Coronavirus disease 2019 pandemic telephone two-week-wait referrals in head and neck cancer - how safe were they?

OBJECTIVE: During the coronavirus disease 2019 pandemic, ENT-UK recommended a move from face-to-face clinics to telephone appointments. This study reviewed the safety of telephone clinics for urgent two-week-wait cancer referrals. METHODS: Patients consulted in telephone clinics between April and November 2020 were identified from an electronic database. Study patients included those diagnosed with malignant disease at six months. The Head and Neck Cancer Risk Calculator version 2 score, outcome of the initial clinic and final diagnoses were reviewed. RESULTS: A total of 1062 patients were triaged in clinic; 9.2 per cent (n = 98) were diagnosed with cancer at 6 months. Of these 98 patients, 69 received an urgent face-to-face appointment, 26 underwent urgent scans and 3 had a delayed telephone review. Twenty patients (20.4 per cent) diagnosed with cancer had a low-risk Head and Neck Cancer Risk Calculator score. CONCLUSION: The late diagnosis rate of 0.28 per cent suggests a small proportion of cancer could have been missed. Telephone clinics, whilst a pragmatic means to maintain patient flow during the pandemic, could result in late diagnoses.

The diagnostic yield of head and neck imaging in symptomatic patients with a normal clinical examination.

AIM: Nationally, concern has been raised about the overuse of diagnostic testing. In patients with unilateral otalgia and no history of Head and Neck Cancer (HNC), 1% had a malignancy detected on imaging that was not detected on clinical examination. METHODS: We performed a retrospective review of "MRI soft tissue neck" scans performed at our hospital from May 2020 to May 2021. Patients were excluded if their scan was not ordered for HNC symptoms. Previous HNC patients undergoing follow-up imaging were also included. RESULTS: In total, 326 scan requests were analyzed. Of the 132 patients without clinical features of overt disease, only one received a new diagnosis of HNC. This patient had previously had a HNC and was undergoing routine follow-up imaging. CONCLUSION: Our data demonstrate that performing MRI scans in symptomatic patients with a normal examination, FNE, and no history of HNC does not benefit the diagnosis or management of these patients.

Concurrent HPV-related oropharyngeal carcinoma in four couples.

OBJECTIVES: Typically, HPV-related cancers are sexually transmitted, however, the natural history of HPV-related oropharyngeal squamous cell carcinoma (OPSCC) is unclear. HPV16 transmission has been reported previously between five couples with OPSCC. We report the clinico-pathological features of a further four couples with HPV-related OPSCC and compare them with the published cases. PATIENTS AND METHODS: We identified four couples in long-term heterosexual relationships that all had HPV-related OPSCC. The couples were treated at three UK hospitals and presented between 2009 and 2015. HPV tests included p16 immunohistochemistry, high-risk HPV DNA in-situ hybridisation and Roche Cobas HPV test. DNA sequencing was used to determine the HPV variant. RESULTS: The four couples represented < 2% of patients with HPV-related OPSCC at the three contributing hospitals (8 of 457 consecutive patients). The couples' tumours all contained HPV16. The mean age was 63 years old (range 52-72 years). The interval between the index cancer and the partner's cancer was 16, 24, 26 and 64 months respectively. The majority of patients had Stage I disease (UICC TNM8). Six of eight patients are disease free, one patient is alive with disease and there was one death from loco-regional recurrence. CONCLUSION: This report highlights the occurrence of HPV-related OPSCC in heterosexual couples and raises the possibility of transmission of HPV16. Despite increasing prevalence of HPV-related OPSCC and increased awareness of the disease, there is a paucity of couples with the disease, suggesting either under-reporting or that the development of OPSCC following HPV transmission between couples is a rare event.

Adenovirus-mediated expression of dominant negative fibroblast growth factor (FGF) receptor 1 in thyroid cells blocks FGF effects and reduces goitrogenesis in mice.

