Saturday, October 22, 2016
(MRI/chemobrain) Brain structure and function in patients with ovarian cancer treated with first-line chemotherapy
Brain structure and function in patients with ovarian cancer treated with first-line chemotherapy: a pilot study (2015)
Women with ovarian cancer often undergo chemotherapy involving multiple agents. However, little is known about treatment-related central neurotoxicity in this population. The goal of this cross-sectional study was to assess brain structure and function and neurocognitive abilities in patients with ovarian cancer following first-line chemotherapy. Eighteen patients with ovarian, peritoneal and fallopian tube cancer and eighteen healthy controls matched for gender, age and education participated in the study. The patients were evaluated 1–4 months following completion of first-line taxane/platinum chemotherapy. All participants underwent structural and functional magnetic resonance imaging (MRI), and completed neuropsychological tests of attention, memory and executive functions. Neuroimaging assessments included voxel-based morphometry (VBM) for measuring gray matter (GM) volume, and functional MRI (fMRI) during the N-back working memory task. The results of VBM showed that patients had significantly reduced GM volume compared to healthy controls in the right middle/superior frontal gyrus, and in the left supramarginal gyrus and left inferior parietal lobule. fMRI results indicated significantly decreased activation in patients relative to healthy controls in the left middle frontal gyrus and left inferior parietal lobule during the N-back task (1/2/3-back >0-back). There were no statistically significant differences between the two groups on the neuropsychological tests. This is the first study showing structural and functional alterations involving frontal and parietal regions in patients with ovarian cancer treated with first-line chemotherapy. These findings are congruent with studies involving women with breast cancer, and provide additional supporting evidence for central neurotoxicity associated with taxane/platinum chemotherapy.
Lynch Syndrome UK (Press Release)
Lynch Syndrome UK | Raising awareness, Saving lives
Families saved from cancer – NICE recommend all patients with bowel cancer are tested for Lynch Syndrome
On
Friday 21st October, the National Institute for Health and Care
Excellence announced draft guidance recommending that everyone who is
diagnosed with bowel cancer should be tested for Lynch syndrome. Lynch
syndrome (LS) is a genetic condition that increases the risk of bowel
cancer and several other cancers including uterus and ovary.
Approximately
175,000 people in the UK have Lynch syndrome but 95% of them do not
know they have it. It is hoped that by checking all patients who have
bowel cancer for LS, many new families will be identified to enable them
to have screening to prevent people getting cancer. People with LS
have a 50% chance of passing on their gene mutation to each child so the
more new families that can be identified, the more help can be given to
keep such families cancer-free.
Lynch
Syndrome UK is the only UK based registered charity which provides
support and advice to people with Lynch syndrome and was part of the
NICE team that developed the draft guidance. The consultation document
from NICE is the first step that brings this very important issue to the
attention of the public. We hope that many more people will be
identified as a result of this initiative and genetic counselling will
be offered to their families.
Pauline Skarrott (retired GP) , Trustee of Lynch Syndrome UK and part of the NICE group who developed the guidance said today,
'This
draft guidance is greatly welcomed by the families who are part of
Lynch Syndrome UK. Lives will be saved and future generations
protected. One of our charity's main aims is to raise awareness of
Lynch Syndrome and we believe this guidance will go a long way in
achieving this. We will continue to support NICE and other
organisations to improve the outcomes for our families. The final
guidance will be published in January 2017.'
Contact number for media enquiries: Helen Bufton/Tracy Smith Tel: 07977 907135 /07792502125
Lynch Syndrome UK
Charity No: 116180
Parents’ Understanding of Genetics and Heritability (Canada)
abstract
Parents have the opportunity to educate their children to facilitate behaviours and lifestyle habits that may prevent or delay genetic disease, or mitigate predispositions within the family. We sought to determine parents’ understanding of genetic knowledge and heritability. Using a quantitative survey methodology 108 volunteer participants were surveyed from a convenience sample of all parents/caregivers within the waiting room of a general children’s outpatient clinic. Results indicated that average genetic knowledge levels were fairly high, with the majority of participants scoring 70–80 % correct on knowledge-based questions. Further, scores were found to be positively correlated with education, but inversely correlated with self-perceived knowledge. This finding suggests that participants with less experience tended to overestimate their knowledge. We suggest that gaps in knowledge of genetics and heritability could be improved by using educational interventions such as media campaigns, provision of informational brochures, or changes to current high school curriculum which would increase exposure to genetics and heritability for both parents and children.
