoplasty.

Background: Postoperative rhinoplasty infection can lead to serious cosmetic deformity, loss of structural integrity to the nose, and functional deficiencies. Understanding the factors contributing to postoperative infection is important. Microbial biofilms and persister cells play an important role in health care-associated infections. The objective of this study is to identify microbial biofilm and persister cells in the nasal soft tissue of patients undergoing revision rhinoplasty. Methods: Fourteen patients undergoing rhinoplasty were recruited for this study. Nasal soft tissue was removed during rhinoplasty and preserved in 2% paraformaldehyde/2.5% glutaraldehyde. High-resolution images were then obtained from these nasal soft tissue samples. Results: Three samples were positive for the presence of microbial persister cells or biofilms. All samples came from patients undergoing revision rhinoplasty. These patients had between one to six previous rhinoplasty procedures and one patient had previous injectable nasal filler. Conclusions: Biofilms and persister cells are able to form in nasal soft tissue of revision rhinoplasty patients in the absence of an implant and may contribute to increased postoperative infection risk.

Device Design Modifications Informed by In Vitro Testing of Bacterial Attachment Reduce Infection Rates of Cochlear Implants in Clinical Practice.

Recalcitrant chronic infections of implanted medical devices are often linked to the presence of biofilms. The prevention and treatment of medical device-associated infections is a major source of antibiotic use and driver of antimicrobial resistance globally. Lowering the incidence of infection in patients that receive implanted medical devices could therefore significantly improve antibiotic stewardship and reduce patient morbidity. Here we determined if modifying the design of an implantable medical device to reduce bacterial attachment, impacted the incidence of device-associated infections in clinical practice. Since the 1980s cochlear implants have provided long-term treatment of sensorineural hearing deficiency in hundreds of thousands of patients world-wide. Nonetheless, a relatively small number of devices are surgically explanted each year due to unresolvable infections. Features associated with the accumulation of bacteria on the Cochlear™ Nucleus® CI24RE™ model of cochlear implant devices were identified using both in vitro bacterial attachment assays and examination of explanted devices. Macro-scale design modifications that reduced bacterial attachment in vitro were incorporated into the design of the CI500™ and Profile™ series of Nucleus implant. Analyses of mandatory post-market vigilance data of 198,757 CI24RE and 123,084 CI500/Profile series implantation surgeries revealed that these design modifications correlated with significantly reduced infection rates. This study demonstrates that a design-centric approach aimed at mitigating bacterial attachment was a simple, and effective means of reducing infections associated with Cochlear Nucleus devices. This approach is likely to be applicable to improving the designs of other implantable medical devices to reduce device-associated infections.

Prevalence, Surgical Management, and Audiologic Impact of Sigmoid Sinus Dehiscence Causing Pulsatile Tinnitus.

OBJECTIVE: To evaluate the prevalence, surgical management, and audiologic impact of pulsatile tinnitus caused by sigmoid sinus dehiscence. STUDY DESIGN AND SETTING: Retrospective chart review at a tertiary care hospital. PATIENTS: Adults with unilateral pulsatile tinnitus attributable to sigmoid sinus dehiscence who underwent resurfacing between January 2010 and January 2020. INTERVENTIONS: Transmastoid sigmoid resurfacing. MAIN OUTCOME MEASURES: Resolution of pulsatile tinnitus; audiologic outcomes; complications; tinnitus etiologies. RESULTS: Nineteen patients (89.4% women) had surgery for suspected sigmoid sinus dehiscence. The mean dehiscence size was 6.1 mm (range, 1-10.7 mm). Eight patients had concurrent sigmoid sinus diverticulum and one patient also had jugular bulb dehiscence. Only two patients (10.5%) had the defect identified by radiology. Low-frequency pure-tone average, measured at frequencies of 250 and 500 Hz, showed a significant median improvement of 8.8 dB following resurfacing (18.8 dB versus 10.0 dB, p = 0.02). The majority of patients had complete resolution of pulsatile tinnitus (16/19, 84.2%). Of those without complete resolution, two patients had partial response and one patient had no improvement. There were no significant complications. Of 41 consecutively tracked patients with a pulsatile tinnitus chief complaint, sigmoid pathology represented 32% of cases. CONCLUSIONS: Sigmoid sinus dehiscence represents a common vascular cause of pulsatile tinnitus that, if properly assessed, may be amenable to surgical intervention. Sigmoid sinus resurfacing is safe, does not require decompression, and may improve low-frequency hearing. Radiographic findings of dehiscence are often overlooked without a high index of clinical suspicion. Its relationship with transverse sinus pathology and idiopathic intracranial hypertension remain unclear.