Levels of fibroblast growth factor 2 (FGF-2) and its receptor, FGFR1, are elevated in goiter, but whether this is a direct effect of TSH is unknown. We have determined the regulation of FGF-2 and FGFR1 synthesis by TSH in a rat thyroid cell line (FRTL5) and have used a replication-defective adenovirus (RAd) expressing dominant negative FGFR1 (RAdDN-FGFR1) to examine the role of FGFR signaling in vitro and in goiter induced in mice. TSH induced FGF-2 and increased the expression of FGFR1 in FRTL5 cells. Infection of TSH-stimulated FRTL5 cells with RAdDN-FGFR1 inhibited growth and prevented FGF-2-mediated inhibition of (125)I uptake. Similar effects were found in primary cultures of human thyroid follicular cells. For in vivo experiments, male BALB/c mice were injected systemically with RAdDN-FGFR1 or RAd encoding green fluorescent protein, and goiter was simultaneously induced. Mouse thyroid follicles were shown to be transduced with RAd encoding green fluorescent protein. Circulating TSH was elevated comparably in the two groups. In the RAdDN-FGFR1-injected animals, goiter induced over 14 d was significantly smaller, and the vascular volume increase seen in goiter was also diminished. We conclude that the FGF axis is important in thyroid growth and that RAdDN-FGFR1 effectively blocks FGF actions, offering a means to control goitrogenesis.

Maintenance therapy with trastuzumab in her2 positive metastatic parotid ductal adenocarcinoma.

Salivary ductal carcinomas (SDCs) are extremely rare and aggressive malignancies, accounting for approximately 6% of all salivary gland malignancies. One distinct feature is their resemblance to ductal carcinomas of breast. A significant percentage of SDCs overexpress Her2 and the use of targeted therapy with trastuzumab can be considered in these patients. We report a rare case of long term disease control with trastuzumab in Her2 positive metastatic parotid ductal carcinoma. Our case also highlights that isolated brain metastasis should be managed aggressively to allow optimal local control when systemic disease is under remission with trastuzumab. We have also reviewed the published literature on the use of trastuzumab in SDCs.

Mucosal changes in laryngopharyngeal reflux--prevalence, sensitivity, specificity and assessment.

OBJECTIVES/HYPOTHESIS: A literature review regarding the use of laryngopharyngeal mucosal signs in diagnosing laryngopharyngeal reflux (LPR). STUDY DESIGN: Literature review. METHODS: A search of MEDLINE in February 2012 using the terms laryngopharyngeal reflux, laryngitis, mucosa, appearances, and signs (English language only). RESULTS: One or more laryngopharyngeal mucosal signs associated with LPR were identified in 64% to 93% of healthy volunteers (3% >5 signs) and in 17% to 85% of gastroesophageal reflux disease sufferers (Reflux Finding Score [RFS] >7 in 24%). Reinke's edema, pseudosulcus, ventricular obliteration, vocal cord nodules, and granulomas have in some, but not all studies, been shown to be more prevalent in those with pH-proven pharyngeal reflux. Pseudosulcus, interarytenoid thickening, and Reinke's edema were more prevalent in those symptomatic of LPR than those not. The use of multiple mucosal signs may improve detection of reflux sufferers from asymptomatic controls. The RFS has a sensitivity and specificity of 87.8% and 37.5%, respectively, for picking up pH-proven pharyngeal reflux individuals. Inter- and intrarater reliability for identifying signs is fair to good in most studies. CONCLUSIONS: The limited evidence for each mucosal finding should be considered in making the diagnosis of LPR. Further quality research in to mucosal findings in LPR is needed.

Role and regulation of the fibroblast growth factor axis in human thyroid follicular cells.

Thyroidal levels of fibroblast growth factor-2 (FGF-2) and fibroblast growth factor receptor 1 (FGFR1) are elevated in human thyroid hyperplasia. To understand the significance of this, effects of FGFR1 activation on normal human thyrocyte growth and function in vitro and the regulation of FGF-2 and FGFR1 expression have been examined. FGF-2 stimulated cell growth, as measured by cell counting, and inhibited thyroid function as measured by 125I uptake. Sensitivity to FGF-2 disappeared after 7 days, although FGFR1 expression was maintained. Thyroid-stimulating hormone (TSH, 300 mU/l) increased FGFR1 mRNA expression within 4 h and protein expression by 8 h. Exogenous FGF-2 decreased FGFR1 protein. Endogenous FGF-2 levels were low (approximately 1-2 pg/microg protein), and TSH treatment decreased these by 50%. Protein kinase C (PKC) activation increased FGF-2 mRNA and FGF-2 secretion within 2 h. This effect was enhanced (4.4-fold) when cells were cultured in TSH. We conclude that TSH stimulates FGFR1 but not FGF-2 expression. PKC activation stimulates FGF-2 synthesis and secretion, and TSH synergizes with PKC activators. Increases in FGFR1 or FGF-2 or in both may contribute to goitrogenesis.