Active surveillance for PTMC warranted for the UK population?

BACKGROUND: The incidence of thyroid cancer is increasing globally due to the increase in detection of subclinical, low volume papillary thyroid microcarcinomas (PTMC) (<1 cm). Several international groups have recommended an active surveillance approach for this low-risk disease. In contrast to many other countries, the United Kingdom's (UK's) approach to thyroid nodules is to avoid detection of incidental lesions where appropriate. OBJECTIVE: This study aims to establish the proportion of patients with thyroid cancer in the UK that would benefit from active surveillance. DESIGN, PARTICIPANTS, AND OUTCOME MEASURES: Individuals with PTMC in NHS Lothian from 2009-2020 were reviewed from a local thyroid cancer database. The mode of detection of PTMC and proportion of patients who might benefit from active surveillance were established. RESULTS: From 651 individuals with differentiated thyroid cancer managed over 12-year period, 185 individuals with PTMC were identified (28.4%). The majority of PTMC 151/185 (81.6%) were either diagnosed post-operatively following thyroidectomy for benign disease or with nodal disease. Only 24 individuals with PTMC were identified following palpable thyroid nodule, incidental finding on imaging, and surveillance screening. Therefore, when the indication for surgery was considered, only 24/651 (3.7%) patients were identified pre-operatively and would, therefore, be realistic candidates for active surveillance. CONCLUSION: Less than 4% of patients with thyroid cancer in the UK would be appropriate for active surveillance. Rather than developing programmes to deal with this minority of patients, focus should be maintained on minimising detection of these low-risk cases.

A UK based two-centre review of multifocality and its role in the treatment of papillary thyroid cancer.

INTRODUCTION: Multifocality is increasingly observed in papillary thyroid carcinoma (PTC) due to improvements in imaging and histopathological analysis. However, its significance in management, particularly as a sole risk-factor, remains controversial. This study aimed to investigate the prognostic value of multifocality in predicting recurrence following thyroid lobectomy in a contemporary group of PTC patients managed in the UK. METHODS: Patients with PTC in NHS Lothian (2009-19) and Guys and St Thomas NHS Foundation Trust (2012-19) were identified. Categorical variables were compared using Chi-squared or Fisher's exact test. Five-year recurrence free survival (RFS) were analysed using Kaplan-Meier method and compared using log-rank. RESULTS: Of 828 patients; 492 (59%) had unifocal and 336 (41%) multifocal disease on final pathology. A higher rate of pathological nodal disease (22%v36%,p < 0.001), total thyroidectomy (TT) (78%v92%,p < 0.001) and radioactive iodine (RAI) (57%v75%,p < 0.001) was demonstrated in patients with multifocality. With a median follow-up of 50 months, overall 5-year RFS was 96.5%; 96.5% for unifocal versus 96.6% for multifocal disease (p = 0.695). Recurrence was not shown to be associated with multifocality on either univariate or multivariate analysis. Amongst patients with T1/2N0M0 disease (n = 341), more patients were treated with TT and RAI with multifocal compared to unifocal disease (<0.001). Only two patients within this group recurred during follow up, both of whom had multifocal disease and were treated with TT and RAI (5yRFS100%v98.1%,p = 0.051). CONCLUSION: Multifocality is a common feature of PTC but does not appear to be an independent predictor of outcome. Therefore, treatment intensification on the basis of multifocality alone seems unwarranted.

The acute lethal dose 50 (LD50) of caffeine in albino rats.

An acute LD50 is a statistically derived amount of a substance that can be expected to cause death in 50% of the animals when given by a specified route as a single dose and the animals observed for a specified time period. Although conducting routine acute toxicity testing in rodents has been criticized, it can serve useful functions and also have practical implications. Material safety data sheets (MSDS) will reflect the acute toxicity of a substance and may require workers to wear protective gear, if appropriate, based on the LD50. There is no information in the scientific published literature which calculates a mean LD50 and standard deviation for caffeine administered orally to rats, using studies performed under good laboratory practice (GLP) or equivalent. This report does that and should be useful to manufacturers, packagers, transporters and regulators of this material. Using data from studies that are reproducible and reliable, the most accurate estimate of the acute LD50 of caffeine administered orally in male albino rats is hereby reported to be 367/mg/kg.

Evaluation of 4-methylimidazole, in the Ames/Salmonella test using induced rodent liver and lung S9.

4-methylimidazole (4-MeI) is formed by the interaction of ammonia with reducing sugars and low levels have been identified as a by-product in coffee, soy sauce, wine, dark beers, soft drinks, and caramel colors. The 4-MeI has been reported to induce alveolar/bronchiolar tumors in mice but not rats. Its mechanism of action is unlikely to be due to genotoxicity as 4-MeI does not induce mutation in Salmonella typhimurium and does not induce micronuclei in rodent peripheral erythrocytes or bone marrow cells. However, the question of whether genetically reactive intermediates could be formed via lung-specific metabolism has not previously been addressed. The 4-MeI was tested for its ability to induce mutation in five standard Ames strains of S. typhimurium using induced rat (F344/N) and mouse (B6C3F1) liver and lung S9 as a source of exogenous metabolism. The chemicals were tested in an OECD 471-compliant bacterial reverse mutation assay, using both plate-incorporation and pre-incubation methodologies, together with 10% S-9 metabolic activation. No induction of mutation (as measured by an increase in revertant colonies) was observed and it was concluded that 4-MeI was not mutagenic in S. typhimurium using either rodent liver or lung S9 for exogenous metabolism.

