Comparison of ovarian crescent sign and risk of malignancy index for prediction of ovarian malignancy in adnexal masses

Background: Objective of the study was to evaluate ovarian crescent sign (OCS) as a sonographic parameter for prediction of ovarian cancer in adnexal masses suspicious of ovarian malignancy and to compare it with risk of malignancy index (RMI).Methods: Presence of OCS and calculation of RMI was done for 50 cases of adnexal masses scheduled to undergo surgery taking histopathology as gold standard.Results: 18% (9/50) of adnexal masses were malignant. OCS was absent in all malignant lesions, giving a sensitivity and negative predictive value of 100%. OCS was present in 33/41 of benign masses (specificity 80.4%). Relation of OCS to mass size<10 cm and menopausal status was significant (p<0.001). RMI≥200 could not diagnose malignancy in 4/9 cases (sensitivity 55.5%). RMI had specificity and negative predictive value of 95.1% and 90.7% respectively. Combining OCS and RMI had a lower specificity. Sequential application using OCS as first node and RMI as second node failed to diagnose 44.4% (4/9) cases as malignant.Conclusions: OCS is cheaper, easy to perform and appears to be a better test than RMI to differentiate between benign and early-stage malignant ovarian tumors. It can be used for triaging patient for referral

Visual examination and dermoscopy, alone or in combination, for the diagnosis of keratinocyte skin cancers in adults

Background Early accurate detection of all skin cancer types is important to guide appropriate management, to reduce morbidity and to improve survival. Basal cell carcinoma (BCC) is almost always a localised skin cancer with potential to infiltrate and damage surrounding tissue, whereas a minority of squamous cell carcinoma (cSCC) and invasive melanoma are higher risk skin cancers with the potential to metastasise and cause death. Dermoscopy has become an important tool to assist specialist clinicians in the diagnosis of melanoma, and is increasingly used in primary care settings. Dermoscopy is a precision-built handheld illuminated magnifier that allows more detailed examination of the skin down to the level of the superficial dermis. Establishing the value of dermoscopy over and above visual inspection for the diagnosis of BCC or cSCC in primary and secondary care settings is critical to understanding its potential contribution to appropriate skin cancer triage, including referral of higher risk cancers to secondary care, the identification of low risk skin cancers that might be treated in primary care and to provide reassurance to those with benign skin lesions who can be safely discharged. Objectives To determine the diagnostic accuracy of visual inspection and dermoscopy, alone or in combination, for the detection of a) BCC and b) cSCC, in adults. Studies were separated according to whether the diagnosis was recorded face-to-face (in-person) or based on remote (image-based) assessment. Search methods We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists and published systematic review articles. Selection criteria Studies of any design that evaluated visual inspection and/or dermoscopy in adults with lesions suspicious for skin cancer, compared with a reference standard of either histological confirmation or clinical follow-up. Data collection and analysis Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). We contacted authors of included studies where information related to the target condition or diagnostic threshold were missing. We estimated accuracy using hierarchical summary ROC methods. Analysis of studies allowing direct comparison between tests was undertaken. To facilitate interpretation of results, we computed values of sensitivity at the point on the SROC curve with 80% fixed specificity and values of specificity with 80% fixed sensitivity. We investigated the impact of in-person test interpretation; use of a purposely developed algorithm to assist diagnosis; and observer expertise. Main results A total of 24 publications reporting on 24 study cohorts were included, providing 27 visual inspection datasets (8805 lesions; 2579 malignancies) and 33 dermoscopy datasets (6855 lesions; 1444 malignancies). The risk of bias was mainly low for the index test (for dermoscopy evaluations) and reference standard domains, particularly for in-person evaluations, and high or unclear for participant selection, application of the index test for visual inspection and for participant flow and timing. Concerns regarding the applicability of study findings were scored as ‘high’ or 'unclear' concern for almost all studies across all domains assessed. Selective participant recruitment, lack of reproducibility of diagnostic thresholds and lack of detail on observer expertise were particularly problematic. The detection of BCC was reported in 28 datasets; 15 on an in-person basis and 13 image-based. Analysis of studies by prior testing of participants and according to observer expertise was not possible due to lack of data. Studies were primarily conducted in participants referred for specialist assessment of lesions with available histological classification. No clear differences in accuracy were noted between dermoscopy studies undertaken in-person and those which evaluated images. The lack of effect observed is likely due to other sources of heterogeneity, including variations in the types of skin lesion studied, in dermatoscopes used, in the use of algorithms and varying thresholds for deciding on a positive test result. Meta-analysis found in-person evaluations of dermoscopy (7 evaluations; 4683 lesions and 363 BCCs) to be more accurate than visual inspection alone for the detection of BCC (8 evaluations; 7017 lesions and 1586 BCCs), with an RDOR of 8.2 (95% CI: 3.5 to 19.3; P < 0.001). This corresponds to predicted differences in sensitivity of 14% (93% vs 79%) at a fixed specificity of 80% and predicted differences in specificity of 22% (99% vs 77%) at a fixed sensitivity of 80%. Very similar results were observed for the image-based evaluations. When applied to a hypothetical population of 1000 lesions, of which 170 are BCC (based on median BCC prevalence across studies), an increased sensitivity of 14% from dermoscopy would lead to 24 fewer BCCs missed, assuming 166 false positive results from both tests. A 22% increase in specificity from dermoscopy with sensitivity fixed at 80% would result in 183 fewer unnecessary excisions assuming 34 BCCs missed for both tests. There was not enough evidence to assess the use of algorithms or structured checklists for either visual inspection or dermoscopy. Insufficient data were available to draw conclusions on the accuracy of either test for the detection of cSCC. Authors’ conclusions Dermoscopy may be a valuable tool for the diagnosis of BCC as an adjunct to visual inspection of a suspicious skin lesion following a thorough history-taking including assessment of risk factors for keratinocyte cancer. The evidence primarily comes from secondary care (referred) populations and populations with pigmented lesions or mixed lesion types. There is no clear evidence supporting the use of currently available formal algorithms to assist dermoscopy diagnosis

