What is whole genome sequencing? How is it used, and how does it apply to
you? Learn more on the Genes in Life blog, and have your questions
answered by our featured experts!....
Tuesday, November 12, 2013
Tumor Mutation Burden Forecasts Outcome in Ovarian Cancer with BRCA1 or BRCA2 Mutations
open access (technical)
Background
Increased number of single nucleotide substitutions is seen in breast and ovarian cancer genomes carrying disease-associated mutations in BRCA1 or BRCA2. The significance of these genome-wide mutations is unknown. We hypothesize genome-wide mutation burden mirrors deficiencies in DNA repair and is associated with treatment outcome in ovarian cancer.
......."Our results are based on a relatively small set of patients carrying BRCA1 ...and BRCA2 mutations, and should be considered hypothesis generating until confirmed in a larger cohort. In addition, tumors may possess de novo mechanisms leading to resistance to chemotherapy and targeted treatments. Our preliminary results suggest low tumor Nmut may identify BRCA-associated primary tumors in which the original deficiency of BRCA1 and BRCA2 pathways, including impaired DNA repair, is compensated for by alternative pathways."
Conclusions
Tumor Nmut (non-synonymous exome mutations) was associated with treatment response and with both PFS and OS in patients with high-grade serous ovarian cancer carrying BRCA1 or BRCA2 mutations. In the TCGA cohort, low Nmut predicted resistance to chemotherapy, and for shorter PFS and OS, while high Nmut forecasts a remarkably favorable outcome in mBRCA-associated ovarian cancer. Our observations suggest that the total mutation burden coupled with BRCA1 or BRCA2 mutations in ovarian cancer is a genomic marker of prognosis and predictor of treatment response. This marker may reflect the degree of deficiency in BRCA-mediated pathways, or the extent of compensation for the deficiency by alternative mechanisms.
Editorial: Conventional evaluations of improvement interventions: more trials or just more tribulations?
open access
......Many of the challenges we regard as unique to QI (quality improvement) in fact exist in clinical research and have been recognised for decades.22 In some cases, we need to choose the right time for an RCT (once the intervention is sufficiently mature). In other cases, we may need to adopt alternative designs, such as step-wedge randomisation, to accommodate the realities of implementing complex interventions in the midst of other institutional activities or adaptive randomisation to minimise the number of sites assigned to the control group. But, we also have to remember that many of the misgivings we feel as providers of healthcare asked to participate in RCTs of improvement interventions echo those made by patients all the time. Our enthusiasm for assignment to active treatment carries no more weight than theirs. Rather than so often avoiding multi-site RCTs in QI, we may just need to find the right spoonful of sugar for ourselves when we end up in the control group.
Characteristics of Adverse Drug Events Originating During the Hospital Stay, 2011 (U.S)
Characteristics
Highlights
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Monday, November 11, 2013
(repost) Learn More About Cancer: Lifestyle Link (evidence or not) By Cancer Site | American Institute for Cancer Research (AICR)
American Institute for Cancer Research (AICR)
By Cancer Site
Evidence shows that our risk for many types of cancer is related to diet, physical activity and weight. But for some types, it is not yet possible to determine if lifestyle plays a role. This does not mean such links are impossible, simply that more research is needed.The AICR/WCRF Expert Report and Continuous Update Project examines the evidence linking various lifestyle factors to cancers at 17 different body sites using a rigorous and objective process called Systematic Literature Reviews (SLRs).
Strong Evidence of Lifestyle Link
For 12 of these cancers, strong evidence emerged that diet, weight and physical activity can raise or lower risk. They are:- Colorectal Cancer — Updated Content
- Breast Cancer — Updated Content
- Endometrial (Lining of the Uterus) Cancer — Updated Content
- Esophageal Cancer — Updated Content
- Gallbladder Cancer
- Kidney Cancer
- Liver Cancer
- Lung Cancer
- Cancers of the Mouth, Pharynx and Larynx
- Pancreatic Cancer
- Prostate Cancer — Updated Content
- Stomach Cancer
No Strong Evidence of a Lifestyle Link
The expert panel also examined the available evidence for five other cancers using the same exacting SLR method. The results are as follows*:- Cervical Cancer
The expert panel concluded that there is as yet no strong evidence that any aspect of diet, physical activity and weight influences the risk of cervical cancer. - Bladder Cancer
The expert panel concluded that there is as yet no strong evidence that any aspect of diet, physical activity and weight influences the risk of bladder cancer. - Ovarian Cancer
To date, the strongest evidence linking any aspect of lifestyle to this cancer is related to adult attained height. This does not mean that being tall is a cause of ovarian cancer, however. Instead, it is believed that various genetic, hormonal and nutritional factors that contribute to adult attained height are likely the true underlying causes of ovarian cancer. - Skin Cancer
That skin cancer is directly caused by excessive sun exposure is well-established. The expert panel specifically examined the evidence linking skin cancer to aspects of diet, weight and physical activity. No strong evidence emerged, with the exception of arsenic in drinking water, for which a probable link to skin cancer was found. - Nasopharyngeal Cancer
This cancer is rare in the United States but common in Southern China. The panel, which examined the global evidence, concluded that consumption of Cantonese-style salted fish is probably a cause of this cancer.
Other Cancers
For the following cancers, evidence was too limited to examine using SLRs. For this reason, the Panel did not issue conclusions about them, but flagged the need for further research on possible lifestyle links*.- Thyroid Cancer
- Testicular Cancer
- Lymphoma (Hodgkin’s and Non-Hodgkin’s)
- Leukemia
- Multiple Myeloma
- Cancers of the Musculoskelatal System (Liposarcoma, fibrosarcoma, osteosarcoma, myosarcoma)
- Cancers of the Nervous system (Glioblastoma, meningoma, sellar tumor, cranial tumor, spinal nerve tumor, central nervous system lymphoma)
*NOTE: Although there is currently insufficient evidence to definitively determine if these cancers are related to diet, weight and physical activity, AICR funds innovative research involving these cancers that seeks to find and map such links.
Treatment of Dexamethasone-Induced Hiccup in Chemotherapy Patients by Methylprednisolone Rotation
abstract
Background.
Dexamethasone-induced hiccup (DIH) is an underrecognized symptom in
patients with cancer, and little information is available
about its treatment. The aims of this study were
to investigate the feasibility of methylprednisolone rotation as
treatment
and to confirm the male predominance among those
with cancer who experienced DIH during chemotherapy.