Childhood tonsillectomy alters the primary distribution of HPV-related oropharyngeal squamous cell carcinoma.

OBJECTIVES: We investigated how tonsillectomy during childhood may influence the distribution of human papillomavirus (HPV) positive cancer of the tonsils in adult life using p16 as a surrogate marker for HPV infection. STUDY DESIGN: Retrospective observational study. METHODS: A total of 280 patients diagnosed with oropharyngeal squamous cell carcinoma (OPSCC) and known p16 status were eligible for this study. Each participant was called to obtain the childhood tonsillectomy history. Respondents were subgrouped by p16 status and the primary tumor location. Patient demographic and clinical information was analyzed for association with Fisher's exact and Wilcoxon rank sum tests. Location of tumor was modeled using univariate (UVA) and multivariate (MVA) logistic regression with associated odds ratios (OR) and 95% confidence intervals. RESULTS: Of the 280 patients, 115 (41%) were respondents: 104 (90.4%) were p16 positive and 11 (9.6%) were p16 negative. For p16 positive patients, we observed a majority (93%) of intact tonsils in those with tonsil cancer, compared to 45% of intact tonsils in patients with p16 positive cancer elsewhere in the oropharynx (P < .001). MVA logistic regression showed that female gender (OR = 4.16, P = .0675), prior smoking history (OR = 2.6, P = .0367), and intact tonsils (OR = 15.2, P < .0001) were associated with tonsillar OPSCC. CONCLUSION: We found that patients with p16 positive OPSCC at a non-tonsil site were much more likely to have had prior tonsillectomy vs those with p16 positive OPSCC arising within the tonsil. Nevertheless, we do not advocate tonsillectomies as a public health policy to reduce HPV-related OPSCC. LEVEL OF EVIDENCE: 6.

Evidence of a microbial etiology for sialoliths.

OBJECTIVES: Sialolithiasis is the primary etiology for parotid and submandibular swelling, potentially resulting in discomfort, bacterial infections, and hospitalization. The etiology of sialolith formation is unknown. Currently, the proposed etiologies range from inflammation, coalescence of organic molecules, sialomicrolith formation, pH changes, and biofilm formation. In this study, we performed a descriptive analysis of images obtained through electron microscopy of sialoliths. Based on our findings and descriptive analysis, we hypothesize that sialolith formation is likely multifactorial and begins with biofilm formation. Biofilm formation then triggers a host immune response, and it is the interaction of biofilm with host immune cells and calcium nanoparticles that forms the nidus and creates a favorable environment for calcium precipitation. METHODS: Sialoliths were extracted from patients and imaged under light and scanning electron microscopy. Specimens for light microscopy were prepared using a diamond saw. Specimens for electron microscopy were freeze-fractured, thus providing an undisturbed view of the core of the sialolith. RESULTS: We were able to identify clear evidence of biofilm caves at the core of each sialolith. These biofilm caves were complex with the presence of bacteria and dehydrated extrapolysaccharide matrix, host cells (immune cells, platelets and erythrocytes), and calcium nanoparticles. CONCLUSION: The etiology of sialolith formation is likely multifactorial. We propose that biofilm formation within a single salivary gland or duct leads to local ductal injury, which results in the influx of host immune cells that interact with the biofilm and calcium nanoparticles, creating a scaffold upon which further calcium deposition can occur. LEVEL OF EVIDENCE: NA Laryngoscope, 130:69-74, 2020.

Rethinking Morbidity and Mortality Conference.

This article will discuss the importance of an effective morbidity and mortality (M&M) conference toward supporting a proactive and preventative approach to patient safety and quality improvement (PSQI). Key characteristics will be discussed that enhance this process for being a mechanism for driving positive PSQI culture change that permeates the department. The focus of this article will be on how to approach the structure and process of this conference for maximal benefit.

Maximizing Exposure of the Internal Auditory Canal Via the Retrosigmoid Approach: An Anatomical, Radiological, and Surgical Study.