Generational Expression of Muir-Torre Syndrome in a Canadian Family (and review)
open access
Muir-Torre syndrome (MTS) is a rare autosomal dominant inherited genodermatosis that is considered to be a phenotypic subtype of hereditary nonpolyposis colorectal cancer (HNPCC), commonly referred to as Lynch syndrome.~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
Genodermatoses are inherited genetic skin conditions often grouped into three categories: chromosomal, single gene, and polygenetic.
Internet based second opinion pathology in a large chemotherapy trial for ovarian cancer – results of a standardized review process
Abstract
Background: It has been suggested that specialized pathology review prior to randomization should become standard procedure in study protocols, because a considerable number of patients in clinical trials of ovarian carcinoma may have histopathological diagnoses in conflict with inclusion criteria. We hypothesized that our new, internet-based high throughput infrastructure would be capable of providing specialized second opinion pathology within 10 days.
Design: Patients scheduled for the AGO OVAR17 ovarian carcinoma chemotherapy trial were registered for expert pathologic case review prior to randomization. All original slides were requested from local pathologist, scanned and uploaded to a secured internet server. Five pathologists specialized in gynecologic pathology from Austria, Switzerland and Germany were available online. If necessary, immunohistochemistry was available through a collaborating pathology lab.
Results: 880 patients with an original diagnosis of ovarian epithelial carcinoma were registered through our internet platform for second opinion pathology review from 10/2011 – 07/2013. In 2.5% (n = 22) of cases, a major diagnostic discrepancy of potential clinical relevance was found leading to exclusion from the chemotherapy trial. Ovarian borderline tumors and ovarian metastasis were the leading discrepant diagnosis. The average time from patient registration until completion of pathology review was 5.2 days.
Conclusion: Our results show that the use of a new internet-based infrastructure makes specialized case review prior to patient randomization feasible within less than 10 working days. Our new approach might further improve quality of patient care through minimization of overtreatment, especially of patients with ovarian borderline tumors and inadequate treatment of patients with ovarian metastases.
Impact of abdominal wall metastases on prognosis in FIGO IV epithelial ovarian cancer
Abstract
Objective: Epithelial ovarian cancer (EOC) patients with the presence of abdominal wall metastasis (AWM) are categorized as stage FIGO IVB, irrespective of other biologic factors. We evaluated the impact of AWM on patients' overall survival (OS).
Patients and methods: In this exploratory study 634 consecutive patients with advanced EOC treated in our center from 2000 – 2014 were included. Patients were categorized as: FIGO IIIC (n = 308), FIGO IVB-only-AWM (n = 86), and FIGO IV-others (metastases other than AWM, n = 240). Clinico-pathological parameters and survival data were extracted from our prospectively maintained tumor registry. Survival analyses were calculated using Kaplan-Meier method and Cox regression models.
Results: The median OS in patients with stage FIGO IIIC, FIGO IVB-only-AWM, and FIGO IV-others was 37, 58, and 25 months (p < 0.001), respectively. Patients with FIGO IVB-only-AWM had a significantly better overall survival than patients with FIGO IV-others (p < 0.001). In multivariate analysis, OS of patients with FIGO IIIC did not differ to patients with FIGO IVB-only-AWM (HR 0.84, 95% CI 0.56 – 12.26, p = 0.398).
Conclusion: Prognosis of patients with AWM as the only site of distant metastasis is superior compared with other stage FIGO IV patients. Therefore, up-staging of patients only because of AWM to FIGO IVB may be questioned. A revision/clarification of the FIGO classification system should be considered to avoid unnecessary stigmatization of patients and to classify better these patients more appropriately with respect to their prognosis.
