Search

Introduction Patients with transposition of the great arteries (TGA) who underwent atrial switch repair (ASR, Senning or Mustard) and patients with congenitally corrected TGA (ccTGA) have a morphological right ventricle in the systemic position. Patient with a systemic right ventricle (SRV) are prone to exercise intolerance and have a significantly worse survival compared to the general population. Risk stratification is an important component of their management and routine clinical assessment. Purpose To describe the severity and mechanisms of exercise limitation in patients with a SRV, and its relation to mortality. Methods All SRV patients who underwent a cardiopulmonary exercise test (CPET) in a tertiary centre from 2000–2019 were included. Demographics, clinical and imaging data were collected around the time of CPET. Cox survival analysis was used to assess the association between exercise parameters and mortality. Results A total of 262 patients underwent at least one CPET during the study period. Mean age at CPET was 37.4±12 and 154 (58.8%) were male. The majority of patients had TGA with ASR (150, 57.3%), while 112 (42.7%) had ccTGA. The majority of patients were in NYHA class I (36%) or II (36%). Moderate or severe right ventricular dysfunction was present in 188 (78.0%), while 59 (26.6%) patients had moderate or severe TR. Baseline oxygen saturation was 96±4% and median BNP was 71 [37–140] ng/L. Co-existent congenital lesions were present in almost one half (48.8%) of patients, including pulmonary stenosis (31,7, 12.1%) and ventricular septal defect (61,3, 23.4%). Average peak VO2 (pVO2) was 22.3±8.1ml/kg/min, (66±22% of predicted). The VE/VCO2 slope was raised (>33) in 128 (49%) patients. Patients who were cyanotic at rest and/or desaturated during exercise had a significantly higher VE/VCO2 slope (40.3±15.9 vs. 33.6±9.0, p=0.0004) and lower pVO2 (20.7±8.0 vs. 24.3±7.7, p=0.0007). A total of 119 (46.1%) patients achieved target heart rate, while 36 (14.0%) patients were unable to achieve a heart rate of at least 60% predicted. Over a median follow up of 3.0 [1.1–5.9] years, 36 (13.7%) patients died. Univariable predictors of mortality from CPET included pVO2, VE/VCO2 slope, heart rate reserve (HRR), anaerobic threshold, peak systolic blood pressure and exercise time (Figure). On bivariable analysis using pVO2 with each of the other exercise parameters, only peak systolic blood pressure remained in the model, even when adding age. In ccTGAs, peak VO2 was the only parameter remaining in the multivariable models. In ASR patients, HRR was stronger than all other parameters. Conclusion In this large cohort of patients with systemic RVs, older than existing reports in this area, peak VO2, peak systolic BP and HRR appear to be stongly related to mortality. These findings reflect the underlying physiology and consequences of previous surgery and should be used in clinical practice to risk stratify patients. Kaplan-Meier curves Funding Acknowledgement Type of funding source: None

Objective The staging of cutaneous squamous cell cancers (cSCC) was revised by the American Joint Committee on Cancer in 2010 to incorporate known prognostic factors and expand the N (node) category. The purpose of this study was to validate this staging system using a North American cohort, and to compare it to the O'Brien P (Parotid) and N staging system. Methods An exhaustive collaborative database search was performed for all patients with cSCC metastasis to the parotid gland treated at three major Canadian tertiary referral centers from December 1999 to March 2015. The data collected for each patient included overall survival; disease-free survival; tumor, node, and metastasis) staging; and postoperative radiation status. Post-hoc analysis was completed to discern the strongest prognostic factors of survival as they relate to the abovementioned staging systems. Results Of 136 patients identified, 80% had a documented history of previously treated head and neck cSCC an average of 27 months prior to presentation. Average size of the parotid lesion at recurrence was 4.5 cm. Ninety-six percent of patients underwent surgical resection of the parotid metastasis. Five-year overall and disease-free survival is 79% and 55%, respectively. Only cSCC staging and cSCC-N category had statistically significant differences between groups. cSCC staging had the largest percentage of variation in overall survival explained. Conclusion Patients with cSCC metastasis to the parotid gland proved to have a moderate survival rate, despite presenting with advanced disease. cSCC staging in the setting of parotid metastasis, despite its limitations, currently offers the most predictive staging system available. Level of Evidence 4. Laryngoscope, 127:2063–2069, 2017

The literature reports various treatment methodologies, such as trans-oral laser microsurgery, radiation therapy, total/partial laryngectomies, and concurrent radiation chemotherapy for patients with early larynx cancer. However, at the forefront of early glottis treatment is trans-oral laser microsurgery and radiation therapy, likely due to better functional and survival outcomes. Here we conduct the largest Canadian head-to-head comparison of consecutive patients treated with either radiation therapy or trans-oral laser microsurgery. Additionally, we compare these two treatments and their 5-year survival rates post treatment to add to the existing literature. Charts of patients who were diagnosed with early glottic cancer between 2006 and 2013 were reviewed. Seventy-five patients were identified, and split into 2 groups based on their primary treatment, trans-oral laser microsurgery and radiation therapy. Kaplan–Meier survival curves, life-tables, and the log-rank statistic were reported to determine if there was a difference between the two treatment groups and their disease-specific survival, disease-free survival, and total laryngectomy-free survival. Additionally, each different survival analysis was stratified by potential confounding variables, to help conclude which treatment is more efficacious in this population. The 5-year disease-specific survival rate is 93.3 % σ = 0.063 and 90.8 % σ = 0.056 for patients treated with trans-oral laser microsurgery and radiation therapy, respectively (χ 2

