Ipsilateral Vestibular Schwannoma after Cochlear Implantation.

OBJECTIVE: The vestibular schwannoma incidence rate is approximately 4.2 per 100,000/year. Thus far, about 700,000 cochlear implantations have been performed worldwide; therefore, the occurrence of vestibular schwannoma postcochlear implantations can be assumed to be infrequent. Recent developments allow safe observation and surveillance of the implanted-side internal auditory canal (IAC) and cochlea by magnetic resonance imaging (MRI), even after cochlear implantation. Patients. A 71-year-old woman with sudden hearing loss and a contralateral vestibular schwannoma without clinical and genetic signs of neurofibromatosis type II. Intervention(s). Ipsilateral cochlear implantation and contralateral vestibular schwannoma extirpation with regular tumor follow-up. Main Outcome Measure(s). Comparison of ipsilateral pre and postcochlear implantation 3T MRI T1 GAD. RESULTS: We observed a tumor growing at the fundus of the internal auditory canal 1 year after cochlear implantation on the ipsilateral side. Although first detected after cochlear implantation beside a known vestibular schwannoma on the contralateral side, a scan slice thickness of 2 mm cannot fully exclude the preoperative persistence of a small tumor. Based on the clinical findings and after genetic exclusion of NFII, the patient was classified as a NFII mosaic type. CONCLUSION: Even after cochlear implantation, tumors in the IAC causing vertigo, facial palsy, and affecting the audiologic outcome can be detected by MRI. The MRI slice thickness used before cochlear implantation should be under 2 mm.

Malignant Transformation of Temporal Bone Schneiderian Papilloma Associated with HPV-6.

INTRODUCTION: Temporal bone Schneiderian papillomas (TBSPs) rarely present as a primary tumors arising from the middle ear and mastoid process. The clinical findings and imaging of TBSPs are not specific. Therefore, diagnosis can only reliably be definitively established by histopathology. OBJECTIVE: To report a novel case of a malignant transformation of TBSP associated with HPV-6 and to present its management. Case Report. A 68-year-old woman presented with conductive hearing loss and recurrent right-sided otorrhoea. Initially, we performed a lateral temporal bone resection and obliteration with abdomen fat. Early histology described TBSP associated with HPV-6. Follow-up detected malignant transformation of the Schneiderian papillomatous variant. Postoperative radiotherapy combined with extended temporal bone resection resulted in a disease-free 17-month period of follow-up. Discussion. TBSPs are not very specific, and the diagnosis can only reliably be established by histopathology. There is a risk of malignant transformation, and due to the absence of reliable prognostic markers, strict postoperative follow-up is mandatory and should consist of regular otoscopy, nasal endoscopy, and imaging. This case also supports the importance of extended temporal bone resections as salvage surgery, combining radical surgery with radiotherapy for improved survival rates.

Skin cancers in skin types IV-VI: Does the Fitzpatrick scale give a false sense of security?

The Fitzpatrick scale has been in use for skin colour typing according to the tanning potential of skin since its inception in 1975-1976. Thomas Fitzpatrick developed the scale to classify persons with 'white skin' in order to select the correct amount of UVA in Joules/cm2 for PUVA treatment for psoriasis. Since then, it has been widely used in Dermatology to gauge the skin's reaction to UV exposure, tanning potential, assessment of sunburn risk and amount of sun protection required for individual patients. However, the use of this scale has been of limited utility because of different self-perception in different areas of the world, particularly among those with skin of colour. Skin cancer risk is loosely inversely correlated with the initial genetic/inherent amount of melanin (most research has focused on eumelanin) present in the skin, although the pattern of exposure and amount of UV radiation required causing DNA damage varies widely according to different cancers. In this review, we have shown that the Fitzpatrick scale is neither correct nor adequate to reflect sunburn and tanning risk for skin of colour. Therefore, it may give both patients and physicians a false sense of security that there is little risk that people of colour can develop skin cancers. We have reviewed the small but not insignificant risk of skin of colour developing skin cancers and emphasise that there remains much research that needs to be done in this field.

