Cervical cancer is a leading cause of death in underserved areas of Brazil. This prospective randomized trial involved 200 women in southern/central Brazil with abnormal Papanicolaou tests. Participants were randomized by geographic cluster and referred for diagnostic evaluation either at a mobile van upon its scheduled visit to their local community, or at a central hospital. Participants in both arms underwent colposcopy, microscopy, and cervical biopsies. We compared rates of diagnostic follow-up completion between study arms, and also evaluated the diagnostic performance of microscopy compared with colposcopy. There was a 23% absolute and 37% relative increase in diagnostic follow-up completion rates for patients referred to the mobile van (102/117, 87%) compared with the central hospital (53/83, 64%; = 0.0001; risk ratio = 1.37, 95% CI, 1.14-1.63). In 229 cervical sites in 144 patients, colposcopic examination identified sites diagnosed as cervical intraepithelial neoplasia grade 2 or more severe (CIN2+; 85 sites) with a sensitivity of 94% (95% CI, 87%-98%) and specificity of 50% (95% CI, 42%-58%). microscopy with real-time automated image analysis identified CIN2+ with a sensitivity of 92% (95% CI, 84%-97%) and specificity of 48% (95% CI, 40%-56%). Women referred to the mobile van were more likely to complete their diagnostic follow-up compared with those referred to a central hospital, without compromise in clinical care. microscopy in a mobile van provides automated diagnostic imaging with sensitivity and specificity similar to colposcopy..
Background: Pilomatrixoma (OMIM ID #132600) is a benign cutaneous tumor originating from the pilosebaceous follicle and characterized by the presence of subcutaneous nodules of up to 3.0 cm in diameter, usually on the head, neck and upper extremities. It is most common in the first two decades of life and after the age of 60.Main observations: An adult female patient was evaluated, presenting a solid tumoral lesion with erythematous surface and purplish tone, with approximately 7.5 x 5.0 cm in size, in the interscapulovertebral region. It was thought to be an epidermoid cyst, sarcoma, calcified hemangioma, giant dermatofibroma, or nodular basal cell carcinoma. The resection of the lesion was carried out and, at the histological examination, specific details were observed that led to the diagnosis of pilomatrixoma. Conclusion:Pilomatrixoma should be suspected in the differential diagnosis of giant adnexal tumors. (J Dermatol Case Rep. 2013; 7(2): 56-59) An unusual presentation of giant pilomatrixoma in an adult patient IntroductionPilomatrixoma (PM; OMIM ID #132600) was first described in 1880 by Malherbe and Chenatais as a "calcified epithelioma of Malherbe" originated from sebaceous glands. In 1961, Forbis and Helwig demonstrated that the tumor originated from the hair matrix; therefore, the name pilomatrixoma. 1-3 PM is the most common hair-follicle tumor and it accounts for one of every 500 specimens submitted by dermatologists. 4 Clinically, the lesion is a benign cutaneous tumor usually characterized by a solitary asymptomatic, firm, and skin-colored faint blue/red nodule in the deep dermis and subcutaneous tissue, with an average size of 0.5 to 3.0 cm. The lesions larger than 5.0 cm are defined as giant pilomatrixomas. Pain and tenderness may be associated symptoms. 3,5 The tumor is generally observed on the head, neck and upper extremities. 6 It is a common skin neoplasm in the pediatric population, but it may be found in all age groups with bimodal peaks under the age of 30 and in the sixth/seventh decades of life. 5,6 Uncommon clinical-pathological variants of PM have been reported, such as bullous like, anetodermic, exophytic, perforating/ulcerated and lymphagiectatic. Multiple and familial cases have been described in association with myotonic dystrophy, Turner's syndrome, Gardner's syndrome, xeroderma pigmentosum, basal cell nevus syndrome and Sotos syndrome. 6,7 The present paper reports an unusual and uncommon case of pilomatrixoma on the back of an adult female patient. Case ReportA 54-year-old female patient sought the medical specialties outpatient service at School of Medical Sciences at Universidade de Marília (UNIMAR) complaining about a back injury three years ago, with progressive growth and sporadic local pain. The patient had undergone a surgery for the removal of the lesion in another hospital two and a half years before, but there was local recurrence 3 months after surgery. Krausen et al. 9 described the first case of giant PM (GPM), few similar lesions were described 5 a...
