S. Danielle MacNeil

Early-stage squamous cell carcinoma of the oropharynx: Radiotherapy vs. Trans-Oral Robotic Surgery (ORATOR) – study protocol for a randomized phase II trial

BackgroundThe incidence of oropharyngeal squamous cell carcinoma (OPSCC) has markedly increased over the last three decades due to newly found associations with human papillomavirus (HPV) infection. Primary radiotherapy (RT) is the treatment of choice for OPSCC at most centers, and over the last decade, the addition of concurrent chemotherapy has led to a significant improvement in survival, but at the cost of increased acute and late toxicity. Transoral robotic surgery (TORS) has emerged as a promising alternative treatment, with preliminary case series demonstrating encouraging oncologic, functional, and quality of life (QOL) outcomes. However, comparisons of TORS and RT in a non-randomized fashion are susceptible to bias. The goal of this randomized phase II study is to compare QOL, functional outcomes, toxicity profiles, and survival following primary RT (± chemotherapy) vs. TORS (± adjuvant [chemo] RT) in patients with OPSCC.Methods/DesignThe target patient population comprises OPSCC patients who would be unlikely to require chemotherapy post-resection: Tumor stage T1-T2 with likely negative margins at surgery; Nodal stage N0-2, ≤3 cm in size, with no evidence of extranodal extension on imaging. Participants will be randomized in a 1:1 ratio between Arm 1 (RT ± chemotherapy) and Arm 2 (TORS ± adjuvant [chemo] RT). In Arm 1, patients with N0 disease will receive RT alone, whereas N1-2 patients will receive concurrent chemoradiation. In Arm 2, patients will undergo TORS along with selective neck dissections, which may be staged. Pathologic high-risk features will be used to determine the requirement for adjuvant radiotherapy +/- chemotherapy. The primary endpoint is QOL score using the M.D. Anderson Dysphagia Inventory (MDADI), with secondary endpoints including survival, toxicity, other QOL outcomes, and swallowing function. A sample of 68 patients is required.DiscussionThis study, if successful, will provide a much-needed randomized comparison of the conventional strategy of primary RT vs. the novel strategy of primary TORS. The trial is designed to provide a definitive QOL comparison between the two arms, and to inform the design of an eventual phase III trial for survival outcomes.Trial registrationNCT01590355

Comparing sutures versus staples for skin closure after orthopaedic surgery: systematic review and meta-analysis

Objective To determine whether there still remains a significant advantage in the use of sutures to staples for orthopaedic skin closure in adult patients. Design Systematic Review/ Meta-Analysis. Data sources MEDLINE-OVID, EMBASE-OVID, CINAHL and Cochrane Library. Grey and unpublished literature was also explored by searching: International Clinical Trial Registry, Grey Matters BIOSIS Previews, Networked Digital Library of Theses and Dissertations, ClinicalTrials.gov, UK Clinical Trials Gateway, UK Clinical Research Network Study Portfolio, Open Grey, Grey Literature Report, and Web of Science. Selection criteria Articles were from any country, written in English and published after 1950. We included all randomised control trials and observational studies comparing adults (≥18 years) undergoing orthopaedic surgery who either received staples or sutures for skin closure. The primary outcome was the incidence of surgical site infection. Secondary outcomes included closure time, inflammation, length of stay, pain, abscess formation, necrosis, discharge, wound dehiscence, allergic reaction and health-related quality of life. Results 13 studies were included in our cumulative meta-analysis conducted using Review Manager V.5.0. The risk ratio was computed as a measure of the treatment effect taking into account heterogeneity. Random-effect models were applied. There was no significant difference in infection comparing sutures to staples. The cumulative relative risk was 1.06 (0.46 to 2.44). In addition, there was no difference in infection comparing sutures to staples in hip and knee surgery, respectively. Lastly, except for closure time, there was no significant difference in secondary outcomes comparing sutures to staples. Conclusions Except for closure time, there was no significant difference in superficial infection and secondary outcomes comparing sutures to staples was found. Given that there may in fact be no difference in effect between the two skin closure and the methodological limitations of included studies, authors should begin to consider the economic and logistic implications of using staples or sutures for skin closure. PROSPERO registration number CRD42015017481.

