SAR-096: Phase II Clinical Trial of Ribociclib in Combination with Everolimus in Advanced Dedifferentiated Liposarcoma (DDL) and Leiomyosarcoma (LMS).

PURPOSE: Dedifferentiated liposarcoma (DDL) and leiomyosarcoma (LMS) are two common subtypes of soft-tissue sarcoma, a rare group of diseases for which new treatments are needed. Chemotherapy remains the standard option for advanced disease. Targeting cyclin-dependent kinase 4 and 6 (CDK4/6) in DDL and mTOR in LMS is of biologic interest. When combined, the CDK4 inhibitor ribociclib and the mTOR inhibitor everolimus have shown synergistic growth inhibition in multiple tumor models, suggesting that this combination could be beneficial in patients. PATIENTS AND METHODS: This was a single arm, open label, multicenter phase II study of the combination of ribociclib and everolimus. Patients were enrolled into one of two cohorts: DDL or LMS with intact Rb. The primary endpoint was progression-free rate (PFR) at 16 weeks. Secondary endpoints included progression-free survival (PFS) and overall survival, safety and biomarker analyses. RESULTS: In the DDL cohort, 33.3% [95% confidence interval (CI), 15.6%-55.3%] of patients were progression-free at 16 weeks. Median PFS in this cohort was 15.4 weeks (95% CI, 8-36 weeks) with 2 partial responses. In the LMS cohort the PFR at 16 weeks was 29.2% (95% CI, 12.6%-51.1%). Median PFS in this cohort was 15.7 weeks (95% CI, 7.7-NA). Most common toxicities included fatigue (66.7%), anorexia (43.8%), and hyperglycemia (43.8%). Concordance between Rb testing methodologies was poor. CONCLUSIONS: The combination of ribociclib and everolimus demonstrates activity in DDL with prolonged stable disease (≥16 weeks) meeting the primary endpoint. Notably partial responses were observed. The primary endpoint was not reached in the LMS cohort. The combination was well tolerated with expected side effects.

Phase 2 trial of palbociclib and ganitumab in patients with relapsed Ewing sarcoma.

BACKGROUND: Ewing sarcoma (EWS) is an aggressive sarcoma with few treatment options for patients with relapsed disease. Cyclin-dependent kinase 4 (CDK4) is a genomic vulnerability in EWS that is synergistic with IGF-1R inhibition in preclinical studies. We present the results of a phase 2 study combining palbociclib (CDK4/6 inhibitor) with ganitumab (IGF-1R monoclonal antibody) for patients with relapsed EWS. PATIENTS AND METHODS: This open-label, non-randomized, phase 2 trial enrolled patients ≥12 years with relapsed EWS. All patients had molecular confirmation of EWS and RECIST measurable disease. Patients initially received palbociclib 125 mg orally on Days 1-21 and ganitumab 18 mg/kg intravenously on Days 1 and 15 of a 28-day cycle. The primary endpoints were objective response (complete or partial) per RECIST and toxicity by CTCAE. An exact one-stage design required ≥4 responders out of 15 to evaluate an alternative hypothesis of 40% response rate against a null of 10%. The study was closed following enrollment of the 10th patient due to discontinuation of ganitumab supply. RESULTS: Ten evaluable patients enrolled [median age 25.7 years (range 12.3-40.1)]. The median duration of therapy was 2.5 months (range 0.9-10.8). There were no complete or partial responders. Three of 10 patients had stable disease for >4 cycles and 2 had stable disease at completion of planned therapy or study closure. Six-month progression-free survival was 30% (95% CI 1.6%-58.4%). Two patients had cycle 1 hematologic dose-limiting toxicities (DLTs) triggering palbociclib dose reduction to 100 mg daily for 21 days. Two subsequent patients had cycle 1 hematologic DLTs at the reduced dose. Eighty percent of patients had grade 3/4 AEs, including neutropenia (n = 8), white blood cell decreased (n = 7), and thrombocytopenia (n = 5). Serum total IGF-1 significantly increased (p = 0.013) and ctDNA decreased during the first cycle. CONCLUSIONS: This combination lacks adequate therapeutic activity for further study, though a subset of patients had prolonged stable disease.

