Saturday, January 24, 2015
Correspondence: Are we ready for conservative treatment in ovarian cancer?
Correspondence: open access
In conclusion, we think we are ready for fertility-sparing surgery in early epithelial ovarian cancer as an effective alternative to conventional radical surgery in younger women but just for selected cases where recurrence rate is very low such as FIGO stage IA/IB-G1/G2, and we need to be very careful with stages IC and G3 individualizing every case.
Original article: open access
[brain tumors] Glioblastomas, astrocytomas and oligodendrogliomas linked to Lynch syndrome
abstract
Glioblastomas, astrocytomas and oligodendrogliomas linked to Lynch syndrome
Background and purpose
Brain tumors represent a rare and relatively uncharacterized tumor type in Lynch syndrome.
Methods
The
national Danish Hereditary Nonpolyposis Colorectal Cancer Register was
utilized to estimate the cumulative life-time risk for brain tumors in
Lynch syndrome, and the mismatch repair (MMR) status in all tumors
available was evaluated.
Results
Primary
brain tumors developed in 41/288 families at a median age of 41.5
(range 2–73) years. Biallelic MMR gene mutations were linked to brain
tumor development in childhood. The risk of brain tumors was
significantly higher (2.5%) in MSH2 gene mutation carriers compared to patients with mutations in MLH1 or MSH6.
Glioblastomas predominated (56%), followed by astrocytomas (22%) and
oligodendrogliomas (9%). MMR status was assessed in 10 tumors, eight of
which showed MMR defects. None of these tumors showed
immunohistochemical staining suggestive of the IDH1 R132H mutation.
Conclusion
In Lynch syndrome brain tumors occurred in 14% of the families with significantly higher risks for individuals with MSH2 gene mutations and development of childhood brain tumors in individuals with constitutional MMR defects.
Reporting and Grading Financial Toxicity (the Art of Oncology series)
open access
Grade | Description |
---|---|
1 | Lifestyle modification (deferral of large purchases or reduced spending on vacation and leisure activities) because of medical expenditure |
Use of charity grants/fundraising/copayment program mechanisms to meet costs of care | |
2 | Temporary loss of employment resulting from medical treatment |
Need to sell stocks/investments for medical expenditure | |
Use of savings accounts, disability income, or retirement funds for medical expenditure | |
3 | Need to mortgage/refinance home to pay medical bills |
Permanent loss of job as a result of medical treatment | |
Current debts > household income | |
Inability to pay for necessities such as food or utilities | |
4 | Need to sell home to pay for medical bills |
Declaration of bankruptcy because of medical treatment | |
Need to stop treatment because of financial burden | |
Consideration of suicide because of financial burden of care |
Exceptions to the Rule: Case Studies in the Prediction of Pathogenicity for Genetic Variants in Hereditary Cancer Genes
abstract
Based on current consensus guidelines and standard practice, many genetic variants detected in clinical testing are classified as disease-causing based on their predicted impact on the normal expression or function of the gene in the absence of additional data. However, our laboratory has identified a subset of such variants in hereditary cancer genes for which compelling contradictory evidence emerged after the initial evaluation following the first observation of the variant. Three representative examples of variants in BRCA1, BRCA2 and MSH2 that are predicted to disrupt splicing, prematurely truncate the protein, or remove the start codon were evaluated for pathogenicity by analyzing clinical data with multiple classification algorithms. Available clinical data for all 3 variants contradicts the expected pathogenic classification. These variants illustrate potential pitfalls associated with standard approaches to variant classification as well as the challenges associated with monitoring data, updating classifications, and reporting potentially contradictory interpretations to the clinicians responsible for translating test outcomes to appropriate clinical action. It is important to address these challenges now as the model for clinical testing moves towards the use of large multi-gene panels and whole exome/genome analysis, which will dramatically increase the number of genetic variants identified.
Usefulness of Diagnostic Indices Comprising Clinical, Sonographic, and Biomarker Data for Discriminating Benign From Malignant Ovarian Masses
abstract
J Ultrasound Med. 2015 Feb
Pazopanib and Liposomal Doxorubicin in the Treatment of Patients with Relapsed/Refractory Epithelial Ovarian Cancer: A Phase Ib Study of the Sarah Cannon Research Institute
abstract
Purpose:
To investigate the combination of liposomal doxorubicin/pazopanib in
advanced relapsed/refractory ovarian cancer.
Patients and Methods: Twenty-two patients received liposomal doxorubicin/pazopanib. Initial doses (liposomal doxorubicin, 40 mg/m2 monthly; pazopanib, 400 mg daily) were too toxic; three subsequent groups received lower doses/altered schedules.
Results: The maximum tolerated doses (MTD) were liposomal doxorubicin, 30 mg/m2, and pazopanib, 400 mg daily. Severe toxicity included neutropenia (18%), rash/desquamation (14%), hypertension (9%), and hand-foot syndrome (9%). Five of the eight patients treated with MTD had grade 3 toxicity during the first two cycles. Dose reductions were frequently required.
Conclusions: Further development of the liposomal doxorubicin/pazopanib combination is not recommended.
Patients and Methods: Twenty-two patients received liposomal doxorubicin/pazopanib. Initial doses (liposomal doxorubicin, 40 mg/m2 monthly; pazopanib, 400 mg daily) were too toxic; three subsequent groups received lower doses/altered schedules.
Results: The maximum tolerated doses (MTD) were liposomal doxorubicin, 30 mg/m2, and pazopanib, 400 mg daily. Severe toxicity included neutropenia (18%), rash/desquamation (14%), hypertension (9%), and hand-foot syndrome (9%). Five of the eight patients treated with MTD had grade 3 toxicity during the first two cycles. Dose reductions were frequently required.
Conclusions: Further development of the liposomal doxorubicin/pazopanib combination is not recommended.
Friday, January 23, 2015
International Profiles of Health Care Systems, 2014: Australia, Canada, Denmark, England, France, Germany, Italy, Japan, The Netherlands, New Zealand, Norway, Singapore, Sweden, Switzerland, and the US
The Commonwealth Fund
Overview
This publication presents overviews of the health care systems of Australia, Canada, Denmark, England, France, Germany, Italy, Japan, the Netherlands, New Zealand, Norway, Singapore, Sweden, Switzerland, and the United States. Each overview covers health insurance, public and private financing, health system organization and governance, health care quality and coordination, disparities, efficiency and integration, use of information technology and evidence-based practice, cost containment, and recent reforms and innovations. In addition, summary tables provide data on a number of key health system characteristics and performance indicators, including overall health care spending, hospital spending and utilization, health care access, patient safety, care coordination, chronic care management, disease prevention, capacity for quality improvement, and public views. Read the report.video: Future of cancer treatment at the World Economic Forum
video CBS news
|CBS News medical contributor Dr. David Agus speaks with Dr. Jose Baselga, physician-in-chief and chief medical officer of Memorial Sloan Kettering Cancer Center, about the future of cancer treatment and genome mapping.
ASCO launches big data effort to study cancer
media
The American Society of Clinical Oncology is teaming up with SAP on an big data initiative that will use EHRs to examine previously inaccessible information that may lead to early identification on potential cancer patients.....
Unexpected Gynecologic Malignancy Diagnosed After Hysterectomy Performed for Benign Indications
abstract
OBJECTIVE: To define the incidence of unexpected
gynecologic malignancies among women who underwent hysterectomy for
benign indications.
METHODS: We conducted a data analysis of hysterectomy
cases from a quality and safety database maintained by the Michigan
Surgical Quality Collaborative, a statewide group of hospitals that
voluntarily reports perioperative outcomes. Cases were abstracted from
January 1, 2013, through December 8, 2013. Benign preoperative surgical
indications included pelvic mass, family history of cancer, hyperplasia
without atypia, prolapse, endometriosis, pelvic pain, abnormal uterine
bleeding, or leiomyomas. Women with a surgical indication of cancer,
cervical dysplasia, or hyperplasia with atypia were excluded.
Costs and Benefits of Opportunistic Salpingectomy as an Ovarian Cancer Prevention Strategy
abstract/full text
OBJECTIVE: To conduct a cost-effectiveness analysis of
opportunistic salpingectomy (elective salpingectomy at hysterectomy or
instead of tubal ligation).
