Progressive genomic alterations in intraductal papillary mucinous tumours of the pancreas and morphologically similar lesions of the pancreatic ducts

Intraductal papillary mucinous tumours (IPMTs) of the pancreas are rare neoplasms characterized by a prominent intraductal component, and by malignant potential. Little data exists concerning numerical chromosome aberrations in IPMTs. The biological significance of mucinous epithelial changes (mucinous hyperplasia) in small branching ducts adjacent to IPMTs also remains unclear. From a series of 12 IPMTs, we investigated by interphase cytogenetics 22 foci with mucinous hyperplasia, 27 foci with borderline lesions, and 11 samples with either intraductal (CIS) or invasive carcinoma. Chromosome 6 loss was detected in areas with mucinous hyperplasia (36.3%), borderline lesions (96.3%), and CIS/invasive carcinoma (100%). Similar losses, indicating clonal progression, were found for chromosome 17 (18.2%, 81.5%, and 100%), and for chromosome 18 (0%, 18.5%, and 100%). Quantitative analysis showed a significant intraductal expansion of cell clones harbouring these numerical aberrations within the spectrum of IPMTs. Mucinous epithelial changes in 11 resection samples with chronic pancreatitis showed monosomy 6 (36%) and monosomy 17 (27%). Conversely, areas with low-grade pancreatic intraepithelial neoplasia (PanIN-1), obtained from eight surgical specimens with ductal adenocarcinoma, showed monosomies for chromosome 6, 17, and 18 (100%, 87%, and 50%, respectively). We conclude that monosomies, as defined by FISH analysis, are frequent in both IPMTs and mucinous hyperplasia of pancreatic ducts adjacent to IPMTs. Monosomy 6 may represent an early event in the stepwise accumulation of genomic mutations necessary for the neoplastic transformation of pancreatic duct epithelia, whereas loss of chromosome 18 may be implicated in the progression of borderline to malignant IPMT. The detection of complex chromosomal aberrations in mucinous epithelial changes, and the quantitative expansion of monosomic cell clones in pancreatic ducts, provide evidence for a continuum between hyperplastic and dysplastic epithelial changes.     

“I just need to know they are going to do what they say they’re going to do with my mom.” Understanding hospice expectations from the patient,caregiver and admission nurse perspective

Objective

The objective of this paper is to understand patient, caregiver and hospice admission nurses needs during the hospice admission conversation so patients and their caregivers can make informed decisions about hospice.

Donor Experiences of Second Marrow or Peripheral Blood Stem Cell Collection Mirror the First,but CD34+ Yields Are Less

Little is known about the experiences of individuals donating peripheral blood stem cells (PBSCs) or marrow for a second time. To study this, unrelated donors making a second donation through the National Marrow Donor Program between 2004 and 2013 were evaluated. Experiences of second-time donors giving marrow (n?=?118: first donation was PBSC in 76 and marrow in 42) were compared with those making only 1 marrow donation (n?=?5829). Experiences of second-time donors giving PBSCs (n?=?602) (first donation was PBSCs in 362; marrow in 240) were compared to first-time PBSC donors (n?=?16,095). For donors giving a second PBSC or marrow donation there were no significant differences in maximum skeletal pain, maximum symptoms measured by an established modified toxicity criteria, and recovery time compared with those who donated only once. Notably, the yield of marrow nucleated cells and PBSC CD34⁺ cells with second donations was less. As previously noted with single first-time donations, female (PBSCs and marrow) and obese donors (PBSCs) had higher skeletal pain and/or toxicity with a second donation. PBSC donors who experienced high levels of pain or toxicity with the first donation also experienced high levels of these symptoms with their second donation and slower recovery times. In conclusion, for most donors second donation experiences were similar to first donation experiences, but CD34⁺ yields were less. Knowledge of the donor's first experience and stem cell yields may help centers decide whether second donations are appropriate and institute measures to improve donor experiences.     