Day case hemithyroidectomy is safe and feasible: experience in Scotland.

BACKGROUND AND AIMS: We aimed to analyse the safety and feasibility of day case hemithyroidectomy. METHODS AND RESULTS: We reviewed all hemithyroidectomies led by two surgeons across two sites between 2010 and the end of 2013. Patients were divided into 'planned inpatient' or 'planned day case'. RESULTS: Day of discharge, conversion to inpatient procedure, intraoperative and postoperative complications and postoperative presentations or readmission to hospital were analysed. Age, gender, American Society of Anaesthesiologists score and indication for surgery were also recorded. One-hundred and eighty hemithyroidectomy cases were analysed, 35 (19.5%) were planned as inpatient procedures. Of the remaining 145 (80.5%) planned day case: 106 (73.1%) were successfully discharged on the same day and 39 (26.9%) were not; 11 (7.6%) were converted to inpatient procedures perioperatively; 8 (5.5%) had additional procedures; 6 (4.1%) had wound infections; 7 (4.8%) presented to ER; 1 (0.7%) of which required readmission to hospital for a reason unrelated to the surgery. None had laryngeal nerve palsy, compressive haematoma or symptomatic hypocalcaemia. CONCLUSION: This study showed that hemithyroidectomy by experienced surgeons can be performed safely as a day surgery. No 'planned day case patients' in this study developed laryngeal nerve palsy, compressive haematoma or symptomatic hypocalcaemia.

Patient self-assessment of nasal fractures and self-referral to an ear, nose, and throat department: a prospective study.

OBJECTIVE: To assess if patients can safely self-assess their need for ear, nose, and throat (ENT) review following initial emergency department attendance for nasal trauma. STUDY DESIGN: This prospective study was divided into 2 parts. The initial part evaluated an information sheet for patients to lead them through a self-assessment to establish if they require ENT review following nasal injury. The second part of the study investigated outcomes following the introduction of the self-assessment. SETTING: This work was conducted at a District General Hospital in Scotland. SUBJECTS AND METHODS: Forty-nine consecutive patients underwent self-assessment plus blinded otolaryngology assessment, after which self-assessment was introduced as routine. This was evaluated comparing outcomes of 49 new consecutive nasal injuries against the original group using subjective patient scores of nasal cosmesis and nasal airway following injury and any subsequent treatment. RESULTS: There was no significant difference in outcome between the 2 study periods. After the introduction of self-assessment, there was a large reduction in the nonattendance rate for nasal injuries and in the attendances of patients with nasal injuries not requiring manipulation. CONCLUSION: In our institution, patients can be relied on to safely self-assess their nasal injuries to decide if they need ENT review when provided with appropriate information. This reduces the outpatient burden on the ENT department with no deterioration in subjective patient outcomes.

Chemical carcinogenesis studies in nonhuman primates.

This review covers chemical carcinogenesis studies in nonhuman primates performed by the National Cancer Institute, USA, to provide hitherto unavailable information on their susceptibility to compounds producing carcinogenic effects in rodents. From autopsy records of 401 breeders and untreated controls, incidences of spontaneous malignant tumors were found to be relatively low in cynomolgus (1.9%) and rhesus monkeys (3.8%), but higher in African green monkeys (8%). Various chemical compounds, and in particular 6 antineoplastic agents, 13 food-related compounds including additives and contaminants, 1 pesticide, 5 N-nitroso compounds, 3 heterocyclic amines, and 7 "classical" rodent carcinogens, were tested during the 34 years period, generally at doses 10 approximately 40 times the estimated human exposure. Results were inconclusive in many cases but unequivocal carcinogenicity was demonstrated for IQ, procarbazine, methylnitrosourea and diethylnitrosamine. Furthermore, negative findings for saccharine and cyclamate were in line with results in other species. Thus susceptibility to carcinogens is at least partly shared by nonhuman primates and rodents.

Juvenile nasopharyngeal angiofibroma: spontaneous resolution.

Juvenile nasopharyngeal angiofibroma is a rare, benign tumor that occurs most often in adolescent males. Common practice is to excise the tumor with open or endoscopic surgery. We report the case of a 17-year-old male who presented in 1995 with a mass filling the left posterior nasal cavity. A diagnosis of juvenile nasopharyngeal angiofibroma was obtained with computed tomography and magnetic resonance imaging. The patient elected to have no treatment. On annual scans, the lesion changed little until 1998, when it began to gradually decrease in size. Although it is not well proven, the natural history of these tumors seems to be regression over time. This case supports the argument that a policy of watchful waiting with regular imaging studies may postpone or eliminate the need for surgery and its attendant risks.

Is the nasal tampon a suitable treatment for epistaxis in Accident & Emergency? A comparison of outcomes for ENT and A&E packed patients.

This retrospective observational study aimed to establish the outcome for patients packed with a nasal tampon as first-line therapy for epistaxis in Accident & Emergency compared to those packed by ENT. During our study period, 189 admissions were treated with a nasal tampon as first-line therapy; 89 were inserted by ENT and 100 by A&E. A significantly higher number of patients packed by A&E required further treatment to control bleeding (p = 0.004; 95 per cent CI 7-34) than those in the group packed by ENT. A significantly greater proportion from the A&E group required additional cautery alone to control bleeding (p = 0.005; 95 per cent CI 5-30). We suggest that this may be due to inadequate initial assessment and inappropriate first-line therapy in the A&E department. It is recommended that ENT review patients prior to packing, in order to reduce the morbidity associated with multiple treatments.