Vaccinia Virus Outperforms a Panel of Other Poxviruses as a Potent Oncolytic Agent for the Control of Head and Neck Squamous Cell Carcinoma Cell Lines

Background: Head and neck squamous cell carcinoma (HNSCC) is the fifth most common cancer worldwide. Existing therapies for advanced tumors have high failure rates and can have severe consequences in terms of pain, disfigurement, and poor speech and swallowing function. New treatment strategies are needed to improve outcomes for patients suffering with this disease and oncolytic viruses represent a promising approach. Methods: We infected six well-characterized HNSCC cell lines (Cal27, Detroit562, FaDu, SCC4, SCC15, SCC25), with increasing doses of a panel of poxviruses (including myxoma, vaccinia, raccoonpox and tanapox viruses) modified to express green fluorescence protein to determine which virus was the most effective oncolytic agent in cell-based assays. Results: While myxoma, raccoonpox and tanapox displayed differing efficacy in the panel of cell lines, vaccinia virus was the most potent of the tested poxviruses and was highly effective in controlling cell growth in all cell lines. Conclusion: Oncolytic poxviruses, particularly vaccinia virus, were effective in killing HNSCC in vitro and hold promise as potential treatments for patients with HNSCC.

Evaluating organ preservation outcome as treatment endpoint for T1aN0 glottic cancer

Common endpoints in reporting the outcomes for early glottic cancer do not highlight the importance of organ preservation. We evaluated the treatment outcomes among patients with T1aN0 laryngeal cancer with laryngectomy‐free disease‐specific survival (LFS‐DSS), which is defined as time to total laryngectomy or time to death from cancer cause, against all other endpoints.

Echocardiogram changes following parathyroidectomy for primary hyperparathyroidism: A systematic review and meta-analysis

Abstract The aim of the study is to systematically review the evidence on post parathyroidectomy (PTX) changes as measured by echocardiogram (ECHO) in patients with primary hyperparathyroidism (PHPT). PHPT may increase risk of cardiovascular morbidity/mortality. Conclusions of studies assessing ECHO changes, pre versus post PTX, are inconsistent. A systematic literature search was conducted to locate published and unpublished studies. Randomized control trials, nonrandomized control trials, and observational studies were included. Variables were reported as means and standard deviations. An inverse variance statistical method, with random-effects analysis model, was applied to continuous data. The effect measure was standardized mean difference, confidence interval of 95%. Primary outcome measure was left ventricular ejection fraction (LVEF). Secondary outcome measures were left ventricular mass index (LVMI), peak early over peak late diastolic velocity ratio (E/A ratio), isovolumetric relaxation time (IVRT), intraventricular septal thickness (IVST), and posterior wall thickness (PWT). Fourteen studies were included. Follow-up time ranged 3 to 67 months. No significant differences (P > .05) in primary outcome measure LVEF (SMD = −0.03, CI = −0.24, 0.19), or secondary outcome measures E/A Ratio (SMD = −0.05, CI = −0.24, 0.14), IVST (SMD = 0, CI = 0.31, 0.32), PWT (SMD = 0.01, CI = −0.38, 0.39), LVMI (SMD = −0.18, CI = −0.74, 0.38), and IVRT (SMD = −0.84, CI = −1.83, 0.14) were observed. There was no significant difference in LVEF pre to post PTX. Due to heterogeneity of current literature, we were unable to determine if other outcome measures of cardiac function are affected after PTX in patients with PHPT. We recommend a randomized control trial be conducted to make concrete conclusions.

Estimating Survival After Salvage Surgery for Recurrent Oral Cavity Cancer

Importance Locoregional recurrence of oral cavity squamous cell carcinoma (OCSCC) continues to be a life-threatening and difficult clinical situation. Salvage surgery can result in significant morbidities, and survival following recurrence is poor. Objective To outline prognostic factors influencing overall survival (OS) following salvage surgery for OCSCC to guide management of treatment for patients with locoregionally recurrent disease. Design, Setting, and Participants The medical records of 293 patients presenting to the London Health Sciences Center with locoregionally recurrent OCSCC between October 5, 1999, and May 2, 2011, were retrospectively reviewed. The primary outcome was OS from salvage treatment to last follow-up or death. Univariate analyses were carried out using the Cox proportional hazards regression model. A recursive partitioning analysis was used to create risk groups based on prognosis. Analysis was conducted from December 8, 2015, to February 26, 2016. Results Of the 293 patients evaluated, 59 (20%) had recurrence identified after their initial OCSCC treatment; 39 (66%) were men, and the mean (SD) age at diagnosis was 62.2 (11.8) years. Thirty-nine (66%) of these patients underwent salvage surgery for locoregional recurrence with curative intent. Five-year OS from the time of salvage surgery was 43%. Recursive partitioning analysis identified 3 risk groups: (1) high risk (patients who received adjuvant chemoradiotherapy or radiotherapy after initial surgery) with 5-year OS rate of 10% (hazard ratio [HR], 9.41; 95% CI, 2.68-33.04), (2) intermediate risk (previous surgery alone, age ≥62 years) with a 5-year OS rate of 39% (HR, 2.95; 95% CI, 0.86-10.09), and (3) low risk (previous surgery alone, age <62 years) with 5-year OS rate of 74%. Conclusions and Relevance This recursive partitioning analysis identified 3 prognostic groups in patients undergoing salvage surgery for recurrent OCSCC. The marked differences in survival between these groups should be taken into consideration when counselling and managing treatment for patients with locoregionally recurrent disease.