METHODS: A Markov Monte Carlo simulation model
estimated the costs and benefits of opportunistic salpingectomy in a
hypothetical cohort of women undergoing hysterectomy for benign
gynecologic conditions or surgical sterilization. The primary outcome
measure was the incremental cost-effectiveness ratio. Effectiveness was
measured in terms of life expectancy gain. Sensitivity analyses
accounted for uncertainty around various parameters. Monte Carlo
simulation estimated the number of ovarian cancer cases associated with
each strategy in the Canadian population.
RESULTS: Salpingectomy with hysterectomy was less
costly ($11,044.32±$1.56) than hysterectomy alone ($11,206.52±$29.81) or
with bilateral salpingo-oophorectomy ($12,626.84±$13.11) but more
effective at 21.12±0.02 years compared with 21.10±0.03 and 20.94±0.03
years, representing average gains of 1 week and 2 months, respectively.
For surgical sterilization, salpingectomy was more costly
($9,719.52±$3.74) than tubal ligation ($9,339.48±$26.74) but more
effective at 22.45±0.02 years compared with 22.43±0.02 years (average
gain of 1 week) with an incremental cost-effectiveness ratio of $27,278
per year of life gained. Our results were stable over a wide range of
costs and risk estimates. Monte Carlo simulation predicted that
salpingectomy would reduce ovarian cancer risk by 38.1% (95% confidence
interval [CI] 36.5–41.3%) and 29.2% (95% CI 28.0–31.4%) compared with
hysterectomy alone or tubal ligation, respectively.
CONCLUSION: Salpingectomy with hysterectomy for benign
conditions will reduce ovarian cancer risk at acceptable cost and is a
cost-effective alternative to tubal ligation for sterilization.
Opportunistic salpingectomy should be considered for all women
undergoing these surgical procedures.
Over the past decade, there is increasing evidence that the majority of
ovarian cancers arise in the fallopian tube and not primarily in the
ovary.1–4
Consequently, in 2010 the British Columbia Ovarian Cancer Research
Group
Dying with Dignity | It's your life. It's your choice. - Take action (Ontario)
Dying with Dignity
Toolkit for Submissions on CPSO's Draft Policy on End-of-Life Care
Looking
to provide feedback on the College of Physicians and Surgeons of
Ontario's draft policy of end-of-life care? We've put together a toolkit
to help you craft a forceful appeal.
As we've said, the CPSO has made it easy to provide feedback on its proposed end-of-life care policies. You can submit your thoughts in the following ways:
2) Include a forceful opening statement. In clear, concise language, tell committee members why the CPSO needs to play a strong role in developing a legal and regulatory framework for assisted dying in Ontario. This can take the form of a short introductory paragraph or a list of bullet points.
3) Stress the importance of timing. With the Supreme Court set to weigh in on the future of the Criminal Code ban on assisted dying, and with end-of-life bills on the table in Parliament, Canadian doctors face the very real possibility that the practice could become legal this year.
4) Bring up Quebec. Physicians were instrumental in the crafting of Bill 52, an end-of-life care bill that passed through Quebec’s National Assembly last year. Set to come into force at the end of 2015, the law ensconces palliative care as a right and grants Quebecers the option to choose medically assisted dying so long as they fulfill certain criteria.
4) Use personal experience. If possible, include a personal anecdote to illustrate why it’s important for the CPSO to take a stand. Have you encountered physicians who were ill-equipped or simply unwilling to discuss a wide range of end-of-life care options, including assisted dying, with you or members of your family? Are you worried that the orders you’ve made in your Advance Care Plan won’t be respected? It is our experience personal stories carry a lot of weight in consultations like these.
5) Include your professional qualifications/background, if appropriate. Do you have a background in the healthcare profession? If so, note it. In addition, state how your work has shaped your perspective on end-of-life care. If you don’t work in health field, feel free to state your professional background affects your point of view, too. The CPSO is asking for the input from people from all walks of life — not just medical practitioners
- By posting to the CPSO's end-of-life care discussion forum;
- By firing off an e-mail to ;
- By filling out a quick and easy online survey (there are text boxes in which you can elaborate on your responses);
- By sending a letter through the mail. (To: College of Physicians and Surgeons of Ontario, 80 College St., Toronto, Ont., M5G 2E2)
Toolkit for written submissions to the College of Physicians and Surgeons of Ontario
1) Read the CPSO’s draft policy, “Planning for and Providing Quality of End-of-Life Care.” It’s not long — only 15-pages, and the font is large. Knowing what’s in the document will help you respond to, and expand upon, the organization’s new policies.2) Include a forceful opening statement. In clear, concise language, tell committee members why the CPSO needs to play a strong role in developing a legal and regulatory framework for assisted dying in Ontario. This can take the form of a short introductory paragraph or a list of bullet points.
3) Stress the importance of timing. With the Supreme Court set to weigh in on the future of the Criminal Code ban on assisted dying, and with end-of-life bills on the table in Parliament, Canadian doctors face the very real possibility that the practice could become legal this year.
4) Bring up Quebec. Physicians were instrumental in the crafting of Bill 52, an end-of-life care bill that passed through Quebec’s National Assembly last year. Set to come into force at the end of 2015, the law ensconces palliative care as a right and grants Quebecers the option to choose medically assisted dying so long as they fulfill certain criteria.
4) Use personal experience. If possible, include a personal anecdote to illustrate why it’s important for the CPSO to take a stand. Have you encountered physicians who were ill-equipped or simply unwilling to discuss a wide range of end-of-life care options, including assisted dying, with you or members of your family? Are you worried that the orders you’ve made in your Advance Care Plan won’t be respected? It is our experience personal stories carry a lot of weight in consultations like these.
5) Include your professional qualifications/background, if appropriate. Do you have a background in the healthcare profession? If so, note it. In addition, state how your work has shaped your perspective on end-of-life care. If you don’t work in health field, feel free to state your professional background affects your point of view, too. The CPSO is asking for the input from people from all walks of life — not just medical practitioners
Salpingectomy as a Means to Reduce Ovarian Cancer Risk
PDF] Salpingectomy as a Means to Reduce Ovarian Cancer Risk
Cancer Prevention 2015
ABSTRACT
Bilateral salpingo-oophorectomy (BSO) has become the standard of care for risk
reduction in women at hereditary risk of ovarian cancer. While this procedure significantly
decreases both the incidence of and mortality from ovarian cancer, it impacts quality of life, and the premature cessation of ovarian function may have long term health hazards. Recent advances in our understanding of the molecular pathways of ovarian cancer point to the fallopian tube epithelium as the origin of most high grade serous cancers (HGSC). This evolving appreciation of the role of the fallopian tube in HGSC has led to the consideration of salpingectomy alone as an option for risk management, especially in premenopausal women. In addition, it is postulated that bilateral salpingectomy with ovarian retention (BSOR), may have a public health benefit for women undergoing benign gynecologic surgery. In this review we provide the rationale for salpingectomy as an ovarian cancer risk reduction strategy.
A Systematic Review of the Bimanual Examination as a Test for Ovarian Cancer
Abstract
Context
An
annual bimanual pelvic examination remains widely recommended for
healthy women, but its inclusion may discourage attendance. Our goal was
to determine the accuracy of the pelvic examination as a screening test
for ovarian cancer and to distinguish benign from malignant lesions.
Evidence acquisition
PubMed
was searched to identify studies evaluating the accuracy of the
bimanual pelvic examination for ovarian cancer diagnosis. Data regarding
study design, study quality, and test accuracy were abstracted.
Heterogeneity was evaluated and meta-analysis performed where
appropriate, including bivariate receiver operating characteristic
curves.
Evidence synthesis
Eight studies in screening populations (n=36,599) and seven studies in symptomatic patients (n=782)
were identified. Search was completed in November 2013; included
studies were published between 1988 and 2009. Screening studies were
homogeneous; the summary estimates of sensitivity and specificity of the
pelvic examination as a screening test for ovarian cancer were 0.44 and
0.98 (positive likelihood ratio, 24.7; negative likelihood ratio,
0.57). For distinguishing benign versus malignant lesions, there was
considerable heterogeneity, with a range of sensitivity from 0.43 to
0.93 and specificity from 0.53 to 0.91.
Conclusions
The
bimanual pelvic examination lacks accuracy as a screening test for
ovarian cancer and as a way to distinguish benign from malignant
lesions. In a typical screening population, the positive predictive
value of an abnormal pelvic examination is only 1% (95% CI=0.67%, 3.0%).
Its inclusion in a health maintenance examination cannot be justified
on the basis of using it to screen for ovarian cancer.
