Optimal surveillance strategies for patients with stage 1 cutaneous melanoma post primary tumour excision: three systematic reviews and an economic model.

BACKGROUND: Malignant melanoma is the fifth most common cancer in the UK, with rates continuing to rise, resulting in considerable burden to patients and the NHS. OBJECTIVES: The objectives were to evaluate the effectiveness and cost-effectiveness of current and alternative follow-up strategies for stage IA and IB melanoma. REVIEW METHODS: Three systematic reviews were conducted. (1) The effectiveness of surveillance strategies. Outcomes were detection of new primaries, recurrences, metastases and survival. Risk of bias was assessed using the Cochrane Collaboration's Risk-of-Bias 2.0 tool. (2) Prediction models to stratify by risk of recurrence, metastases and survival. Model performance was assessed by study-reported measures of discrimination (e.g. D-statistic, Harrel's c-statistic), calibration (e.g. the Hosmer-Lemeshow 'goodness-of-fit' test) or overall performance (e.g. Brier score, R2). Risk of bias was assessed using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). (3) Diagnostic test accuracy of fine-needle biopsy and ultrasonography. Outcomes were detection of new primaries, recurrences, metastases and overall survival. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Review data and data from elsewhere were used to model the cost-effectiveness of alternative surveillance strategies and the value of further research. RESULTS: (1) The surveillance review included one randomised controlled trial. There was no evidence of a difference in new primary or recurrence detected (risk ratio 0.75, 95% confidence interval 0.43 to 1.31). Risk of bias was considered to be of some concern. Certainty of the evidence was low. (2) Eleven risk prediction models were identified. Discrimination measures were reported for six models, with the area under the operating curve ranging from 0.59 to 0.88. Three models reported calibration measures, with coefficients of ≥ 0.88. Overall performance was reported by two models. In one, the Brier score was slightly better than the American Joint Committee on Cancer scheme score. The other reported an R2 of 0.47 (95% confidence interval 0.45 to 0.49). All studies were judged to have a high risk of bias. (3) The diagnostic test accuracy review identified two studies. One study considered fine-needle biopsy and the other considered ultrasonography. The sensitivity and specificity for fine-needle biopsy were 0.94 (95% confidence interval 0.90 to 0.97) and 0.95 (95% confidence interval 0.90 to 0.97), respectively. For ultrasonography, sensitivity and specificity were 1.00 (95% confidence interval 0.03 to 1.00) and 0.99 (95% confidence interval 0.96 to 0.99), respectively. For the reference standards and flow and timing domains, the risk of bias was rated as being high for both studies. The cost-effectiveness results suggest that, over a lifetime, less intensive surveillance than recommended by the National Institute for Health and Care Excellence might be worthwhile. There was considerable uncertainty. Improving the diagnostic performance of cancer nurse specialists and introducing a risk prediction tool could be promising. Further research on transition probabilities between different stages of melanoma and on improving diagnostic accuracy would be of most value. LIMITATIONS: Overall, few data of limited quality were available, and these related to earlier versions of the American Joint Committee on Cancer staging. Consequently, there was considerable uncertainty in the economic evaluation. CONCLUSIONS: Despite adoption of rigorous methods, too few data are available to justify changes to the National Institute for Health and Care Excellence recommendations on surveillance. However, alternative strategies warrant further research, specifically on improving estimates of incidence, progression of recurrent disease; diagnostic accuracy and health-related quality of life; developing and evaluating risk stratification tools; and understanding patient preferences. STUDY REGISTRATION: This study is registered as PROSPERO CRD42018086784. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol 25, No. 64. See the NIHR Journals Library website for further project information.

Malignant melanoma is the deadliest of skin cancers; in the UK, > 2500 people die from it every year. Initially, the cancer is removed surgically, which cures it for most people, but, for some, the cancer returns. For this reason, after a melanoma is removed, patients are followed up to see if the melanoma reoccurs or if new melanomas have developed. It is felt that early cancer detection improves the chance of future treatment working. A key question is how best to follow up patients after initial melanoma surgery. This study concentrates on the earliest stage of melanoma (American Joint Committee on Cancer stage I), which accounts for more than 7 out of 10 of all melanoma diagnoses. The study also investigates if new ways of follow-up could be at least as good as current practice and a better use of NHS money. We systematically reviewed studies comparing different ways of organising follow-up, and then methods to identify those patients at high risk of developing a further melanoma and how good different tests are at detecting this cancer. We then compared different possible follow-up strategies. For each strategy, we considered its impact on quality and length of life, and how well it used NHS resources. We found little evidence to support a change in how follow-up should be organised currently. There were some ways of organising follow-up that might be better than current care, but further research is needed. We found that new research on whether or not follow-up should be performed by a cancer nurse specialist, rather than a dermatologist or surgeon, would be worthwhile. We also found that more research could be worthwhile on how frequently melanoma recurs and spreads, as well as how accurately a diagnosis of further cancer is made and how to identify those most at risk of further melanoma spread.