Methods. Persons with
cancer who experienced hiccups during chemotherapy treatment and who
were receiving treatment with dexamethasone
were presumed to have DIH. The following
algorithmic practice was implemented for antiemetic corticosteroid use:
rotation
from dexamethasone to methylprednisolone in the
next cycle and dexamethasone re-administration in the second cycle of
chemotherapy
after recognition of hiccups to confirm DIH. All
other antiemetics except corticosteroid remained unchanged. Patients (n = 40) were recruited from eight cancer centers in Korea from September 2012 to April 2013. Data were collected retrospectively.
Results. Hiccup
intensity (numeric rating scale [NRS]: 5.38 vs. 0.53) and duration
(68.44 minutes vs. 1.79 minutes) were significantly
decreased after rotation to methylprednisolone,
while intensity of emesis was not increased (NRS: 2.63 vs. 2.08). Median
dose
of dexamethasone and methylprednisolone were 10
mg and 50 mg, respectively. Thirty-four (85%) of 40 patients showed
complete
resolution of hiccups after methylprednisolone
rotation in the next cycle. Of these 34 patients, 25 (73.5%) had
recurrence
of hiccups after dexamethasone
re-administration. Compared with baseline values, hiccup intensity (NRS:
5.24 vs. 2.44) and
duration (66.43 minutes vs. 22.00 minutes) were
significantly attenuated after dexamethasone re-administration. Of the
40
eligible patients, 38 (95%) were male.
Conclusion. DIH during
chemotherapy could be controlled without losing antiemetic potential by
replacing dexamethasone with methylprednisolone.
We also identified a male predominance of DIH.
Further prospective studies are warranted.
FDA Documents Paint Disturbing Picture Of Burzynski Cancer Clinic (antineoplastons)
Burzynski Cancer Clinic
....Earlier this year, the FDA finally visited the Burzynski Clinic to take a peek around. Through FOIA request, a number of bloggers have been looking over the documents for a few months, but now they have been released publicly. The findings are very disturbing and paint a picture of a clinic that fails to follow even basic practices to protect patients. Among the published observations:.......
Vitamin and Mineral Supplements in the Primary Prevention of Cardiovascular Disease and Cancer: An Updated Systematic Evidence Review for the U.S. Preventive Services Task Force
open access
"We developed an analytic framework (Appendix Figure 1 of the Supplement) with 4 key questions that we adapted from a 2006 review by Huang and colleagues (6). Our full report describes our methods in detail (7). We specifically sought studies of the following vitamins and minerals: vitamins A, B1, B2, B6, B12, C, D, and E; calcium; iron; zinc; magnesium; niacin; folic acid; β-carotene; and selenium. We included studies that evaluated single, paired, and combinations of three or more vitamins and minerals; we use the term “multivitamin” to refer to these combinations of vitamins and minerals."
.....In conclusion, we found no evidence of an effect of nutritional doses on CVD, cancer, or mortality in healthy individuals without known nutritional deficiencies for most supplements we examined. In most cases there are insufficient data to draw any conclusion, although for vitamin E and β-carotene a lack of benefit is consistent across several trials. We identified 2 multivitamin trials that both found lower overall cancer incidence in men (19, 21). Both these trials were both methodologically sound, but the lack of an effect for women (albeit in 1 trial), the borderline significance in men in both trials, and the lack of any effect on CVD in either study makes it difficult to conclude that multivitamin supplementation is beneficial."
A Double-Blind, Randomized Phase II Study to Evaluate the Safety and Efficacy of Acetyl-L-Carnitine in the Prevention of Sagopilone-Induced Peripheral Neuropathy
Acetyl-L-Carnitine
Background. Peripheral neuropathy (PN) is a recognized side effect of microtubule-targeting agents and the most clinically relevant toxicity observed with the epothilone sagopilone (SAG). Studies suggest that acetyl-L-carnitine (ALC) may prevent chemotherapy-induced PN. We conducted a prospective, placebo (PBO)-controlled, double-blind, randomized trial to investigate the safety and efficacy of ALC for the prevention of SAG-induced PN.
Methods. Patients with ovarian cancer (OC) or castration-resistant prostate cancer (CRPC) and no evidence of neuropathy received SAG
(16 mg/m2 intravenously over 3 hours every 3 weeks) with ALC (1,000 mg every 3 days) or placebo (PBO). The primary endpoint was incidence
of PN within six or fewer cycles in both treatment groups.
Results. Overall, 150
patients enrolled (98 OC patients, 52 CRPC patients), with 75 per
treatment arm. No significant difference in
overall PN incidence was observed between
treatment arms. The incidence of grade ≥3 PN was significantly lower in
the ALC
arm in OC patients. Median duration of
neuropathy was similar between treatment arms. The best overall response
(according
to the modified Response Evaluation Criteria in
Solid Tumors), response according to tumor markers, time-to-event
variables,
and discontinuations because of adverse events
(AEs) were comparable between treatment arms.
Conclusion.
Administration of ALC with SAG did not result in a significant
difference in overall PN incidence compared with a PBO. OC
patients in the SAG/ALC arm had a significantly
lower incidence of grade 3 or 4 PN compared with OC patients in the
SAG/PBO
arm.
Reported Reasons for Non-Use of an Internet-Based Patient-Provider Communication Service: Qualitative Interview Study | Varsi | Journal of Medical Internet Research
JMIR--Patients
Background: The adoption of Internet-based patient–provider communication services (IPPC) in health care has been slow. Patients want electronic communication, and the quality of health care can be improved by offering such IPPCs. However, the rate of enrollment in such services remains low, and the reasons for this are unclear. Knowledge about the barriers to use is valuable during implementation of IPPCs in the health care services, and it can help timing, targeting, and tailoring IPPCs to different groups of patients.
Objective: The goal of our study was to investigate patients’ views of an IPPC that they could use from home to pose questions to nurses and physicians at their treatment facility, and their reported reasons for non-use of the service.
Methods: This qualitative study was based on individual interviews with 22 patients who signed up for, but did not use, the IPPC.
Results: Patients appreciated the availability and the possibility of using the IPPC as needed, even if they did not use it. Their reported reasons for not using the IPPC fell into three main categories: (1) they felt that they did not need the IPPC and had sufficient access to information elsewhere, (2) they preferred other types of communication such as telephone or face-to-face contact, or (3) they were hindered by IPPC attributes such as login problems.
