John Panayiotides

A simple digital image processing system to aid in melanoma diagnosis in an everyday melanocytic skin lesion unit: a preliminary report.

Background  For early melanoma diagnosis, experienced dermatologists have an accuracy of 64–80% using clinical diagnostic criteria, usually the ABCD rule, while automated melanoma diagnosis systems are still considered to be experimental and serve as adjuncts to the naked‐eye expert prediction. In an attempt to aid in early melanoma diagnosis, we developed an image processing program with the aim to discriminate melanoma from melanocytic nevi, establishing a mathematical model to come up with a melanoma probability.

Human Papillomavirus (HPV) Detection Using In Situ Hybridization in Histologic Samples Correlations With Cytologic Changes and Polymerase Chain Reaction HPV Detection

Although in situ hybridization (ISH) and polymerase chain reaction (PCR) have extensively been used on cytology specimens, there have been limited reports of the usefulness of these techniques in relation to confirmed histologic findings. In this study, we used PCR and ISH to detect human papillomavirus (HPV) in cytologic and histologic specimens, respectively. By using positive and negative likelihood ratios, we attempted to identify any predictive role of ISH testing alone or in combination with PCR for the development of high-grade histologic lesions (cervical intraepithelial neoplasia [CIN] 2+). In our study, ISH was a useful method for detection of HPV, even in a large fraction of samples with normal cytologic or biopsy findings. We suggest that when used together and evaluated in conjunction with histologic sections, ISH is a useful tool for ancillary molecular testing of HPV infection in cervical lesions, especially in CIN 2+ histological lesions where its analytic sensitivities and specificities were as good as those of PCR testing.

Carboplatin and paclitaxel in metastatic or recurrent cervical cancer.

Objectives: The purpose of this study was to evaluate the activity and toxicity of carboplatin and paclitaxel combination in advanced or recurrent carcinoma of the cervix. Methods: Fifty-one eligible patients with measurable advanced or recurrent cervical carcinoma were treated with carboplatin (area under the curve, 5) and paclitaxel 175 mg/m2 every 3 weeks for 6 to 9 cycles or until disease progression or unacceptable toxicity. Results: Eight complete (16%) and 19 partial responses (37%) occurred, for an overall response rate (RR) of 53% (95% confidence interval [CI], 39%-67%). The median progression-free survival was 6 months (95% CI, 5.4-6.5 months), and the median overall survival was 13 months (95% CI, 11.4-14.5 months). The RR was higher in patients with disease outside a previously irradiated site compared with those with disease in a previously irradiated field (68% vs 30%) (P = 0.011). Patients previously treated with chemoradiation had an RR of 28%, whereas in those previously treated with radiotherapy alone, the RR was 68% (P = 0.023). There was no statistically significant difference between histology and response to therapy. Patients with performance status of 0 or 1 had a higher RR than those with worse performance status. Toxicity was generally mild except for myelotoxicity. Neutropenia grade 3/4 was recorded in 44% of patients, and 6% experienced febrile neutropenia. Twenty-two percent of patients experienced anemia grade 3-4, whereas 14% had thrombocytopenia grade 3-4. Three patients (6%) developed grade 3 sensory neuropathy. Conclusion: The combination of carboplatin and paclitaxel seems to have activity in advanced or recurrent cervical carcinoma with an acceptable toxicity profile.

Combination chemotherapy with carboplatin, paclitaxel and pegylated liposomal doxorubicin for advanced or recurrent carcinosarcoma of the uterus: Clinical experience of a single institution

OBJECTIVES The purpose of this study was to evaluate the activity and toxicity of carboplatin, paclitaxel and pegylated liposomal doxorubicin combination in advanced or recurrent of the uterine carcinosarcoma. METHODS Twenty-nine eligible patients with measurable disease were treated with carboplatin [area under the curve (AUC) 5], paclitaxel 175 mg/m(2) and pegylated liposomal doxorubicin 25 mg/m(2) every 3 weeks for 6-8 cycles. RESULTS There were 10 complete responses (CRs) (34%) and 8 partial responses (PRs) (28%) for an overall response rate (RR) of 62% (95% confidence interval [CI], 43-81%). The median progression-free survival (PFS) was 8.2 months (95% CI, 4.1-12.2 months) and the median overall survival (OS) was 16.4 months (95% CI, 14.7-18.0 months). There was no statistically significant difference between histology and response to therapy. Patients with PS of 0 or 1 had a higher RR than those with worst PS. Toxicity was generally mild except for myelotoxicity. Neutropenia grade 3/4 was recorded in 52% of patients and 10% experienced febrile neutropenia. Anemia grade 3 or 4 developed in 27% of patients and thrombocytopenia grade 3 or 4 in 31% of patients. Three patients (10%) developed grade 3 sensory neuropathy and only 2 patients (8%) grade 3 palmar-plantar erythrodysesthesias. No treatment-related deaths were recorded in our series. CONCLUSION The combination of carboplatin, paclitaxel and pegylated liposomal doxorubicin appears to have activity in advanced, persistent or recurrent endometrial carcinosarcoma with an acceptable toxicity profile.

Cutaneous alternariosis in a patient with idiopathic pulmonary fibrosis

A 78‐year‐old farmer presented with symptomless skin lesions for evaluation. Two years prior, he had developed idiopathic pulmonary fibrosis (IPF) and had been treated thereafter with oral prednisolone 20 mg/day and occasionally with colchicine 1 mg/day.