Bilateral ovarian metastases from ureteric urothelial cancer: Initial case report and distinguishing role of immunohistochemistry
Blogger's Note: of interest to Lynch Syndrome patients
abstract
Full Text: PDF
Abstract
Urothelial cancers of the upper tract are aggressive malignancies
with a propensity for distant metastases. Transitional cell carcinoma
can also develop de novo in the ovaries and differentiation between
these lesions requires immunohistochemistry. We report a case of right
lower ureteric urothelial carcinoma with metastases to both ovaries. To
our knowledge, this is the first reported case of bilateral ovarian
metastases from an upper tract primary, diagnosed with
immunohistochemistry.
case, the ovarian lesions were positive for CK7 and CK20,
and negative for WT1, indicating the primary was in the
urinary tract. Differentiation is important as ovarian primaries
are more chemosensitive and have a better prognosis.5"
Paradoxes of follow-up – health professionals’ views on follow-up after surgical treatment in gynecological cancer care
Blogger's Note: "shift in focus is needed from relapse to quality of life after cancer"
In absence of the full text, a case could be made for prevention and/or early detection of second primary cancers. Myriad Genetics recently published stats on Lynch Syndrome patients of which 50% will face a second primary within 15 years of original diagnosis.
abstract
Objective. Evidence now reveals that attending a
follow-up program may not improve survival for low-stage gynecological
cancer patients. The aim of this study was to explore health
professionals’ experiences with the follow-up programs and their views
on follow-up in the future.
Methods. A qualitative approach was undertaken with semi-structured focus group interviews. Three focus group interviews were conducted at neutral ground. One group with onco-gynecologists, one group with specialist nurses, and one mixed group. The main themes of the interviewguide were: Existing follow-up program, life after cancer and future follow-up. The interviews were transcribed verbatim. Patterns and themes were uncovered from the data inspired by interpretive description.
Results. The doctors described most advantages, such as: Quality control of their own work, detection of sequelae after surgery, and credit and appraisal from the patients. A disadvantage was the inadequate use of the nurses’ main competencies. Some dilemmas were described by the nurses as well as doctors: First, both groups were aware of the existing evidence that attendance of follow-up programs may not improve survival and yet, health professionals still performed the follow-ups and most often did not address this paradox for the patients. Second, the existing follow-up program seemed to bring the patients comfort and security on one hand, but on the other hand it seemed to induce insecurity and anxiety. The health professionals agreed that future follow-up should be individualized with focus on the single patients’ needs and psychological wellbeing. The health professionals identified a great challenge in communicating the evidence and the forthcoming changes in the follow-up programs to the patients.
Methods. A qualitative approach was undertaken with semi-structured focus group interviews. Three focus group interviews were conducted at neutral ground. One group with onco-gynecologists, one group with specialist nurses, and one mixed group. The main themes of the interviewguide were: Existing follow-up program, life after cancer and future follow-up. The interviews were transcribed verbatim. Patterns and themes were uncovered from the data inspired by interpretive description.
Results. The doctors described most advantages, such as: Quality control of their own work, detection of sequelae after surgery, and credit and appraisal from the patients. A disadvantage was the inadequate use of the nurses’ main competencies. Some dilemmas were described by the nurses as well as doctors: First, both groups were aware of the existing evidence that attendance of follow-up programs may not improve survival and yet, health professionals still performed the follow-ups and most often did not address this paradox for the patients. Second, the existing follow-up program seemed to bring the patients comfort and security on one hand, but on the other hand it seemed to induce insecurity and anxiety. The health professionals agreed that future follow-up should be individualized with focus on the single patients’ needs and psychological wellbeing. The health professionals identified a great challenge in communicating the evidence and the forthcoming changes in the follow-up programs to the patients.
Conclusions.
This study revealed that the existing follow-up regime contains several
dilemmas. According to the health professionals, future follow-up must
be more individualized, and a shift in focus is needed from relapse to
quality of life after cancer.
Thursday, January 22, 2015
Editorial: Cancer: mixed messages, common purpose (Lancet)
full text
On Jan 2, a research paper published in Science by Cristian Tomasetti and Bert Vogelstein proclaimed that most individual cancers, 65%, could be attributed to “bad luck”—random events such as errors in DNA replication—rather than to environmental or inherited risk factors. This eyecatching message has drawn comment, partly because of the inbuilt uncertainty in the study's methods and headline estimate (with its 95% confidence interval of 39–81) and partly because of the conclusion's incompatibility with public health evidence and thinking......
Breast Cancer Patients Referred for Genetic Testing Likely to Have Mutations Other Than BRCA1/2
Mutations
Results
revealed that 1608 (9.5%) of females and 32 (16.2%) of males were
positive for at least one deleterious or suspected deleterious mutation.
Interestingly, among these mutations:
- 48.9% were detected in the Hereditary Breast and Ovarian Cancer (HBOC) genes BRCA1 and BRCA2.
- 42.1% were detected in other genes associated with breast cancer.
- 6.6% were detected in Lynch syndrome genes (MLH1, MSH2, MSH6, PMS2, EPCAM).
- 2.3% were detected in other genes not associated with breast cancer (APC, MUTYH, RAD51D, CDKN2A, SMAD4).
Results
revealed that 1608 (9.5%) of females and 32 (16.2%) of males were
positive for at least one deleterious or suspected deleterious mutation.
Interestingly, among these mutations:
- 48.9% were detected in the Hereditary Breast and Ovarian Cancer (HBOC) genes BRCA1 and BRCA2.
- 42.1% were detected in other genes associated with breast cancer.
- 6.6% were detected in Lynch syndrome genes (MLH1, MSH2, MSH6, PMS2, EPCAM).
- 2.3% were detected in other genes not associated with breast cancer (APC, MUTYH, RAD51D, CDKN2A, SMAD4).
Cancer mortality trends in Mexico, 1980-2011
abstract
Objective. To evaluate trends in cancer mortality in Mexico between 1980-2011.
Material and methods. Through direct method and using World Population 2010 as standard population, mortality rates for all cancers and the 15 most frequent locations, adjusted for age and sex were calculated. Trends in mortality rates and annual percentage change for each type of cancer were estimated by joinpoint regression model.
Results. As a result of the reduction in mortality from lung cancer (-3.2% -1.8% in men and in women), stomach (-2.1% -2.4% in men and in women) and cervix (-4.7%); since 2004 a significant (~1% per year) decline was observed in cancer mortality in general, in all ages, and in the group of 35-64 years of both sexes. Other cancers such as breast and ovarian cancer in women; as well as for prostate cancer in men, showed a steady increase.
Conclusions. Some of the reductions in cancer mortality may be partially attributed to the effectiveness of prevention programs. However, adequate records of population-based cancer are needed to assess the real impact of these programs; as well as designing and evaluating innovative interventions to develop more cost-effective prevention policies.
Wednesday, January 21, 2015
Environmental (nongenetic) factors in gynecological cancers: update and future perspectives
abstract
Globally, gynecological cancers comprise three of the seven most common female cancers and are responsible for more than 1,000,000 new cases and 500,000 deaths annually. This review summarizes current knowledge regarding the role of environmental factors in gynecological cancer etiology and survival, focusing on those that are potentially amenable to intervention. Strong associations with use of exogenous hormones are countered by opposing risks of breast cancer, thus current hormonal preparations are not an option for prevention. Weight control would reduce risk of endometrial cancer but this and other lifestyle modifications are unlikely to have a major effect on gynecological cancer mortality rates. There is little information regarding the potential for lifestyle changes to improve outcomes for women with gynecological cancer.