OBJECTIVE: The purpose of this study was to identify anatomic landmarks and surgical techniques that maximize bone removal for exposure of the distal internal auditory canal (IAC) to avoid labyrinthine injury during retrosigmoid removal of tumors within the IAC. STUDY DESIGN: Anatomic dissection, radiological assessment and retrospective case series. SETTING: Tertiary referral center. METHODS: On the basis of previously conducted temporal bone anatomic dissections of the temporal bone, the authors performed intraoperative measurement of the undissected distal IAC, performed pre- and postoperative radiological assessment of vestibular schwannoma (VS) patients. The surgical and anatomic information was used to determine the anatomic limits of labyrinth sparing bone dissection and the landmarks most critical to maximal IAC exposure. The authors describe surgical techniques using these data. An edited video of representative surgery highlights important principles. Review of 251 patients requiring IAC bony dissection for tumor removal from January 2005 through October 2017 is described. RESULTS: Achieving complete exposure of the IAC fundus is not possible, without labyrinthine injury, via retrosigmoid approach. Anatomic dissection, intraoperative photography, and postoperative radiographs demonstrate that bone removal within 2 to 3 mm of the fundus is routinely possible. The endolymphatic sac and duct is the optimal landmark for optimizing IAC exposure. CONCLUSION: The course of the endolymphatic sac and duct in the posterior petrous bone is the most important landmark determining the lateral limit of bony removal during IAC exposure for tumor resection. Surgical techniques based on these anatomic findings facilitate tumor resection while preserving the labyrinth.

The changing face of petrous apicitis-a 40-year experience.

OBJECTIVES/HYPOTHESIS: Petrous apicitis (PA) is a rare complication of otitis media. Gradenigo syndrome, with the classic triad of otitis, deep pain, and abducens paralysis, is rarer still. The objective of this study was to determine if clinical presentation and management has changed over time. STUDY DESIGN: Retrospective chart review. METHODS: Forty-four patients with PA over a 40-year period were studied. Symptoms, signs, and management outcomes were studied. Historical review, surgical anatomy and approaches, pathology, and microbiology, and an illustrative case are included as appendices. RESULTS: The classical Gradenigo triad of retro-orbital pain, otitis, and abducens palsy occurred in only six of 44 patients (13.6%). Over the 40-year observation period, those needing surgery has decreased. CONCLUSIONS: Antibiotics remain the primary treatment modality. Surgery is reserved for cases failing to respond to antibiotics. One of the 44 patients in this series died of his disease. Diagnosis and management algorithms based on these observations are suggested. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:195-201, 2018.

Evidence against the mucosal traction theory in cholesteatoma.

OBJECTIVES: To investigate the distribution of ciliated epithelium in the human middle ear and its potential role in the formation of cholesteatoma. STUDY DESIGN: Comparative human temporal bone study. METHODS: We selected temporal bones from 14 donors with a diagnosis of cholesteatoma, 15 with chronic otitis media without retraction pockets, 14 with chronic otitis media with retraction pockets, 14 with cystic fibrosis (CF), and 16 controls. We mapped the distribution of the ciliated cells in the mucosal lining of the middle ear and tympanic membrane using three-dimensional reconstruction analysis, and counted the number of ciliated cells in the middle ear mucosa. RESULTS: Ciliated cells are extremely sparse in the epithelial lining of the lateral surface of the ossicles in the epitympanum and the medial surface of the tympanic membrane. Furthermore, there is a significant decrease in the number of ciliated cells in these areas in temporal bones with cholesteatoma, chronic otitis media, chronic otitis media with retraction pockets, and CF compared to controls. Ciliated cells most commonly are located at the hypotympanum and the Eustachian tube opening but not the tympanic membrane or epitympanum. CONCLUSION: The paucity of ciliated epithelial cells on the medial side of the tympanic membrane and the lateral surface of the ossicles in the epitympanum in cases with cholesteatoma and/or chronic otitis media do not support the mucosal migration theory of cholesteatoma formation. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:1663-1667, 2018.

Surface charge modification decreases Pseudomonas aeruginosa adherence in vitro and bacterial persistence in an in vivo implant model.