Lacrimal scintigraphy BNMS Guidelines.

PURPOSE: The purpose of this guideline is to assist specialists in Nuclear Medicine and Radionuclide Radiology in recommending, performing, interpreting and reporting the results of lacrimal scintigraphy (also known as Dacroscintigraphy). This guideline will assist individual departments to formulate their own local protocols. This does not aim to be prescriptive regarding technical aspects of individual camera acquisitions, which need to be developed in conjunction with the local experts in medical physics. There are numerous radiological techniques to assess the physiology of the lacrimal system. This guideline will describe the application of a drop of radiotracer into each eye and consecutive imaging to demonstrate the level of impaired drainage, with the possibility of quantifying such impairment. This guideline is a recent and updated version of a previously published guideline on the British Nuclear Medicine Society website in 2018 [1].

Current status of tropical theileriosis in Northern Africa: A review of recent epidemiological investigations and implications for control.

Tropical theileriosis caused by the apicomplexan hemoparasite Theileria annulata is a tick-borne disease that constraints livestock production in parts of Europe, Asia and Africa. Four Hyalomma tick species transmit T. annulata in at least eight Africa countries (Mauritania, Morocco, Algeria, Tunisia, Egypt, Sudan, South Sudan and Ethiopia). The two dominant T. annulata vector ticks present in Africa, H. scupense and H. anatolicum, underlie two different patterns of transmission, which in turn greatly influence the epidemiology of tropical theileriosis. H. dromedarii and H. lusitanicum are also capable of transmitting T. annulata in North Africa, but their roles are associated with specific production systems and agro-ecological contexts. The emergence of resistance to the most widely used theilericidal compound, buparvaquone, continues to limit the effectiveness of chemotherapy. In addition, acaricide use is increasingly becoming unsustainable. Deployable T. annulata attenuated live vaccines established from local strains in Tunisia, Sudan and Egypt are available, and recent work has indicated that these vaccines can be protective under conditions of natural transmission. However, vaccination programmes may vary over space and time due to differences in the prevalence of disease amongst cattle populations, as well seasonal variation in vector activity. We review recent descriptive and analytical surveys on the epidemiology of T. annulata infection with reference to (a) demographic aspects such as breeds and ages of cattle herds previously exposed to distinct T. annulata infection pressures and (b) seasonal dynamics of tick activity and disease transmission. We then discuss how the wider endemic patterns that we delineate can underpin the development and execution of future vaccination programmes. We also outline options for integrated control measures targeting tick vectors and husbandry practices.

Quantitative Computed Tomography (QCT) of the Distal Forearm in Men Using a Spiral Whole-Body CT Scanner - Description of a Method and Reliability Assessment of the QCT Pro Software.

The Mr F study investigates the pathogenesis of low trauma distal forearm fractures in men and includes volumetric bone mineral density (vBMD) measurements at the ultradistal forearm as there are no current data. A standard 64 slice CT scanner was used to determine if it was possible to adapt the existing Mindways quantitative computed tomography Pro software for measuring vBMD values at the hip and spine sites. For calculation of intra- and interobserver reliability 40 forearm scans out of the 300 available were chosen randomly. The images were analyzed using the Slice Pick module and Bone Investigational Toolkit. The 4% length of the radius was chosen by measuring the length of the radius from the scaphoid fossa distally to the radial head. The acquired image then underwent extraction, isolation, rotation, and selection of region of interest in order to generate a report on vBMD. A cross-sectional image was created to allow the generation of data on the cortical and trabecular components separately. Repeat analyses were undertaken by 3 independent observers who were blinded as to whether the image was from a participant with or without fracture. The images were presented in random order at each time point. The following parameters were recorded: cortical cross sectional area, total vBMD, trabecular vBMD, and cortical vBMD (CvBMD). Data were analyzed by calculating intraclass correlation coefficients for intra- and interobserver reliability. The lowest values occurred at the CvBMD with intraobserver reliability of 0.92 (95% confidence interval [CI] of 0.86-0.96) and interobserver reliability of 0.92 (95% CI 0.89-0.96). All other parameters had reliability values between 0.97 and 0.99 with tighter 95% CI than for CvBMD. The method of adapting the Mindways Pro software using a standard CT to produce vBMD and structural data at the ultradistal radius is reliable.

