Evaluation of the management of Hr-HPV+/PapTest- women. Results at 1-year recall

With cervical cancer screening the choice of 1-year as a period of follow-up in positive high-risk HPV women without cytological lesions is still under discussion. We evaluated the management of these women and the role of HPV genotyping test. We did a cervical cancer screening study of women aged 35-64 with primary high-risk HPV test. Women positive for high-risk HPV with negative cytology were followed-up after 1 year. In this study we selected women with high-risk HPV+/PapTest- resulted high-risk HPV+ at recall and performed the PapTest and HPV genotyping test. The detection rate of squamous high grade (CIN2+) relative to the total screened cohort was 2.1‰, and it was 0.2‰ at the 1-year recall. The colposcopy performed in women referred at the 1-year recall accounted for 48.8% of the total (baseline + 1-year recall), and 84.3% of these women had no cytological lesions. The most frequent hr-HPV genotype detected was HPV16 and 66.7% of co-infections were due to HPV16 and HPV18. 54.5% of women presented a persistent infection at 1-year recall with the same HPV subtype, 50% of persistent infections was due to HPV16 and 16.7% of these were determined to be CIN2+ histological lesions. Our data show that it may be useful to extend the period of follow-up for women hr-HPV+/PapTest- so as to reduce the number of unnecessary colposcopies due to the transitory infections and that the genotyping test could help to identify the persistent infections in which HPV16 is involved

Joint and individual analysis of breast cancer histologic images and genomic covariates

A key challenge in modern data analysis is understanding connections between complex and differing modalities of data. For example, two of the main approaches to the study of breast cancer are histopathology (analyzing visual characteristics of tumors) and genetics. While histopathology is the gold standard for diagnostics and there have been many recent breakthroughs in genetics, there is little overlap between these two fields. We aim to bridge this gap by developing methods based on Angle-based Joint and Individual Variation Explained (AJIVE) to directly explore similarities and differences between these two modalities. Our approach exploits Convolutional Neural Networks (CNNs) as a powerful, automatic method for image feature extraction to address some of the challenges presented by statistical analysis of histopathology image data. CNNs raise issues of interpretability that we address by developing novel methods to explore visual modes of variation captured by statistical algorithms (e.g. PCA or AJIVE) applied to CNN features. Our results provide many interpretable connections and contrasts between histopathology and genetics

Metabolic Profiling of IDH Mutation and Malignant Progression in Infiltrating Glioma.

Infiltrating low grade gliomas (LGGs) are heterogeneous in their behavior and the strategies used for clinical management are highly variable. A key factor in clinical decision-making is that patients with mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/2) oncogenes are more likely to have a favorable outcome and be sensitive to treatment. Because of their relatively long overall median survival, more aggressive treatments are typically reserved for patients that have undergone malignant progression (MP) to an anaplastic glioma or secondary glioblastoma (GBM). In the current study, ex vivo metabolic profiles of image-guided tissue samples obtained from patients with newly diagnosed and recurrent LGG were investigated using proton high-resolution magic angle spinning spectroscopy (1H HR-MAS). Distinct spectral profiles were observed for lesions with IDH-mutated genotypes, between astrocytoma and oligodendroglioma histologies, as well as for tumors that had undergone MP. Levels of 2-hydroxyglutarate (2HG) were correlated with increased mitotic activity, axonal disruption, vascular neoplasia, and with several brain metabolites including the choline species, glutamate, glutathione, and GABA. The information obtained in this study may be used to develop strategies for in vivo characterization of infiltrative glioma, in order to improve disease stratification and to assist in monitoring response to therapy

E-cadherin expression is associated with somatostatin analogue response in acromegaly

Acromegaly is a rare disease resulting from hypersecretion of growth hormone (GH) and insulin‐like growth factor 1 (IGF1) typically caused by pituitary adenomas, which is associated with increased mortality and morbidity. Somatostatin analogues (SSAs) represent the primary medical therapy for acromegaly and are currently used as first‐line treatment or as second‐line therapy after unsuccessful pituitary surgery. However, a considerable proportion of patients do not adequately respond to SSAs treatment, and therefore, there is an urgent need to identify biomarkers predictors of response to SSAs. The aim of this study was to examine E‐cadherin expression by immunohistochemistry in fifty‐five GH‐producing pituitary tumours and determine the potential association with response to SSAs as well as other clinical and histopathological features. Acromegaly patients with tumours expressing low E‐cadherin levels exhibit a worse response to SSAs. E‐cadherin levels are associated with GH‐producing tumour histological subtypes. Our results indicate that the immunohistochemical detection of E‐cadherin might be useful in categorizing acromegaly patients based on the response to SSAs.ISCIII‐Subdirección General de Evaluación y Fomento de la Investigación PI13/02043 PI16/00175FEDER PI13/02043 PI16/00175Junta de Andalucía A‐0023‐2015 A‐0003‐2016 CTS‐1406 BIO‐0139Andalusian Ministry of Health C‐0015‐2014CIBERobn PI13/ 02043 PI16/0017