OBJECTIVE: Chronic, persistent infections complicate otologic procedures utilizing implantable devices such as cochlear implants or tympanostomy tubes. These infections are thought to be due to the establishment of microbial biofilms on implant surfaces. To address this issue, we hypothesized that surface charge modification may inhibit the formation of Pseudomonas aeruginosa biofilms on implant surfaces in vitro and in vivo. STUDY DESIGN: We evaluated the effect of surface charge modification on bacterial biofilm formation by assessing the effect of the surface charge on bacterial adhesion in vitro and bacterial persistence in vivo. METHODS: To study the effect of surface charge in vitro, the surface wells in culture plates were modified using a layer-by-layer polyelectrolyte assembly method. Bacterial adherence was measured at 30-, 60-, and 120-minute intervals. To study the effect of surface charge modification in vivo, the surface of titanium microscrews was similarly modified and then surgically implanted into the dorsal calvaria of adult rats and inoculated with bacteria. Two weeks after implantation and inoculation, the number of bacteria remaining in vivo was evaluated. RESULTS: Surface charge modification results in a significant decrease in adherence of bacteria in vitro. Surface charge modification of titanium microscrew implants also resulted in a significant decrease in P. aeruginosa recovered 2 weeks after surgical implantation. CONCLUSION: Charge modification decreases the number of bacteria adherent to a surface in vitro and decreases the risk and severity of implant infection in an in vivo rat infection model. These results have promising biomedical applications. LEVEL OF EVIDENCE: NA. Laryngoscope, 127:1655-1661, 2017.

Otoconia and otolithic membrane fragments within the posterior semicircular canal in benign paroxysmal positional vertigo.

OBJECTIVES/HYPOTHESIS: Benign paroxysmal positional vertigo (BPPV) is the most common vestibular disorder with an incidence between 10.7 and 17.3 per 100,000 persons per year. The mechanism for BPPV has been postulated to involve displaced otoconia resulting in canalithiasis. Although particulate matter has been observed in the endolymph of affected patients undergoing posterior canal occlusion surgery, an otoconial origin for the disease is still questioned. STUDY DESIGN: In this study, particulate matter was extracted from the posterior semicircular canal of two patients and examined with scanning electron microscopy. METHODS: The samples were obtained from two patients intraoperatively during posterior semicircular canal occlusion. The particles were fixed, stored in ethanol, and chemically dehydrated. The samples were sputter coated and viewed under a scanning electron microscope. Digital images were obtained. RESULTS: Intact and degenerating otoconia with and without linking filaments were found attached to amorphous particulate matter. Many otoconia appeared to be partially embedded in a gel matrix, presumably that which encases and anchors the otoconia within the otolith membrane, whereas others stood alone with no attached filaments and matrix. The otoconia measured roughly 2 to 8 µm in length and displayed a uniform outer shape with a cylindrical bulbous body and a 3 + 3 rhombohedral plane at each end. CONCLUSIONS: These findings suggest that the source of the particulate matter in the semicircular canals of patients with BPPV is broken off fragments of the utricular otolithic membrane with attached and detached otoconia. LEVEL OF EVIDENCE: NA Laryngoscope, 127:709-714, 2017.

FleQ, a Transcriptional Activator, Is Required for Biofilm Formation In Vitro But Does Not Alter Virulence in a Cholesteatomas Model.

HYPOTHESIS: Bacterial biofilm formation within cholesteatomas is responsible for increased persistence and tissue destruction and Pseudomonas aeruginosa deficient in biofilm formation (PAO1 ΔfleQ) are less virulent than the parent bacteria. BACKGROUND: Infected aural cholesteatomas have been demonstrated to be more destructive than uninfected cholesteatomas and infections are more persistent. The chronicity and persistence of infections within cholesteatomas may be because of the presence of biofilm formation. METHODS: Twenty-seven mutant strains of PAO1 were screened for surface adherence. These strains were also screened for static biofilm formation. The biofilms were quantified by staining with crystal violet. Aural cholesteatomas were then induced in Mongolian gerbils by ligation of the ear canal. At the time of ligation, the ear canals were inoculated with wild-type PAO1 and a biofilm deficient PAO1 ΔfleQ strain of P. aeruginosa. A 7 weeks course of ciprofloxacin (20 mg/kg/day) was started on postoperative day 7. Eight weeks after induction of cholesteatomas, the cholesteatoma size, levels of bone destruction, and levels of bone remodeling were evaluated using microCT imaging. RESULTS: PAO1 ΔfleQ was identified as a poorly adherent and deficient biofilm forming mutant strain of P. aeruginosa. Infected cholesteatomas had more growth, bone destruction and bone remodeling than uninfected cholesteatomas. However, there was no difference observed between cholesteatomas infected with PAO1 (biofilm competent strain) and PAO1 ΔfleQ (biofilm deficient strain). CONCLUSION: We demonstrate that the biofilm phenotype is not an important virulence factor in cholesteatomas infected with P. aeruginosa.

