Spinal versus conventional fine needle for ultrasound-guided thyroid nodule biopsy: a protocol for a randomised clinical trial.

INTRODUCTION: Thyroid nodules are very common and constitute an increasing clinical challenge since improved imaging capabilities and utilisation have led to a higher number of incidental findings. Ultrasound-guided fine-needle aspiration biopsy (FNAB) is the standard diagnostic tool in the work-up of thyroid nodules suspected of malignancy. Non-diagnostic results remain common and require repeated FNAB, leading to increased costs and delayed treatment of thyroid diseases, including treatment of thyroid cancer. If cytological diagnoses cannot be achieved, surgery may be warranted, which may potentially lead to overtreatment. Optimisation of the FNAB procedure is therefore essential. Spinal needles with a stylet have been found to lead to fewer non-diagnostic results, but studies on the subject are few. METHODS: This is a multicentre, two-arm, randomised clinical trial. Adults with thyroid nodules suspected of malignancy will be included consecutively. A total of 350 patients will be assigned randomly 1:1 to have a FNAB with either a spinal (25G) or a conventional (25G) needle. The primary outcome is the rate of diagnostic cytological samples according to the Bethesda system. Secondary outcomes are patient-experienced pain, complication rate and sensitivity and specificity. CONCLUSIONS: This trial will explore whether FNAB from thyroid nodules employing spinal needles compared with conventional fine needles improves diagnostic results, thereby providing evidence-based recommendations for a future choice of the FNAB needle. Secondary outcomes are patient-experienced pain, complication rate and sensitivity and specificity. FUNDING: This trial received funding from Erik and Susanna Olesens Fond. The funding source had no influence on trial design, data collection, analysis or publication. CLINICALTRIALS: gov Identifier: NCT04879355. Registration date: 07032021; version: 29062022.

Human papillomavirus testing in metastatic squamous cell carcinoma of the neck with unknown primary using PCR on fine-needle aspiration smears: a prospective clinical study.

PURPOSE: Squamous cell carcinoma metastasis of the head and neck with unknown primary tumor (CUP) comprises a diagnostic challenge. Human papillomavirus (HPV) testing on cytologic specimens is gaining increasing focus as this may facilitate an early diagnosis of HPV-induced oropharyngeal carcinoma. This study aimed to prospectively assess PCR-based HPV-DNA testing on FNA smears in a clinical setting. METHODS: Patients referred to a tertiary Head and Neck Cancer Center with suspected CUP were included from November 2016 to November 2018. Scraped cell material from FNA smears was analyzed for HPV-DNA with PCR using general primers (GP5 + /GP6 +) and correlated with the origin and histology of the primary tumor (oropharynx vs. outside oropharynx or benign tumor). The turn-around time reflecting the workflow for HPV-DNA testing by PCR was also calculated. RESULTS: A total of 93 patients were enrolled in the study. The sensitivity and specificity were 86.7% [95% CI 75.4-94.1%] and 92.0% [95% CI 74.0-99.0%], and the positive and negative predictive values were 96.3% [95% CI 87.3-99.0%] and 74.2% [95% CI 59.9-84.7%], respectively. The turn-around time for HPV testing was a mean four calendar days. CONCLUSION: HPV-DNA testing on FNA smears can be performed within a reasonable timeframe and can guide for the detection of an HPV-positive oropharyngeal primary tumor in the clinical setting for patients presenting with CUP of the head and neck.

Clinical Features and Disease Course of Primary Angioedema Patients in a Tertiary Care Hospital.