Factors contributing to nurse resignation during COVID-19: A qualitative descriptive study.

AIMS: To explore and describe registered nurses' perceptions and experiences of work well-being extending from what inspired them to join the healthcare organization, what created a great day at work for them, through to what may have supported them to stay. DESIGN: Qualitative descriptive study. METHODS: Thirty-nine Australian nurses who resigned in 2021 from two metropolitan healthcare organizations in Victoria were interviewed in 2022, each for 30-60 min. The semi-structured interview transcripts were transcribed verbatim and analysed inductively and thematically. RESULTS: Four themes were constructed for each of the key research questions. Inspiration to join the organizations transpired through organizational reputation, recruitment experiences, right position and right time, fit and feel. A great day at work was created through relationships with colleagues, experiences with managers, adequate resourcing and delivering quality care. Factors contributing to nurses resigning included COVID-19, uncertainty of role, workload and rostering, and finally, not feeling supported, respected and valued. Factors that may have supported the nurses to stay included flexible work patterns and opportunities, improved workplace relationships, workload management and support, and supportive systems and environments. Cutting across these themes were five threads: (1) relationships, (2) communication, (3) a desire to learn and develop, (4) work-life balance and (5) providing quality patient care. CONCLUSIONS: Novel ways of working and supporting individuals, teams and organizations are needed to maintain and sustain nurses. The nurses' inspiration, what created a great day at work, and support needed to stay highlighted the importance of workplace initiatives to build nursing career pathways, provide equitable opportunities for professional development, workload and roster flexibility and implement professional relationship-enhancing actions to foster authentic civility. IMPACT: This study contributes an in-depth exploration of the perceptions and experiences of nurses who resigned from two healthcare organizations and provides a description of (1) what inspired these nurses to initially join the organization, (2) what they perceived created a great day at work for them, (3) the factors contributing to their resignation and (4) what may have supported them to stay. The reasons nurses resign from an organization were identified as complex and multi-factorial, with opportunities for promoting nursing career pathways, addressing equity in opportunities and implementing professional relationship-enhancing actions. These contributions add both context and opportunity to strengthen organizational initiatives to attract, sustain and retain nurses.

Bi-allelic Pathogenic Variants in HS2ST1 Cause a Syndrome Characterized by Developmental Delay and Corpus Callosum, Skeletal, and Renal Abnormalities.

Heparan sulfate belongs to the group of glycosaminoglycans (GAGs), highly sulfated linear polysaccharides. Heparan sulfate 2-O-sulfotransferase 1 (HS2ST1) is one of several specialized enzymes required for heparan sulfate synthesis and catalyzes the transfer of the sulfate groups to the sugar moiety of heparan sulfate. We report bi-allelic pathogenic variants in HS2ST1 in four individuals from three unrelated families. Affected individuals showed facial dysmorphism with coarse face, upslanted palpebral fissures, broad nasal tip, and wide mouth, developmental delay and/or intellectual disability, corpus callosum agenesis or hypoplasia, flexion contractures, brachydactyly of hands and feet with broad fingertips and toes, and uni- or bilateral renal agenesis in three individuals. HS2ST1 variants cause a reduction in HS2ST1 mRNA and decreased or absent heparan sulfate 2-O-sulfotransferase 1 in two of three fibroblast cell lines derived from affected individuals. The heparan sulfate synthesized by the individual 1 cell line lacks 2-O-sulfated domains but had an increase in N- and 6-O-sulfated domains demonstrating functional impairment of the HS2ST1. As heparan sulfate modulates FGF-mediated signaling, we found a significantly decreased activation of the MAP kinases ERK1/2 in FGF-2-stimulated cell lines of affected individuals that could be restored by addition of heparin, a GAG similar to heparan sulfate. Focal adhesions in FGF-2-stimulated fibroblasts of affected individuals concentrated at the cell periphery. Our data demonstrate that a heparan sulfate synthesis deficit causes a recognizable syndrome and emphasize a role for 2-O-sulfated heparan sulfate in human neuronal, skeletal, and renal development.