Ovarian stimulation and in-vitro fertilization outcomes of cancer patients
abstract
CONCLUSIONS:
Most IVF outcomes appear comparable for cancer patients and age-matched controls. Higher twin pregnancy rates in cancer patients may reflect lack of underlying infertility or need for cancer-specific transfer guidelines.A Systematic Review of the Bimanual Examination as a Test for Ovarian Cancer
Abstract
CONTEXT:
An annual bimanual pelvic examination remains widely recommended for healthy women, but its inclusion may discourage attendance. Our goal was to determine the accuracy of the pelvic examination as a screening test for ovarian cancer and to distinguish benign from malignant lesions.EVIDENCE ACQUISITION:
PubMed was searched to identify studies evaluating the accuracy of the bimanual pelvic examination for ovarian cancer diagnosis. Data regarding study design, study quality, and test accuracy were abstracted. Heterogeneity was evaluated and meta-analysis performed where appropriate, including bivariate receiver operating characteristic curves.EVIDENCE SYNTHESIS:
Eight studies in screening populations (n=36,599) and seven studies in symptomatic patients (n=782) were identified. Search was completed in November 2013; included studies were published between 1988 and 2009. Screening studies were homogeneous; the summary estimates of sensitivity and specificity of the pelvic examination as a screening test for ovarian cancer were 0.44 and 0.98 (positive likelihood ratio, 24.7; negative likelihood ratio, 0.57). For distinguishing benign versus malignant lesions, there was considerable heterogeneity, with a range of sensitivity from 0.43 to 0.93 and specificity from 0.53 to 0.91.CONCLUSIONS:
The bimanual pelvic examination lacks accuracy as a screening test for ovarian cancer and as a way to distinguish benign from malignant lesions. In a typical screening population, the positive predictive value of an abnormal pelvic examination is only 1% (95% CI=0.67%, 3.0%). Its inclusion in a health maintenance examination cannot be justified on the basis of using it to screen for ovarian cancer.Population-Based Lynch Syndrome Screening by Microsatellite Instability in Patients ≤50 (Louisiana, U.S.)
abstract
Population-Based Lynch Syndrome Screening by Microsatellite Instability in Patients ≤50: Prevalence, Testing Determinants, and Result Availability Prior to Colon Surgery.
Objectives:As there are no US population-based studies examining Lynch syndrome (LS) screening frequency by microsatellite instability (MSI) and immunohistochemistry (IHC), we seek to quantitate statewide rates in patients aged ≤50 years using data from a Centers for Disease Control and Prevention-funded Comparative Effectiveness Research (CER) project and identify factors associated with testing. Screening rates in this young, high-risk population may provide a best-case scenario as older patients, potentially deemed lower risk, may undergo testing less frequently. We also seek to determine how frequently MSI/IHC results are available preoperatively, as this may assist with decisions regarding colonic resection extent.
Methods:
Data from all Louisiana colorectal cancer (CRC) patients aged ≤50 years diagnosed in 2011 were obtained from the Louisiana Tumor Registry CER project. Registry researchers and physicians analyzed data, including pathology and MSI/IHC.
Results:
Of the 2,427 statewide all-age CRC patients, there were 274 patients aged ≤50 years, representing health care at 61 distinct facilities. MSI and/or IHC were performed in 23.0% of patients. Testing-associated factors included CRC family history (P<0.0045), urban location (P<0.0370), and care at comprehensive cancer centers (P<0.0020) but not synchronous/metachronous CRC or MSI-like histology. Public hospital screening was disproportionately low (P<0.0217). Of those tested, MSI and/or IHC was abnormal in 21.7%. Of those with abnormal IHC, staining patterns were consistent with LS in 87.5%. MSI/IHC results were available preoperatively in 16.9% of cases.
Conclusions:
Despite frequently abnormal MSI/IHC results, LS screening in young, high-risk patients is low. Provider education and disparities in access to specialized services, particularly in underserved populations, are possible contributors. MSI/IHC results are infrequently available preoperatively
Randomized trial of oral cyclophosphamide and veliparib in high-grade serous ovarian, primary peritoneal, or fallopian tube cancers, or BRCA-mutant ovarian cancer
abstract
Purpose: Veliparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, demonstrated clinical activity in combination with oral cyclophosphamide in patients with BRCA-mutant solid tumors in a phase 1 trial. To define the relative contribution of PARP inhibition to the observed clinical activity, we conducted a randomized phase 2 trial to determine the response rate of veliparib in combination with cyclophosphamide compared to cyclophosphamide alone in patients with pretreated BRCA-mutant ovarian cancer or in patients with pretreated primary peritoneal, fallopian tube, or high-grade serous ovarian cancers (HGSOC).
Experimental Design: Adult patients were randomized to receive cyclophosphamide alone (50 mg orally once daily) or with veliparib (60 mg orally once daily) in 21-day cycles. Crossover to the combination was allowed at disease progression.
Results: Seventy-five patients were enrolled and 72 were evaluable for response; 38 received cyclophosphamide alone and 37 the combination as their initial treatment regimen. Treatment was well tolerated. One complete response was observed in each arm, with three partial responses (PR) in the combination arm and six PRs in the cyclophosphamide alone arm. Genetic sequence and expression analyses were performed for 211 genes involved in DNA repair; none of the detected genetic alterations were significantly associated with treatment benefit.
Conclusions: This is the first trial that evaluated single agent, low dose cyclophosphamide in HGSOC, peritoneal, fallopian tube, and BRCA-mutant ovarian cancers. It was well tolerated and clinical activity was observed; the addition of veliparib at 60 mg daily did not improve either the response rate or the median progression free survival.
Stopping ovarian cancer screening in BRCA1/2 mutation carriers: Netherlands
abstract
Stopping ovarian cancer screening in BRCA1/2 mutation carriers: Effects on risk management decisions & outcome of risk-reducing salpingo-oophorectomy specimens
OBJECTIVE:
Ovarian cancer screening (OCS) for BRCA1/2 mutation carriers was stopped in our family cancer clinic in 2009 because of its ineffectiveness. The study objective was to investigate the effect of stopping OCS on the timing and uptake of risk-reducing salpingo-oophorectomy (RRSO) and on the percentage of occult cancers in the specimens.METHODS:
419 BRCA1/2 mutation carriers were recruited between January 1999 and June 2013. Uptake, timing and the outcome of the RRSO specimens before stopping OCS (period I) were compared to those after stopping OCS (period II).RESULTS:
The percentage of women undergoing RRSO within the recommended age range increased from 81% to 95%. Receiving DNA test results in period II independently predicted a shorter time interval to RRSO (hazard ratio: 2.48, 95% confidence interval: 1.81-3.39). The incidence of detecting occult cancers in RRSO specimens before and after stopping OCS was 1.3% and 1.8%, respectively, and was not statistically significantly different.CONCLUSIONS:
The presentation of risk management options to women may influence their decision. The increased patient awareness of the ineffectiveness of OCS could have led to a higher percentage of women undergoing RRSO and doing so more often within the recommended age range.Impact of investigations in general practice on timeliness of referral for patients subsequently diagnosed with cancer: UK
open access
"....We analysed data on patients with lung (1494), colorectal (2111), stomach (246), oesophagus (513), pancreas (327), and ovarian (345) cancer. These six cancer sites were selected because they each have a range of presenting symptoms from high to low risk, and because for each there is one or more investigation that may be appropriately ordered as part of the patient’s assessment in primary care and that is generally available to GPs in England.....
"Occult" ovarian Leydig cell tumor: when laboratory tells more than imaging
abstract
Hyperandrogenism
is a common finding in premenopausal age and is generally caused by
polycystic ovarian syndrome or other benign disease. Androgen-secreting
tumors represent only 0.2 % of the causes of hyperandrogenism and
usually present with severe clinical features, abrupt onset, and very
high androgens levels. We describe here three cases of occult ovarian
Leydig cell tumors suspected on the basis of severe clinical features of
hyperandrogenism rapidly worsening, with elevated serum total
testosterone levels, in which bilateral ovariectomy was performed and
tumor was confirmed by post-operative histology. In all three cases,
imaging was negative for ovarian tumor. Moreover, in one case the
confounding concomitant finding of bilateral adrenal masses posed an
additional challenge. Our experience highlights that testosterone levels
represent the most helpful marker in the diagnosis of
androgen-secreting ovarian tumor. In the absence of imaging findings,
bilateral ovariectomy should be indicated, if supported by unequivocal
clinical and laboratory data.
Is There a Role for Oral or Intravenous Ascorbate (Vitamin C) in Treating Patients With Cancer?
A Systematic Review
Conclusion. There is no high-quality evidence to suggest that ascorbate supplementation in cancer patients either enhances the antitumor effects of chemotherapy or reduces its toxicity. Given the high financial and time costs to patients of this treatment, high-quality placebo-controlled trials are needed.
A Meta-Analysis on the Impact of Platinum-Based Adjuvant Treatment on the Outcome of Borderline Ovarian Tumors With Invasive Implants
Gynecologic Oncology
The Oncologist first published on January 19, 2015; doi:10.1634/theoncologist.2014-0144
Borderline ovarian tumors
(BOTs) have been a challenge for patients, pathologists, and
oncologists. For the group of patients with invasive implants, there is
no consensus regarding standard therapy. This meta-analysis examines the
benefits, or lack thereof, of platinum-based adjuvant treatment for
BOT, showing that at present there is no evidence to support this
treatment form.