The role of the androgen receptor in ovarian cancer carcinogenesis and its clinical implications | Zhu | Oncotarget
open access
AR expression in human ovarian cancer
A large body of evidence has consistently vindicated over-expression of AR in ovarian cancers. In an early report, Hamilton et al. [18] demonstrated AR expression in ovarian cancers using ligand binding assays. Further studies showed AR expression was detected in about 90% of epithelial ovarian cancers by biochemical receptor assay [19] and 43.5-86% by immunohistochemistry. [20-23] Curiously in recent studies, AR expression has commonly been detected just as frequently as the estrogen receptor and more frequently than the progesterone receptor in ovarian cancer samples [21, 24]....
Table 2: Prognostic significance of AR and AR alleles in ovarian cancer
Increased AR expression likely predicts a favorable prognosis in epithelial ovarian cancer.
Impact of the new FIGO 2013 classification on survival analysis of stage I epithelial ovarian cancer
Abstract
Introduction: The FIGO classification for ovarian cancer, has recently been revised: FIGO IC subdivided in IC1 (intraoperative surgical spill), IC2 (capsule rupture before surgery, tumor on surface) and IC3 (positive peritoneal washing). Our aim is to compare the outcome of patients in the new FIGO I subgroups as this might influence adjuvant therapy desicion.
Materials and Methods: Patient databases of three gynecological oncology centers were retrospectively analyzed. Patients with FIGO I ovarian or tubal cancer were included and restaged according to the revised version and compared them to patient outcome data.
Results: 208 patients were analyzed (IA 59.1%; IB 7.2%; IC1 8.7%; IC2 7.7%; IC3 17.3%). In FIGO IA we found 11.5% recurrences and 4.3% deaths, comparing to 23% and 3.8% respectively in FIGO IC and time to recurrence was 190 vs. 158 months (p = 0.061). Within all new subgroups of FIGO IC, there was no difference in time to recurrence; 91.2 (IC1), 83.7 (IC2), and 78.2 (IC3) months (p = 0.68). There was also no difference in survial when FIGO IA was compared to FIGO IC in comparison to the new classifications (IA to IC or IA to IC1, 2 or 3, respectively; p = 0.93, p = 0.66, p = 0.71, p = 0.64) or within the different subgroups (p = 0.47). No difference in regards to the tumorboard when comparing FIGO IC1 and IC3.
Conclusion: The new FIGO staging of IC ovarian cancers didn't predict prognosis nor change tumorboard decisions. Larger numbers and individual histotype depending analyses may be warranted.
Incidence of germline mutations in risk genes including BRCA1/2 in consecutive ovarian cancer (OC) patients (AGO TR-1)
Abstract
Background: Identification of families at risk for OC including recommendation for prophylactic surgery is the only effective method to reduce OC mortality. In addition, BRCA1/2 mutations are known as prognostic factor and target for treatment.
Methods: Prospective counseling and testing of consecutive patients with first diagnosis or platinum sensitive relapse of invasive epithelial OC. Testing of 25 risk genes related to ovarian cancer. A positive mutation was defined as class 4/5 mutation and a positive family history was defined as at least one relative with breast cancer (BC) or OC or BC in personal history.
Results: In total, 529 pts entered the study, of which 507 were analyzed so far: 270 (53%) patients with first diagnosis of OC and 237 (47%) patients with platinum sensitive relapse. In total, 21% were BRCA1/2 positive (BRCA positive) and 27% for a mutation in at least one risk gene. The incidence of mutations in BRCA1 was 15%, BRCA2: 6%, RAD51C: 1.8%, PALB2: 1.2%. Mutations in all others were found less frequently (< 1%). In elderly patients (> 70 years), 13% carried a mutation in a risk gene compared to 31% of patients ≤70 years (p < 0.001). Family history identified 69% of the BRCA1/2 positive patients, but missed 31%.
Conclusions: 27% of all OC pts harbor a positive mutation in the genes analyzed. Age and FH are insufficient for identifying these patients. Genetic testing should therefore be offered to every patient with invasive epithelial ovarian cancer; limiting testing to BRCA1/2 analysis seems insufficient.