Workforce survey of Australian graduate health information managers: Employability, employment, and knowledge and skills used in the workplace.

BACKGROUND: Employability, employment destinations and utilisation of knowledge-skill domains of new graduate health information managers (HIMs) have not been explored. OBJECTIVES: To capture the timing from course completion to employment and employment locations of a 5-year cohort of health information management graduates of La Trobe University, Australia, in 2017-2018; identify professional knowledge and skills used by the graduates in executing their roles; and map these to four domains of the health information management curriculum. METHOD: A mixed-methods descriptive study utilising a survey investigated early career pathways of new graduates of health information management courses from 2012 to 2016. Demographic data included age, year of graduation, lead time from course completion to employment, position title, number of positions held post-graduation and knowledge-skills used in the workplace. RESULTS: Eighty percent (n = 167) of graduates working in Australia with known contact details responded to the survey. Of these, 96.4% (n = 161) worked in at least one "health information management-related" position since graduation. Forty-five percent (n = 72) of graduates obtained a position before course completion, and over 94% (n = 150) were employed in the profession within 6 months of completion. Sixty percent (n = 97) of graduates had worked in two or more positions from 2012 to 2016. The large majority of new graduate HIMs (82.4%) were employed in the public healthcare sector in "health information management" (44%), or "health classification" (28.1%) roles. Most graduates (61%) had utilised at least three or four domains of professional knowledge-skills in the workplace. Whereas 16% (n = 26) of graduates used, solely, their health classification knowledge-skill set, almost 74% (n = 117) undertook some health classification-related activities. Only 16% (n = 26) of graduates were over 40 years of age, and there were no statistically significant differences between Bachelor and Master (Combined Degree Programs) graduates and Graduate-entry Master degree graduates in terms of lead time to employment, number of positions held, type of employing agency and professional knowledge-skills utilised in the workplace. CONCLUSION: Graduate HIMs have very high employability, demonstrate job mobility consistent with the national trends, are largely represented in the public sector but have presence throughout the healthcare system and utilise most or all of the specialised domains of professional knowledge and skills studied at university.

The visual nonverbal memory trace is fragile when actively maintained, but endures passively for tens of seconds.

Despite attempts at active maintenance in the focus of attention, the fragile nature of the visual nonverbal memory trace may be revealed when the retention interval between target memoranda and probed recall on a trial is extended. In contrast, a passively maintained or unattended visual memory trace may be revealed as persisting proactive interference extending across quite extended intervals between trials in a recent probes task. The present study, comprising five experiments, used this task to explore the persistence of such a passive visual memory trace over time. Participants viewed some target visual items (for example, abstract colored patterns) followed by a variable retention interval and a probe item. The task was to report whether the probe matched one of the targets or not. A decaying active memory trace was indicated by poorer performance as the memory retention interval was extended on a trial. However, when the probe was a member of the target set from the preceding trial, task performance was poorer than a comparison novel probe, demonstrating proactive interference. Manipulations of the intertrial interval revealed that the temporal persistence of the passive memory trace of an old target was impressive, and proactive interference was largely resilient to a simple 'cued forgetting' manipulation. These data support the proposed two-process memory conception (active-passive memory) contrasting fragile active memory traces decaying over a few seconds with robust passive traces extending to tens of seconds.

Calcium channel blockers are associated with improved survival and lower cardiovascular mortality in patients with renovascular disease.