Conclusions: Patients were satisfied with having the opportunity to send messages to health care providers through an IPPC, even if they did not use the service. IPPCs should be offered to the patients at an appropriate time in the illness trajectory, both when they need the service and when they are receptive to information about the service. A live demonstration of the IPPC at the point of enrollment might have increased its use.
JMIR--Analysis of the Purpose of State Health Departments' Tweets: Information Sharing, Engagement, and Action | Thackeray | Journal of Medical Internet Research
Tweets
Conclusions: This is the first study to assess the purpose of public health tweets among state health departments. State health departments are using Twitter as a one-way communication tool, with tweets focused primarily on personal health. A state health department Twitter account may not be the primary health information source for individuals. Therefore, state health departments should reconsider their focus on personal health tweets and envision how they can use Twitter to develop relationships with community agencies and partners. In order to realize the potential of Twitter to establish relationships and develop connections, more two-way communication and interaction are essential.
Attachment Theory and Spirituality: Two Threads Converging in Palliative Care?
Aopen access
Introduction
The goal of palliative care is to improve the quality of life of terminally ill patients by preventing or relieving them from suffering. Relieving suffering does not only mean to insulate patients from physical pain. There are many more aspects which contribute to the patient’s wellbeing such as social, psychological, and spiritual support [1]. This is why palliative medicine has to take a multidisciplinary approach to patient care. In the present paper, two important concepts come into focus, both founding a multivariate understanding of the patient’s needs and challenges in the palliative situation: attachment theory and the concept of spirituality. Attachment Theory is a concept that is concerned with human relationship behavior in situations of loss, separation, or helplessness and can help to understand the patient’s behavior, needs, and challenges [2, 3]. The patient’s spirituality in health care and research is addressed by the field of Spiritual care. spiritual care is an interdisciplinary and cross-cultural discipline [4] in health care that scientifically addresses the spiritual and religious needs of patients and has become a part of medical care and education. Both concepts have been treated by palliative research in diverse the and multiform ways, as we will propound in the overview of research literature in the following section. But no effort has been made to integrate them into one theoretical framework in reference to the palliative context. The aim of this paper is to discuss the relevance of both concepts to palliative care, in order to develop a theoretical foundation for both aspects of the palliative situation.....
Research results in big savings for cancer treatment (neurotoxicity/oxaliplatin/magnesium/calcium)
healthnews
"....An intervention to counter the neurotoxic
effects of a chemotherapy treatment for cancer has been withdrawn after
research showed it was ineffective.
This resulted in big savings in the cost of the intervention
and in treatment time by nurses, at Auckland City Hospital’s medical
oncology service, one of the largest cancer treatment centres in
Australasia. Medical oncologist and doctoral student clinician Catherine Han carried out the research at the University of Auckland and Auckland City Hospital, as part of her work investigating the origins of neurotoxicity from oxaliplatin chemotherapy treatment. Her research is funded for three years by a Health Research Council Clinical Research Training fellowship for $250,000 awarded in 2012.
Research into the effectiveness of the calcium and magnesium infusions given to cancer patients to counter the neurotoxic effects of chemotherapy treatment with oxaliplatin showed it was not working.
“Catherine’s research showed clearly that the magnesium and calcium infusion does not work, and has led to a change in clinical practice in our cancer treatment centre at Auckland Hospital,” says her research supervisor, Associate Professor Mark McKeage who is a clinical pharmacologist and cancer specialist, and a co-director of the University-based Auckland Cancer Society Research Centre....
Olaparib Enters Phase III Clinical Testing
Olaparib
"After halting development of its PARP inhibitor olaparib nearly 2 years ago, AstraZeneca is reviving the drug and launching two phase III trials based on a retrospective analysis of phase II data that showed a marked effect in ovarian cancer patients with a BRCA mutation."
Sunday, November 10, 2013
Compartment syndrome after gynecologic operations: evidence from case reports and reviews
abstract
"Compartment syndrome (CS) of the lower leg is a rare
but severe complication of operations in the lithotomy (LT) position
after urologic, gynecologic and general surgery. A delay in diagnosis
and treatment can lead to loss of function and even life-threatening
complications. The pathophysiology is still not fully understood but it
is believed that ischemia as a result of increased compartment pressure
and decreased perfusion pressure may lead to CS. The type of leg support
and intraoperative hypotension have been discussed as risk factors but
evidence is mainly based on case reports and expert opinion. Studies
suggest that time spent in the LT position and the addition of head-down
tilt are associated with CS. As these positions are routinely applied
during various gynecologic procedures, forensically CS has to be
considered as a specific complication of gynecologic surgery in the LT
position. Despite the low incidence there is a need for prospective
studies and guidelines for its prevention.
Sixteen
case reports describing 19 cases of CS following gynecologic surgery in
lithotomy position were found during a literature search. This review is
based on 14 of these case reports (17 cases), which describe a
postoperative compartment syndrome in a previously healthy leg. We
summarize the reported cases and literature on CS after gynecologic
procedures in order to increase awareness among medical staff and to
give careful recommendations regarding perioperative management based on
available information."
Anatomy and Physiology: The 5 Unsung Heroes of the Abdominal Cavity
Anatomy and Physiology (excellent graphics)
1. Gallbladder: The Bile Keeper
2. Renal Pyramids: Cleansing Masters
3. Pancreas: Digestion Wunderkind
4. Adrenal Glands: Endocrine Celebrity
5. Cecum: Miss Congeniality (of the Abdomen)
Religiosity and Spirituality and the Intake of Fruit, Vegetable, and Fat: A Systematic Review
open access
Conclusion
Overall, the denominational studies showed that religious denomination is significantly related to fruit, vegetable, and fat intake. Specifically, the Adventists consumed more fruit and vegetable and less fat than non-Adventists. However, the relationship between the degree of R/S and dietary intake is mixed. The results of this review suggest that future research on R/S and diet may help explain the possible mechanism between religion and health. Methodology more sophisticated than observational studies is required. Longitudinal study methodologies (while still often observational) may enhance our understanding of underlying mechanisms. As religion is important for many people and affects their diet, improved methodological quality of R/S and diet research will surely shed more light on this area.