Endovascular management of internal carotid artery injuries secondary to endonasal surgery: case series and review of the literature.

OBJECTIVE Internal carotid artery (ICA) injury is a rare but severe complication of endonasal surgery. The authors describe their endovascular experience managing ICA injuries after transsphenoidal surgery; they review and summarize the current literature regarding endovascular techniques; and they propose a treatment algorithm based on the available evidence. METHODS A retrospective review of 576 transsphenoidal pituitary adenoma resections was performed. Cases of ICA injury occurring at our institution and transfers from other hospitals were evaluated. Endovascular treatments for ICA injury reported in the literature were also reviewed and summarized. RESULTS Seven cases were identified from the institutional cohort (mean age 46.3 years, mean follow-up 43.4 months [1-107 months]) that received endovascular treatment for ICA injury. Five injuries occurred at our institution (5 [0.9%] of 576), and 2 injuries occurred at outside hospitals. Three patients underwent ICA sacrifice by coil placement, 2 underwent lesion embolization (coil or stent-assisted coil placement), and 2 underwent endoluminal reconstruction (both with flow diversion devices). Review of the literature identified 98 cases of ICA injury treated with endovascular methods. Of the 105 total cases, 46 patients underwent ICA sacrifice, 28 underwent lesion embolization, and 31 underwent endoluminal reconstruction. Sacrifice of the ICA proved a durable solution in all cases; however, the rate of persistent neurological complications was relatively high (10 [21.7%] of 46). Lesion embolization was primarily performed by coil embolization without stenting (16 cases) and stent-assisted coiling (9 cases). Both techniques had a relatively high rate of at least some technical complication (6 [37.5%] of 16 and 5 [55.6%] of 9, respectively) and major technical complications (i.e., injury, new neurological deficit, or ICA sacrifice) (5 [31.3%] of 16 and 2 [22.2%] of 9, respectively). Endoluminal reconstruction was performed by covered stent (24 cases) and flow diverter (5 cases) placement. Covered stents showed a reasonably high rate of technical complications (10 [41.7%] of 24); however, 8 of these problems were resolved, leaving a small percentage with major technical complications (2 [8.3%] of 24). Flow diverter placement was also well tolerated, with only 1 minor technical complication. CONCLUSIONS Endovascular treatments including vessel sacrifice, coil embolization (with or without stent assistance), and endoluminal reconstruction offer a tailored approach to ICA injury management after endonasal surgery. Vessel sacrifice remains the definitive treatment for acute, uncontrolled bleeding; however, vessel preservation techniques should be considered carefully in select patients. Multiple factors including vascular anatomy, injury characteristics, and risk of dual antiplatelet therapy should guide best treatment, but more study is needed (particularly with flow diverters) to refine this decision-making process. Ideally, all endovascular treatment options should be available at institutions performing endonasal surgery.

Histologic, Molecular, and Clinical Evaluation of Explanted Breast Prostheses, Capsules, and Acellular Dermal Matrices for Bacteria.

BACKGROUND: Subclinical infections, manifest as biofilms, are considered an important cause of capsular contracture. Acellular dermal matrices (ADMs) are frequently used in revision surgery to prevent recurrent capsular contractures. OBJECTIVE: We sought to identify an association between capsular contracture and biofilm formation on breast prostheses, capsules, and ADMs in a tissue expander/implant (TE/I) exchange clinical paradigm. METHODS: Biopsies of the prosthesis, capsule, and ADM from patients (N = 26) undergoing TE/I exchange for permanent breast implant were evaluated for subclinical infection. Capsular contracture was quantified with Baker Grade and intramammary pressure. Biofilm formation was evaluated with specialized cultures, rtPCR, bacterial taxonomy, live:dead staining, and scanning electron microscopy (SEM). Collagen distribution, capsular histology, and ADM remodeling were quantified following fluorescent and light microscopy. RESULTS: Prosthetic devices were implanted from 91 to 1115 days. Intramammary pressure increased with Baker Grade. Of 26 patients evaluated, one patient had a positive culture and one patient demonstrated convincing evidence of biofilm morphology on SEM. Following PCR amplification 5 samples randomly selected for 16S rRNA gene sequencing demonstrated an abundance of suborder Micrococcineae, consistent with contamination. CONCLUSIONS: Our data suggest that bacterial biofilms likely contribute to a proportion, but not all diagnosed capsular contractures. Biofilm formation does not appear to differ significantly between ADMs or capsules. While capsular contracture remains an incompletely understood but common problem in breast implant surgery, advances in imaging, diagnostic, and molecular techniques can now provide more sophisticated insights into the pathophysiology of capsular contracture. LEVEL OF EVIDENCE: 4 Therapeutic.