BACKGROUND AND OBJECTIVE: Results of interventional trials in renovascular hypertension have been disappointing, and medical therapy is the current recommended gold standard. However, the comparative long-term benefits of different antihypertensive drug classes in atherosclerotic renal artery stenosis are not known. We aim to assess the effect of different antihypertensive drug classes on outcomes in renovascular hypertension DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Using Tayside Health Informatics Centre database, anonymized data over a 6-year period was analyzed. Biochemistry, prescribing data, morbidity, mortality, and demographic data were accessed via hospital medical records and electronic data stored in the Tayside Health Informatics Centre Safe Haven. General Registrar's Office data were used to identify patients who died from cardiovascular disease. Independent predictors of survival in each group were analyzed using Kaplan-Meier survival curves and Cox proportional hazard models, adjusted for a range of covariates, using time-updated drug analysis. Blood pressure data were obtained from primary and secondary care clinic blood pressure records for each patient. Adjustments for mean systolic blood pressure over the follow-up period and baseline blood pressure were made. RESULTS: A total of 579 patients with atherosclerotic renal artery stenosis were identified. In the unilateral renal artery stenosis cohort, calcium channel blockers but not ACE inhibitors/ARBs were associated with a significant reduction in all-cause (HR = 0.45, CI = 0.31, 0.65; P = <0.0001) and cardiovascular (HR = 0.51, CI = 0.29-0.90 P = 0.019) mortality. This was maintained after adjustment for blood pressure. In the bilateral renal artery stenosis cohort, both classes of drugs reduced all-cause but not cardiovascular mortality. Patients with moderate disease benefitted more than those with mild or severe disease. CONCLUSIONS: Calcium channel blockers are associated with significantly increased survival and lower cardiovascular mortality particularly in patients with moderate RAS disease.

Rail-suicide prevention: Systematic literature review of evidence-based activities.

BACKGROUND: Rail-related suicide is a relatively rare but extremely lethal method of suicide that can have far-reaching consequences. OBJECTIVE: The aim of the systematic literature review was to analyze the existing literature on the effectiveness of rail-suicide prevention activities. DATA SOURCES: Databases used were Scopus, Medline, and ProQuest. SEARCH TERMS: The search terms used were "suicid*," "prevent*," "rail*," or "train." ELIGIBILITY CRITERIA: English-language studies published in peer-reviewed journals between 1 January 1990 and 30 April 2015 that presented an overview of rail-related suicide prevention activities and included an analysis of effectiveness were used. RESULTS: We retrieved 1,229 results in the original search with nine papers presenting empirical evidence. Three studies in the review analyzed the effectiveness of platform screen doors and another three analyzed the installation of blue lights, two papers analyzed the effectiveness of suicide pits, and one included the influence of media reporting guidelines. CONCLUSION: Platform screen doors, suicide pits, blue lights, and improved media guidelines all have the potential to reduce rail-related suicide events and deaths. LIMITATIONS: The review was restricted to English-language peer-reviewed papers published within the chosen time period.

Allergies and suicidal behaviors: a systematic literature review.

BACKGROUND: Allergies are among the most common chronic conditions. In addition to physical and social impacts, a number of studies have consistently linked allergies to poor psychological outcomes, including depression and anxiety. OBJECTIVES: The aim of the present systematic literature review was to analyze the existing literature about the relationship between allergies and fatal and nonfatal suicidal behaviors. METHODS: Data sources include articles retrieved from Scopus, PubMed, ProQuest, and Web of Knowledge. Search terms: "suicid* and (allerg* or hay fever or atop* or eczema or aeroallergen*)" in English-language peer-reviewed journals between 1990 and 2014. ELIGIBILITY CRITERIA: Original research articles that provide empiric evidence about the potential link between allergies and suicidal behaviors. RESULTS: The initial search identified a total of 769 articles with 17 original research articles that present empiric evidence. Nine articles analyzed the relationship between allergies and fatal suicidal behavior, and nine analyzed nonfatal suicidal behaviors (one article included both). There currently is little research into the relationship between allergies and suicidal behavior. LIMITATIONS: The review was restricted to English-language articles published within the chosen time period; other limitations included the small number of articles that involve suicide mortality, and the fact that the majority of articles originated from the United States and Scandinavia. CONCLUSIONS: Analysis of the results indicates a link between allergies and suicidality, particularly suicide mortality; however, results for nonfatal suicidal behaviors are mixed. It is important that further research by using more rigorous study designs be carried out to lend strength to these findings.

