The pericranial flap for inner lining of full-thickness nasal defects: a retrospective cohort study.

BACKGROUND: Effective nasal reconstruction requires skin and soft tissue cover, cartilage or bone structure, and mucosal lining. Ideal lining is thin, pliable and vascularised, making reconstruction challenging. This paper presents the first case series with long-term outcomes of pericranial flaps used as inner lining for nasal reconstruction. METHODS: Patients undergoing paramedial forehead flaps from 2007 to 2019 were identified using second-stage nasal reconstruction billing codes. Patients with pericranial flaps for lining, for whom there were data on resulting outcomes and complications, were identified. RESULTS: Sixty-six patients underwent second-stage nasal reconstruction. Eighteen patients had paramedian forehead and pericranial flaps for inner lining reconstruction. The flap lining had no immediate post-operative complications. Three patients suffered partial to major reconstructive failure post radiotherapy. Other complications included nasal stenosis and orocutaneous fistula. CONCLUSION: Combined with paramedian forehead flaps, the pericranial flap is reliable as inner lining for nasal reconstruction. It is easily accessible and useful in resections with limited mucosal options.

A Case of HPV-Associated Oropharyngeal Squamous Cell Carcinoma with Block-Like, Partial Loss of p16 Expression.

BACKGROUND: Oropharyngeal squamous cell carcinoma is frequently associated with high-risk HPV infection, which confers a good prognosis. Immunohistochemistry for p16 is used as a surrogate for HPV status, but discrepant results are occasionally seen. Here, we report a case with a unique pattern of partial loss of p16. METHODS: A 63 year old male presented with a base of tongue nonkeratinizing squamous cell carcinoma and a large metastatic neck mass. The primary lesion and multiple regions of the metastatic mass were assessed with p16 immunohistochemistry, RNA in situ hybridization for high-risk HPV, and HPV16 genome sequencing. RESULTS: The primary lesion was p16 negative, and the metastatic neck mass had large, confluent regions that were either strongly p16 positive or entirely p16 negative. All of these regions were positive for high-risk HPV with identical HPV16 genomes. CONCLUSION: This unusual case illustrates a potential diagnostic pitfall, and it raises important questions regarding molecular mechanisms and prognostic implications of p16 staining in oropharyngeal squamous cell carcinoma.

Revised recommendations from the CSO-HNS taskforce on performance of tracheotomy during the COVID-19 pandemic - what a difference a year makes.

BACKGROUND: During the early part of the COVID-19 pandemic, the Canadian Society of Otolaryngology - Head & Neck Surgery (CSO-HNS) task force published recommendations on performance of tracheotomy. Since then, our understanding of the virus has evolved with ongoing intensive research efforts. New literature has helped us better understand various aspects including patient outcomes and health care worker (HCW) risks associated with tracheotomy during the COVID-19 pandemic. Accordingly, the task force has re-evaluated and revised some of the previous recommendations. MAIN BODY: Based on recent evidence, a negative reverse transcription polymerase chain reaction (RT-PCR) COVID-19 swab status is no longer the main deciding factor in the timing of tracheotomy. Instead, tracheotomy may be considered as soon as COVID-19 swab positive patients are greater than 20 days beyond initial symptoms and 2 weeks of mechanical ventilation. Furthermore, both open and percutaneous surgical techniques may be considered with both techniques showing similar safety and outcome profiles. Additional recommendations with discussion of current evidence are presented. CONCLUSION: These revised recommendations apply new evidence in optimizing patient and health care system outcomes as well as minimizing risks of COVID-19 transmission during aerosol-generating tracheotomy procedures. As previously noted, additional evidence may lead to further evolution of these and other similar recommendations.

Implementation of a uniform nationwide medical licensing examination in general practice. A feasibility study.