(video) BBC - Future - Health - A doctor's touch
The most important innovation in medicine to come in the next 10 years: the power of the human hand. — Abraham Verghese
Saturday, November 09, 2013
Dartmouth researcher finds novel genetic patterns that make us rethink biology and individuality
Health News
Hanover, NH—Professor of Genetics Scott Williams, PhD, of the Institute for Quantitative Biomedical Sciences (iQBS) at Dartmouth's Geisel School of Medicine, has made two novel discoveries: first, a person can have several DNA mutations in parts of their body, with their original DNA in the rest—resulting in several different genotypes in one individual—and second, some of the same genetic mutations occur in unrelated people.....
(open access):
Click here to see the full paper at PLOS Genetics
Cancer-related neuropathic pain in out-patient oncology clinics: a European survey
open access
Background
Although pain is frequently experienced by patients with cancer, it remains under-treated.
The primary aim of this study was to estimate the prevalence of cancer-related neuropathic
pain (CRNP) in patients with chronic pain who attended an outpatient clinic for standard
care in Europe (irrespective of the reason or stage of the cancer). The secondary
aims of this study were to characterise pain and cancer in patients with CRNP (including
treatment) and to evaluate the usefulness of the painDETECT (PD-Q) screening tool
to help physicians identify a potential neuropathic component of cancer-related pain.
Methods
An observational, non-interventional, cross-sectional, multi-centre study of adult
patients with cancer using patient and physician case report forms (CRFs). Patients
with CRNP were identified by physicians' clinical assessments after examining the
completed PD-Q.
Results
A total of 951 patients visiting outpatient clinics across Europe were enrolled in
this study between August 2010 and July 2011. Of these, 310 patients (32.60%; 95%
confidence interval 29.62, 35.58) were identified as having CRNP. Twenty-nine of 39
(74.4%) physicians who completed the CRF relating to the PD-Q considered it a useful
tool to help detect CRNP in daily practice and 28 of 39 (71.8%) indicated that they
would use this tool in the future for most or some of their patients. Data from physicians
before and after review of the completed PD-Qs showed a shift in clinical opinion
(either to positive CRNP diagnosis [yes] or negative CRNP diagnosis [no]) in respect
of 142 patients; about half of which (74) were categorised with an initial diagnosis
of unknown. Opinions also shifted from a no to a yes diagnosis in 10 patients and
from a yes to a no diagnosis in 51 patients.
Conclusions
Approximately one-third of adults with cancer experiencing chronic pain attending
outpatient clinics as part of routine care were considered to have CRNP in the opinion
of the physicians after considering scores on the PD-Q. While physicians did not consider
the PD-Q to be a useful tool for all patients, shifts in diagnosis before and after
the use of this tool indicate that it may help physicians identify CRNP, especially
where there is initial uncertainty.
The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production. |
close
Knowledge is not power for patients: A systematic review and thematic synthesis of patient-reported barriers and facilitators to shared decision making
abstract
Objectives
To systematically
review patient-reported barriers and facilitators to shared decision
making (SDM) and develop a taxonomy of patient-reported barriers.
Methods
Systematic
review and thematic synthesis. Study findings/results for each included
paper were extracted verbatim and entered into qualitative software for
inductive analysis.
Results
Electronic
and follow-up searches yielded 2956 unique references; 289 full-text
articles were retrieved, of which 45 articles from 44 unique studies met
inclusion criteria. Key descriptive themes were grouped under two broad
analytical themes: how the healthcare system is organized (4
descriptive themes) and what happens during the decision-making
interaction (4 descriptive themes, 10 sub-themes). Predominant emergent
themes related to patients’ knowledge and the power imbalance in the
doctor-patient relationship. Patients need knowledge and power to
participate in SDM–knowledge alone is insufficient and power is more
difficult to attain.
Conclusions
Many
barriers are potentially modifiable, and can be addressed by
attitudinal changes at the levels of patient, clinician/healthcare team,
and the organization. The results support the view that many patients
currently can’t participate in SDM, rather than they won’t participate
because they do not want to.
Practice implications
Future
implementation efforts should address patient-reported factors together
with known clinician-reported barriers and the wider organizational
context.
How can we explain physician accuracy in assessing patient distress? A multilevel analysis in patients with advanced cancer
abstract
Objective
To examine the
determinants of the accuracy with which physicians assess metastatic
cancer patient distress, also referred to as their empathic accuracy
(EA). Hypothesized determinants were physician empathic attitude,
self-efficacy in empathic skills, physician-perceived rapport with the
patient, patient distress and patient expressive suppression.
Methods
Twenty-eight
physicians assessed their patients’ distress level on the distress
thermometer, while patients (N = 201) independently rated their distress
level on the same tool. EA was the difference between both scores in
absolute value. Hypothesized determinants were assessed using
self-reported questionnaires. Multilevel analyses were carried out.
Results
Little
of the variance in EA was explained by physician variables. EA was
higher with higher levels of patient distress. Physician-perceived
quality of rapport was positively associated with EA. However, for
highly distressed patients, good rapport was associated with lower EA.
Patient expressive suppression was also related to lower EA.
Conclusion
This
study adds to the understanding of EA in oncological settings,
particularly in challenging the common assumption that EA depends
largely on physician characteristics or that better rapport would always
favor higher EA.
Practice implications
Physicians
should ask patients for feedback regarding their emotions. In parallel,
patients should be prompted to express their concerns.
‘What they’re not telling you’: A new scale to measure grandparents’ information needs when their grandchild has cancer
abstract
Conclusions
Grandparents of
children with cancer desire more information for their own reassurance,
to reduce their reliance on ‘second-hand’ information from their
grandchild's parents and to improve the support they provide their
families. Grandparents strongly endorse the development of
grandparent-targeted educational resources.
Gender-specific quality of life after cancer in young adulthood: a comparison with the general population
young adulthood
Conclusions
Results clearly
indicate that young adult cancer patients have a reduced quality of life
in comparison with the general population even long after the treatment
of their disease is complete. Women had a lower quality of life than
men. Age-specific interventions should be offered that lead to
improvements in quality of life for this age group. And future studies
should clarify what factors lead to women’s quality of life being worse
than men’s.
Venous Thromboembolism Risk in Patients With Cancer Receiving Chemotherapy: A Real-World Analysis
abstract
Types
of tumor associated with the highest VTE risk are hematologic
cancers,followed by lung,pancreatic,stomach,ovarian,uterine,bladder,and
brain
tumors.