Artificial Neural Networks as Decision Support Tools in Cytopathology: Past, Present, and Future

Objective This study aims to analyze the role of artificial neural networks (ANNs) in cytopathology. More specifically, it aims to highlight the importance of employing ANNs in existing and future applications and in identifying unexplored or poorly explored research topics. Study Design A systematic search was conducted in scientific databases for articles related to cytopathology and ANNs with respect to anatomical places of the human body where cytopathology is performed. For each anatomic system/organ, the major outcomes described in the scientific literature are presented and the most important aspects are highlighted. Results The vast majority of ANN applications are related to cervical cytopathology, specifically for the ANN-based, semiautomated commercial diagnostic system PAPNET. For cervical cytopathology, there is a plethora of studies relevant to the diagnostic accuracy; in addition, there are also efforts evaluating cost-effectiveness and applications on primary, secondary, or hybrid screening. For the rest of the anatomical sites, such as the gastrointestinal system, thyroid gland, urinary tract, and breast, there are significantly less efforts relevant to the application of ANNs. Additionally, there are still anatomical systems for which ANNs have never been applied on their cytological material. Conclusions Cytopathology is an ideal discipline to apply ANNs. In general, diagnosis is performed by experts via the light microscope. However, this approach introduces subjectivity, because this is not a universal and objective measurement process. This has resulted in the existence of a gray zone between normal and pathological cases. From the analysis of related articles, it is obvious that there is a need to perform more thorough analyses, using extensive number of cases and particularly for the nonexplored organs. Efforts to apply such systems within the laboratory test environment are required for their future uptake.

Molecular epidemiology of HPV infection using a clinical array methodology in 2952 women in Greece

The molecular epidemiology of human papillomavirus (HPV) infection in a sample of Greek women (n = 2952, mean age 42.2 ± 13.3 years) was examined. HPV prevalence was 50.7% (95% confidence interval, 48.8-52.6). The most frequent HPV types were HPV 53, 51 and 66 (10.2%, 9.4% and 9.3%, respectively). HPV positivity was associated with age, age of sexual debut, number of sexual partners and duration of sexual relationship, while marriage or multiparity protected against infection (all p <0.001). Follow-up of this cohort will assist in predicting the effect of vaccination with the new HPV vaccines on future screening with HPV-based tests for cervical cancer.

Personalised management of women with cervical abnormalities using a clinical decision support scoring system

OBJECTIVES To develop a clinical decision support scoring system (DSSS) based on artificial neural networks (ANN) for personalised management of women with cervical abnormalities. METHODS We recruited women with cervical abnormalities and healthy controls that attended for opportunistic screening between 2006 and 2014 in 3 University Hospitals. We prospectively collected detailed patient characteristics, the colposcopic impression and performed a series of biomarkers using a liquid-based cytology sample. These included HPV DNA typing, E6&E7 mRNA by NASBA or flow cytometry and p16INK4a immunostaining. We used ANNs to combine the cytology and biomarker results and develop a clinical DSSS with the aim to improve the diagnostic accuracy of tests and quantify the individuals risk for different histological diagnoses. We used histology as the gold standard. RESULTS We analysed data from 2267 women that had complete or partial dataset of clinical and molecular data during their initial or followup visits (N=3565). Accuracy parameters (sensitivity, specificity, positive and negative predictive values) were assessed for the cytological result and/or HPV status and for the DSSS. The ANN predicted with higher accuracy the chances of high-grade (CIN2+), low grade (HPV/CIN1) and normal histology than cytology with or without HPV test. The sensitivity for prediction of CIN2 or worse was 93.0%, specificity 99.2% with high positive (93.3%) and negative (99.2%) predictive values. CONCLUSIONS The DSSS based on an ANN of multilayer perceptron (MLP) type, can predict with the highest accuracy the histological diagnosis in women with abnormalities at cytology when compared with the use of tests alone. A user-friendly software based on this technology could be used to guide clinician decision making towards a more personalised care.

Rhodotorula mucilaginosa associacted meningitis: A subacute entity with high mortality. Case report and review.

A fatal case of meningitis due to Rhodotorula mucilaginosa in a 28 year-old HIV-negative male with a history of Hodgkin lymphoma who underwent salvage chemotherapy is presented. Reviewing the literature we identified 13 cases with central nervous system infection due Rhodotorula spp. The disease usually occurs in HIV negative immunosupressed middle-aged males. It takes the form of subacute or chronic meningitis accompanied by fever with an overall mortality of 46.2% despite antifungal therapy.

Post-operative Aspergillus mediastinitis in a man who was immunocompetent: a case report

IntroductionAspergillus spp. infections mainly affect patients who are immunocompromised, and are extremely rare in immunocompetent individuals.Case presentationAspergillus post-operative mediastinitis is considered to be a devastating infection, usually affecting patients undergoing cardiothoracic surgery with specific predisposing factors. We describe the case of an immunocompetent 68-year-old Caucasian man with severe chronic thromboembolic pulmonary hypertension, who underwent pulmonary thromboendarterectomy and developed post-operative mediastinitis due to Aspergillus flavus. The environmental control did not reveal the source of A. flavus infection and, despite combined antifungal therapy, our patient died as a result of septic shock and multiple organ failure.ConclusionAspergillus mediastinitis mainly affects patients after cardiosurgery operations with predisposing factors, and it is unusual in patients who are immunocompetent. The identification of the Aspergillus spp. source is often difficult, and there are no guidelines for the administration of pre-emptive therapy in this population of at-risk patients.