Objective: A competency-based training of medical students that is adapted to the realities of care is required internationally and is being intended in Germany with the Master Plan for Medical Studies 2020. In order to test these competencies, the German National Institute for state examinations in Medicine, Pharmacy and Psychotherapy (IMPP) has developed a concept for the redesign of the final part of the medical licensing examination in Germany. It focuses on general and interprofessional healthcare in the examination with outpatients. The aim of this work is to assess the feasibility of the new final examination on the basis of pilot examinations in family practices and to derive further steps for the national implementation. Methods: Fourteen medical students in their internship year completed a full examination with patients aged 42 to 84 years. Examiners evaluated the examination performance using standardised evaluation forms. Feasibility was qualitatively assessed in terms of compliance with content and time limits, examination results, patient reflections, and implementation in the practice. Results: Students were able to complete all tasks within the given time frame. Based on the evaluation forms, the examiners assessed the performance of the students. Patients appreciated the structured course of the examination in the familiar location of their family practice. For the nationwide implementation of the examination, 2,500 examination practices are required for about 10,000 examinees per year. Four students can then be examined on two days per year in each practice. Conclusions: Oral-practical examinations with outpatients in general medical practices can be carried out successfully throughout the nation. An implementation of the examinations throughout Germany requires that medical studies are restructured and that this new curriculum is implemented as intended by the Master Plan for Medical Studies 2020. Furthermore, training and remuneration of examiners together with a legal framework for the new examination must be established.

Recommendations from the CSO-HNS taskforce on performance of tracheotomy during the COVID-19 pandemic.

INTRODUCTION: The performance of tracheotomy is a common procedural request by critical care departments to the surgical services of general surgery, thoracic surgery and otolaryngology - head & neck surgery. A Canadian Society of Otolaryngology - Head & Neck Surgery (CSO-HNS) task force was convened with multi-specialty involvement from otolaryngology-head & neck surgery, general surgery, critical care and anesthesiology to develop a set of recommendations for the performance of tracheotomies during the COVID-19 pandemic. MAIN BODY: The tracheotomy procedure is highly aerosol generating and directly exposes the entire surgical team to the viral aerosol plume and secretions, thereby increasing the risk of transmission to healthcare providers. As such, we believe extended endotracheal intubation should be the standard of care for the entire duration of ventilation in the vast majority of patients. Pre-operative COVID-19 testing is highly recommended for any non-emergent procedure. CONCLUSION: The set of recommendations in this document highlight the importance of avoiding tracheotomy procedures in patients who are COVID-19 positive if at all possible. Recommendations for appropriate PPE and environment are made for COVID-19 positive, negative and unknown patients requiring consideration of tracheotomy. The safety of healthcare professionals who care for ill patients and who keep critical infrastructure operating is paramount.

Oncological and functional outcomes after repeat transoral laser microsurgery for the treatment of recurrent early glottic cancer.

BACKGROUND: Transoral laser microsurgery for glottic squamous cell carcinoma is the standard of care at many institutions. Repeat transoral laser microsurgery for recurrence may avoid the need for radiotherapy and total laryngectomy. This study aimed to identify oncological and functional outcomes in a cohort of patients who had undergone repeat transoral laser microsurgery procedures. METHOD: A retrospective review of prospectively collected data of patients treated with transoral laser microsurgery for carcinoma in situ or tumour stages T1 or T2 glottic cancer, from 2003 to 2018. RESULTS: Twenty patients were identified. Additional treatment was not needed in 45 per cent of patients. The five-year overall survival rate was 90 per cent. The disease-specific survival rate was 100 per cent. The laryngeal preservation rate was 85 per cent. There was improvement in mean Voice Handicap Index-10 scores following repeat transoral laser microsurgery treatment, when comparing the pre- and post-operative periods (mean scores = 15.5 vs 11.5, p = 0.373). CONCLUSION: Repeat transoral laser microsurgery can be an oncologically safe alternative to other salvage therapies for glottic squamous cell carcinoma recurrence, without sacrificing functional outcomes.

SU-E-J-205: Modeling Fiducial Marker Movement in Prostate.