Editorial: Breaking Down the Evidence for Bevacizumab in Ovarian Cancer
Editorial
Breaking Down the Evidence for Bevacizumab in Ovarian Cancer
The Oncologist first published on January 19, 2015; doi:10.1634/theoncologist.2014-0302
Bevacizumab has been
FDA-approved for use in combination with single-agent chemotherapy for
platinum-resistant ovarian cancer; however, its optimal role remains
unclear. In this editorial, the timing, efficacy, safety, and rationale
for use of bevacizumab in ovarian cancer are discussed.
Tuesday, January 20, 2015
A Note about DWD Canada's Charity Status | Dying with Dignity
Dying with Dignity
Dying
with Dignity Canada (DWD Canada) has learned it will lose its
registered charity status as the result of recent political-activity
audits by the Canada Revenue Agency (CRA).
In
a letter dated January 16, the CRA said DWD Canada’s charitable status
will be annulled as soon as next month because the organization, in the
federal agency’s view, had been “registered in error” in 1982 and again
when DWD Canada was re-registered in 2011.“Based on our findings, it is our opinion that the Organization was, in fact, registered in error and, as a result, its registration under the [Income Tax Act] should be annulled,” the letter reads.
Founded in 1982, DWD Canada is a health and educational charity focused on promoting choice and dignity at end of life. The organization educates about the case for physician assisted dying, provides information about patient rights and advance care planning, and offers one-on-one support to individuals who are dying and want to do so on their own terms. In addition to making the case for the legalization of physician assisted dying, the charity had categorized a number of its activities as advancing education, such as its: • workshops and presentations
• quarterly newsletter,
• website and
• advance care planning resource kits.
However, the CRA determined that DWD Canada does not conduct “any activities advancing education in the charitable sense”. DWD Canada has a small staff (there were four staff positions during the audit period) and relies on volunteers for much of its work. In 2013, supporters donated approximately 8,000 volunteer-hours to the cause.
After fully assessing all options, the charity’s board of directors has voted not to oppose the annulment, which is expected to come into effect on or after February 15. The change in status will not affect the tax deductibility of any donations made to DWD Canada prior to that date. Until the annulment is finalized, DWD Canada will remain a registered charity to which Canadians can make tax-deductible donations. After that point, the organization will become a non-profit without registered charity status.
Because the CRA is proposing to annul DWD Canada’s registered status — as opposed to revoking it — all assets belonging to DWD Canada will remain with the organization. As a result, DWD Canada will not only be able to continue its important work in the area of promoting choice and dignity at end of life, but it will also, after its conversion to a non-profit, be free to focus on political advocacy without constraints.
More information about DWD Canada's next steps will be forthcoming in the weeks ahead. If you have any immediate concerns, please call us at 1-800-495-6156 or send an e-mail
Saturday, January 10, 2015
Small Bowel Cancer: Scoping Out a Rarity
medscape
Medscape: What predisposing factors are associated with an increased risk for small bowel adenocarcinoma?
Michael J. Overman, MD: There are three big factors. The first is hereditary nonpolyposis colorectal cancer (HNPCC), or Lynch syndrome, which predisposes not only to colorectal cancer but also to a number of other cancers, including small bowel adenocarcinoma. The second is inflammatory bowel disease (IBD), particularly Crohn's disease; these patients can have involvement of the distal small bowel (ileal adenocarcinoma). Celiac disease would be the third factor. Celiac disease is a gluten-associated enteropathy in which you have an autoimmune attack against gluten in your diet. You'll have inflammation in the epithelial lining of your small bowel as your body reacts to the gluten in your diet, and that inflammation can lead to an increased risk for small bowel adenocarcinoma. Those are the big three predisposing factors. However, the majority of small bowel adenocarcinomas, approximately 70%, are sporadic and have unclear factors associated with them.
Friday, January 09, 2015
Paclitaxel/carboplatin with or without sorafenib in the first-line treatment of patients with stage III/IV epithelial ovarian cancerry
open access: Paclitaxel/carboplatin with or without sorafenib in the first-line treatment of patients with stage III/IV epithelial ovarian cancer: a randomized phase II study of the Sarah Cannon Research Institute
".....Unfortunately, interpretation of the results is hindered since the trial accrued slowly and was closed after 85 of a planned 120 patients had been randomized. However, comparisons of the efficacy of the two regimens showed no differences in overall response rates, PFS, or overall survival. The PFSs for both groups of patients (paclitaxel/carboplatin/sorafenib, 15.4 months; paclitaxel/carboplatin, 16.3 months) were similar to those previously reported using standard therapy for advanced ovarian cancer. As anticipated, the patients who received sorafenib had more toxicity. The additional toxicity consisted primarily of well described sorafenib-related toxicity including skin toxicity, hand–foot syndrome, mucositis, and hypertension. The difficulty in tolerating the sorafenib-containing regimen resulted in a high rate of sorafenib dose reductions and discontinuations, and may have had an adverse impact on the efficacy of the regimen..........
As more evidence accumulates, it is evident that sorafenib is not the angiogenesis inhibitor-of-choice in the treatment of patients with advanced ovarian cancer.
Anti-vascular therapies in ovarian cancer: moving beyond anti-VEGF approaches
Abstract
Resistance to chemotherapy is among the most important issues in the management of ovarian cancer. Unlike cancer cells, which are heterogeneous as a result of remarkable genetic instability, stromal cells are considered relatively homogeneous. Thus, targeting the tumor microenvironment is an attractive approach for cancer therapy. Arguably, anti-vascular endothelial growth factor (anti-VEGF) therapies hold great promise, but their efficacy has been modest, likely owing to redundant and complementary angiogenic pathways. Components of platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and other pathways may compensate for VEGF blockade and allow angiogenesis to occur despite anti-VEGF treatment. In addition, hypoxia induced by anti-angiogenesis therapy modifies signaling pathways in tumor and stromal cells, which induces resistance to therapy. Because of tumor cell heterogeneity and angiogenic pathway redundancy, combining cytotoxic and targeted therapies or combining therapies targeting different pathways can potentially overcome resistance. Although targeted therapy is showing promise, much more work is needed to maximize its impact, including the discovery of new targets and identification of individuals most likely to benefit from such therapies.
Contraceptive methods and ovarian cancer risk among Chinese women: A report from the Shanghai women's health study
International Journal of Cancer
Oral contraceptive (OC) use is associated with reduced ovarian cancer risk; however, associations with other contraceptive methods, such as intrauterine device (IUD) and tubal ligation (TL), are less clear. Women in China differ from western women in regard to mechanisms and duration of use of contraception. This study was undertaken to evaluate associations between contraceptive methods and ovarian cancer risk using data from the prospective Shanghai Women's Health Study...... A total of 174 epithelial ovarian cancer cases were found to occur among 70,259 women that were followed for a total of 888,258 person years. The majority of women had ever used any contraception (77.0%), including IUD use (55.6%), OC use (20.4%), TL (14.7%), and contraceptive shots (2.6%). Ever use of any contraception was associated with a non-significant reduction in ovarian cancer risk (HR: 0.86, 95% CI: 0.60-1.24). Longer duration of IUD use was associated with lower ovarian cancer risk (P-value for trend=0.04). Compared to never users, women with durations of IUD use longer than the median (20 years) were 38% less likely to develop ovarian cancer (HR: 0.62, 95% CI: 0.40-0.97). Based on the high prevalence and long duration of IUD use among Chinese women, we estimate a preventive fraction of 9.3%, corresponding to approximately 16 ovarian cancer cases. High prevalence of long-term IUD use may therefore contribute to the low incidence of ovarian cancer observed in China.
Validation of Family Cancer History Data in High-Risk Families: The Influence of Cancer Site, Ethnicity, Kinship Degree, and Multiple Family Reporters
abstract
Information on family cancer history (FCH) is often collected for first-degree relatives, but more extensive FCH information is critical for greater accuracy in risk assessment. Using self-reported diagnosis of cancer as the gold standard, we examined differences in the sensitivity and specificity of relative-reported FCH by cancer site, race/ethnicity, language preference, and kinship degree (1,524 individuals from 557 families; average number of relatives per family = 2.7). We evaluated the impact of FCH data collected in 2007-2013 from multiple relatives by comparing mean values and proportions for the number of relatives with any cancer, breast cancer, or ovarian cancer as reported by a single relative and by multiple relatives in the same family. The sensitivity of FCH was lower in Hispanics, Spanish-speaking persons, and third-degree relatives (e.g., for all cancers, sensitivities were 80.7%, 87.4%, and 91.0% for third-, second-, and first-degree relatives, respectively). FCH reported by multiple relatives included a higher number of relatives with cancer than the number reported by a single relative (e.g., mean increase of 1.2 relatives with any cancer), with more relatives diagnosed with any cancer, breast cancer, and ovarian cancer in 52%, 36% and 12% of families, respectively. Collection of FCH data from multiple relatives may provide a more comprehensive picture of FCH and may potentially improve risk assessment and preventive care.