A Population-Based Study of 30-day Incidence of Ischemic Stroke Following Surgical Neck Dissection.

AbstractThe objective of this study was to determine the 30-day incidence of ischemic stroke following neck dissection compared to matched patients undergoing non-head and neck surgeries.A surgical dissection of the neck is a common procedure performed for many types of cancer. Whether such dissections increase the risk of ischemic stroke is uncertain.A retrospective cohort study using data from linked administrative and registry databases (1995–2012) in the province of Ontario, Canada was performed. Patients were matched 1-to-1 on age, sex, date of surgery, and comorbidities to patients undergoing non-head and neck surgeries. The primary outcome was ischemic stroke assessed in hospitalized patients using validated database codes.A total of 14,837 patients underwent surgical neck dissection. The 30-day incidence of ischemic stroke following the dissection was 0.7%. This incidence decreased in recent years (1.1% in 1995 to 2000; 0.8% in 2001 to 2006; 0.3% in 2007 to 2012; P for trend <0.0001). The 30-day incidence of ischemic stroke in patients undergoing neck dissection is similar to matched patients undergoing thoracic surgery (0.5%, P = 0.26) and colectomy (0.5%, P = 0.1). Factors independently associated with a higher risk of stroke in 30 days following neck dissection surgery were of age ≥75 years (odds ratio (OR) 1.63, 95% confidence interval (CI) 1.05–2.53), and a history of diabetes (OR 1.60, 95% CI 1.02–2.49), hypertension (OR 2.64, 95% CI 1.64–4.25), or prior stroke (OR 4.06, 95% CI 2.29–7.18).Less than 1% of patients undergoing surgical neck dissection will experience an ischemic stroke in the following 30 days. This incidence of stroke is similar to thoracic surgery and colectomy.

A case report and genetic characterization of a massive acinic cell carcinoma of the parotid with delayed distant metastases.

We describe the presentation, management, and clinical outcome of a massive acinic cell carcinoma of the parotid gland. The primary tumor and blood underwent exome sequencing which revealed deletions in CDKN2A as well as PPP1R13B, which induces p53. A damaging nonsynonymous mutation was noted in EP300, a histone acetylase which plays a role in cellular proliferation. This study provides the first insights into the genetic underpinnings of this cancer. Future large-scale efforts will be necessary to define the mutational landscape of salivary gland malignancies to identify therapeutic targets and biomarkers of treatment failure.

Spontaneous intrathyroidal hematoma causing airway obstruction: A case report.

Introduction:Spontaneous thyroid hemorrhage is a rare occurrence that results in pain, discomfort, and occasionally compressive symptoms. Infrequently, extensive thyroid hemorrhage can result in a rapidly expanding hematoma resulting in airway compromise. This is a case of an otherwise healthy young woman, 3 months postpartum, with a slowly expanding spontaneous thyroid hemorrhage that measured at 7 × 5.5 × 5 cm by computed tomography. She ultimately required intubation to manage respiratory distress and subsequently a hemithyroidectomy for definitive treatment. The case presentation is followed by a literature review where known etiologies of thyroid hematoma including traumatic and nontraumatic causes, precipitating anticoagulation, and spontaneous rupture of branches of the external carotid artery are outlined. The potential links to pregnancy are explored. The roles of bedside thyroid ultrasound in the emergency department and lateral neck roentgenogram in diagnosis are explored. The importance of airway management and indications for conservative versus surgical treatments are discussed. Conclusions:This is a case of a spontaneous intrathyroidal hemorrhage, which progressed over days to ultimately cause airway compromise. It is imperative that physicians are educated on the appropriate detection and management of the potentially life-threatening spontaneous thyroid hematoma.

Predictors of plate extrusion in oromandibular free flap reconstruction

Plate extrusions after free tissue transfer for mandibular reconstruction can be problematic and generally require revision surgery. Our objective was to assess the predictors of plate extrusion and compare outcomes between fibular free flaps (FFF), lateral border scapular flaps (LBSF), and scapular tip free flaps (STFF).