Covid-19 dermatoses: Acral vesicular pattern evolving into bullous pemphigoid.

Bullous pemphigoid (BP) appears to be rising in incidence across the Western World, especially in the elderly. Some of the pathogenetic mechanisms involving antigen mimicry and antibody cross-reactivity have been elucidated for cases associated with neurological disease and certain drugs. There have been reports of cutaneous manifestations of Covid-19 (SARS-Cov2 infection) as the pandemic has raged across the world. We report here a case of prolonged Covid-19, symptomatic with dermatoses only, which was seen to evolve initially from a maculo-papular exanthema with acral vesicular dermatitis, into classical BP disease. This was confirmed histologically by positive skin autoantibody serology, direct IMF on peri-lesional skin and also salt-split IMF. Although possible that the development of BP could be a purely co-incidental finding during Covid-19, we suggest that it is more likely that prolonged SARS-Cov2 infection triggered an autoimmune response to the basement membrane antigens, BP 180 and 230. To our knowledge, this is the first case of BP developing during concurrent Covid-19 disease. It will be necessary to continue dermatological surveillance as the pandemic continues, to collate data on BP incidence and to test these patients for Covid-19 disease. As the pandemic continues, even potential and rare associations such as this will be clarified eventually. What's already known about this topic? Covid-19 disease has been associated with a spectrum of dermatosesCommon presentations in up to 20% of patients include exanthema, pseudo-chilblain like acral lesions 'Covid toes', livedo-/retiform purpuric/necrotic vascular lesions, acute urticarial lesions, and vesicular/varicella-like lesionsA multi-system inflammatory syndrome in children akin to Kawasaki syndrome has been described What does this study add? To our knowledge, this is the first description of classic Bullous Pemphigoid evolving from vesicular lesions caused by prolonged SARS-Cov2 induced skin inflammation.

Merkel Cell Carcinoma: rising incidence in the East of England.

BACKGROUND: Merkel Cell Carcinoma (MCC) is an infrequent but highly aggressive skin cancer. Five-year survival rates are poor, as there are high rates of metastases at primary diagnoses. Recurrences are also common. There is controversy about actual incidence rates which vary considerably between developed countries with majority populations of fair skin types. OBJECTIVES: We report the age-standardized incidence rates of MCC for both males and females from the East of England, and use linear regression analyses to estimate numbers of cases for 2020 and 2025 to aid healthcare planning and allocation of resources. METHODS: All cases of MCC diagnosed histopathologically between 1st January 2004 and 31st December 2013 were extracted from the databases of the Eastern Office, National Cancer Registration Service, Public Health England, and the Pathology department of the Norfolk and Norwich University Hospital, which serves as the tertiary referral centre for the region. Age-standardization incidence rate calculations (ASIs) and linear regression analyses were performed. RESULTS: The ASIs for males and females were 0.70 and 1.08 per 100 000 person-years respectively. The total age-adjusted incidence rate was therefore 1.78 per 100 000 person-years. The ratio of female: male disease was 3:2. The total number of cases for this region over the time period studied was 73. There has been a threefold increase over this period. Estimated cases for this region are 17 in 2020, and 22 in 2025. Estimated UK cases for 2020 are 920, and 1134 in 2025. CONCLUSIONS: MCC is increasing steadily in the East of England, and has risen threefold over the last 10 years and is similar to the highest reported rates from Western Australia. These data are 12-fold higher than previous UK estimates, and suggest that the incidence rate is also rising in other regions of the UK.

High resolution anoscopy may be useful in achieving reductions in anal cancer local disease failure rates.