Assessment of normal reference values for thyroid uptake of technetium-99m pertechnetate in a single centre UK population.

OBJECTIVE: This study aims to explore the normal reference values for thyroid uptake of technetium-99m (Tc) pertechnetate in a UK population. PATIENTS AND METHODS: A retrospective review of 60 euthyroid patients who underwent thyroid imaging with Tc pertechnetate between January 2012 to April 2014 as part of dual-tracer subtraction parathyroid scintigraphy. Tc pertechnetate thyroid uptake values were determined for each patient. Medical records and biochemical thyroid function tests were reviewed to ensure that all patients were not on medication that could affect thyroid function and they were both clinically and biochemically euthyroid 6 months before and following the scan. RESULTS: Median and interquartile uptake range of Tc pertechnetate in euthyroid patients were 0.9 and 0.5-1.4%, respectively. The normal reference range in the study population was 0.2-2.0%. Thyroid uptake inversely correlated with age in females (r=-0.40, P=0.04), males (r=-0.50, P=0.04), and whole group (r=-0.40, P=0.002). CONCLUSION: The calculated normal reference range in this study was found to be less than that used in our own and many other UK institutions. The results demonstrate the importance of periodic evaluation of normal uptake values and provide support for prospective studies defining the normal reference range to be performed.

99m-Technetium Sestamibi Uptake in a Gastric Schwannoma.

We report the case of a 74-year-old woman with primary hyperparathyroidism who underwent 99m-technetium-sestamibi single photon emission computed tomography-computed tomography for preoperative localization of parathyroid adenoma. Unexpected focal sestamibi uptake was observed at a 5 cm submucosal tumor arising from the greater curve of the stomach. The patient underwent partial gastrectomy and the histological and immunohistochemical findings were consistent with the diagnosis of gastric schwannoma.

Molecular Detection of Rickettsia africae in Amblyomma variegatum Collected from Sudan.

Despite the increasing awareness of the importance of emerging vector-borne diseases, human tick-borne diseases, particularly rickettsial infections, are overlooked, especially in the countries such as Sudan with limited resources to perform molecular-based surveys. This study aimed at detection and genetic characterization of Rickettsia spp. in ticks collected from Sudan. The samples were first screened for the presence of rickettsial agents by gltA real-time PCR and subsequently characterized by gltA and ompA PCR and size-based multispacer typing. The results demonstrated the wide distribution of Rickettsia africae and/or closely related species across Sudan. The results of this report highlight the need for careful consideration of rickettsial infections in patients with nonmalarial febrile illness in this country. Nationwide surveillance on ticks associated with human rickettsial infections in Sudan is warranted.

Looking outside the "cardiac" box: incidental detection of a metastatic lung tumor on cardiac position emission tomography/computed tomography.

Incidental extracardiac findings are not uncommon in patients undergoing cardiac positron emission tomography/computed tomography (PET/CT) and some of these findings can have significant clinical impact. We report a case of a 74-year-old man who presented with dyspnea and left sided chest pain. 82-rubidium PET/CT imaging showed normal myocardial perfusion. Review of the low dose CT scan performed for attenuation correction purposes (CTAC) incidentally revealed a 4 cm mass in the left lung, which was histologically shown to be a squamous cell carcinoma. A subsequent staging CT showed chest wall metastases and rib destruction in the upper left thorax, which were outside the image reconstruction field of view of the CTAC. This report illustrates the importance of vigilant review of all acquired images by the PET/CT reader to look for extracardiac abnormalities that may explain symptoms in the absence of coronary artery disease. It also raises the question as to whether a larger field of CT image acquisition should be routinely performed to scan the entire chest during cardiac PET/CT imaging. However, the latter needs to be weighed against the increase in patient dose, which we estimated to be an additional 15%.

Attenuation correction of myocardial perfusion SPET in patients of normal body mass index.