Background Fine-needle aspiration biopsy has become the standard of care for the evaluation of thyroid nodules. More recently, the use of ultrasound guided fine-needle aspiration biopsy (UG-FNAB) has improved adequacy of sampling. Now there has been improved access to UG-FNAB as ultrasound technology has become more accessible. Here we review the adequacy rate and learning curve of a single surgeon starting at the adoption of UG-FNAB into surgical practice. Methods UG-FNABs performed at Sunnybrook Health Sciences Centre from 2010 to 2015 were reviewed retrospectively. Nodule characteristics were recorded along with cytopathology and final pathology reports. Chi-square analysis, followed by the reporting of odds ratios with confidence intervals, were used to assess the statistical significance and frequencies, respectively, of nodule characteristics amongst both diagnostic and non-diagnostic samples. A multiple regression analysis was conducted to determine if any nodule characteristic were predictive of adequacy of UG-FNABs. The learning curve was assessed by calculating the eventual adequacy rates across each year, and its statistical significance was measured using Fischer’s Exact Test. Results In total 423 biopsies were reviewed in 289 patients. The average nodule size was 23.05 mm. When examining if each patient eventually received a diagnostic UG-FNAB, regardless of the number attempts, adequacy was seen to increase from 70.8 % in 2010 to, 81.0 % in 2011, 90.3 % in 2012, 85.7 % in 2013, 89.7 % in 2014, and 94.3 % in 2015 (Fischer’s Exact Test, p = 0.049). Cystic (χ2 = 19.70, p

Extracellular nucleotides induce a biphasic change in the transepithelial electrical conductance (GT) of human cervical cells grown on filters: a rapid increase (phase I) followed by a sustained decrease (phase II). To probe the involvement of the intercellular space, its magnitude was varied by manipulating cell volume through changes in extracellular osmolarity. Under baseline conditions [GT = 115 mS/cm2 (approximately 9 omega.cm2)] and during phase II, hypertonic challenges resulted in an increase in GT (0.98% .mosmol-1.l-1 and 0.73%.mosmol-1.l-1, respectively). However, a hypertonic challenge during phase I decreased GT (-0.16%.mosmol-1.l-1). Hypotonic challenges decreased GT during baseline, phase I, and phase II conditions by -1%.mosmol-1.l-1. Similar trends were observed with regard to pyranine permeability. Reduction of extracellular calcium increased GT, abrogated the phase II effect of extracellular ATP, and reversed the effect of a hypertonic challenge. The additive nature of the permeability changes in response to osmotic challenges and to ATP during phase II suggests that different sites are involved in each response, i.e., the resistance of the intercellular space changes with osmolarity and that of the tight junction during phase II.

The purpose of the present study was to compare the permeaiility and regulation of paracellular transport in human cervical cells with those in epithelial cells of other organs. Cervical cells (ECE16–1, Caski, and HT3) were grown on filters, and trans-epithelial electrical conductance (GT) and the permeability to pyranine (PPyr) were determined. Cervical cultures were characterized by high GT (83–125 mS•cm−2 ) and high PPyr (6.2–18•10−6 •sec−1). The GT was not significantly affected by cell density but was increased by 20% by lowering extracellular calcium to 0.45 mmol/L or less. The high values of GT and PPyr and the regulation by extracellular calcium indicate that all three cervical cell lines have “leaky” tight junctional complexes. Addition of extracellular adenosine triphosphate (ATP) at 50 μmol/L to the cervical cultures evoked a biphasic change in GT- that was unique to the cervical cells: an initial increase, followed by a sustained decrease by 30 /o frorn baseline GT. The decrease oj GT- was associated with a decrease in PPyr by 17%, indicating that ATP had an effect on the tight junctional/paracellular permeability. The ATP effect was reversible either by washing or by chemical hydrolysis with ATPse. 1 he non-cervical cell lines all responded to extracellular ATP with a transient increase in GT, but not with the pronounced decrease. The permeability of the paracellular pathway can be regulated in cervical epithelia by mechanisms that may be different frorn those in epithelial cells frorn other organs.

