Common features between neoplastic and preneoplastic lesions of the biliary tract and the pancreas

The bile duct system and pancreas show many similarities due to their anatomical proximity and common embryological origin. Consequently, preneoplastic and neoplastic lesions of the bile duct and pancreas share analogies in terms of molecular, histological and pathophysiological features. Intraepithelial neoplasms are reported in biliary tract, as biliary intraepithelial neoplasm (BilIN), and in pancreas, as pancreatic intraepithelial neoplasm (PanIN). Both can evolve to invasive carcinomas, respectively cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (PDAC). Intraductal papillary neoplasms arise in biliary tract and pancreas. Intraductal papillary neoplasm of the biliary tract (IPNB) share common histologic and phenotypic features such as pancreatobiliary, gastric, intestinal and oncocytic types, and biological behavior with the pancreatic counterpart, the intraductal papillary mucinous neoplasm of the pancreas (IPMN). All these neoplastic lesions exhibit similar immunohistochemical phenotypes, suggesting a common carcinogenic process. Indeed, CCA and PDAC display similar clinic-pathological features as growth pattern, poor response to conventional chemotherapy and radiotherapy and, as a consequence, an unfavorable prognosis. The objective of this review is to discuss similarities and differences between the neoplastic lesions of the pancreas and biliary tract with potential implications on a common origin from similar stem/progenitor cells

Blastic plasmacytoid dendritic cell neoplasm: Genomics mark epigenetic dysregulation as a primary therapeutic target

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy for which there is still no effective B therapy. In order to identify genetic alterations useful for a new treatment design, we used whole-exome sequencing to analyze 14 BPDCN patients and the patient-derived CAL-1 cell line. The functional enrichment analysis of mutational data reported the epigenetic regulatory program to be the most significantly undermined (P<0.0001). In particular, twenty-five epigenetic modifiers were found mutated (e.g. ASXL1, TET2, SUZ12, ARID1A, PHF2, CHD8); ASXL1 was the most frequently affected (28.6% of cases). To evaluate the impact of the identified epigenetic mutations at the gene-expression and Histone H3 lysine 27 trimethylation/acetylation levels, we performed additional RNA and pathology tissue-chromatin immunoprecipitation sequencing experiments. The patients displayed enrichment in gene signatures regulated by methylation and modifiable by decitabine administration, shared common H3K27-acetylated regions, and had a set of cell-cycle genes aberrantly up-regulated and marked by promoter acetylation. Collectively, the integration of sequencing data showed the potential of a therapy based on epigenetic agents. Through the adoption of a preclinical BPDCN mouse model, established by CAL-1 cell line xenografting, we demonstrated the efficacy of the combination of the epigenetic drugs 5’-azacytidine and decitabine in controlling disease progression in vivo

Evaluating Modelling Approaches for Medical Image Annotations

Information system designers face many challenges with regards to selecting appropriate semantic technologies and deciding on a modeling approach for their system. However, there is no clear methodology yet to evaluate “semantically enriched” information systems. In this paper we present a case study on different modeling approaches for annotating medical images and introduce a conceptual framework that can be used to analyze the fitness of information systems and help designers to spot the strengths and weaknesses of various modeling approaches as well as managing trade-offs between modeling effort and their potential benefits

Cancer mortality in Portugal

Following Population News, Trends and Attitudes #6 it was possible to identify that, despite circulatory system diseases represent the leading causes of death (COD) in Portugal, the share of deaths caused by neoplasms is increasing with time. Analysing data from 10th International Classification of Diseases available at Statistics Portugal (INE), one can observe that since 2010 mortality associated to neoplasms is the major COD for males. In 2015, males presented almost twice the number of deaths caused by neoplasms when compared to females: 356.0 against 169.9 per 100.000 individuals

Odontoameloblastoma with extensive chondroid matrix deposition in a guinea pig

Odontoameloblastomas (previously incorporated within ameloblastic odontomas) are matrix-producing odontogenic mixed tumors and are closely related in histologic appearance to the 2 other types of matrix-producing odontogenic mixed tumors: odontomas and ameloblastic fibro-odontomas. The presence or absence of intralesional, induced non-neoplastic tissue must be accounted for in the diagnosis. Herein we describe a naturally occurring odontoameloblastoma with extensive chondroid cementum deposition in a guinea pig (Cavia porcellus). Microscopically, the mass featured palisading neoplastic odontogenic epithelium closely apposed to ribbons and rings of a pink dental matrix (dentinoid), alongside extensive sheets and aggregates of chondroid cementum. The final diagnosis was an odontoameloblastoma given the abundance of odontogenic epithelium in association with dentinoid but a paucity of pulp ectomesenchyme. Chondroid cementum is an expected anatomical feature of cavies, and its presence within the odontoameloblastoma was interpreted as a response of the ectomesenchyme of the dental follicle to the described neoplasm. Our case illustrates the inductive capabilities of odontoameloblastomas while highlighting species-specific anatomy that has resulted in a histologic appearance unique to cavies and provides imaging and histologic data to aid diagnosis of these challenging lesions

Cancers of unknown primary diagnosed during hospitalization: a population-based study

Background: Cancers of Unknown Primary (CUP) are the 3-4th most common causes of cancer death and recent clinical guidelines recommend that patients should be directed to a team dedicated to their care. Our aim was to inform the care of patients diagnosed with CUP during hospital admission. Methods: Descriptive study using hospital admissions (Scottish Morbidity Record 01) linked to cancer registrations (ICD-10 C77-80) and death records from 1998 to 2011 in West of Scotland, UK (population 2.4 m). Cox proportional hazards models were used to assess effects of baseline variables on survival. Results: Seven thousand five hundred ninety nine patients were diagnosed with CUP over the study period, 54.4% female, 67.4% aged ≥ 70 years, 36.7% from the most deprived socio-economic quintile. 71% of all diagnoses were made during a hospital admission, among which 88.6% were emergency presentations and the majority (56.3%) were admitted to general medicine. Median length of stay was 15 days and median survival after admission 33 days. Non-specific morphology, emergency admission, age over 60 years, male sex and admission to geriatric medicine were all associated with poorer survival in adjusted analysis. Conclusions: Patients with a diagnosis of CUP are usually diagnosed during unplanned hospital admissions and have very poor survival. To ensure that patients with CUP are quickly identified and directed to optimal care, increased surveillance and rapid referral pathways will be required