Intralabyrinthine schwannomas mimic cochleovestibular disease: symptoms from tumor mass effect in the labyrinth.

OBJECTIVE: To describe symptoms from intralabyrinthine schwannomas specific from more common vestibular schwannomas of the internal auditory canal or cerebellopontine angle resulting from mass effect from the tumor within the labyrinth. PATIENTS: Eight patients diagnosed as having intralabyrinthine schwannomas from 2000 to 2014 were examined retrospectively from two tertiary neurotologic centers. INTERVENTIONS: Diagnosis of intralabyrinthine schwannoma was made with gadolinium-enhanced magnetic resonance imaging scans. Heavily T2-weighted sequences were used to verify mass within the fluid-filled labyrinth. Patients then underwent audiometric and vestibular testing when appropriate. Treatment consisted of observation or surgical resection. MAIN OUTCOME MEASURES: Clinical symptoms, magnetic resonance imaging scans, audiometric and videonystagmography data, and operative findings were reviewed. RESULTS: Five of the eight patients had positional vertigo or nystagmus on testing. One patient's only complaint was positional vertigo without auditory symptoms. Three of the patients demonstrated mixed hearing loss. Two patients underwent resection of their tumors, one because of tumor growth and the other because of intractable vertigo. CONCLUSION: These data show that a high proportion within our series displayed symptoms of positional vertigo and mixed hearing loss, which are symptoms not typical of nonintralabyrinthine schwannomas. One patient's only reported symptom was positional vertigo. These symptoms may arise from the effect of the tumor's mass exerted on the cochlear and vestibular end organs.

Combined high-field intraoperative magnetic resonance imaging and endoscopy increase extent of resection and progression-free survival for pituitary adenomas.

PURPOSE: The clinical benefit of combined intraoperative magnetic resonance imaging (iMRI) and endoscopy for transsphenoidal pituitary adenoma resection has not been completely characterized. This study assessed the impact of microscopy, endoscopy, and/or iMRI on progression-free survival, extent of resection status (gross-, near-, and sub-total resection), and operative complications. METHODS: Retrospective analyses were performed on 446 transsphenoidal pituitary adenoma surgeries at a single institution between 1998 and 2012. Multivariate analyses were used to control for baseline characteristics, differences during extent of resection status, and progression-free survival analysis. RESULTS: Additional surgery was performed after iMRI in 56/156 cases (35.9%), which led to increased extent of resection status in 15/156 cases (9.6%). Multivariate ordinal logistic regression revealed no increase in extent of resection status following iMRI or endoscopy alone; however, combining these modalities increased extent of resection status (odds ratio 2.05, 95% CI 1.21-3.46) compared to conventional transsphenoidal microsurgery. Multivariate Cox regression revealed that reduced extent of resection status shortened progression-free survival for near- versus gross-total resection [hazard ratio (HR) 2.87, 95% CI 1.24-6.65] and sub- versus near-total resection (HR 2.10; 95% CI 1.00-4.40). Complication comparisons between microscopy, endoscopy, and iMRI revealed increased perioperative deaths for endoscopy versus microscopy (4/209 and 0/237, respectively), but this difference was non-significant considering multiple post hoc comparisons (Fisher exact, p = 0.24). CONCLUSIONS: Combined use of endoscopy and iMRI increased pituitary adenoma extent of resection status compared to conventional transsphenoidal microsurgery, and increased extent of resection status was associated with longer progression-free survival. Treatment modality combination did not significantly impact complication rate.