Anal cancer is uncommon, with an incidence rate of 0.5-1.0 per 100,000 of the population but incidence rates have been steadily increasing over the last 3 decades. Biological and epidemiological evidence have been mounting and demonstrate that anal cancer has many similarities to cervical cancer, especially in regard to its aetiology. High-resolution anoscopy (HRA) of the anal region ­ analogous to colposcopy of the cervix, is a technique that is not well-known in the medical and surgical fraternity. Evidence to support the use of HRA for detection and treatment in the surveillance of AIN exists and strongly suggests that it is beneficial, resulting in reduced rates of cancer progression. Pilot data from our study showed a local disease failure rate of 1.73 per 1000 patient-months compared with a published rate of 9.89 per 1000 patient-months. This demonstrates a 5.72-fold reduction in local disease failure rates of patients with T1-T3 tumours; the data therefore suggests that use of HRA for detection and treatment in surveillance of anal cancer patients will help prevent local regional relapse at the anal site. There is an urgent need for a large, randomised controlled clinical trial to definitively test this hypothesis.

Evidence for a causal association for HPV in head and neck cancers.

Current data have now attributed a viral etiology and causality of Human papillomavirus (HPV). Epidemiological analysis of the last decade demonstrates a rapid increase of HPV-associated HNSCC. Genomic detection of HPV DNA in the nuclei of certain oro-pharyngeal cancer cells gives strong evidence of a viral etiology in HNSCC. Non-smokers, non-drinkers, and a sexual debut at a younger age and other sexual risk factors have an increased risk of HPV-positive oropharyngeal cancer. Sexual transmission is considered to play a causal role. In contrast to HPV-negative HNSCC most studies reveal a favorable prognosis for HPV-positive tumors. There is evidence of alterations in the p53 pathway through expression of E6 oncogene with subsequent induction of tumor cell proliferation. Synergies between viral oncogenes and other carcinogens are hypothesized. HPV alone appears to be insufficient as the sole cause of HNSCC; this may explain the long latency period between HPV infection and cancer development. There is now sufficient evidence for a causal role for HPV in HNSCC. As in cervical cancer, HPV requires oncogenes and co-factors for tumor development. Thus, inhibition or loss of such co-factors may lead to tumor regression. The vast amounts of epidemiological, molecular pathological and in vitro experimental data are consistent with the hypothesis that HPV does indeed have a causal role. We await final validation from animal experimentation in which regression of HPV-positive tumors will follow from loss or inhibition of E6 and E7.

The effects of exercise stress testing, diurnal variation and temporal decline on circulating progenitor cells.

Endothelial damage/dysfunction is involved in numerous cardiovascular disease processes. Given that the mature endothelial cells have limited capacity for self regeneration, circulating progenitor cells (CPCs) may modulate the balance between vascular damage and regeneration. The three aims of the present study were 1) to define the influence of exercise treadmill testing (ETT) on peripheral CPC levels; 2) to assess the diurnal variation of CPC counts; and 3) to investigate the rate of temporal decline in CPCs once ex vivo . The dynamics of CPC count changes following an ETT were assessed on consecutive 20 patients referred to our 'rapid-access' chest pain clinic (70% male, age 69.9 +/- 7.8) with venous blood samples taken pre-exercise, immediately post-exercise and at 30 minutes post-exercise. Diurnal variation in CPCs was assessed in 13 stable in-hospital patients (46% male, age 69.1 +/- 7.5 years) with blood samples were taken five times every 6 hours. To investigate the temporal decline, blood samples from 12 patients (58.3% male, age 69.9 +/- 7.9 years) were reprocessed for CPC counts at 4 hours and at 24 hours after sample collection. Plasma levels of von Willebrand factor (vWf) and soluble E-selectin (sE-selectin) were assessed by ELISA. CPCs were enumerated with flow cytometry as CD34+, CD133+, CD45dim events. Exercise led to significant increases in vWF and sE-selectin levels, but no significant influence on CPC counts were observed. Baseline CPC numbers demonstrated a negative correlation with vWf (r=-0.551, p=0.012) and sE-selectin levels (r=-0.494, p=0.027). CPC counts showed a significant diurnal variation, being significantly higher at 12 a.m. compared to 12 p.m. (p=0.046) and 6 p.m. (p=0.023). A 4 hour delay in sample preparation did not affect CPCs counts, but there was a significant decline in CPC recovery when sample processing was delayed by 24 hours (p<0.05). Routine exercise stress testing does not significantly affect CPC counts. Peripheral CPC levels showed a significant diurnal variation. Delays in sample preparation for CPC counts should be avoided as they may influence the accuracy of the test by resulting in a significant decline in CPC recovery. Thus, various factors may affect accuracy of CPC enumeration that may limit their role as a reliable clinical marker and biomarker of endothelial damage.