Implications for Practice:
This large observational study of unselected patients receiving cancer
chemotherapy demonstrates considerably greater rates of venous
thromboembolism (VTE) than commonly reported in patients accrued to clinical trials.The risk of VTE appears to increase progressively over the year following initiation of treatment. Cancer patients
developing VTE also experience a greater risk of major bleeding and greater health care costs than patients without VTE.
Patients considered at high risk for VTE should be considered for
thromboprophylaxis after assessing the balance of potential benefits and harms.
Progesterone receptor PROGINS and +331G/A polymorphisms confer susceptibility to ovarian cancer: a meta-analysis based on 17 studies
abstract
Progesterone
and its receptor, progesterone receptor (PGR), have been widely studied
for their roles in the onset and development of ovarian cancer.
Although numerous epidemiological studies have focused on the
association of PGR PROGINS and +331G/A polymorphisms with ovarian cancer
susceptibility, presently, available results remain controversial, in
part due to low sample sizes. Thus, a meta-analysis is required to
evaluate this association. A literature search of PubMed, Embase, Web of
Science, CNKI, and CBM databases was performed to retrieve eligible
studies published before August 15, 2013. Summary odds ratios (ORs) with
95 % confidence intervals (CIs) were used to evaluate the strength of
this association. All analyses were done using STATA 12.0 software
(Stata Corp., College Station, TX, USA). Seventeen case-control studies
with a total of 6,365 cases and 9,998 controls were identified. While no
statistically significant association between the PROGINS allele and
ovarian cancer risk was found in an overall analysis, a stratified
analysis revealed that for Caucasians, never-oral contraceptive (OC)
users, and serous tumor patients, there were statistically significant
ORs for ovarian cancer risk associated with the mutated PROGINS allele.
No significant association, however, between the +331G/A polymorphism
and ovarian cancer susceptibility was observed in the overall analyses
and subgroup analyses based on ethnicity and histological type. This
meta-analysis provides evidence that the PROGINS allele occurs more
frequently in ovarian cancer patients and especially in non-OC users and
serous cancer patients, indicating that PROGINS may be a risk modifier.
No significant association between the +331G/A polymorphism and ovarian
cancer was found, even in stratified analyses by ethnicity and
histological type. More detailed and well-designed studies are still
needed to confirm the role of the PROGINS allele in ovarian cancer
development.
A study of ovarian cancer biomarker amplification using ultrasound for early stage detection
open access
Highlights
- •
- We amplify ovarian cancer biomarkers by using ultrasound for early stage detection.
- •
- Ultrasound at 1 MHz, 0.3 W cm−2 and 50% duty cycle is applied on ovarian cancer cells (SKOV3).
- •
- After 5 min sonication, the CA125 and CA19-9 levels are increased by 2.02 and 4.21-fold respectively.
Monoclonal antibody-based immunotherapy of ovarian cancer: targeting ovarian cancer cells with the B7-H3-specific mAb 376.96
abstract
Highlights
- •
- The mAb 376.96 defined B7-H3 epitope is expressed by chemosensitive and chemoresistant ovarian cancer cells, as well as patient tumors
- •
- mAb 376.96 enhanced the cytotoxicity of Sunitinib in vitro
- •
- Further studies are warranted examining B7-H3 as a potential target of mAb-based immunotherapy in ovarian cancer
Cleveland Clinic - Quantitative Health Sciences - Risk Calculators
Risk Calculators
This information is provided by Cleveland Clinic as a convenience service only to physicians and is not intended to replace the physicians' medical advice. Please remember that this information, in the absence of a visit with a physician's patient, must always be considered as an educational service only and are not designed to replace a physician's independent judgment about the appropriateness or risks of a procedure or recommendations for a given patient. CCF makes no representation or warranty concerning the accuracy or reliability of this information and does not warrant the results of using this tool. In no event shall CCF be liable for any damages, direct, indirect, consequential or otherwise, relating to the use of this information or this tool.
Topics:
Acute Coronary Syndrome
Benign Prostatic Hyperplasia:
Bladder Cancer
Brain Cancer
Breast Cancer
Colorectal Cancer
Complex Colorectal Surgery
Suspected Coronary Artery Disease
Cardiac Surgery
Type 2 Diabetes
Gastric Cancer
Suspected Kidney Cancer
Chronic Kidney Disease
Oral Cancer
Ovarian Cancer
Pancreatic Cancer
Penile Cancer
First Pregnancy
Prostate Cancer
Sarcoma
Thyroid Cancer
Total Joint Replacement
Friday, November 08, 2013
Prevalence and characteristics of moderate to severe fatigue
abstract
BACKGROUND
The
effective management of fatigue in patients with cancer requires a
clear delineation of what constitutes nontrivial fatigue. The authors
defined numeric cutpoints for fatigue severity based on functional
interference and described the prevalence and characteristics of fatigue
in patients with cancer and survivors.
METHODS
In
a multicenter study, outpatients with breast, prostate, colorectal, or
lung cancer rated their fatigue severity and symptom interference with
functioning on the M. D. Anderson Symptom Inventory numeric scale of 0
to 10. Ratings of symptom interference guided the selection of numeric
rating cutpoints between mild, moderate, and severe fatigue levels.
Regression analysis identified significant factors related to reporting
moderate/severe fatigue.
RESULTS
The
statistically optimal cutpoints were ≥ 4 for moderate fatigue and ≥ 7
for severe fatigue. Moderate/severe fatigue was reported by 983 of 2177
patients (45%) undergoing active treatment and was more likely to occur
in patients receiving treatment with strong opioids (odds ratio [OR],
3.00), those with a poor Eastern Cooperative Oncology Group performance
status (OR, 2.00), those who had > 5% weight loss within 6 months
(OR, 1.60), those who were receiving > 10 medications (OR, 1.58),
those with lung cancer (OR, 1.55), and those with a history of
depression (OR, 1.42). Among survivors (patients with complete remission
or no evidence of disease, and not currently receiving cancer
treatment), 29% of patients (150 of 515 patients) had moderate/severe
fatigue that was associated with poor performance status (OR, 3.48) and a
history of depression (OR, 2.21).