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Invitae approaches variant classification from a strict Mendelian perspective and employs the recommended five-tier classification system recommended by ACMG. A sequence change can be classified as:
- (5) Pathogenic — This variant directly contributes to the development of disease. Some pathogenic variants may not be fully penetrant. In the case of recessive or X-linked conditions, a single pathogenic variant may not be sufficient to cause disease on its own. Additional evidence is not expected to alter the classification of this variant.
- (4) Likely pathogenic — This variant is very likely to contribute to the development of disease however, the scientific evidence is currently insufficient to prove this conclusively. Additional evidence is expected to confirm this assertion of pathogenicity, but we cannot fully rule out the possibility that new evidence may demonstrate that this variant has little or no clinical significance.
- Uncertain significance — There is not enough information at this time to support a more definitive classification of this variant.
- Likely benign — This variant is not expected to have a major effect on disease however, the scientific evidence is currently insufficient to prove this conclusively. Additional evidence is expected to confirm this assertion, but we cannot fully rule out the possibility that new evidence may demonstrate that this variant can contribute to disease.
- Benign — This variant does not cause disease.
- Pathogenic (low penetrance) — This variant is commonly accepted as a contributing factor of disease, but the penetrance of this particular change is sufficiently low (<25%) to be often seen in individuals without disease. As a result, the predictive value of this information is considered to be low.
Analysis Towards evidence based research (waste/duplications research)
The BMJ (partial view)
Whether
or not today’s medical researchers, like Isaac Newton, see themselves
as “standing on the shoulders of giants,” they might still be expected
to build systematically on previous research when planning new studies.
Even though this issue was highlighted as early as 2005,1 2
numerous studies indicate that researchers do not use a systematic
methodology to identify and refer to earlier research when justifying,
designing, or discussing new research.3 4 5 6 7 8 9 10 11 This is true, even in high quality clinical studies published in the most prestigious medical journals.4 5 8 12 Rather, medical researchers select studies to cite based primarily on preferences and strategic considerations.13 14 15 16 17 18
The term “evidence based research” was coined in 2009 to indicate the
approach that is needed to reduce this practice, which is an important
source of research waste19 and risks unnecessary harm for patients and study participants.
In
view of the easy access to both electronic research databases and high
quality systematic reviews—spearheaded by groups such as the Cochrane
Collaboration, and numerous evidence synthesis centres worldwide—there
is little excuse for researchers failing to refer to current systematic
assessments of previous research. Nevertheless, authors seem to get away
with being very selective,13 14 preferentially citing studies with results that support the intervention they are evaluating.15 16 17 18
Some research funders have already taken action. For example, the
National Institute for Health Research in England now requires that
applicants for primary research funding justify any proposed research by
referencing a current systematic review of relevant existing research
to show that they have taken account of the …
Friday, October 21, 2016
Cancer researcher retracts 19 ovarian cancer studies at once - Retraction Watch
Cancer researcher retracts 19 studies at once - Retraction Watch
October 21st, 2016
Tracking retractions as a window into the scientific process
without comments
Jin Cheng, who studies how ovarian cancer develops, withdrew 19 papers from the Journal of Biological Chemistry originally published over the last 15 years, and corrected another. All of the retractions are for image manipulation.
For example, here’s the notice for “Activation of phosphatidylinositol 3-kinase/Akt pathway by androgen through interaction of p85α, androgen receptor, and Src,” a paper originally published in 2003:
This article has been withdrawn by the authors. The same data were used to represent different experimental conditions. Specifically, lanes 1–3 of the H2B panel of Fig. 4Bwere reused in lanes 1–3 of the H2B panel from Fig. 6B. Lanes 1 and 6 of the phospho-Akt panel from Fig. 4C were duplicated. Lanes 3 and 4 of the lower FLAG panel in Fig. 4Cwere reused in lanes 7 and 8 of the lower FLAG panel in Fig. 5A. The PI(3,4)P2 spots from lanes 1 and 2 from Fig. 7 were reused in lanes 7 and 8 of the same panel. Additionally, some PI(4)P1 spots were pasted in. The authors state that the overall conclusions of this work are not affected.Cheng has been awarded multiple NIH R01 grants, totaling millions of dollars, according to NIH RePORTER. A person answering the phone number listed for Cheng’s lab said he had retired. The email address listed on many of his papers bounced.