PURPOSE: To understand fiducial marker movement in prostate and to improve prostate patient positioning with fiducial markers. METHODS: Patient planning CT and positioning CBCT were retrospectively analyzed. CBCT images were automatically registered to the corresponding CT ones based on their bony structures in Eclipse. The coordinates of the markers in the CT and CBCT were recorded. The status of bladder and rectum fillings, and gas in rectum were indexed into four levels and recorded. An algorithm was developed to optimally register the (three) fiducial markers in CBCT with those in the CT so that only the information on prostate deformation and marker migration remained. A mathematical model was built to estimate the marker migration and the relative contribution to the deformation from the status change of bladder and rectum. RESULTS: The registration error from our optimal registration algorithm indicates the minimal patient setup error by using fiducial markers. The results from our analyzed 3 patients were average(standard deviation) = 1.10(0.40), 1.27(0.67) and 0.62(0.38) mm, but there were some fractions when the registration errors were over 2 mm. From our mathematical model, it was found that the marker migration could be as large as 2.9 mm. If 2 mm tolerance is required in such as SBRT, then soft tissue based registration may be more appreciated when the optimal registration error is greater than 2 mm or from the date when the migration is greater than 2 mm because the migrated marker may not change the location thereafter. In addition, for one investigated patient, the relative contribution to the deformation from the bladder, rectum filling and gas in the rectum is 0.43:0.31:0.26. More patient data are in analysis, and other interesting results will be reported. CONCLUSIONS: Fiducial marker migration can be over 2 mm. The migration will Result in a conclusion that small registration error does not mean good patient positioning.

Cost-effectiveness of a topically applied pre-operative tissue expansion device for radial forearm free flaps: a cohort study.

OBJECTIVES: The objective of this study is to test the hypothesis that using a non-invasive and inexpensive pre-operative tissue expansion device (DynaClose) for radial forearm free-flap donor sites will result in a significant reduction in the cost of both in-hospital and out-of-hospital wound care compared with that of unexpanded radial forearm free-flap donor sites. DESIGN: A cohort study consisting of patients previously randomised in a randomised controlled trial. An intention to treat design was utilised. SETTING: A large tertiary care centre in eastern Ontario, Canada. PATIENTS: Thirty-four patients presenting to Otolaryngology Head and Neck clinic were enroled. Of these patients, 29 were previously enroled in a randomised controlled trial, while an additional five patients were enroled and randomised for the purpose of this study. INTERVENTIONS: Patients were randomised to either the treatment (pre-operative tissue expansion, DynaClose Expansion System) or control group. MAIN OUTCOME MEASURES: Wound care costs (in US dollars) were calculated for all patients for both in-hospital care and for patients requiring home care. Non-parametric data analysis was utilised for statistical assessment. RESULTS: There was a 93% reduction in the use of split-thickness skin grafts in the treatment group. There was a significant reduction in total wound care cost for patients in the treatment group versus the control group (P < 0.0001). Patients in the treatment group required a mean (SD) total of $36.00 (23.50) per patient, while the control group required $277.00 (325.00) of wound care. After excluding the cost of home care, the treatment group continued to have a significant reduction in total and in-hospital wound care costs compared with the control group (P < 0.001). CONCLUSIONS: Using a simple, inexpensive and non-invasive method of pre-operative tissue expansion results in a significant reduction in the costs of wound care for both in-hospital and out-of-hospital treatment. The DynaClose dynamic skin expansion system results in a cost-effective method to reduce the need of a split-thickness skin graft for coverage of a radial forearm free-flap donor site.

Intravital microscopic studies of angiogenesis during bone defect healing in mice calvaria.