CONCLUSIONS
The current study statistically defined fatigue severity categories related to significantly increased symptom interference. The high prevalence of moderate/severe fatigue in both actively treated patients with cancer and survivors warrants the promoting of the routine assessment and management of patient-reported fatigue.A Patient with Recurrent Ovarian Clear Cell Adenocarcinoma and Chronic Kidney Disease Exhibited Complete Response to Paclitaxel plus Carboplatin (Japan)
abstract
A
41-year-old woman receiving hemodialysis 3 times a week for chronic
kidney disease caused by interstitial nephritis was referred to our
hospital because of a pelvic mass and subsequently underwent primary
surgery . The patient was diagnosed with FIGO stage Ic(b)clear cell
adenocarcinoma. She did not receive postoperative chemotherapy. However,
9 months after surgery, ascites and a pelvic mass developed, on the
basis of which recurrence was confirmed. She received combination
chemotherapy with paclitaxel plus carboplatin(TC). Paclitaxel was
administered at 175mg/m2, and the carboplatin dosage was calculated by
the Calvert formula. The glomerular filtration rate was considered to be
0, and the target area under the plasma concentration versus time curve
was 5. Hemodialysis was performed 24 hours after the infusion of
carboplatin. After 6 courses of combination chemotherapy, complete
response was confirmed by computed tomography. The patient developed
grade 3 neutropenia, grade 1 sensory neuropathy , and grade 2 alopecia,
but the other adverse events were mild. In conclusion, TC combination
chemotherapy was well tolerated and generated a good response in a
patient with recurrent ovarian clear cell adenocarcinoma who was
receiving hemodialysis for chronic kidney disease.
Preventing Ovarian Cancer through Genetic Testing: a Population-Based Study
abstract
"Genetic testing for BRCA1 and BRCA2 gene mutations, in conjunction with preventive oophorectomy for mutation carriers, may be used to prevent a proportion of invasive ovarian cancers (‘personalized medicine’). We evaluated the potential utility of this approach at a population level by reviewing the pedigree information and genetic test results from 1,342 ovarian cancer patients in Ontario. Of the 1,342 patients tested, 176 patients had a BRCA1 or BRCA2 mutation; of these, 48 women would have qualified for testing prior to the development of cancer based on the eligibility criteria in place for the province of Ontario. In summary, 48 of 1,342 unselected cases of ovarian cancer (3.6 %) might have been prevented if genetic testing criteria were universally applied to all women in Ontario at risk for ovarian cancer."
Thursday, November 07, 2013
Small fallopian tube carcinoma with extensive upper abdominal dissemination: a case report (Portugal)
a case report - open access
Introduction
Fallopian tube carcinoma is a rare gyncological malignancy with low accuracy detection
preoperatively. The symptoms are unspecific and imaging can be misleading. Since it
was first described in 1847, there have been only a little over 2000 case reports.
Case presentation
This case report describes a 66-year-old Caucasian woman who presented with progressive
diffuse abdominal pain, without other symptoms. After abdominopelvic magnetic resonance
imaging, she was sent to the Portuguese Oncology Institute of Oporto with the suspicion
of peritoneal carcinomatosis of unknown primary tumor. Due to a pelvic palpable mass
(calcified giant uterine fibroid) she was directed to the Gynecology team. Surgery
was performed and a large mass in her upper abdomen was identified. The extemporary
examination revealed a high-grade adenocarcinoma. During surgery a small change of
color and consistency of her left fallopian tube was noted and unilateral adnexectomy
was performed. After pathologic and immunohistochemistry tests, the diagnosis of fallopian
tube carcinoma with peritoneal dissemination was made.
Conclusions
This case is very unique in the way that a small primary fallopian tube carcinoma
was able to disseminate to the upper abdominal quadrant with little pelvic dissemination.
The symptoms and imaging were unspecific. Although a rare occurrence, we should not
forget fallopian tube carcinoma in the differential diagnosis of peritoneal carcinomatosis,
even in the absence of Latzke's triad (symptoms).
Epidermal Growth Factor Receptor (EGFR), HER2 and Insulin Growth Factor Receptor-1 (IGFR-1) Status in Ovarian Adult Granulosa Cell Tumours
abstract
Aims
Adult
granulosa cell tumours (AGCTs) are uncommon ovarian sex cord-stromal
tumours which recur following surgical removal in up to 50% of patients.
Treatment options for recurrent and advanced stage AGCTs are limited
with poor response to chemotherapy and radiotherapy. We aimed to assess
the Epidermal Growth Factor Receptor (EGFR) (HER1), HER2 and Insulin
Growth Factor Receptor-1 (IGFR-1) status in AGCTs with a view to
investigating whether these receptors might be potential therapeutic
targets in these neoplasms.
Methods And Results
Immunohistochemical
staining for EGFR, HER2 and IGFR-1 was undertaken in 31 AGCTs. Tumour
DNA was also analysed for mutations in the tyrosine kinase domain of EGFR
(exons 18-21) by Cobas mutation RT-PCR. 23/31 (74%) AGCTs showed some
degree of EGFR expression, generally with cytoplasmic or mixed
membranous and cytoplasmic staining of variable intensity. 11/27 (41%)
cases exhibited strong membranous and cytoplasmic expression of IGFR-1.
HER2 expression was not seen. No mutations were found in exons 18-21 of
the EGFR gene in hotspots of therapeutic relevance.
Conclusions
This
study raises the possibility that anti-EGFR and/or anti-IGFR-1
therapies may be potential agents in ovarian AGCTs and this requires
further study. Lack of known mutations within the tyrosine kinase domain
of EGFR suggests that EGFR-related tyrosine kinase inhibitors may not
be useful therapeutically.
How well is our health system working? · Canada
NHS England » NHS England launches major exercise to shape the future of specialised services
NHS England-future of specialised services
The scoping event will be held in London on 9 December. Anybody who is interested in being involved in the debate about the future of specialised services and wishes to apply for a place should email dorothy.chen@shca.info.
Canadian Doctors for Medicare: Fraser Institute report on wait times flawed
Canadian Doctors for Medicare E-News November 2013
CDM: Fraser Institute report on wait times flawed
Dr. Ryan Meili questions the usefulness of the Fraser Institute’s latest report on wait times in the National Post.
The Fraser Institute’s annual wait times report is based on a survey,
not objective data, and it looks only at specialists providing elective
surgeries, ignoring Canada’s good record with acute and emergency
surgeries. Respondents are therefore self-selected, and responses are
solicited with the incentive of winning an iPad.
