Molecular imaging of cell death in vivo by a novel small molecule probe

Apoptosis has a role in many medical disorders, therefore assessment of apoptosis in vivo can be highly useful for diagnosis, follow-up and evaluation of treatment efficacy. ApoSense is a novel technology, comprising low molecular-weight probes, specifically designed for imaging of cell death in vivo. In the current study we present targeting and imaging of cell death both in vitro and in vivo, utilizing NST-732, a member of the ApoSense family, comprising a fluorophore and a fluorine atom, for both fluorescent and future positron emission tomography (PET) studies using an 18F label, respectively. In vitro, NST-732 manifested selective and rapid accumulation within various cell types undergoing apoptosis. Its uptake was blocked by caspase inhibition, and occurred from the early stages of the apoptotic process, in parallel to binding of Annexin-V, caspase activation and alterations in mitochondrial membrane potential. In vivo, NST-732 manifested selective uptake into cells undergoing cell-death in several clinically-relevant models in rodents: (i) Cell-death induced in lymphoma by irradiation; (ii) Renal ischemia/reperfusion; (iii) Cerebral stroke. Uptake of NST-732 was well-correlated with histopathological assessment of cell-death. NST-732 therefore represents a novel class of small-molecule detectors of apoptosis, with potential useful applications in imaging of the cell death process both in vitro and in vivo

A Protocol for a Pan-Canadian Prospective Observational Study on Active Surveillance or Surgery for Very Low Risk Papillary Thyroid Cancer

BackgroundThe traditional management of papillary thyroid cancer (PTC) is thyroidectomy (total or partial removal of the thyroid). Active surveillance (AS) may be considered as an alternative option for small, low risk PTC. AS involves close follow-up (including regularly scheduled clinical and radiological assessments), with the intention of intervening with surgery for disease progression or patient preference.MethodsThis is a protocol for a prospective, observational, long-term follow-up multi-centre Canadian cohort study. Consenting eligible adults with small, low risk PTC (< 2cm in maximal diameter, confined to the thyroid, and not immediately adjacent to critical structures in the neck) are offered the choice of AS or surgery for management of PTC. Patient participants are free to choose either option (AS or surgery) and the disease management course is thus not assigned by the investigators. Surgery is provided as usual care by a surgeon in an institution of the patient’s choice. Our primary objective is to determine the rate of ‘failure’ of disease management in respective AS and surgical arms as defined by: i) AS arm – surgery for progression of PTC, and ii) surgical arm - surgery or other treatment for disease persistence or progression after completing initial treatment. Secondary outcomes include long-term thyroid oncologic and treatment outcomes, as well as patient-reported outcomes.DiscussionThe results from this study will provide long-term clinical and patient reported outcome evidence regarding active surveillance or immediate surgery for management of small, low risk PTC. This will inform future clinical trials in disease management of small, low risk papillary thyroid cancer.Registration detailsThis prospective observational cohort study is registered on clinicaltrials.gov (NCT04624477), but it should not be considered a clinical trial as there is no assigned intervention and patients are free to choose either AS or surgery

Reconstruction following EEA: a 0.5% CSF leak rate in 200 consecutive cases

INTRODUCTION: Reconstruction of the ventral skull base after the Expanded Endonasal Approach (EEA) remains a controversial issue. The development of the pedicled nasoseptal flap (NSF) has been a seminal event in the maturation of EEA, resulting in a marked reduction in cerebrospinal fluid (CSF) leak rates after the procedure. However, other reconstructive options exist, including the use of non-vascularized tissue such as autografts of fat or fascia lata, homografts and tissue adhesives. In addition, many centers now use a hybrid approach, reserving the use of the NSF for high risk cases, and using non-vascularized reconstructions for low risk situations or when the NSF is unavailable because of previous resections or tumor involvement. Our group has routinely used the NSF when available for all EEA cases, with resections of the nasopharynx and drainage of skull base infections and cholesterol granulomas being the most notable exceptions. In addition, we have used other vascularized reconstructions (including the lateral vault flap and, in one case, free tissue transfer) in situations where the NSF is unavailable. This paper will report on our protocol for ventral skull base reconstruction after EEA and examine our CSF leak rate over our last 200 consecutive cases. METHODS: Retrospective chart review of 200 EEA cases performed at two institutions by a single surgical team. The variables measured were method of reconstruction, pathology, and incidence of CSF leak. RESULTS: A total of 200 cases were performed by this single surgical team. There was one episode of CSF leak in these 200 consecutive cases (0.5%). DISCUSSION: Although there are numerous centers using non-vascularized reconstruction of the ventral skull base after in a significant proportion of cases, our protocol has been to use vascularized reconstruction as a routine in all but very selected cases. This has resulted in an extremely low rate of CSF leak

Peri-operative factors predisposing to pharyngocutaneous fistula after total laryngectomy: analysis of a large multi-institutional patient cohort

BACKGROUND: Pharyngocutaneous fistula (PCF) is a problematic complication following total laryngectomy. Disagreement remains regarding predisposing factors. This study examines perioperative factors predicting PCF following total laryngectomy using a large multicenter data registry. METHODS: Retrospective cohort analysis was performed using patients undergoing total laryngectomy in the ACS-NSQIP database for 2006-2014. Sub-analysis was performed based on reconstruction type. Outcome of interest was PCF development within 30 days. RESULTS: Multivariate analysis of 971 patients was performed. Three variables showed statistical significance in predicting PCF: wound classification of 3 and 4 vs. 1-2 (OR 6.42 P \u3c 0.0004 and OR 8.87, P \u3c 0.0042), pre-operative transfusion of \u3e 4 units of packed red blood cells (OR 6.28, P = 0.043), and free flap versus no flap reconstruction (OR 2.81, P = 0.008). CONCLUSIONS: This study identifies important risk factors for development of PCF following total laryngectomy in a large, multi-institutional cohort of patients, thereby identifying a subset of patients at increased risk

A case report: Primary malignant melanoma of the glottic larynx – A very rare entity

Background: Primary mucosal melanoma of the larynx is an extremely rare entity. Our case represents the seventeenth case reported to date globally, and the first Canadian case to be reported. Case presentation: We present the case of a 70-year-old male who was referred for hoarseness and found to have a T3N0M0 glottic mucosal melanoma involving the left true vocal cord. The laryngeal tumour was resected via a transoral laser microsurgery approach with a CO2 laser, wherein an extended partial laryngectomy with negative margins was achieved. There were no regional or distant metastases. Mucosal melanoma is a rare, but an aggressive malignancy as it is generally discovered at an advanced stage. Herein we present our diagnostic, treatment, and post-operative follow-up approaches. Conclusion: Owing to the rarity of mucosal melanoma, especially of the larynx, we believe additional reported cases to the literature will contribute to better understanding of this malignancy and improve treatment strategies