The relationship between asthma and suicidal behaviours: a systematic literature review.

Asthma is a highly prevalent chronic condition worldwide, and is particularly common in younger people compared to other chronic conditions. Asthma can result in a number of symptoms that are detrimental to the quality of life of sufferers. The aim of the present systematic literature review was to analyse the existing literature on the relationship between asthma and fatal and nonfatal suicidal behaviours. Articles were retrieved from Scopus, PubMed, ProQuest and Web of Knowledge. We searched for the terms (suicid* OR self-harm) AND (asthma* OR "bronchial hyperreactivity") published in English-language peer-reviewed journals between 1990 and December 2014. Original research papers providing empirical evidence about the potential link between asthma and suicidal behaviours were included. The initial search identified 746 articles. Specific limiting criteria reduced the number of articles to the 19 articles that were finally included in the systematic review. The review found a potential link between asthma and suicide mortality, ideation and attempts across the age groups. Limitations of the review include the restriction to English-language papers published within the chosen time period, the limited number of papers involving suicide mortality, and the fact that the majority of papers originated from the USA.

Suicide around anniversary times.

The anniversary of the loss of a loved one is known to induce negative emotions, which for some can be significant. The present study examined the incidence of suicide around the time of such anniversaries using data from the Queensland Suicide Register for the years 1998 to 2008. There were statistically significant increases in suicide events immediately after the loss of a loved one and around the anniversary of the loss. Limitations of the study are noted.

Mechanical Faraday effect for orbital angular momentum-carrying beams.

When linearly polarised light is transmitted through a spinning window, the plane of polarisation is rotated. This rotation arises through a phase change that is applied to the circularly polarised states corresponding to the spin angular momentum (SAM). Here we show an analogous effect for the orbital angular momentum (OAM), where a differential phase between the positive and negative modes (±â„“) is observed as a rotation of the transmitted image. For normal materials, this rotation is on the order of a micro radian, but by using a slow-light medium, we show a rotation of a few degrees. We also note that, within the bounds of our experimental parameters, this rotation angle does not exceed the scale of the spatial features in the beam profile.

Management of suicidal and self-harming behaviors in prisons: systematic literature review of evidence-based activities.

The purpose of this study was to systematically analyze existing literature testing the effectiveness of programs involving the management of suicidal and self-harming behaviors in prisons. For the study, 545 English-language articles published in peer reviewed journals were retrieved using the terms "suicid*," "prevent*," "prison," or "correctional facility" in SCOPUS, MEDLINE, PROQUEST, and Web of Knowledge. In total, 12 articles were relevant, with 6 involving multi-factored suicide prevention programs, and 2 involving peer focused programs. Others included changes to the referral and care of suicidal inmates, staff training, legislation changes, and a suicide prevention program for inmates with Borderline Personality Disorder. Multi-factored suicide prevention programs appear most effective in the prison environment. Using trained inmates to provide social support to suicidal inmates is promising. Staff attitudes toward training programs were generally positive.

Suicide around public holidays.

OBJECTIVE: To examine the frequency of suicides on holidays and special days of the year, specifically in Queensland, Australia. METHODS: We analysed data from the Queensland Suicide Register between 1990 and 2009. The days examined were: Easter, Christmas, New Year, Valentine's Day and Anzac Day. We compared suicide cases on these days with the average counts for periods before and after the days. RESULTS: There was a statistically significant increase in suicides on Christmas Eve and on New Year's Day. Our results are discussed in light of trends reported in the literature. CONCLUSION: The beginning and end of the festive season are times when special attention is warranted for those with a heightened risk of suicide.