PURPOSE: To give a better understanding of primary AE, the clinical characteristics and the possible therapeutic approaches. BACKGROUND: Angioedema (AE) is a non-pitting, non-itching swelling of skin or mucosa. The symptom can become life-threatening if located in the airways. Primary (monosymptomatic) AE is a manifestation of several different diseases and the diagnosis is not always straight-forward. The aetiological and pathophysiological factors of primary AE are not completely clarified. There is a need for further investigation. PATIENTS AND METHODS: This was a retrospective cohort study of patients referred to an outpatient dermatology clinic in a tertiary care hospital for clinical assessment due to primary AE in the period from 1996 to 2014. RESULTS: A total of 315 patients were identified with primary AE. The most frequent subtype was idiopathic AE (42.5%) and the second most common was angiotensin-converting enzymeinhibitor (ACEi)-induced AE (31.1%). Three patients were diagnosed with hereditary AE and one patient was diagnosed with acquired C1-inhibitor deficiency. At least 107 (34.0%) patients had established histaminergic AE. More than 1/3 of the patients were treated in an emergency room or hospitalized due to AE. A 98.1% of patients had experienced AE in the head and neck area. Seven patients were in the need of acute airway intervention. Six of these had ACEi-induced AE. Female sex and smoking were found to be risk factors for developing AE. CONCLUSION: The most frequent diagnoses were histaminergic-, non-histaminergic idiopathic AE and ACEi-induced AE, whereas complement C1-inhibitor deficiency was rare. Histaminergic AE made up a substantial group of patients with primary AE. Even though there are different pathophysiological causes of AE, many cases have overlapping clinical manifestations, which make diagnosis and treatment difficult.

Calcium electroporation for recurrent head and neck cancer: A clinical phase I study.

BACKGROUND: Calcium electroporation is a novel cancer treatment, which combines temporary cell permeability from electroporation with a high influx of calcium intracellularly resulting in cancer cell necrosis. METHODS: A phase I trial performing calcium electroporation on 6 patients suffering from recurrent head and neck cancer. In general anesthesia, intratumoral calcium injections were followed by electroporation. Safety was monitored by adverse events registration, serum Ca2+, ECG, and pain scores. Tumor response was measured on PET/MRI scans. RESULTS: Procedures were performed without complications. No serious adverse events, signs of hypercalcemia, or cardiac arrhythmias were observed. Two months post-treatment tumor responses on MRI: three partial responses, one stable disease, and two progression. Responses on PET: one partial metabolic disease, four with stable metabolic disease, and one not evaluable. One patient was without clinical evidence of disease after 12 months of observation. CONCLUSION: Calcium electroporation is feasible and safe in head and neck tumors. Clinical responses were observed in three of six patients, warranting further studies. LEVEL OF EVIDENCE: Level 4.

[Transoral robotic surgery for head and neck cancer].

Oropharyngeal squamous cell carcinoma (OPSCC) induced by human papillomavirus (HPV) is highly prevalent in the western part of the world. Patients with HPV-induced OPSCC are often younger and have a much better prognosis than patients with HPV-negative OPSCC. The newly introduced transoral robotic surgery offers the ability to perform en bloc tumour resection with good margin control. It may be an alternative to the traditional radiation therapy for early-stage OPSCC. A Danish randomised clinical trial is now aiming at comparing these two treatments with a focus on long-term functional outcomes.

Prognostic value of intact and cleaved forms of the urokinase plasminogen activator receptor in a retrospective study of 518 colorectal cancer patients.

BACKGROUND: The levels of the soluble urokinase plasminogen activator receptor (suPAR) in blood have been shown to correlate with prognosis in various cancers. Plasma levels of the combined suPAR forms have previously shown to be a strong prognostic marker in the present cohort of CRC patients and could potentially identify high-risk patients among those with early stage disease. In order to investigate whether the individual suPAR forms are stronger prognostic markers than the combined amount we measured the different uPAR forms in serum from the same cohort and evaluated their prognostic significance. MATERIAL AND METHODS: The different suPAR forms were measured in serum preoperatively collected from 518 patients. Patients were followed up to nine years (median 7.9 years) and the primary endpoint was overall survival. The different suPAR forms were measured using Time Resolved Fluorescence Immunoassays(TR-FIAs): Intact, suPAR(I-III) by TR-FIA 1; intact and cleaved, suPAR(I-III)+(II-III) by TR-FIA 2; and liberated uPAR(I) by TR-FIA 3. RESULTS: All three uPAR variants demonstrated prognostic significance when evaluated individually. In a multivariable analysis suPAR(I-III)+(II-III) and the liberated uPAR(I) were shown to be independent markers of prognosis (HR=1.74, CI:1.33-2.26; p <0.0001 and HR=1.32; CI:1.02-1.71; p=0.036 respectively), and independent of the clinical baseline variables: age, gender, tumor stage and localization. CONCLUSION: This study demonstrated that suPAR(I-III)+(II-III) and the liberated uPAR(I) in serum are independent prognostic markers in CRC.