CDM knows that this isn’t a credible way to gather data on wait times. We can be doing better on wait times, but we should be looking at the evidence, not surveys of a self-selected group, to tell us how we’re doing.
National Post
But some question the Fraser Institute report and the conclusions of its authors.
“It is the same old sky-is-falling report,” said Dr. Ryan Meili, a family physician in Saskatoon who is vice-chairman of Canadian Doctors For Medicare.
“Wait times don’t get shorter when you introduced more delivery of care outside of the public system, they get longer. You don’t just draw patients away from the public system, you also draw away providers,” he said.
Dr. Michael Rachlis, a health policy analyst associated with the Canadian Health Coalition, a pro-universal-healthcare organization, said the co-payment plans from abroad “which allow some people to jump the queue” is not the answer to Canada’s wait times.
“We do tend to wait too long but it has nothing to do with us having a public system. It has a lot to do with how we organize services,” Dr. Rachlis said. “We can eliminate virtually every wait time by better management.”
The institute’s (Fraser) questionnaire was sent to practitioners between the beginning of January and the end of April. The response rate to the surveys was 21%.
CDM knows that this isn’t a credible way to gather data on wait times. We can be doing better on wait times, but we should be looking at the evidence, not surveys of a self-selected group, to tell us how we’re doing.
National Post
But some question the Fraser Institute report and the conclusions of its authors.
“It is the same old sky-is-falling report,” said Dr. Ryan Meili, a family physician in Saskatoon who is vice-chairman of Canadian Doctors For Medicare.
“Wait times don’t get shorter when you introduced more delivery of care outside of the public system, they get longer. You don’t just draw patients away from the public system, you also draw away providers,” he said.
Dr. Michael Rachlis, a health policy analyst associated with the Canadian Health Coalition, a pro-universal-healthcare organization, said the co-payment plans from abroad “which allow some people to jump the queue” is not the answer to Canada’s wait times.
“We do tend to wait too long but it has nothing to do with us having a public system. It has a lot to do with how we organize services,” Dr. Rachlis said. “We can eliminate virtually every wait time by better management.”
The institute’s (Fraser) questionnaire was sent to practitioners between the beginning of January and the end of April. The response rate to the surveys was 21%.
Characteristics, treatment and prognostic factors of patients with gynaecological malignancies treated in a palliative care unit at a university hospital
abstract
Background: Limited clinical data have been published on patients suffering from advanced gynaecological malignancies treated in palliative care units, and little is known about prognostic factors.
Methods: In a retrospective study, the data of 225 patients with breast, ovarian and cervical cancer treated in the palliative care unit of a university hospital between 1998 and 2009 were assembled. Clinical aspects and baseline symptoms, laboratory parameters, the clinical course, and outcome were evaluated.
Results: 225 patients (497 cases; cancer diagnoses: breast 79%, ovarian 13%, and cervix 8%) were included in the analysis. The main symptoms were weakness/fatigue (71%), pain (65%), anorexia/nausea (62%), and dyspnea (46%). Pain control was achieved in 85% of all cases, satisfying control of other symptoms in 80%.
Wednesday, November 06, 2013
Is CA72-4 a Useful Biomarker in Differential Diagnosis between Ovarian Endometrioma and Epithelial Ovarian Cancer?
open access
Abstract
Background. Surgical excision of ovarian endometriomas in patients desiring pregnancy has recently been criticized because of the risk of damage to healthy ovarian tissue and consequent reduction of ovarian reserve. A correct diagnosis in cases not scheduled for surgery is therefore mandatory in order to avoid unexpected ovarian cancer misdiagnosis. Endometriosis is often associated with high levels of CA125. This marker is therefore not useful for discriminating ovarian endometrioma from ovarian malignancy. The aim of this study was to establish if the serum marker CA72-4 could be helpful in the differential diagnosis between ovarian endometriosis and epithelial ovarian cancer.
Methods. Serums CA125 and CA72-4 were measured in 72 patients with ovarian endometriomas and 55 patients with ovarian cancer.
Results. High CA125 concentrations were observed in patients with ovarian endometriosis and in those with ovarian cancer. A marked difference in CA72-4 values was observed between women with ovarian cancer (71.0%) and patients with endometriosis (13.8%) ( ).
Conclusions. This study suggests that CA72-4 determination can be useful to confirm the benign nature of ovarian endometriomas in women with high CA125 levels.
1. Introduction
Endometriosis is a common chronic disease, affecting 5–10% of women in reproductive age [1]. The disease is characterized by the presence and growth of endometrial tissue outside the uterine cavity, often associated with infertility and pelvic pain and that tends to recur [2–5]. Endometriosis can be diagnosed by clinical and ultrasound examinations (US), but the most accurate procedure to confirm the diagnosis is laparoscopy that allows visualization of lesions and histological confirmation [6].
Endometriosis is a benign disease but it shares several characteristics with invasive cancer. Cancer antigen 125 (CA125) is a tumor marker used for the differential diagnosis in a postmenopausal woman with an adnexal mass [7]. However, in premenopausal age, CA125 is characterized by a low diagnostic specificity, as abnormally high concentrations can be found in malignancies of different origin including nonovarian gynecological cancer [8], in women with nongynecological diseases such as tuberculosis and liver cirrhosis, and also in pelvic inflammatory disease, uterine fibroids, or physiological conditions such as pregnancy or different phases of the menstrual cycle [9, 10]. In patients with endometriosis, CA125 levels can be high. In fact, CA125 is the most extensively investigated and used peripheral biomarker for monitoring the disease [11]. Thus, CA125 has a limited role in the differential diagnosis between endometriosis and ovarian cancer due to the lack of specificity [12].....
Cancer Drug Trial Put on Partial Hold After Death (Curis - CUDC-427)
CUDC-427 Phase 1 Trial Placed on Partial Clinical Hold by FDA
"The current open-label, single-agent, dose escalation Phase 1 study of CUDC-427 was initiated in the third quarter of 2013 in patients with advanced and refractory solid tumors or lymphomas."