© The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.
Costs and Benefits of Opportunistic Salpingectomy as an Ovarian Cancer Prevention Strategy
abstract
OBJECTIVE::
To
conduct a cost-effectiveness analysis of opportunistic salpingectomy
(elective salpingectomy at hysterectomy or instead of tubal ligation).
METHODS::
A Markov Monte Carlo simulation model estimated the costs and benefits of opportunistic salpingectomy in a hypothetical cohort of women undergoing hysterectomy for benign gynecologic conditions or surgical sterilization. The primary outcome measure was the incremental cost-effectiveness ratio. Effectiveness was measured in terms of life expectancy gain. Sensitivity analyses accounted for uncertainty around various parameters. Monte Carlo simulation estimated the number of ovarian cancer cases associated with each strategy in the Canadian population.RESULTS::
Salpingectomy with hysterectomy was less costly ($11,044.32±$1.56) than hysterectomy alone ($11,206.52±$29.81) or with bilateral salpingo-oophorectomy ($12,626.84±$13.11) but more effective at 21.12±0.02 years compared with 21.10±0.03 and 20.94±0.03 years, representing average gains of 1 week and 2 months, respectively. For surgical sterilization, salpingectomy was more costly ($9,719.52±$3.74) than tubal ligation ($9,339.48±$26.74) but more effective at 22.45±0.02 years compared with 22.43±0.02 years (average gain of 1 week) with an incremental cost-effectiveness ratio of $27,278 per year of life gained. Our results were stable over a wide range of costs and risk estimates. Monte Carlo simulation predicted that salpingectomy would reduce ovarian cancer risk by 38.1% (95% confidence interval [CI] 36.5-41.3%) and 29.2% (95% CI 28.0-31.4%) compared with hysterectomy alone or tubal ligation, respectively.CONCLUSION::
Salpingectomy with hysterectomy for benign conditions will reduce ovarian cancer risk at acceptable cost and is a cost-effective alternative to tubal ligation for sterilization. Opportunistic salpingectomy should be considered for all women undergoing these surgical procedures.Risk Factors for Early-Occurring and Late-Occurring Incisional Hernias After Primary Laparotomy for Ovarian Cancer
abstract
OBJECTIVE::
To evaluate a cohort of gynecologic oncology patients to discover risk factors for early- and late-occurring incisional hernia after midline incision for ovarian cancer.METHODS::
We collected retrospective data from patients undergoing primary laparotomy for ovarian cancer at the University of Wisconsin Hospitals and Clinics from 2001 to 2007. Patient characteristics and potential risk factors for hernia formation were noted. Physical examination, abdominal computerized assisted tomography scans, or both were used to detect hernias 1 year after surgery (early hernia) and 2 years after surgery (late hernia).RESULTS::
There were 265 patients available for the 1-year analysis and 189 patients for the 2-year analysis. Early and late hernia formation occurred in 9.8% (95% confidence interval [CI] 6.2-12%) and an additional 7.9% (95% CI 4.1-12%) of patients, respectively. Using multiple logistic regression, poor nutritional status (albumin less than 3 g/dL) and suboptimal cytoreductive surgery (1 cm or greater residual tumor) were significantly associated with the formation of early incisional hernia after midline incision (P<.001 for both). Late hernia formation was associated only with age 65 years or older (P=.01).CONCLUSION::
The formation of early incisional hernias after midline incision is associated with poor nutritional status and suboptimal cytoreductive surgery, whereas late hernia formation is associated with advanced age. LEVEL OF EVIDENCE:: II.Unexpected Gynecologic Malignancy Diagnosed After Hysterectomy Performed for Benign Indications
abstract
OBJECTIVE::
To define the incidence of unexpected gynecologic malignancies among women who underwent hysterectomy for benign indications.
METHODS::
We conducted a data analysis of hysterectomy cases from a quality and safety database maintained by the Michigan Surgical Quality Collaborative, a statewide group of hospitals that voluntarily reports perioperative outcomes. Cases were abstracted from January 1, 2013, through December 8, 2013. Benign preoperative surgical indications included pelvic mass, family history of cancer, hyperplasia without atypia, prolapse, endometriosis, pelvic pain, abnormal uterine bleeding, or leiomyomas. Women with a surgical indication of cancer, cervical dysplasia, or hyperplasia with atypia were excluded.RESULTS::
During the study period, 7,499 women underwent a hysterectomy and 85.24% (n=6,360) were performed for benign indications. The incidence of unexpected gynecologic malignancy among hysterectomies performed for benign indications was 2.7% (n=172) and included ovarian, peritoneal, and fallopian tube cancer (n=69 [1.08%]), endometrial cancer (n=65 [1.02%]), uterine sarcoma (n=14 [0.22%]), metastatic cancer (n=13 [0.20%]), and cervical cancer (n=11 [0.17%]). The most common indications for hysterectomy were leiomyomas and abnormal uterine bleeding. There was no difference in the mean age (46.86±10.57 compared with 47.0±10.76 years, P=.96) of women with unexpected sarcoma compared with benign disease. Women with unexpected sarcoma were more likely to have a history of venous thromboembolism and preoperative blood transfusion, but this did not reach statistical significance.CONCLUSION::
The 2.7% incidence of unexpected gynecologic malignancy includes a 0.22% incidence of uterine sarcoma and 1.02% incidence of endometrial cancer. No reliable predictors of uterine sarcoma exist and caution is warranted in preoperative planning for hysterectomy. LEVEL OF EVIDENCE:: II.Thursday, January 08, 2015
Ovarian Cancer: New Measure of Benefit Proposed - HOPE study
medscape
.....Conditional disease-free survival, however, takes into account changes in the probability of remaining disease-free over time, as well as the amount of time since achieving remission, Dr Diergaarde explained.....
.....Although conditional disease-free survival always increases as the number of years spent in remission increases, certain subgroups in this study experienced larger increases, Alexia Iasonos, PhD, a biostatistician at the Memorial Sloan Kettering Cancer Center in New York City, pointed out in an accompanying podcast.
Mammary and rectal metastases from an ovarian cancer: report of two cases and review of literature
article: open access
See referee responses
Conclusion
To
our knowledge, this is the first case reported in literature that
describes both rectal- and breast metastases mimicking an inflammatory
breast cancer, that derived from a serous papillary ovarian
cancer. Our second case illustrates the role of PET-CT in detecting
subclinical metastases, which leads to an increase in the diagnosis of
uncommon sites of secondary dissemination of ovarian
cancer. The differential diagnosis between a primary and a secondary
breast cancer is crucial to provide the appropriate treatment.
Unfortunately, the occurrence of breast metastases in an ovarian carcinoma is linked to an extensive disease and a poor prognosis.
Role of the folate receptor in ovarian cancer treatment: evidence, mechanism, and clinical implications
abstract
Folate can be transported into the cell by the reduced folate carrier (RFC), the proton-coupled folate transporter (PCFT), or the folate receptor (FR), of which various isoforms exist. While the RFC and PCFT are expressed by many normal cells, the FR is present only in a small proportion of normal tissues. In these tissues, the FR expression level is often low and restricted to the apical surface of polarized epithelial cells. In contrast, FR is expressed on the blood-accessible basal and lateral membranes of many types of epithelial cancer. Considering that FR is expressed in few nonmalignant cell types on luminal membranes generally not accessible for molecules transported in the blood, FR is considered a promising antitumor target. As FR expression seems associated with tumor progression and prognosis, anticancer therapies targeting FR are currently being developed, such as farletuzumab (Morphotek, Exton, PA, USA), IMGN853 (ImmunoGen, Waltham, MA, USA), vintafolide, and EC1456 (both Endocyte Inc., West Lafayette, IN, USA). FR expression could be used as a response-predictive biomarker for these treatments. The ability to identify patients and treat them with an effective therapy based on the known expression of the tumor marker would, indeed, be the next step in predictive medicine for these patients. This review summarizes the role of FR in ovarian cancer and the value of FR as a prognostic biomarker for ovarian cancer and a response-predictive biomarker for folate-targeted therapeutics.