PURPOSE: Due to the great availability of specific antibodies, gene-targeted animals and knockout strains, mouse models came into the focus of musculoskeletal research. Herein, we introduce a calvarian defect model in mice that allows the repetitive analysis of blood vessel formation during bone repair by intravital microscopy. METHODS: The right parietal calvaria of 20 adult CD-1 mice were exposed by skin excision. Under continuous irrigation, a circular defect (Ø0.75 mm) was drilled into the calvarium without penetrating the inner cortical shell. A circular glass (Ø12 mm; thickness 0.15 mm) was fixed by two microscrews (M1; length 2mm) to cover the bone defect. Angiogenesis was analysed by intravital microscopy at days 0, 3, 6, 9, 12, 15, 18 and 21. In addition, bone repair was evaluated by histomorphometry at days 3, 6, 9 and 15. Immunohistochemical stainings for the angiogenic growth factor vascular endothelial growth factor (VEGF) and the cell proliferation marker proliferating cell nuclear antigen (PCNA) were performed to assess angiogenic and proliferative activity during healing of the calvarian defect. RESULTS: Histomorphometry showed a typical pattern of intramembranous bone repair. Osseous bridging of the defect was observed at day 9. This was associated with the formation of a neo-periosteum, which covered the new woven bone and contained a dense network of newly formed blood vessels. At day 9, particularly cells of the neo-periosteum showed intense staining for VEGF, whilst PCNA-positive staining was found mainly in osteoblasts. At day 15, the major fraction of fibrous tissue was replaced by bone undergoing extensive remodelling. Intravital microscopy revealed an increase of vascular density between days 3 and 15. Blood vessel diameters showed an increase between days 3 and 9 and a subsequent decrease between days 9 and 21. CONCLUSIONS: The present calvarian defect model provides a powerful tool to evaluate the process of angiogenesis during intramembranous bone repair in mice.

Tumour growth following portal branch ligation in an experimental model of liver metastases.

BACKGROUND: Portal branch ligation (PBL) is being used increasingly before hepatectomy for colorectal metastases. This study evaluated the effect of PBL on angiogenesis, growth factor expression and tumour growth in a mouse model of hepatic colorectal metastases. METHODS: CT26.WT cells were implanted into the left liver lobe of BALB/c mice. Animals underwent PBL of the left liver lobe or sham treatment. Angiogenesis, microcirculation, growth factor expression, cell proliferation and tumour growth were studied over 14 and 21 days by intravital multifluorescence microscopy, laser Doppler flowmetry, immunohistochemistry and western blotting. RESULTS: Left hilar blood flow and tumour microcirculation were significantly diminished during the first 7 days after PBL. This resulted in tumour volume being 20 per cent less than in sham controls by day 14. Subsequently, PBL-treated animals demonstrated recovery of left hilar blood flow and increased expression of hepatocyte growth factor and transforming growth factor alpha, associated with increased cell proliferation and acceleration of growth by day 21. CONCLUSION: PBL initially reduced vascular perfusion and tumour growth, but this was followed by increased growth factor expression and cell proliferation. This resulted in delayed acceleration of tumour growth, which might explain the stimulated tumour growth observed occasionally after PBL.

Socio-economic factors and stage at presentation of head and neck cancer patients in Ottawa, Canada: a logistic regression analysis.

To determine if socio-economic status (SES) affects the stage at presentation of head and neck cancer (HNC) patients in Ottawa, Canada. To determine if the method of diagnosis affects the stage at presentation in these patients. We obtained data on SES, method of diagnosis, and stage at presentation for patients presenting to the head and neck cancer clinic at The Ottawa Hospital Regional Cancer Centre (TORCC). We performed a logistic regression analysis using stage at presentation as the dependent variable. We found no statistically significant association between average family income (by postal code) and stage at presentation. We found that oral cancers presented at a later stage compared with other HNCs but that who made the diagnosis was an important factor. Oral cancers diagnosed by a dentist had 3.44 times the odds of being at a later stage than other HNCs (CI 1.01-11.96), but oral cancers diagnosed by other means had 11.42 times the odds of being at a later stage than other HNCs. We found that male patients presented at a later stage than female patients (OR 2.62, CI 1.03-6.63). Finally, former smokers had about 1/3 the odds of presenting at a later stage than current smokers (OR 0.33, CI 0.13-0.84) although nonsmokers were not significantly less likely than current smokers to present later (OR 0.47, CI 0.17-1.32). We found no evidence that in Ottawa, Canada patients of a lower SES with HNC presented at an different stage than patients with higher SES. We found that patients presenting with oral cancers presented at an earlier stage if they were diagnosed by a dentist.