Here are the 19 retractions:
- Activation of phosphatidylinositol 3-kinase/Akt pathway by androgen through interaction of p85α, androgen receptor, and Src, cited 125 times, according to Clarivate Analytics’ Web of Science, formerly part of Thomson Reuters.
- Identification of Aurora-A as a direct target of E2F3 during G2/M cell cycle progression, cited 23 times
- Akt attenuation of the serine protease activity of HtrA2/Omi through phosphorylation of serine 212, cited 30 times
- Molecular cloning and characterization of the human AKT1 promoter uncovers its up-regulation by the Src/Stat3 pathway, cited 36 times
- ArgBP2γ interacts with Akt and p21-activated kinase-1 and promotes cell survival, cited 24 times
- Akt phosphorylation and stabilization of X-linked inhibitor of apoptosis protein (XIAP), cited 298 times
- AKT2 inhibition of cisplatin-induced JNK/p38 and Bax activation by phosphorylation of ASK1. IMPLICATION OF AKT2 IN CHEMORESISTANCE, cited 158 times
- Phosphatidylinositol 3-kinase/Akt pathway regulates tuberous sclerosis tumor suppressor complex by phosphorylation of tuberin, cited 289 times
- Inhibition of JNK by cellular stress- and tumor necrosis factor α-induced AKT2 through activation of the NFκB pathway in human epithelial cells, cited 37 times
- Positive feedback regulation between Akt2 and MyoD during muscle differentiation. CLONING OF Akt2 PROMOTER, cited 42 times
- MicroRNA MiR-214 regulates ovarian cancer cell stemness by targeting p53/Nanog, cited 57 times
- Identification of Akt interaction protein PHF20/TZP that transcriptionally regulates p53, cited 11 times
- IKBKE protein activates Akt independent of phosphatidylinositol 3-kinase/PDK1/mTORC2 and the pleckstrin homology domain to sustain malignant transformation, cited 52 times
- Phosphorylation and activation of androgen receptor by Aurora-A, cited 18 times
- MicroRNA-155 regulates cell survival, growth, and chemosensitivity by targeting FOXO3a in breast cancer, cited 181 times
- A small molecule inhibits Akt through direct binding to Akt and preventing Akt membrane translocation, cited 33 times
- IKKϵ phosphorylation of estrogen receptor α Ser-167 and contribution to tamoxifen resistance in breast cancer, cited 35 times
- Phosphoinositide 3-kinase/Akt inhibits MST1-mediated pro-apoptotic signaling through phosphorylation of threonine 120, cited 49 times
- MicroRNA-221/222 negatively regulates estrogen receptor α and is associated with tamoxifen resistance in breast cancer, cited 302 times
Two novel sequence variants in MSH2 gene in a patient who underwent cancer genetic counseling for a very early-onset (clear cell) epithelial ovarian cancer
Two novel sequence variants in MSH2 gene in a patient who underwent cancer genetic counseling for a very early-onset epithelial ovarian cancer | Hereditary Cancer in Clinical Practice | Full Text
Discussion
Cancer
genetic counseling should be always offered during the work-up of young
patients with epithelial ovarian cancer, in order to screen the
presence of a hereditary syndrome and to improve the oncological
follow-up including intensified surveillance. Clinicians should be
particularly careful to the evaluation of a positive family history of
cancer, being ovarian cancer involved in three different syndromes, such
as site-specific, HBOC and Lynch Syndrome.
Treatment preferences of advanced ovarian cancer patients for adding bevacizumab to first-line therapy
abstract (Korea)
Highlights
- •
- We explored patients' preferences for adding bevacizumab to first-line therapy.
- •
- A discrete choice experiment and trade-off question were designed and distributed to ovarian cancer patients.
- •
- Patients' preferences for bevacizumab depend primarily on drug costs.