Survival prediction in mesothelioma using a scalable lasso regression model: instructions for use and initial performance using clinical predictors

Introduction: Accurate prognostication is difficult in malignant pleural mesothelioma (MPM). We developed a set of robust computational models to quantify the prognostic value of routinely available clinical data, which form the basis of published MPM prognostic models. Methods: Data regarding 269 patients with MPM were allocated to balanced training (n=169) and validation sets (n=100). Prognostic signatures (minimal length best performing multivariate trained models) were generated by least absolute shrinkage and selection operator regression for overall survival (OS), OS <6 months and OS <12 months. OS prediction was quantified using Somers DXY statistic, which varies from 0 to 1, with increasing concordance between observed and predicted outcomes. 6-month survival and 12-month survival were described by area under the curve (AUC) scores. Results: Median OS was 270 (IQR 140–450) days. The primary OS model assigned high weights to four predictors: age, performance status, white cell count and serum albumin, and after cross-validation performed significantly better than would be expected by chance (mean DXY0.332 (±0.019)). However, validation set DXY was only 0.221 (0.0935–0.346), equating to a 22% improvement in survival prediction than would be expected by chance. The 6-month and 12-month OS signatures included the same four predictors, in addition to epithelioid histology plus platelets and epithelioid histology plus C-reactive protein (mean AUC 0.758 (±0.022) and 0.737 (±0.012), respectively). The <6-month OS model demonstrated 74% sensitivity and 68% specificity. The <12-month OS model demonstrated 63% sensitivity and 79% specificity. Model content and performance were generally comparable with previous studies. Conclusions: The prognostic value of the basic clinical information contained in these, and previously published models, is fundamentally of limited value in accurately predicting MPM prognosis. The methods described are suitable for expansion using emerging predictors, including tumour genomics and volumetric staging

Borderline Ovarian Malignancies : A Single Institute Retrospective Study.

Background: Borderline ovarian tumors are histologically characterized as epithelial tumors with a stratified growth pattern but without destructive stromal invasion. Little is known about the histological subtypes and outcome, role of fertility sparing surgery and role of postoperative therapy in advanced stage in Indian scenario. While there is ample data in the world literature about this disease, prognosis in Indian patients is largely unknown due to dearth of studies in our setting. Objective: To study the demographic profile, clinical features, imaging, treatment and outcome of borderline ovarian tumors. Methods: This is a retrospective study of eighty seven patients with pathologically proven diagnosis of borderline ovarian tumor, diagnosed and treated from January 2006 to October 2011 at our institution. Most patients underwent surgical staging which incuded total abdominal hysterectomy and bilateral salphingo-oophorectomy, infracolic omentectomy, bilateral pelvic and para aortic lymphadenectomy. Young patients who had not completed their family underwent fertility sparing surgery. Patients with invasive metastatic implants received adjuvant chemotherapy. The outcome of these patients was correlated with stage, type of peritoneal implant, type of surgical procedure and with histological subtype. Results: At a median follow-up of 48 months, 100 percent survival was noted. One patient with stage III disease had recurrence. Conclusions: Borderline ovarian tumors occur at a younger age compared to invasive tumors. In patients with early stage disease who wish to preserve fertility, hysterectomy and contralateral oophorectomy are not necessary. Serous tumors occur at a younger age. They can be associated with invasive peritoneal implants and raised CA125 values. Majority of the serous tumors are bilateral and smaller in size compared to mucinous and endometroid tumors. Raised CA125 values did not correlate with the stage of disease. These patients have an excellent prognosis even in Indian scenario where majority of patients present with big ovarian masses

Warty carcinoma of uterine cervix - review of the literature and case report

Introduction. The Histological Classification of Epithelial Tumors of the Uterine Cervix of the World Health Organization includes inter alia warty carcinoma as a variant of squamous cell carcinoma. Until now several case reports and studies have shown that this particular cancer is associated with human papillomavirus/ HPV infection. Case presentation. A 58-year-old woman presented with a vegetant cervical tumour. Biopsy samples were collected from the tumour, and the histological exam successively confirmed the warty cell carcinoma. Additional tests revealed the presence of single human papillomavirus/ type-45. An immunohistochemistry exam was performed in order to confirm the diagnosis, and also to highlight the relationship between the potential causal factors and the morphological appearance. This allowed the confirmation of the diagnosis, and added new elements able to define the characteristics of this form of cancer. The treatment included radiotherapy and radical hysterectomy with anexectomy, and pelvic lymphadenectomy. The evolution was favorable, with no signs of local recurrence or metastasis in the past five years. Conclusions. Warty carcinoma, relatively similar to condyloma acuminatum or verrucous carcinomas, has specific immune-histochemical features that differentiate it from other variants of squamous cell carcinoma. The HPV genotype 45 can be considered a causative factor in the pathogenesis of cervical warty carcinoma. Even so, warty carcinoma appears not to be caused by a specific HPV subtype (or a combination of several specific genotypes), being rather a multifactorial affection