We conducted a prospective evaluation of the diagnostic performance of high-resolution microendoscopy (HRME) to detect cervical intraepithelial neoplasia (CIN) in women with abnormal screening tests. Study participants underwent colposcopy, HRME and cervical biopsy. The prospective diagnostic performance of HRME using an automated morphologic image analysis algorithm was compared to that of colposcopy using histopathologic detection of CIN as the gold standard. To assess the potential to further improve performance of HRME image analysis, we also conducted a retrospective analysis assessing performance of a multi-task convolutional neural network to segment and classify HRME images. One thousand four hundred eighty-six subjects completed the study; 435 (29%) subjects had CIN Grade 2 or more severe (CIN2+) diagnosis. HRME with morphologic image analysis for detection of CIN Grade 3 or more severe diagnoses (CIN3+) was similarly sensitive (95.6% vs 96.2%, P = .81) and specific (56.6% vs 58.7%, P = .18) as colposcopy. HRME with morphologic image analysis for detection of CIN2+ was slightly less sensitive (91.7% vs 95.6%, P < .01) and specific (59.7% vs 63.4%, P = .02) than colposcopy. Images from 870 subjects were used to train a multi-task convolutional neural network-based algorithm and images from the remaining 616 were used to validate its performance. There were no significant differences in the sensitivity and specificity of HRME with neural network analysis vs colposcopy for detection of CIN2+ or CIN3+.Using a neural network-based algorithm, HRME has comparable sensitivity and specificity to colposcopy for detection of CIN2+. HRME could provide a low-cost, point-of-care alternative to colposcopy and biopsy in the prevention of cervical cancer.
Cervical cancer is the fourth most common cancer in women. Although cure rates are high for early stage disease, clinical outcomes for advanced, metastatic, or recurrent disease remain poor. To change this panorama, a deeper understanding of cervical cancer biology and novel study models are needed. Immortalized human cancer cell lines such as HeLa constitute crucial scientific tools, but there are few other cervical cancer cell lines available, limiting our understanding of a disease known for its molecular heterogeneity. This study aimed to establish novel cervical cancer cell lines derived from Brazilian patients. We successfully established one (HCB-514) out of 35 cervical tumors biopsied. We confirmed the phenotype of HCB-514 by verifying its’ epithelial and tumor origin through cytokeratins, EpCAM and p16 staining. It was also HPV-16 positive. Whole-exome sequencing (WES) showed relevant somatic mutations in several genes including BRCA2, TGFBR1 and IRX2. A copy number variation (CNV) analysis by nanostring and WES revealed amplification of genes mainly related to kinases proteins involved in proliferation, migration and cell differentiation, such as EGFR, PIK3CA, and MAPK7. Overexpression of EGFR was confirmed by phospho RTK-array and validated by western blot analysis. Furthermore, the HCB-514 cell line was sensitive to cisplatin. In summary, this novel Brazilian cervical cancer cell line exhibits relevant key molecular features and constitutes a new biological model for pre-clinical studies.
Nearly 90% of cervical cancer cases and deaths occur in low- and middle-income countries that lack comprehensive national HPV immunization and cervical cancer screening programs. In these settings, it is difficult to implement screening programs due to a lack of infrastructure and shortage of trained personnel. Screening programs based on visual inspection with acetic acid (VIA) have been successfully implemented in some low-resource settings. However, VIA has poor specificity and up to 90% of patients receiving treatment based on a positive VIA exam are over-treated. A number of studies have suggested that high-resolution cervical imaging to visualize nuclear morphology in vivo can improve specificity by better distinguishing precancerous and benign lesions. To enable high-resolution imaging in low-resource settings, we developed a portable, low-cost, high-resolution microendoscope that uses a mobile phone to detect and display images of cervical epithelium in vivo with subcellular resolution. The device was fabricated for less than $2,000 using commercially available optical components including filters, an LED and triplet lenses assembled in a 3D-printed opto-mechanical mount. We show that the mobile high-resolution microendoscope achieves similar resolution and signal-to-background ratio as previously reported high-resolution microendoscope systems using traditional cameras and computers to detect and display images. Finally, we demonstrate the ability of the mobile high-resolution microendoscope to image normal and precancerous squamous epithelium of the cervix in vivo in a gynecological referral clinic in Barretos, Brazil.
