NeuroSAFE PROOF: study protocol for a single-blinded, IDEAL stage 3, multi-centre, randomised controlled trial of NeuroSAFE robotic-assisted radical prostatectomy versus standard robotic-assisted radical prostatectomy in men with localized prostate cancer.

BACKGROUND: Robotic radical prostatectomy (RARP) is a first-line curative treatment option for localized prostate cancer. Postoperative erectile dysfunction and urinary incontinence are common associated adverse side effects that can negatively impact patients' quality of life. Preserving the lateral neurovascular bundles (NS) during RARP improves functional outcomes. However, selecting men for NS may be difficult when there is concern about incurring in positive surgical margin (PSM) which in turn risks adverse oncological outcomes. The NeuroSAFE technique (intra-operative frozen section examination of the neurovascular structure adjacent prostate margin) can provide real-time pathological consult to promote optimal NS whilst avoiding PSM. METHODS: NeuroSAFE PROOF is a single-blinded, multi-centre, randomised controlled trial (RCT) in which men are randomly allocated 1:1 to either NeuroSAFE RARP or standard RARP. Men electing for RARP as primary treatment, who are continent and have good baseline erectile function (EF), defined by International Index of Erectile Function (IIEF-5) score > 21, are eligible. NS in the intervention arm is guided by the NeuroSAFE technique. NS in the standard arm is based on standard of care, i.e. a pre-operative image-based planning meeting, patient-specific clinical information, and digital rectal examination. The primary outcome is assessment of EF at 12 months. The primary endpoint is the proportion of men who achieve IIEF-5 score ≥ 21. A sample size of 404 was calculated to give a power of 90% to detect a difference of 14% between groups based on a feasibility study. Oncological outcomes are continuously monitored by an independent Data Monitoring Committee. Key secondary outcomes include urinary continence at 3 months assessed by the international consultation on incontinence questionnaire, rate of biochemical recurrence, EF recovery at 24 months, and difference in quality of life. DISCUSSION: NeuroSAFE PROOF is the first RCT of intra-operative frozen section during radical prostatectomy in the world. It is properly powered to evaluate a difference in the recovery of EF for men undergoing RARP assessed by patient-reported outcome measures. It will provide evidence to guide the use of the NeuroSAFE technique around the world. TRIAL REGISTRATION: NCT03317990 (23 October 2017). Regional Ethics Committee; reference 17/LO/1978.

Parathyroid cancer: A systematic review of diagnostic biomarkers.

INTRODUCTION: Parathyroid cancers are rare and difficult to distinguish from benign parathyroid tumours. Prediction of malignancy often relies on intraoperative assessment of invasion. Standard histology is also inadequate; especially in the absence of local invasion, lymph nodal disease and metastasis. The aim of this project was to systematically review published literature on potential bio-markers used for the diagnosis of parathyroid cancer. METHODS: Pubmed, Web of Science and Medline databases were searched. Inclusion criteria included English language papers published after 1985 and reporting on biomarkers in human studies of parathyroid cancer and benign disease. RESULTS: 118 relevant papers were appraised; all were observational studies. At least 2 papers studied 8 serum, 4 urine and 27 tissue biomarkers on the diagnosis of parathyroid cancer. Of these, 5 serum and 13 tissue markers have been demonstrated in at least one study to be statistically different in benign and malignant disease. We present a synthesis of data for each biomarker and measures of diagnostic accuracy where possible. CONCLUSIONS: Consideration should be given to the use of a panel of biomarkers to review patients with suspected parathyroid cancer. A profile including serum calcium and PTH levels and tissue expression of APC, Parafibromin, PGP9.5, Galectin 3 and Ki67 is proposed. Systematic Review Registration Number - CRD42019127833.

Transoral Laser Surgery for Adenosquamous Carcinoma of the Glottis: First Case Report and Review of the Literature.

Adenosquamous carcinoma of the head and neck is a rare cancer associated with poor prognosis. Histologically, it is identified through the presence of both adenocarcinoma and squamous cell carcinoma, although it may be difficult to diagnose from initial endoscopic biopsies. We report a case of adenosquamous carcinoma of the glottis in an 82-year-old female patient who presented with progressive hoarseness of voice and in whom initial biopsies had shown only moderate to severe dysplasia. This is the first case in the literature of a primary adenosquamous carcinoma of the glottis managed successfully with a CO2 laser left type Va cordectomy. The patient remained disease-free 28 months postoperatively.

Collision Tumor of Urothelial Cell Carcinoma and Clear Cell Renal Cell Carcinoma: A Case Report and Review of the Contemporary Literature.

We present a case of synchronous renal cell carcinoma and urothelial carcinoma. Our case was a true collision tumor and both components were high grade. Metastasis to the adrenal gland by the urothelial carcinoma was observed. The morphologic impression was confirmed with GATA3 expression by the urothelial carcinoma component and PAX8 expression by the renal cell carcinoma component. We have reviewed the contemporary literature of this unusual dual diagnosis.

Simultaneous presentation of parathyroid carcinoma, papillary thyroid cancer and ACTH-independent hypercortisolism due to benign cortical adenoma.

A 46-year-old woman presented with hypertension and renal disease. Investigations showed severe hypercalcaemia due to primary hyperparathyroidism. Imaging demonstrated renal calculi and an incidental left adrenal lesion. Additional biochemistry confirmed adrenocorticotropic hormone-independent hypercortisolism. Ultrasound and sestamibi scan found an enlarged right-sided parathyroid gland and a suspicious right thyroid nodule, biopsy of which suggested papillary carcinoma. The right parathyroid mass, right thyroid lobe and right central compartment tissue along with a segment of the right recurrent laryngeal nerve was resected en-bloc Completion thyroidectomy and left adrenalectomy were performed 6 months later. Histology showed parathyroid cancer, multifocal papillary thyroid cancer and adrenal clear cell cortical adenoma. Genetic tests were normal. There was no evidence of recurrence at 12 months follow-up. Parathyroid cancer should be suspected in the presence of significant hypercalcaemia, very high parathyroid hormone and end organ damage. Suspicious thyroid nodules on imaging should be appropriately investigated.

Immunoglobulin G4-related disease of the paranasal sinuses.

Immunoglobulin G4-related disease (IgG4-RD) is becoming increasingly documented. It was first described in relation to autoimmune pancreatitis. Features of the disease include tissue infiltration by IgG4 plasma cells with associated fibrosis and the growth of pseudotumours. A 71-year-old woman presented with increasing right cheek swelling and mild proptosis. Ten years earlier, she had a similar presentation and was diagnosed with an inflammatory pseudotumour. Examination revealed a lesion in the right nasal cavity. CT and MRI confirmed a mass within the right maxillary antrum extending into the nasal cavity. Endoscopic biopsies showed florid plasma cell infiltrate with marked increase in IgG+ plasma cells. Immunostaining expressed IgG4 (70%). She was started on a course of prednisolone and her symptoms resolved. IgG4-RD is becoming an emerging disease entity. Its involvement in the paranasal sinuses can mimic nasal tumours. Major surgical resection should be avoided as patients can often be treated medically.