PET and SPECT imaging of apoptosis in vulnerable atherosclerotic plaques with radiolabeled Annexin A5.

Atherosclerosis still represents killer number one in industrialized nations, and is starting to have increased impact in developing countries. Atherosclerotic plaques are the net result of a complex interplay between vascular cholesterol deposition, inflammatory activity and extracellular matrix formation. The result is luminal narrowing of arteries, which may ultimately lead to compromised blood flow to essential body organs, most notoriously to the heart. Most of the cardiovascular events that are caused by atherosclerosis, such as acute myocardial infarction or stroke, are the result of a transition of so-called stable atherosclerotic plaques to vulnerable plaques, that are prone to rupture. The direct consequence of atherosclerotic plaque rupture is exposure of thrombogenic plaque constituents to the blood, leading to instant local thrombus formation. The formation of this localized thrombus may ultimately result in sudden obstruction of blood flow and consequent infarction of distal tissue. Clinical risk profiling methods, such as the Framingham and Procam risk scores, are reasonable predictors of myocardial infarction over a 10-year time-span. However, the challenge remains to identify those patients with a very high risk of suffering from myocardial infarction in the coming months. Imaging may provide the necessary diagnostic information to identify such individuals. The transition of stable atherosclerotic plaques to vulnerable plaques is typically heralded by inflammation, thinning of the overlying fibrous cap, and the presence of a large necrotic core. Apoptosis is linked to all of these features of plaque vulnerability, and may, therefore, provide uniquely useful targets for the identification of plaque vulnerability. In recent years, a number of molecular imaging technologies have been developed to image apoptosis, which will be discussed in this review. Further development of apoptosis imaging technologies may aid us in the years to come in the quest to identify patients with critical cardiovascular risks, to treat myocardial infarction in its imminent, instead of its evident phase.

Cardiovascular molecular imaging of apoptosis.

INTRODUCTION: Molecular imaging strives to visualise processes at the molecular and cellular level in vivo. Understanding these processes supports diagnosis and evaluation of therapeutic efficacy on an individual basis and thereby makes personalised medicine possible. APOPTOSIS AND MOLECULAR IMAGING: Apoptosis is a well-organised mode of cell suicide that plays a role in cardiovascular diseases (CVD). Apoptosis is associated with loss of cardiomyocytes following myocardial infarction, atherosclerotic plaque instability, congestive heart failure and allograft rejection of the transplanted heart. Thus, apoptosis constitutes an attractive target for molecular imaging of CVD. Our current knowledge about the molecular players and mechanisms underlying apoptosis offers a rich palette of potential molecular targets for molecular imaging. However, only a few have been successfully developed so far. AIMS: This review highlights aspects of the molecular machinery and biochemistry of apoptosis relevant to the development of molecular imaging probes. It surveys the role of apoptosis in four major areas of CVD and portrays the importance and future perspectives of apoptosis imaging. The annexin A5 imaging protocol is emphasised since it is the most advanced protocol to measure apoptosis in both preclinical and clinical studies.

The effect of wall thickness on the response of a spherical ionization chamber.

Air-filled ionization chambers are used widely for radiation dosimetry. For some applications it is important to know the effect on the chamber response of photon attenuation and scattering in the chamber walls. Traditionally, the wall effect is determined by measuring the chamber response as a function of wall thickness and extrapolating linearly to zero thickness. We have constructed a spherical graphite chamber with variable wall thickness. The change in the chamber response with wall thickness has been measured in a 137Cs gamma-ray beam. Our data show that the change in response is not linear with wall thickness, in agreement with the theoretical prediction of Bielajew (1990 Med. Phys. 17 583-7). A linear versus non-linear extrapolation of the measured data to zero wall thickness leads to a difference of almost 1% in the estimate of the wall correction factor, Kw. The value of Kw obtained using the non-linear extrapolation is in good agreement with the result obtained using Monte Carlo techniques.