Squamous cell carcinoma of the buccal mucosa: outcomes of treatment in the modern era.

OBJECTIVES/HYPOTHESIS: The objective of this study was to analyze the patterns of failure and to determine clinical and pathologic factors predictive of recurrence and survival of patients treated for squamous cell carcinoma of the buccal mucosa at Princess Margaret Hospital. STUDY DESIGN: Retrospective chart review. METHODS: A retrospective chart review of patients treated for buccal carcinoma between 1994 and 2004 was performed. Seventy patients with newly diagnosed and previously untreated squamous cell carcinoma of the buccal mucosa were included. Demographic, clinical, and pathological parameters were identified and correlated with outcomes. RESULTS: The patient cohort consisted of 33 males and 37 females. Most patients presented with early-stage local disease (T1-T2). Surgery was the primary treatment in 61 patients. Twenty-three patients were treated with postoperative radiotherapy. Median follow-up was 3.3 years. The 5-year local, regional, and overall control rates were 57.5%, 83.5%, and 50%, respectively. The 5-year overall survival rate was 69%. The 5-year disease-specific and recurrence-free survival rates were 76.4% and 46%, respectively. The only significant predictors of survival were the nodal status and extranodal extension. CONCLUSIONS: Carcinoma of the buccal mucosa is an aggressive disease, characterized by a high rate of locoregional failure. Transoral wide excision is an adequate treatment for early-stage lesions; however, a combined approach and an elective neck dissection should be considered in advanced lesions.

Visualization of anterior skull base defects with intraoperative cone-beam CT.

BACKGROUND: The role of cone-beam CT (CBCT) in demonstrating anterior skull base defects (ASBDs), differing in size and location, was investigated. The study was designed to describe the potential advantage of CBCT in the setting of an intraoperative cerebrospinal fluid (CSF) leak. METHODS: In all, 120 ASBD were evaluated in 5 cadaver heads. Orthogonal and oblique slices were reconstructed. Observer studies assessed the visibility of ASBD in each location as a function of defect size. RESULTS: For 1-, 2-, and 4-mm defects, the percentage that were undetectable ranged from 20% to 33%, 0% to 14%, and 0% to 5%, respectively. Confident breach detection increased with defect size and was most challenging in the lateral lamella and cribriform. CBCT permitted confident detection of ASBD as small as about 2 mm in the fovea ethmoidalis and planum. Oblique views were found to be superior to orthogonal planes. CONCLUSIONS: The ability to identify ASBD depended on the size and location of defect. Oblique viewing planes were optimal for ASBD visualization.

microRNA evaluation of unknown primary lesions in the head and neck.

Unknown primary malignancy in the head and neck is not an infrequent diagnosis for patients with metastatic cervical lymph nodes. Although linked with a relatively good prognosis following radiation treatment, widespread radiation is coupled with significant morbidity. Altered microRNA (miRNA) expression has been associated with both cancer progression and metastasis. We sought to determine whether miRNA expression analysis could be used as a diagnostic tool to discover the primary site of malignancy, within the head and neck. We used quantitative real-time PCR to identify miRNA expression profiles of squamous cell carcinoma of the tonsil, base of tongue and post-nasal space, as well as their corresponding metastatic lymph nodes, from 6 patients. Our results revealed that each cancer maintained its expression profile between the primary site and the nodal metastasis (r = 0.82, p < 0.0001). In addition, each anatomical sub-site maintained a distinct miRNA profile between individual patients (r = 0.79, p < 0.0001). Finally, between sub-sites, the miRNA profiles were distinct (p < 0.0001). As proof of principle, our study provides an indication that miRNA expression analysis may be useful to compare the primary lesion and local metastatic disease. This may be clinically relevant to predict the primary site of origin of metastatic disease, when the primary site remains obscure.