Background
The
GOG-218 and ICON-7 studies recently showed that adding bevacizumab to
first-line therapy for patients with advanced ovarian cancer increased
progression-free survival. However, the high cost and long treatment
duration prevents the incorporation of bevacizumab in practice. The aim
of this study was to explore and quantify patients' preferences for
adding bevacizumab to first-line therapy.
Thursday, October 20, 2016
Adhesive Small Bowel Obstruction Managed by a Surgical Team (NY)
medscape
Conclusions
This study demonstrates that primary management of patients with adhesive-SBO by medical services is associated with longer LOS, larger cost, and higher readmission rates, as well as a delay in time to surgery and higher mortality rates following surgical intervention. While complex patients with multiple comorbidities may benefit from medical optimization by hospitalists, institutional policies favoring primary management by surgical services may greatly reduce healthcare utilization and improve outcomes for patients admitted with adhesive-SBO.Trauma Patients Not to Blame for Opioid Epidemic: Study
med news
WEDNESDAY, Oct. 19, 2016 -- Patients who survived major trauma may not be a significant factor in the U.S. opioid epidemic, a new study suggests.
Almost 75 percent of major trauma patients who were prescribed narcotic painkillers such as OxyContin and Percocet had stopped using them a month after leaving the hospital. And only 1 percent were still taking the drugs on a prescription basis a year later, researchers found....
Many officials attribute some of this abuse to overprescribing practices, arguing that use of legitimate pain pills frequently leads to addiction.
However, "our findings in patients who sustain traumatic injury contradict the popular narrative about the role that appropriate use of opioids may play in the rate of opioid abuse in this country," Schoenfeld said.
The report was scheduled for presentation Wednesday at the annual meeting of the American College of Surgeons in Washington, D.C. Data and conclusions presented at meetings are generally considered preliminary until published in a peer-reviewed medical journal.
Wednesday, October 19, 2016
Perspective: A Precision Medicine Approach to Clinical Trials (note reference to patients/Facebook)
Cancer Biomarkers | JAMA
“They say, ‘Dr Hong, I want to be in this trial,’” said Hong, deputy chair of the department of investigational cancer therapeutics at the University of Texas MD Anderson Cancer Center. “Patients are incredibly savvy. Especially if they have end-stage cancer and their doctor has told them, ‘there’s nothing more I can do for you,’ they will find a trial.”
Conflicts of Interest Among Patient and Consumer Representatives to U.S. Food and Drug Administration Drug Advisory Committees
abstract
Background: Drug advisory
committees provide independent advice to the U.S. Food and Drug
Administration (FDA) on policy matters. Committee members are special
government employees and are subject to federal employee
conflict-of-interest guidelines under 18 U.S.C. § 208 and § 712 (1994).
Although these regulations prohibit actual or apparent conflicts of
interest, regulatory policy allows waivers to be issued when the
participant's expertise is deemed essential to evaluating a specific
matter before the advisory committee. The issuance of waivers can be
complicated, but the FDA is clear that relevant scientific expertise is a
necessary and primary criterion (1). Therefore, patient and consumer representatives are ineligible to receive waivers for conflicts of interest (1).
In addition, committee members with more than $50 000 in financial
relationships are typically ineligible for waivers regardless of
expertise.
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Injuries before and after diagnosis of cancer: nationwide register based study + comment/s
i·at·ro·gen·ic Ä«ËŒatrəˈjenik/ adjective adjective: iatrogenic
- of or relating to illness caused by medical examination or treatment.
We used the Swedish revision of ICD-7 (international classification of diseases, seventh revision) to classify cancers as prostate cancer (n=123 837), breast cancer (n=101 458; women only), colorectal cancer (n=84 527), non-melanoma skin cancer (n=33 409), lymphatic or hematopoietic cancers (n=52 266), lung cancer (n=49 491), cancers of the central nervous system (n=21 199), cancers with an expectedly short survivalopen access
(n=34 627; “severe cancers” including cancers in the oesophagus, liver, and pancreas), and other cancers (n=220 087).
Based on this register, we included 740 114 unique patients with a first cancer diagnosed during 1991-2009.
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