The iron chelator deferasirox synergises with chemotherapy to treat triple‐negative breast cancers

To ensure their high proliferation rate, tumor cells have an iron metabolic disorder causing them to have increased iron needs, making them more susceptible to iron deprivation. This vulnerability could be a therapeutic target. In breast cancers, the development of new therapeutic approaches is urgently needed for patients with triple‐negative tumors, which frequently relapse after chemotherapy and suffer from a lack of targeted therapies. In this study, we demonstrated that deferasirox (DFX) synergises with standard chemotherapeutic agents such as doxorubicin, cisplatin and carboplatin to inhibit cell proliferation and induce apoptosis and autophagy in triple‐negative breast cancer (TNBC) cells. Moreover, the combination of DFX with doxorubicin and cyclophosphamide delayed recurrences in breast cancer patient‐derived xenografts without increasing the side‐effects of chemotherapies alone or altering the global iron storage of mice. Antitumor synergy of DFX and doxorubicin seems to involve downregulation of the phosphoinositide 3‐kinase and nuclear factor‐κB pathways. Iron deprivation in combination with chemotherapy could thus help to improve the effectiveness of chemotherapy in TNBC patients without increasing toxicity. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Unusual association of a unique CAG interruption in 5′ of DM1 CTG repeats with intergenerational contractions and low somatic mosaicism

Myotonic dystrophy type 1 (DM1) is a dominant multisystemic disorder associated with high variability of symptoms and anticipation. DM1 is caused by an unstable CTG repeat expansion that usually increases in successive generations and tissues. DM1 family pedigrees have shown that ～90% and 10% of transmissions result in expansions and contractions of the CTG repeat, respectively. To date, the mechanisms of CTG repeat contraction remain poorly documented in DM1. In this report, we identified two new DM1 families with apparent contractions and no worsening of DM1 symptoms in two and three successive maternal transmissions. A new and unique CAG interruption was found in 5′ of the CTG expansion in one family, whereas multiple 5′ CCG interruptions were detected in the second family. We showed that these interruptions are associated with maternal intergenerational contractions and low somatic mosaicism in blood. By specific triplet‐prime PCR, we observed that CTG repeat changes (contractions/expansions) occur preferentially in 3′ of the interruptions for both families.     

Delivery devices for exposure of biological cells to nanosecond pulsed electric fields

In this paper, delivery devices for nanosecond pulsed electric field exposure of biological samples in direct contact with electrodes or isolated are presented and characterized. They are based on a modified electroporation cuvette and two transverse electromagnetic cells (TEM cells). The devices were used to apply pulses with high intensity (4.5 kV) and short durations (3 and 13 ns). The delivery devices were electromagnetically characterized in the frequency and time domains. Field intensities of around 5, 0.5, and 12 MV m^?1 were obtained by numerical simulations of the biological sample positioned in the three delivery devices. Two delivery systems had a homogenous electric field spatial distribution, and one was adapted to permit a highly localized exposure in the vicinity of a needle. Experimental biological investigations were carried out at different field intensities for five cancer cell lines. The results using flow cytometry showed that cells kept polarized mitochondrial membrane but lost plasma membrane integrity following a dose–response trend after exposure to different electric field intensities. Certain cell types (U87, MCF7) showed higher sensitivities to nsPEFs than other lines tested.     

Enterprise-wide Implementation of Digital Radiography in Oral and Maxillofacial Imaging: The University of Florida Dentistry System

The implementation of digital radiography in dentistry in a large healthcare enterprise setting is discussed. A distinct need for a dedicated dental picture archiving and communication systems (PACS) exists for seamless integration of different vendor products across the system. Complex issues are contended with as each clinical department migrated to a digital environment with unique needs and workflow patterns. The University of Florida has had a dental PACS installed over 2 years ago. This paper describes the process of conversion from film-based imaging from the planning stages through clinical implementation. Dentistry poses many unique challenges as it strives to achieve better integration with systems primarily designed for imaging; however, the technical requirements for high-resolution image capture in dentistry far exceed those in medicine, as most routine dental diagnostic tasks are challenging. The significance of specification, evaluation, vendor selection, installation, trial runs, training, and phased clinical implementation is emphasized.