BackgroundEndometrial cancer presents well-defined risk factors: myometrial invasion, histological subtype, tumor grade, lymphovascular space invasion (LVSI). Some low and intermediate-risk endometrioid endometrial cancer patients exhibited unexpected outcomes. This study aimed to investigate other clinical-pathological factors that might influence the recurrence rates of patients diagnosed with low and intermediate-risk endometrioid endometrial cancer.MethodsA case-control study from a cohort retrospective of 196 patients diagnosed with low and intermediate-risk endometrioid endometrial cancer at a single institution from 2009 to 2014 was conducted. Medical records were reviewed to compare clinical (race, smoking, menopause age, body mass index) and pathological (endometrioid vs endometrioid with squamous differentiation, tumor differentiation grade, tumor location, endocervical invasion, LVSI) features of patients with recurrence (case) and without recurrence (control) of disease. Three controls for each case were matched for age and staging.ResultsTwenty-one patients with recurrence were found (10.7%), of which 14 were stage IA, and 7 were stage IB. In accordance, 63 patients without recurrence were selected as controls. There were no significant differences in any clinical characteristics between cases and controls. Among pathological variables, presence of squamous differentiation (28.6% vs. 4.8%, p = 0.007), tumor differentiation grade 2 or 3 (57.1% vs. 30.2%, p = 0.037) and presence of endocervical invasion (28.6% vs. 12.7%, p = 0.103) were associated with disease recurrence on a univariate analysis. On multivariable analysis, only squamous differentiation was a significant risk factor for recurrence (p = 0.031).ConclusionOur data suggest that squamous differentiation may be an adverse prognostic factor in patients with low and intermediate-risk endometrioid endometrial cancer, that showed a 5.6-fold increased risk for recurrence.
BackgroundThe molecular profile of endometrial cancer has become an important tool in determining patient prognosis and their optimal adjuvant treatment. In addition to The Cancer Genome Atlas (TCGA), simpler tools have been developed, such as the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE). We attempted to determine a genetic signature to build a recurrence risk score in patients diagnosed with low- and intermediate-risk endometrial cancer.MethodsA case-control study was conducted. The eligible patients were women diagnosed with recurrence low- and intermediate-risk endometrial cancer between January 2009 and December 2014 at a single institution; the recurrence patients were matched to two nonrecurrence patients with the same diagnosis by age and surgical staging. Following RNA isolation of 51 cases, 17 recurrence and 34 nonrecurrence patients, the expression profile was determined using the nCounter® PanCancer Pathways Panel, which contains 770 genes.ResultsThe expression profile was successfully characterized in 49/51 (96.1%) cases. We identified 12 genes differentially expressed between the recurrence and nonrecurrence groups. The ROC curve for each gene was generated, and all had AUCs higher than 0.7. After backward stepwise logistic regression, four genes were highlighted: FN1, DUSP4, LEF1, and SMAD9. The recurrence risk score was calculated, leading to a ROC curve of the 4-gene model with an AUC of 0.93, sensitivity of 100%, and specificity of 72.7%.ConclusionWe identified a four-gene signature that may be associated with recurrence in patients with low- and intermediate-risk endometrial cancer. This finding suggests a new prognostic factor in this poorly explored group of patients with endometrial cancer.
29 Background: 30 Endometrial cancer presents well-defined risk factors (myometrial invasion, 31 histological subtype, tumor grade, lymphovascular space invasion (LVSI)). Some 32 low and intermediate-risk endometrioid endometrial cancer patients exhibited 33 unexpected outcomes. The aim of this study was to investigate other clinical-34 pathological factors that might influence the recurrence rates of patients diagnosed 35 with low and intermediate-risk endometrioid endometrial cancer. 36 Methods: 37 A case-control study from a cohort retrospective of 196 patients diagnosed with 38 low and intermediate-risk endometrioid endometrial cancer at a single institution 39 between 2009 and 2014 was conducted. Medical records were reviewed to 40 compare clinical (race, smoking, menopause age, body mass index) and 41 pathological (histological characteristics (endometrioid vs endometrioid with 42 squamous differentiation), tumor differentiation grade, tumor location, endocervical 43 invasion, LVSI) features of patients with recurrence (case) and without recurrence 44 (control) of disease. Three controls for each case were matched for age and 45 staging.46 Results:47 Twenty-one patients with recurrence were found (10.7%), of which 14 were stage 48 IA, and 7 were stage IB. In accordance, 63 patients without recurrence were 49 selected as controls. There were no significant differences in any clinical 50 characteristics between cases and controls. Among pathological variables, 3 51 presence of squamous differentiation (28.6% vs. 4.8%, p=0.007), tumor 52 differentiation grade 2 or 3 (57.1% vs. 30.2%, p=0.037) and presence of 53 endocervical invasion (28.6% vs. 12.7%, p=0.103) were associated with disease 54 recurrence on univariate analysis. On multivariable analysis, only squamous 55 differentiation was a significant risk factor for recurrence (p=0.031). Conclusion:57 Our data suggest that squamous differentiation may be an adverse prognostic 58 factor in patients with low and intermediate-risk endometrioid endometrial cancer, 59 that showed a 5.6-fold increased risk for recurrence. 60 Keywords: Low and intermediate-risk endometrioid endometrial carcinoma, 61 prognostic factors, squamous differentiation
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