A logical approach to the thoracic inlet: the Dartevelle approach revisited.

BACKGROUND: Traditionally, Pancoast tumors have been associated with an extremely poor outlook. Recently, Dartevelle and colleagues have noted a significant survival advantage in patients treated by wide en bloc excision. METHODS: Utilizing an illustrative case example, step by step exposure of the lung apex and first rib is provided with the Dartevelle approach. RESULTS: Safe exposure was provided by this combined transcervical and transthoracic approach. CONCLUSIONS: The Dartevelle approach appears to be the favored approach to anterior lung apex or first rib lesions. The combined efforts of an Otolaryngolist-Head and Neck Surgeon and a Thoracic Surgeon may allow for safe, wide en bloc excision of these otherwise difficult to access lesions.

Extra-abdominal fibromatosis (desmoid tumor) arising in the infratemporal fossa: a case report.

Aggressive fibromatosis (or desmoid tumor) refers to a histologically benign but locally aggressive lesion arising from musculoaponeurotic structures in various anatomic sites. Extra-abdominal desmoids represent about one third of all desmoid tumors; of these only about 11 to 15% arise in the head and neck. Desmoid tumors arising in the infratemporal fossa are exceedingly rare; to our knowledge only one such tumor has been reported in the literature. We present a desmoid tumor arising in the infratemporal fossa with intracranial extension in a twenty-seven year old male and review the literature on this rare condition.

Optimal treatment of descending necrotising mediastinitis.

BACKGROUND: Descending necrotising mediastinitis is caused by downward spread of neck infection and has a high fatality rate of 31%. The seriousness of this infection is caused by the absence of barriers in the contiguous fascial planes of neck and mediastinum. METHODS: The recent successful treatment of seven adult patients with descending necrotising mediastinitis emphasises the importance of optimal early drainage of both neck and mediastinum and prolonged antibiotic therapy. The case is also presented of a child with descending necrotising mediastinitis, demonstrating the rapidity with which the infection can develop and lead to death. Twenty four case reports and 12 series of adult patients with descending necrotising mediastinitis published since 1970 were reviewed with meta-analysis. In each case of confirmed descending necrotising mediastinitis the method of surgical drainage (cervical, mediastinal, or none) and the survival outcome (discharge home or death) were noted. The chi 2 test of statistical significance was used to detect a difference between cases treated with cervical drainage alone and cases where mediastinal drainage was added. RESULTS: Cervical drainage alone was often insufficient to control the infection with a fatality rate of 47% compared with 19% when mediastinal drainage was added (p < 0.05). CONCLUSIONS: Early combined drainage with neck and chest incisions, together with broad spectrum intravenous antibiotics, should be considered standard care for this disease.

Synthesis of two analogues of the Sda determinant. Replacement of the sialic acid residue by a sulfate or a carboxymethyl group.

Two analogues of the Sda determinant tetrasaccharide have been synthesized in order to investigate the physiological role of this carbohydrate moiety. These saccharides, having two different anionic substitutes for the sialic acid residue, are: beta-D-GalpNAc-(1-->4)-3-O-SO3 H- beta-D-Galp-(1-->4)-beta-D-GlcpNAc-(1-->O)(CH2)5NH2 and beta-D-GalpNAc-(1-->4)-3-O- COOH-beta-D-Galp-(1-->4)-beta-D-GlcpNAc-(1-->O)(CH2)5NH2. 5-Azidopentyl (2,6-di-O- benzyl-beta-D-galactopyranosyl)-(1-->4)-3,6-di-O-benzyl-2-deoxy-2- phthalimido-beta-D-glucopyranoside served as a general building block. The trisaccharides were obtained after prior selective derivatization of HO-3' of the disaccharide derivative via a dibutyltin oxide mediated reaction, followed by coupling at HO-4' with 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-beta-D-galactopyranosyl trichloroacetimidate, and processing of the formed trisaccharide derivatives into their free forms.