Bevacizumab-induced transient sixth nerve palsy in ovarian cancer: A case report
abstract
"We report a case of transient sixth nerve palsy after systemic administration of bevacizumab. Two days after systemic administration of bevacizumab in conjunction with gemcitabine and carboplatin in a 67-year-old woman with recurrent primary ovarian cancer, the patient developed sixth nerve palsy. After bevacizumab was stopped, the complete left sixth nerve palsy resolved spontaneously over the course of 3 months. This is the first reported case of bevacizumab-induced cranial sixth nerve palsy in the treatment of gynecologic malignancy."
Prevalence of Occult Gynecologic Malignancy at the Time of Risk Reducing and Non Prophylactic Surgery in Patients with Lynch Syndrome
abstract
Highlights
- •
- Surgeons should consider the possibility of malignancy in patients with Lynch syndrome who are undergoing risk-reducing surgery.
- •
- Surgeons should consider pre-operative testing and sending operative specimens for frozen pathology to determine the need for staging.
Objective:
The primary aim of this study was to determine the prevalence of occult
gynecologic malignancy at the time of risk reducing surgery in patients
with Lynch Syndrome. A secondary aim was to determine the prevalence of
occult gynecologic malignancy at the time of surgery for
non-prophylactic indications in patients with Lynch Syndrome.
Methods:
A retrospective review of an Inherited Colorectal Cancer Registry found
76 patients with Lynch syndrome (defined by a germline mutation in a
DNA mismatch repair gene) or hereditary nonpolyposis colorectal cancer
(HNPCC) (defined by Amsterdam criteria) who had undergone hysterectomy
and/or salpingo-oophorectomy for a prophylactic or non-prophylactic
indication. Indications for surgery and the prevalence of cancer at the
time of each operation were reviewed.
Results: 24 of
76 patients underwent prophylactic hysterectomy and/or bilateral
salpingo-oophorectomy for Lynch syndrome or HNPCC. In 9 of these
patients, a benign indication for surgery was also noted. 4 of 24
patients (17%, 95% CI = 5-38%) were noted to have cancer on final
pathology. 20 of 76 patients (26%) undergoing operative management for
any indication were noted to have occult malignancy on final pathology.
Conclusions:
Patients should be counseled about the risks of finding gynecologic
cancer at the time of prophylactic or non-prophylactic surgery for Lynch
syndrome and HNPCC, and the potential need for additional surgery.
Prognostic value of baseline survival determined for 11 types of cancer
science news
Nov. 6, 2013 — Results of an EORTC study published in Cancer point out the prognostic value of baseline recorded health-related quality of life for survival for eleven types of cancer: brain, breast, colorectal, esophageal, head and neck, lung, melanoma, ovarian, pancreatic, prostate, and testicular cancer. For each cancer site, at least one health-related quality of life parameter provided additional prognostic information over and above the clinical and sociodemographic variables.....
"nausea and vomiting for ovarian cancer"
abstract
A global analysis of multitrial data investigating quality of life and symptoms as prognostic factors for survival in different tumor sites
BACKGROUND
The
objective of this study was to examine the prognostic value of baseline
health-related quality of life (HRQOL) for survival with regard to
different cancer sites using 1 standardized and validated patient
self-assessment tool.
METHODS
In
total, 11 different cancer sites pooled from 30 European Organization
for Research and Treatment of Cancer (EORTC) randomized controlled
trials were selected for this study. For each cancer site, univariate
and multivariate Cox proportional hazards modeling was used to assess
the prognostic value (P < .05) of 15 HRQOL parameters using
the EORTC Core Quality of Life Questionnaire (QLQ-C30). Models were
adjusted for age, sex, and World Health Organization performance status
and were stratified by distant metastasis.
RESULTS
In
total, 7417 patients completed the EORTC QLQ-C30 before randomization.
In brain cancer, cognitive functioning was predictive for survival; in
breast cancer, physical functioning, emotional functioning, global
health status, and nausea and vomiting were predictive for survival; in
colorectal cancer, physical functioning, nausea and vomiting, pain, and
appetite loss were predictive for survival; in esophageal cancer,
physical functioning and social functioning were predictive for
survival; in head and neck cancer, emotional functioning, nausea and
vomiting, and dyspnea were predictive for survival; in lung cancer,
physical functioning and pain were predictive for survival; in melanoma,
physical functioning was predictive for survival; in ovarian cancer,
nausea and vomiting were predictive for survival; in pancreatic cancer,
global health status was predictive for survival; in prostate cancer,
role functioning and appetite loss were predictive for survival; and, in
testis cancer, role functioning was predictive for survival.
CONCLUSIONS
The current results demonstrated that, for each cancer site, at least 1 HRQOL domain provided prognostic information that was additive over and above clinical and sociodemographic variables.eNews: Live at the AICR Annual Research Conference (AICR)
eNews
This article appears in the November 7, 2013 issue of AICR's eNews.
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Editorial: A structured approach to uncommon cancers: what should a clinician do?
Abstract
In this issue of Annals of Oncology, Pecuchet et al. [1]
have produced an elegant, original paper describing an innovative
approach to the management of metastatic collecting duct
carcinoma, using bevacizumab, gemcitabine and a
platinum complex. They have shown surprising anticancer activity, which
appears
to have been sustained. They have addressed the
usual concerns about case selection bias, positive response bias and
pathology
review of an uncommon tumor, and thus, this
regimen certainly will bear confirmatory testing in other structured
trials, especially
as this triplet really does seem to give a
different result from the more conventional gemcitabine–cisplatin
combination or
the established MVAC regimen (notwithstanding
the absence of level 1 data at this time).
The editorial review of this manuscript
raised an important generic question, viz. what should a clinician do
when approaching
a patient with a truly uncommon or rare tumor?
Using a cut-off figure of 15 new cases/100 000 of population per year as
a
definition for ‘rare cancers’, Greenlee et al. [2]
have suggested that these tumors cumulatively account for around 25% of
incident cases in the United States. This figure
seems inflated to me, because of their cut-off
value, especially as I do not view testicular cancer as a rare tumor
(yet it
has an incidence of 6.8/100 000 males per year).
Nonetheless, Greenlee et al. make an important point—rare tumors
cumulatively
do constitute a significant proportion of the
total cancers presenting, yet we have remarkably little information
available
to guide management, when compared with the
common tumors that arise in breast, lung, prostate, colon, pancreas and
bladder.
A similar situation appears to apply to oncology
practice in Europe, in a report using a cut-off of less than six new
cases/100
000 of population per year, with the
accompanying suggestion …...
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