Extracellular ATP changes the transepithelial electrical conductance (GT) across cultures of human cervical cells acutely, in a biphasic manner that is characterized by a rapid increase (phase I) followed by a sustained decrease in GT (phase II). We tested the hypothesis that the phase II response is mediated by decreases in the permeability of tight junctions. We studied the effect of ATP on the relative mobilities of Cl- vs. Na+ (uCl/uNa) as calculated from changes in the dilution potential (Vdil). Vdil was induced by lowering NaCl from 130 to 10 mM in either the luminal or subluminal solutions bathing filters containing cells. uCl/uNa was 1.27 across cervical cultures and 1.34 across blank filters, compared with a level of 1.52 in free solution. Increases in GT induced by transepithelial hydrostatic or hypertonic gradients (which increase permeability of lateral intercellular space) had no effect on uCl/uNa. Increases in GT induced by lowering extracellular Ca2+ to < 0.1 mM increased uCl/uNa to levels obtained in blank filters, indicating abrogation of tight-junctional resistance. Phase I response and ionomycin (which produces a sustained phase I-like increase in GT) had no effect on uCl/uNa. The phase II response, however, decreased uCl/uNa from 1.27 to 1.24, and the effect could be abrogated by lowering extracellular Ca2+. These results indicate that phase II decreases in GT across cultured human cervical epithelium are mediated by acute decreases in tight-junctional permeability.

The effects of extracellular ATP (ATPe) were characterized in human cervical cells grown on filters. ATPe changed the transepithelial conductance (GT) in a biphasic manner with an initial acute increase of 13 +/- 3% (phase I), lasting approximately 2 min, followed by a sustained decrease of 49 +/- 17% (phase II). ATPe also effected decreases of permeabilities to pyranine and to sucrose, which correspond to the phase II decrease in GT. Both phase I and II effects appear to be mediated by apical nucleotide receptors. However, the phase I effect differed from the phase II effect as follows: 1) a higher 50% effective concentration for ATPe, 22 vs. 3 microM; 2) different nucleotide specificity; 3) lack of influence of pretreatment with pertussis toxin; 4) independence from time in culture after seeding; and 5) involvement of cytosolic calcium, rather than diacylglycerol, as intracellular messenger. These differences suggest the presence of two different types of nucleotide receptors that use different intracellular signaling systems and have opposite effects on the paracellular permeability and electrical conductance. These results suggest that ATPe could regulate cervical mucus production in vivo by regulating the paracellular permeability. Depending on the specific receptors present, ATPe could either increase or decrease mucus production.

We studied the effect of ATP on transepithelial transport through the paracellular pathway in human cervical cells. Transepithelial conductance and transepithelial permeability (determined from the measurements of unidirectional flux of inert molecules) were measured in Caski cells grown on permeable support. Transepithelial conductance was 55.9 +/- 17.7 mS/cm2 and permeability was 12.5 +/- 2.7 x 10(-6) cm/s for a 0.51-kDa probe. Addition of ATP to the medium decreased acutely and reversibly the conductance and the permeability to probes between 0.18 and 10 kDa by 23-31% in a dose-related fashion; the 50% effective concentration was 1 microM, with a maximal effect at 5-10 microM extracellular ATP. The ATP effect was observed regardless of the pressure gradient across the epithelium. These results indicate that extracellular ATP in micromolar concentrations decreases acutely and reversibly the permeability through the paracellular pathway in cervical cells, possibly by affecting the permeability of the tight junctions and the resistance of the intercellular space. On the basis of these data, we speculate that ATP may play a role in the regulation of solutes and fluid transport across the cervical epithelium in vivo.

Background Total laryngectomy (TL) is an appropriate oncologic operation for many patients with laryngeal cancer delivering excellent oncologic outcomes, however it remains beset with significant functional consequences. Following TL, the upper and lower airways are permanently disconnected, which causes unfiltered, cold air with reduced humidity to enter the tracheobronchial tree, resulting in mucus overproduction and an increase in the viscosity of the mucus. In response to this, Heat and moisture exchangers were developed to compensate for the lost functions of the upper respiratory tract and their effect on the patients’ respiratory performance in addition to their quality of life. Methods The case records of 48 patients undergoing total laryngectomy were reviewed and data concerning demographics, surgical details, post-operative care requirements and adverse events was retrieved. Post hoc analysis of the case patients was undertaken to identify any benefit of using a heat and moisture exchanger (HME) system with particular reference to post-operative respiratory outcomes. Results There was no significant difference between case and control subjects based on demographics, extent of surgery or need for flap repair. 16 patients had used a HME and 32 patients had used external humidification (EH). Of those experiencing mucous plugging, only 3/24 (12.5 %) had used a HME system, in contrast to 21/24 (87.5 %) who used EH (Chi square = 9.375, p = 0.002). The odds ratio of having an adverse event if not using HME was 8.27 (CI = 1.94 – 35.71). Use of HME also significantly reduced the number of days requiring physiotherapy (1.75 days vs. 3.20 days, p = 0.034). Conclusion Use of an HME system can reduce in-hospital complications, in particular episodes of mucus plugging, and post-operative care requirements. Furthermore, there is a cost benefit to using HME systems that warrants more widespread introduction of these devices in head and neck surgery centers.