Critical molecular events in early skin carcinogenesis

PhDBackground: Cutaneous squamous cell carcinoma (SCC) is the second most common cancer to affect populations of European descent. It is potentially fatal and causes substantial morbidity. Up to 70% of SCC arise from clinically identifiable precancerous lesions, known as actinic keratoses (AK), permitting early diagnosis and intervention. Keratinocyte Intra-epidermal Neoplasia (KIN) are the histological representation of AK. Immunosuppressed organ transplant recipients have 60 – 200 fold higher rates of SCC that are characteristically multiple, aggressive, recurrent and have higher metastatic tendency. The molecular pathogenesis of SCC involves the accumulation of multiple genetic and epigenetic aberrations, but in spite of the magnitude of the problem, the cellular basis for SCC has received little scientific attention compared with other epithelial cancers. Methodology: Skin samples representing sequential keratinocyte carcinogenesis (from non sun-exposed, sun-exposed and AK/KIN skin) were collected from 53 individuals (31 immunosuppressed and 22 immunocompetent), 30 of whom underwent an additional biopsy after prospective treatment with one of three commercially available topical agents. Genome-wide single nucleotide polymorphism (SNP) profiling was performed on all samples and transcriptional profiling was performed on 7 series from each treatment group. Results: The mean number of SNP changes was 3.57 and 3.48 in NSE and SE skin, respectively, increasing to 6.93 in KIN. Several recurrent areas of loss or gain were identified in KIN, specifically deletion at 3p, 9p, 12q, 16q, 18q and X and amplification of 8q, 9p and 17p. Expression profiling identified 428 genes (false discovery rate 0.05) with altered expression in KIN skin compared to paired normal skin. Of these genes, 31% displayed concordant change with regions of copy number change. Several gene networks of interest were identified including F- and -actin, NFB, PPAR and TGF suggesting that they may be key pathways in KIN evolution. Several candidate genes in KIN skin continue to be dysregulated in SCC, some of which, such as ANG, S100A9, ACVR2A, FHL1 and SFN resolve after topical chemoprevention and others, WIF1, CCL27 and LEPR persist. Conclusions: This is the first systematic, in-depth, in vivo study of molecular events characterising KIN and provides a detailed profile of the critical events contributing to malignant progression in keratinocyte neoplasia and the molecular effects of widely used topical chemopreventive agents Together, these data provide clinically relevant insights into cutaneous squamous tumour biology and identify biomarkers with diagnostic, prognostic and therapeutic potential. Acknowledgement

Chemokine Receptor CCR5 Expression in Conjunctival Epithelium of Patients With Dry Eye Syndrome

Objective To characterize chemokine receptor CCR5 expression on the conjunctival epithelium in dry eye syndromes. Methods Conjunctival impression cytology samples were obtained from normal subjects (n = 15) and patients with dry eye syndrome (n = 45). Cells were harvested from impression cytology samples, and flow cytometry was performed to quantitatively analyze the cell surface expression of chemokine receptor CCR5. Characterization of CCR5-positive cells was done by 2-color flow cytometry using fluorescein-conjugated anti-CCR5 and phycoerythrin-conjugated anti-CD45 antibodies (where CD45 is a marker for bone marrow–derived cells). To study CCR5 messenger RNA transcripts, real-time polymerase chain reaction was done on RNA isolated from the impression cytology samples of normal subjects (n = 5) and patients with dry eye syndrome (n = 14). Results We found significant up-regulation in cell surface expression of CCR5 in patients with both aqueous tear–deficient and evaporative forms of dry eye syndrome (P<.001). The real-time polymerase chain reaction results (for messenger RNA) corroborated the flow cytometry data (for protein). The majority of the cells expressing CCR5 were non–bone marrow–derived resident epithelial cells of the conjunctiva. Conclusion Our findings suggest that CCR5 up-regulation is significantly associated with dry eye syndrome–associated ocular surface disease