Soft tissue attenuation artefacts are more likely to occur in patients with high body mass index (BMI) undergoing myocardial perfusion imaging (MPI) and therefore it is routine practice in our department to perform attenuation correction in this group of patients. However, we suspected that attenuation artefacts may also occur in patients with normal BMI. We collected data prospectively on 57 patients with BMI less than 25kg/m(2) who underwent stress-rest MPI single photon emission tomography (SPET) as part of their standard management at our institution. The differences between the attenuation corrected (AC) and non attenuation corrected (NC) images were evaluated by two experienced readers blinded to patient gender and clinical details. Visual improvement in perfusion with attenuation correction was seen in 54.4% of patients with normal BMI and was more common in males (84.2%) than females (39.5%). Discordances between AC and NC were most frequent in the inferior, inferolateral and anteroseptal segments in both males and females and were also seen in the apical and anterior segments in some patients, mainly in females, in keeping with the well-recognized distribution pattern for attenuation artefacts. In conclusion, although a small sample size was used in this study, changes in appearance with attenuation correction likely to represent attenuation artefacts were seen in 54.4% of patients with normal BMI and were two times more common in males than females. These changes were felt to be clinically relevant in that they could lead to a change in the final report and may ultimately affect the diagnosis and clinical management. Thus, attenuation correction could be of value in patients of normal BMI. Further larger studies with correlation with clinical follow-up or invasive coronary angiography are warranted.

Unilateral adrenal metastasis from non­small-cell lung cancer demonstrating very high FDG uptake with a standardized uptake value in excess of sixty.

We report the case of a 52-year-old man who presented with a 2-week history of dyspnea and wheeze. CT scan of the chest showed a large soft-tissue lesion in the right main bronchus extending into the trachea. Pathologic examination of endoscopic tracheal biopsies showed features consistent with a non­small-cell lung carcinoma. 18F-FDG PET/CT showed very high uptake of FDG in the bronchial tumor (high standardized uptake values: 25.1) and unexpected very intense uptake in the left adrenal gland (high standardized uptake values: 62.5). Laparoscopic adrenalectomy was performed, and subsequent histopathological examination confirmed metastatic non­small-cell carcinoma in the adrenal gland. Although adrenal malignancies are generally metabolically active, such high uptake of FDG within a metastatic lesion has not been reported previously.

Heterotopic ossification of the hips in a patient with Guillain Barre syndrome demonstrated on SPECT/CT.

A 55-year-old man developed bilateral hip pain following admission with Guillain Barre syndrome. Hip radiographs showed minor degenerative changes. 99mTc-methylene diphosphonate bone scintigraphy showed bilateral abnormal activity extending from the acetabula to the trochanteric regions. SPECT/CT localized the abnormal activity to the soft tissues surrounding the hips. Heterotopic ossification is a rare complication of Guillain Barre syndrome.

Drop off rhythm and survival periods of Amblyomma lepidum (Acari: Ixodidae) under field conditions.

In this study, engorged Amblyomma lepidum ticks were found to drop off in two peaks, one in the morning and one in the evening. Most larvae and females engorged during the morning hours between 06.00 h and 10.00 h with a peak around 08.00 h, whereas the majority of the nymphs dropped in the evening between 18.00 h and 24.00 h with the peak around 22.00 h. Although the effect of time on drop-off patterns of the ticks was statistically significant (p< or = 0.001), there were no significant seasonal influences. Survival of unfed stages of A. lepidum was also studied and was found to increase from larvae to adult ticks. The longest survival periods of 10, 11 and 14 weeks were recorded during the wet season for larvae, nymphs and adults, respectively. It is concluded that environmental conditions required for survival of A. lepidum are optimal only during the wet season and that during other seasons the tick depends primarily on prevailing micro-climatic conditions for its survival.

Spotted fever group rickettsiae from ticks captured in Sudan.

Ticks were collected from ruminants in various areas of Sudan in 1998 and 2000. Primer pairs of rickettsial citrate synthase gene (gltA) and a spotted fever group (SFG) rickettsial 190-kDa surface antigen gene (rompA), respectively, were used for identification. Polymerase chain reaction (PCR)-positive products were used for DNA sequencing. The gltA gene was detected in 55% of the ticks examined (57/104). Among the 57 ticks studied, 19 were positive for the rompA gene. Thus, 18% of the ticks examined were found to be infected with SFG rickettsiae. The nucleotide sequences of the amplified rompA gene fragment of Hyalomma spp. and Amblyomma spp. were similar to those of Rickettsia aeschlimannii and Rickettsia africae, respectively. In this study, we succeeded in detecting the SFG rickettsiae gene in ticks, and established that there were at least two species of SFG rickettsiae in field ticks in Sudan.