Adnexal Mass in the Postmenopausal Patient
Abstract
The adnexal mass in a postmenopausal patient poses an important diagnostic and management dilemma for primary care providers and gynecologists. Postmenopausal women are at a significantly increased risk of gynecologic malignancy; yet even in this population the majority of adnexal masses are benign. Evaluation and management of these lesions centers on the identification of malignancy, especially ovarian cancer, while avoiding unnecessary intervention in patients with benign lesions. Tumor markers and imaging can help in the evaluation of adnexal mass in postmenopausal women. Transvaginal ultrasound has long been considered the imaging modality of choice for the evaluation of adnexal masses. Particularly in the setting of high frequency utilization of transvaginal probes, which project high quality images allowing for detailed descriptions of the macroscopic appearance of the mass, and remains the least expensive of all imaging modalities currently available. For adnexal masses that are highly suspicious for cancer, women should be referred a gynecologic oncologist and facility for optimal care.
The Prognostic Role of Optimal Cytoreduction in Advanced, Bowel Infiltrating Ovarian Cancer
abstract
Aim: In locally advanced ovarian cancer with bowel involvement appropriate surgical treatment is still controversial.
Objective was to delineate factors to select those most likely to benefit from radical surgery in patients with locally advanced ovarian cancer.
Methods: Therefore, we retrospectively evaluated 207 consecutive patients with primary stage IIB-IV ovarian cancer who underwent primary surgery between 2000 and 2007. Every patient received stage-related surgery and adjuvant platinum-based chemotherapy. Median follow-up was 53.5 months. Data collected included stage, histology, extent of cytoreduction and type of bowel resection. Univariate survival analyses were performed to investigate variables associated with outcome.
Results: Optimal cytoreduction (OCR) (R ≤ 1 cm) was achieved in 76.8%. Most patients presented histologic grade 2/3 (96.6%), serous ovarian cancers (84.1%) and lymph node involvement (52.2%). Complete cytoreduction (R = 0 mm) has significant best prognostic impact in FIGO IIB-IV (p = .026).
Regarding bowel involvement, bowel resection was performed in 82 patients (39.6%). In this subgroup of patients complete cytoreduction led to significant better overall survival than R > 0 mm-1 cm, even in FIGO IIIC-IV patients (p = .027); this fact is independent of bowel resection. Noticeably, for survival bowel resection achieving residual tumor mass below 1 cm was also one main prognostic factor and even recurrence rate was associated with residual tumor mass.
Conclusion: Our findings suggest that the major prognostic factor in patients with advanced ovarian cancer needing colorectal resection is completeness of cytoreduction. Therefore, in advanced ovarian cancer patients, multivisceral surgery is indicated to achieve OCR (R ≤ 1 cm) with or without bowel resection with best prognostic impact.
Breast and ovarian cancer survivors' experience of participating in a cognitive-existential group intervention addressing fear of cancer recurrence
abstract
PURPOSE:
Currently, very few clinical approaches are offered to cancer survivors dealing with fear of cancer recurrence (FCR). This paper provides an overview of cancer survivors' experience and satisfaction after taking part in a six-week, cognitive-existential (CE) group intervention that aimed to address FCR.
METHOD:
In this qualitative descriptive study, 12 women with breast or ovarian cancer provided in-depth interviews of their experience in taking part in the CE group intervention.RESULTS:
Analysis of their accounts revealed struggles to face their fears. Yet, by embracing their group experience, the women learned how to confront their fears and gain emotional control. The women reported that the group work was highly valuable.CONCLUSION:
From the women's analysed accounts, the authors have proposed recommendations for changes to the group work process before moving the study to a full clinical trial. The study's findings also provide valuable insights to other cancer survivor groups who may also be experiencing FCR.Endogenous estrogens and the risk of breast, endometrial, and ovarian cancersI
abstract
Data from laboratory and epidemiologic studies support a relationship between endogenous hormones and the increased risk of several female cancers. In epidemiologic studies, consistent associations have been observed between risk of breast, ovarian and endometrial cancers and reproductive and hormonal risk factors such as high postmenopausal body mass index (BMI) and postmenopausal hormone use, which suggest the importance of endogenous hormones in the etiology of these diseases. The relationship between circulating estrogen levels in postmenopausal women and the risk of breast cancer is well established, with an approximately 2-fold higher risk among women in the top 20-25% (versus bottom 20-25%) of levels. However, data evaluating the relationship between endogenous estrogens and premenopausal breast cancer risk are more limited and less consistent. Two studies to date have evaluated the relationship between circulating estrogens and breast cancer risk by menstrual cycle phase at blood collection and only one study has examined this relationship by menopausal status at diagnosis. Three prospective studies have evaluated circulating estrogen levels and endometrial cancer risk in postmenopausal women, with consistent strong positive associations reported (with relative risks of 2-4 comparing high versus low hormone levels), while this relationship has not been studied in premenopausal women. Compared to breast and endometrial cancers, reproductive and hormonal characteristics such as postmenopausal hormone use are generally weaker and less consistent risk factors for ovarian cancer, and the only small prospective study conducted to date indicated a non-significant positive relationship between circulating estrogen levels and ovarian cancer risk. In this review, we summarize current evidence and identify key areas to be addressed in future epidemiologic studies of endogenous estrogens and the risk of breast, endometrial, and ovarian cancers.
Wednesday, January 07, 2015
Evaluation of the Effectiveness of a Surgical Checklist in in Medicare patients (Michigan/Ontario)
abstract
Background:
Surgical checklists are increasingly used to improve compliance with evidence-based processes in the perioperative period. Although enthusiasm exists for using checklists to improve outcomes, recent studies have questioned their effectiveness in large populations.
Objective:
We sought to examine the association of Keystone Surgery, a statewide implementation of an evidence-based checklist and Comprehensive Unit–based Safety Program, on surgical outcomes and health care costs.
Methods:
We performed a study using national Medicare claims data for patients undergoing general and vascular surgery (n=1,002,241) from 2006 to 2011. A difference-in-differences approach was used to evaluate whether implementation was associated with improved surgical outcomes and decreased costs when compared with a national cohort of nonparticipating hospitals. Propensity score matching was used to select 10 control hospitals for each participating hospital. Costs were assessed using price-standardized 30-day Medicare payments for acute hospitalizations, readmissions, and high-cost outliers.
Results:
Keystone Surgery implementation in participating centers (N=95 hospitals) was not associated with improved outcomes. Difference-in-differences analysis accounting for trends in nonparticipating hospitals (N=950 hospitals) revealed no differences in adjusted rates of 30-day mortality [relative risk (RR)=1.03; 95% confidence intervals (CI), 0.97–1.10], any complication (RR=1.03; 95% CI, 0.99–1.07), reoperations (RR=0.89; 95% CI, 0.56–1.22), or readmissions (RR=1.01; 95% CI, 0.97–1.05). Medicare payments for the index admission increased following implementation ($516 average increase in payments; 95% CI, $210–$823 increase), as did readmission payments ($564 increase; 95% CI, $89–$1040 increase). High-outlier payments ($965 increase; 95% CI, $974decrease to $2904 increase) did not change.
Conclusions:
Implementation of Keystone Surgery in Michigan was not associated with improved outcomes or decreased costs in Medicare patients.
Surgical checklists are increasingly used to improve compliance with evidence-based processes in the perioperative period. Although enthusiasm exists for using checklists to improve outcomes, recent studies have questioned their effectiveness in large populations.
Objective:
We sought to examine the association of Keystone Surgery, a statewide implementation of an evidence-based checklist and Comprehensive Unit–based Safety Program, on surgical outcomes and health care costs.
Methods:
We performed a study using national Medicare claims data for patients undergoing general and vascular surgery (n=1,002,241) from 2006 to 2011. A difference-in-differences approach was used to evaluate whether implementation was associated with improved surgical outcomes and decreased costs when compared with a national cohort of nonparticipating hospitals. Propensity score matching was used to select 10 control hospitals for each participating hospital. Costs were assessed using price-standardized 30-day Medicare payments for acute hospitalizations, readmissions, and high-cost outliers.