Intraoperative use of cone-beam computed tomography in a cadaveric ossified cochlea model.

OBJECTIVES: To describe a cadaveric temporal bone model of labyrinthitis ossificans and investigate the utility of intraoperative cone-beam computed tomography (CBCT) in the facilitating cochlear implantation. DESIGN: Cadaveric temporal bone study. METHODS: Five cadaveric heads had cement introduced into the 10 cochleas. CBCT and a conventional CT scan were compared to assess the extent of cochlear obliteration. The cement was drilled-out (under CBCT guidance, if required) and cochlear implant electrode arrays (from 3 different manufacturers) inserted. RESULTS: CBCT images demonstrated temporal bone anatomy and the extent of cochlear obliteration as clearly as conventional CT in all cases. Intraoperative CBCT guided drilling and facilitated electrode placement in two of five heads (3 of 10 ears). Streak-artifact from the electrodes of two devices partially obscured image clarity. CONCLUSIONS: The obliterated cochlear model reproduced a disease-ossified cochlear both radiographically and surgically. CBCT is useful for intraoperative imaging to facilitate electrode array placement in the obliterated or congenitally abnormal cochlea.

Quality of life in patients with maxillectomy prostheses.

BACKGROUND: This cross-sectional study sought to determine patient quality of life and function after prosthetic rehabilitation for maxillary and palate defects following cancer resection. METHODS: Sixty-nine patients were identified, 42 participated in the study (61%). The Obturator Functioning Scale (OFS) and 4 general quality of life measures (Mental Health Inventory [MHI], Impact of Events Scale [IES], Illness Intrusiveness Ratings Scale [IIRS], and Centre for Epidemiologic Studies Depression Scale [CES-D]) were correlated with clinical parameters. RESULTS: Leakage when swallowing foods was the most frequently reported problem with the obturator (29%). Positive correlation was noted between the OFS and both the IES subscales (p < .01) and CES-D (p < .001). Difficulty with speech and eating was associated with increased avoidance of social situations. The surgical approach had a significant effect on the OFS, IES, and MHI subscales (p < .01). CONCLUSION: These results support the findings that good obturator function is associated with a better quality of life.

Three-dimensional tomosynthesis and cone-beam computed tomography: an experimental study for fast, low-dose intraoperative imaging technology for guidance of sinus and skull base surgery.

OBJECTIVES: To describe three-dimension (3-D) tomosynthesis and cone beam computed tomography (CBCT) as an intraoperative imaging system to guide both sinus and skull-base surgery in a cadaveric model. METHODS: Five cadaveric heads underwent baseline CBCT imaging. Surgical targets were resected from each head (uncinectomy, ethmoidectomy, medial maxillectomy, pituitary gland resection, and clivus ablation). Intraoperative imaging was provided so that for a given task, the acquisition arc (theta(tot) = 20 degrees , 45 degrees , 60 degrees , 90 degrees , 178 degrees ) of the tomosynthesis scan was fixed. Different heads and tasks were allocated different acquisition angles. There was no limit to the number of scans that could be requested. Residual target was highlighted with 3-D visualization software. RESULTS: The larger the image acquisition angle, the better the image. Only CBCT (theta(tot) approximately 178 degrees ) provided nearly isotropic 3-D spatial resolution and soft-tissue visibility in all three views. The volume of residual tissue remaining and the volume of adjacent-normal tissue that was resected were calculated as a function of tomosynthesis angle. For the easier surgical tasks (uncinectomy, ethmoidectomy) the residual tissue was not related to the tomosynthesis angle. However, for the difficult ablative tasks, the image quality became more important and tomosynthesis angle was related to the residual tissue. CONCLUSIONS: We describe an intraoperative imaging platform that can deliver near-real-time images of the target and related structures with low radiation dose. Tomosynthesis scanning angles higher than 60 degrees provided quantifiable benefits to the surgeon and facilitated total target ablation while helping to spare surrounding structures.