Chemokine receptor CCR5 expression in conjunctival epithelium of patients with dry eye syndrome

OBJECTIVE: To characterize chemokine receptor CCR5 expression on the conjunctival epithelium in dry eye syndromes. METHODS: Conjunctival impression cytology samples were obtained from normal subjects (n = 15) and patients with dry eye syndrome (n = 45). Cells were harvested from impression cytology samples, and flow cytometry was performed to quantitatively analyze the cell surface expression of chemokine receptor CCR5. Characterization of CCR5-positive cells was done by 2-color flow cytometry using fluorescein-conjugated anti-CCR5 and phycoerythrin-conjugated anti-CD45 antibodies (where CD45 is a marker for bone marrow-derived cells). To study CCR5 messenger RNA transcripts, real-time polymerase chain reaction was done on RNA isolated from the impression cytology samples of normal subjects (n = 5) and patients with dry eye syndrome (n = 14). RESULTS: We found significant up-regulation in cell surface expression of CCR5 in patients with both aqueous tear-deficient and evaporative forms of dry eye syndrome (P&lt;.001). The real-time polymerase chain reaction results (for messenger RNA) corroborated the flow cytometry data (for protein). The majority of the cells expressing CCR5 were non-bone marrow-derived resident epithelial cells of the conjunctiva. CONCLUSION: Our findings suggest that CCR5 up-regulation is significantly associated with dry eye syndrome-associated ocular surface disease. Clinical Relevance Chemokine receptor CCR5 or its ligands may serve as useful targets for modulation of tissue immunoinflammatory responses in dry eye syndromes

Thyroid peroxidase antibody positivity among euthyroid pregnant women and its association with foeto-maternal outcome

Background: Thyroid peroxidase antibody (TPO-Ab) positivity is associated with increased risk of adverse pregnancy outcomes. The present study was planned to find out the prevalence of TPO-Ab and its association with adverse foeto-maternal outcome in euthyroid pregnant women.Methods: A total of 510 euthyroid pregnant women with &lt;20 weeks gestation were recruited from antenatal clinic. Serum TPO-Ab testing was done and women were divided into 2 groups. The study group comprised of TPO-Ab positive women and control group comprised of age and parity matched TPO-Ab negative women, double in number to that of the study group. Repeat Serum TSH was done at term/delivery and women were followed till delivery for foeto-maternal outcome.Results: The prevalence of TPO-Ab positivity in euthyroid pregnant women was 11.3%. A significant number of women in the study group developed hypothyroidism at term/delivery, 18.61% vs 7.61%, respectively, p=0.02. None of the women in the study or control group developed gestational diabetes or placental abruption, or had babies with NND or RDS. There was one IUD in the study group, rest of the maternal and foetal outcomes studied were not statistically significant between two the groups. The caesarean section rates in both groups was not statistically different, however, there were more caesarean sections done for foetal distress in the study group, p=0.04.Conclusions: Thyroid peroxidase positivity is present in 11.3% of euthyroid women and is associated with an increased risk of developing hypothyroidism during pregnancy. It is not associated with adverse foeto-maternal outcome

Thyroid peroxidase antibody positivity among euthyroid pregnant women and its association with foeto-maternal outcome

Background: Thyroid peroxidase antibody (TPO-Ab) positivity is associated with increased risk of adverse pregnancy outcomes. The present study was planned to find out the prevalence of TPO-Ab and its association with adverse foeto-maternal outcome in euthyroid pregnant women.Methods: A total of 510 euthyroid pregnant women with &lt;20 weeks gestation were recruited from antenatal clinic. Serum TPO-Ab testing was done and women were divided into 2 groups. The study group comprised of TPO-Ab positive women and control group comprised of age and parity matched TPO-Ab negative women, double in number to that of the study group. Repeat Serum TSH was done at term/delivery and women were followed till delivery for foeto-maternal outcome.Results: The prevalence of TPO-Ab positivity in euthyroid pregnant women was 11.3%. A significant number of women in the study group developed hypothyroidism at term/delivery, 18.61% vs 7.61%, respectively, p=0.02. None of the women in the study or control group developed gestational diabetes or placental abruption, or had babies with NND or RDS. There was one IUD in the study group, rest of the maternal and foetal outcomes studied were not statistically significant between two the groups. The caesarean section rates in both groups was not statistically different, however, there were more caesarean sections done for foetal distress in the study group, p=0.04.Conclusions: Thyroid peroxidase positivity is present in 11.3% of euthyroid women and is associated with an increased risk of developing hypothyroidism during pregnancy. It is not associated with adverse foeto-maternal outcome