Results:
Keystone Surgery implementation in participating centers (N=95 hospitals) was not associated with improved outcomes. Difference-in-differences analysis accounting for trends in nonparticipating hospitals (N=950 hospitals) revealed no differences in adjusted rates of 30-day mortality [relative risk (RR)=1.03; 95% confidence intervals (CI), 0.97–1.10], any complication (RR=1.03; 95% CI, 0.99–1.07), reoperations (RR=0.89; 95% CI, 0.56–1.22), or readmissions (RR=1.01; 95% CI, 0.97–1.05). Medicare payments for the index admission increased following implementation ($516 average increase in payments; 95% CI, $210–$823 increase), as did readmission payments ($564 increase; 95% CI, $89–$1040 increase). High-outlier payments ($965 increase; 95% CI, $974decrease to $2904 increase) did not change.
Conclusions:
Implementation of Keystone Surgery in Michigan was not associated with improved outcomes or decreased costs in Medicare patients.
Non-Steroidal Anti-Inflammatory Drugs Use Is Associated with Reduced Risk of Inflammation-Associated Cancers: NIH-AARP Study
open access
.....Non-steroidal anti-inflammatory drug (NSAID) use, especially of aspirin, has been linked to reduced risk of cancers in several, [5]–[8] but not all [5]–[11] observational studies. Data from clinical trials of NSAIDs have shown that NSAID use can lower ovarian and colorectal cancer risk [12]–[15]. However, the role of NSAID use in less common cancers is unclear due to the small numbers of these cancers in previous studies. In addition, cancers that have inflammation-related causes in common have not been jointly evaluated. Evaluating these cancers as a group could help eliminate some of the uncertainty from previous studies and elucidate the role of NSAIDs in inflammation-related cancers.....
Conclusions
After accounting for potential selection bias, our data showed an inverse association between NSAID use and alcohol-related, infection-related, obesity-related, and smoking-related cancers and support the hypothesis that inflammation is related to an increased risk of certain cancers.All in the Family: Barriers and Motivators to the Use of Cancer Family History Questionnaires and the Impact on Attendance Rates
Abstract
Data
has demonstrated that family history questionnaires (FHQs) are an
invaluable tool for assessing familial cancer risk and triaging patients
for genetic counseling services. Despite their benefits, return rates
of mailed FHQs from newly referred patients remain low, suggesting
potential barriers to their use. To investigate this, a total of 461
participants, 239 who completed a FHQ (responders) and 222 who did not
(non-responders), were surveyed at a subsequent appointment regarding
potential barriers and motivators to using the FHQ. With respective
rates of 51 and 56 %, there was no significant difference in the
proportion of responders and non-responders who reported difficulty in
completing the FHQ; however, for both groups factors related to family
dynamics (large family size, lack of contact with relatives, and lack of
knowledge of family history) were reported as major variables
confounding completion of the FHQ. Responders were also significantly
more likely to have a personal diagnosis of cancer (p = 0.02) and to
report that their physician had discussed the reason for the appointment
with them (p = 0.01). Overall, 19 % of non-responders returned their
FHQ after being mailed an appointment letter and 67 % attended their
scheduled genetic counseling appointment. These findings demonstrate
that difficulty completing the FHQ is not inherent to its design but due
to difficulty accessing one's family history, and that mailed
appointment letters are a highly successful way to increase attendance
rates in the non-responder population. Furthermore, these results
demonstrate the important role that referring physicians play in the
utilization of genetic counseling services.
HE4 as biomarker for the differentiation between epithelial ovarian cancer and ovarian metastases of gastrointestinal origin
abstract
OBJECTIVE:
About 5-15% of all malignant ovarian tumors are metastases from other malignancies such as gastrointestinal tumors, breast cancer or melanoma. Also other gynecological tumors can metastasize to the ovaries. It is crucial to differentiate between primary epithelial ovarian cancer (EOC) and ovarian metastases because different treatment is required. The clinical value of Human Epididymal secretory protein 4 (HE4) as a serum biomarker in primary ovarian cancer has been established. The use of HE4 in the differentiation between primary ovarian cancer and ovarian metastases from other malignancies has never been investigated.METHODS:
HE4, CA125 and CEA were measured in 192 patients with EOC (n=147) or ovarian metastases (n=40). Univariate and multivariate logistic regression analyses were done. Sensitivity, specificity and area under the curve (AUC) were calculated for all markers and ratios hereof using receiver operating characteristics methodology.RESULTS:
Median serum HE4 concentration was significantly higher in patients with EOC compared to patients with ovarian metastases (431 pmol/L vs 68 pmol/L, p<0.001). HE4 and CEA were independent factors in differentiating between EOC and ovarian metastases (both p<0.001) while CA125 was not (p=0.33). The HE42.5/CEA ratio demonstrated the highest discriminative value (ROC-AUC 0.94) compared to HE4, CEA, CA125 or CA125/CEA ratio (0.88, 0.78, 0.80 and 0.89 respectively) and showed a specificity of 82.5% at set sensitivity of 90% in discriminating EOC from ovarian metastases.CONCLUSION:
HE4 can be used in combination with CEA to make the distinction between EOC and ovarian metastases from gastrointestinal origin.Surgical staging and prognosis in serous borderline ovarian tumours (BOT): A subanalysis of the AGO ROBOT study : British Journal of Cancer
Abstract
Background:
Incomplete surgical
staging is a negative prognostic factor for patients with borderline
ovarian tumours (BOT). However, little is known about the prognostic
impact of each individual staging procedure.
Methods:
Clinical
parameters of 950 patients with BOT (confirmed by central reference
pathology) treated between 1998 and 2008 at 24 German AGO centres were
analysed. In 559 patients with serous BOT and adequate ovarian surgery,
further recommended staging procedures (omentectomy, peritoneal
biopsies, cytology) were evaluated applying Cox regression models with
respect to progression-free survival (PFS).
Results:
For patients with one missing staging procedure, the hazard ratio (HR) for recurrence was 1.25 (95%-CI 0.66–2.39; P=0.497). This risk increased with each additional procedure skipped reaching statistical significance in case of two (HR 1.95; 95%-CI 1.06–3.58; P=0.031) and three missing steps (HR 2.37; 95%-CI 1.22–4.64; P=0.011).
The most crucial procedure was omentectomy which retained a
statistically significant impact on PFS in multiple analysis (HR 1.91;
95%-CI 1.15–3.19; P=0.013) adjusting for previously established prognostic factors as FIGO stage, tumour residuals, and fertility preservation.
Conclusion:
Individual
surgical staging procedures contribute to the prognosis for patients
with serous BOT. In this analysis, recurrence risk increased with each
skipped surgical step. This should be considered when re-staging
procedures following incomplete primary surgery are discussed.
It is not all about BRCA: Cullin-Ring ubiquitin Ligases in ovarian cancer
British Journal of Cancer - open access (technical)
Mutations in the BRCA1 and BRCA2 genes predispose individuals to the development of breast and ovarian cancers. As a result, biochemical functions of BRCA1 and BRCA2 proteins are being characterised in great detail. These studies have prompted the use of PARP inhibitors to treat BRCA1 and BRCA2-deficient ovarian cancers. This example of synthetic lethality represents a conceptual progress made recently in the approach to cancer treatment and is being currently tested in multiple clinical trials. Other than BRCA1 and BRCA2, many other factors might influence the survival of ovarian cancer patients. Currently, ovarian cancer remains the fifth most common cancer in the United Kingdom among women. Recent evidence suggests benefit in the modulation of the ubiquitin-proteasome system for the treatment of ovarian cancer. In this manuscript, we review the role of Cullin-Ring ubiquitin Ligases (CRLs) in the pathogenesis of ovarian cancer and their potential therapeutic exploitation. CRLs comprise a large family of proteins that, like kinases, might represent ideal candidates for targeted therapy and provide a large repertoire for the development of new anti-cancer compounds......
" An accumulating body of evidence suggests strongly that multiple genetic aberrations work independently or together to confer survival ability to cancer cells. In summary, it is only the combination of functional studies and genomic signatures that will allow us to make progress in ovarian cancer treatment. In the future, we will need to learn how diverse pathways interact and integrate them in order to predict the development of drug resistance by cancer cells."
Consumer guide to hospice - Washington Post
Washington Post
'Hospices vary widely in ways that can affect patient care.
The
Washington Post has gathered data largely from government sources on
more than 3,000 hospices that participate in Medicare, which pays for
the vast majority of hospice care in this country. No single factor can
predict the quality of a hospice’s care, and these figures do not offer a
complete picture of any single hospice. But consumers can benefit from
knowing how a hospice compares to others on these important measures......
Select a state below to explore its hospices or read on to learn more about a hospice's important traits.
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