Effects of atorvastatin on circulating CD34+/CD133+/ CD45- progenitor cells and indices of angiogenesis (vascular endothelial growth factor and the angiopoietins 1 and 2) in atherosclerotic vascular disease and diabetes mellitus.

BACKGROUND: Cardiovascular disease (CVD) remains a major cause of morbidity and mortality, especially in the presence of diabetes, possibly because of endothelial damage. Increased circulating progenitor cells (CPCs) and increased plasma markers of angiogenesis [vascular endothelial growth factor (VEGF) and the angiopoietins (Ang-1 and -2)] may be evidence of this damage. Treatment with hydroxy-methyl-glutaryl (HMG-CoA) reductase inhibitors ('statins') improves outcomes in patients with vascular disease, including diabetic patients. We hypothesized that 80 mg per day atorvastatin influences CPC counts of VEGF and the angiopoietins in patients with atherosclerotic CVD with or without diabetes mellitus. METHODS: Cardiovascular disease patients with diabetes mellitus (Group A, n = 14) and nondiabetic patients with CVD only (Group B, n = 10) took atorvastatin 80 mg per day for a period of 8-10 weeks. CPCs (CD34+/CD133+/CD45-) were defined by flow cytometry, plasma levels VEGF and Ang-1 and Ang-2 by ELISA). RESULTS: Circulating progenitor cell counts increased (P < 0.001) in Group A compared with a nonsignificant change in Group B (P = 0.37). VEGF levels fell significantly in Group A (P = 0.04) but no significant change was seen in Group B (P = 0.16). Whilst Ang-1 remained unchanged (P = 0.41), Ang-2 levels increased markedly in both groups (P < 0.05). These effects were independent of LDL and total cholesterol changes but were associated with HDL changes. CONCLUSION: High-dose atorvastatin increased circulating CPCs, reduced VEGF and increased Ang-2 in patients with diabetes and CVD, providing another possible pathophysiological mechanism for the beneficial effects of statins in CVD.

Frequently asked questions about genital warts in the genitourinary medicine clinic: an update and review of recent literature.

Genital warts are the commonest viral STI in the UK, and the incidence continues to rise. Diagnosing, treating and advising patients about this infection remain a large part of the work in any department of GU Medicine. This article reviews and provides the levels of evidence currently available on data about genital warts, and is primarily to advise and guide clinicians when faced with commonly asked questions in the clinic.

Circulating endothelial cells, endothelial progenitor cells, and endothelial microparticles in cancer.

Cancer, a proliferative disease hallmarked by abnormal cell growth and spread, is largely dependent on tumor neoangiogenesis, with evidence of vascular endothelial dysfunction. Novel ways to assess vascular function in cancer include measuring levels of circulating endothelial cells (CEC). Rare in healthy individuals, increased CEC in peripheral blood reflects significant vascular damage and dysfunction. They have been documented in many human diseases, including different types of cancers. An additional circulating cell population are endothelial progenitor cells (EPC), which have the ability to form endothelial colonies in vitro and may contribute toward vasculogenesis. At present, there is great interest in evaluating the role of EPC as novel markers for tumor angiogenesis and drug therapy monitoring. Recently, exocytic procoagulant endothelial microparticles (EMP) have also been identified. CEC, EPC, and EMP research works may have important clinical implications but are often impeded by methodological issues and a lack of consensus on phenotypic identification of these cells and particles. This review aims to collate existing literature and provide an overview on the current position of CEC, EPC, and EMP in cell biology terms and to identify their significance to clinical medicine, with particular emphasis on relationship with cancer.