full free access: Recent progress in the diagnosis and treatment of ovarian cancer - worth reading

Note: comments in brackets/italicized are blogger's comments; worthwhile reading with several key points of interest such as:

"It should be noted that stage II disease is the least commonly diagnosed stage of ovarian cancer. This is likely because there is no anatomic boundary between the pelvis and upper abdomen. If disease has spread outside of the ovary to pelvic structures, it is also likely to spread to the upper abdomen. In the past, trials of the Gynecologic Oncology Group (GOG) have combined stages I and II as a definition of “early” ovarian cancer, with stages III and IV designated as “advanced” ovarian cancer. However, given the observed higher recurrence rate seen for stage II disease, the GOG is now including stage II in the category of advanced disease for trial purposes."

"Studies (note: over decades) have documented that almost one-third (note: an average) of apparent early stage patients will have more advanced stage disease when full staging is done. In contrast, chemotherapy improves progression-free survival (PFS) for patients with stage IA or IB poorly differentiated disease, stage IC, or stage II disease, and these patients should receive adjuvant chemotherapy."

"There is a clear need for additional clinical trials to assess whether the clinical benefits such as quality of life, symptom control, and survival advantages outweigh the added exposure to the side effects of the agents or treatments used in the maintenance or consolidation setting."

Best way to screen for Lynch syndrome in women with endometrial cancer identified - - ModernMedicine (U of B.C./BCCA)

"Because endometrial (uterine) cancers associated with Lynch syndrome most likely present at an earlier age than colorectal cancer -- which is also commonly associated with the syndrome -- screening in these women could provide benefit and help extend overall life expectancy.

Testing all women with endometrial cancer would carry substantial costs, so researchers led by Dr. Janice Kwon, of the University of British Columbia and the British Columbia Cancer Agency in Vancouver, performed a cost-benefit analysis to determine the ideal screening criteria."...

Annual Report to the Nation (U.S.) Shows Continuing Decline in Cancer Mortality

".. The decreases (in deaths) for ovary, lung, and cervical cancers were limited to the most recent 5-year period."

PLoS Medicine: Meta-analyses of Adverse Effects Data Derived from Randomised Controlled Trials as Compared to Observational Studies: Methodological Overview

Note: PLOS Medicine is an open-text publisher (free full access), below are a couple of excerpts of interest

.....................................................

Background

There is considerable debate as to the relative merits of using randomised controlled trial (RCT) data as opposed to observational data in systematic reviews of adverse effects. This meta-analysis of meta-analyses aimed to assess the level of agreement or disagreement in the estimates of harm derived from meta-analysis of RCTs as compared to meta-analysis of observational studies.

Discussion Top

"............The increased risk in adverse effects in some studies was not consistently related to any particular study design—RCTs found a significant risk of adverse effects associated with the intervention under investigation in eight instances, while observational studies showed a significantly elevated risk in 11 cases.
............Although reasons for discrepancies are unclear, specific factors which may have led to differences in adverse effect estimates were discussed by the respective authors.................
..........While there are a few instances of sizeable discrepancies, the pooled estimates in Figure 2 and Table 2 indicate that in the scheme of things (particularly where larger, more precise primary studies are available), meta-analysis of observational studies yield adverse effects estimates that broadly match those from meta-analysis of RCTs..........."

OHA - Quality and Patient Safety Governence Toolit (eg family/patient experiences to the board level) eg. patient stories

Note: language/implementation issues

---------------------------------------------------------------------------------------
The following templates provide self-assessment tools, leading practices and key considerations for the board to draw upon when engaging patients and families.
4.1 Framework and Principles for Patient and Family Engagement4.2 Declaration of Values4.3 Bringing Patient Experiences to the Board4.4 Patient Relations Self-Assessment Tool for Organizations
Click here to download all Section 4 templates.

May 2 blog: (privacy-Freedom of Information and Protection of Privacy Act - FIPPA) Ontario Hospital Association - The Facts on FOI and Hospitals' Quality of Care Records

Note: the facts from the perspective of the OHA; references patient safety, communication, data sharing
------------------------------------------------------------------------
The Facts on FOI and Hospitals' Quality of Care Records

"I’m going to use today’s blog to address an issue that has recently generated a great deal of controversy: whether Ontario’s Freedom of Information and Protection of Privacy Act (FIPPA) should be amended to protect a specific, narrow and well-defined class of information created by hospitals for the purposes of quality improvement.

Schedule 15 of Bill 173, Better Tomorrow for Ontario Act (Budget Measures), 2011, proposes to exempt, from the FIPPA, “information provided to, or records prepared by, a hospital committee for the purpose of assessing or evaluating the quality of health care and directly related programs and services provided by the hospital.” Bill 173 is currently being considered by the Standing Committee on Finance and Economic Affairs (SCFEA). This proposed amendment would align Ontario with other jurisdictions in Canada, as well as the United Kingdom and Australia, with respect to the treatment of quality of care information.

Without this kind of protection documented, conversations that health care professionals regularly have about enhancing patient care, as well as documents developed relating to quality, safety, and risk management, may be subject to public disclosure. This would have a chilling effect on the willingness of hospital staff to identify or comment on patient care and quality issues.

To read our submission to the Standing Committee on Finance and Economic Affairs respecting this amendment to FIPPA, click here.

Ontario hospitals unequivocally support openness and transparency; they also support continuous quality improvement. They are keen to strike an appropriate balance between improving care and improving access to information.

The proposed amendment has been criticized by organizations that either do not fully understand its purpose, or are deliberately trying to mislead the public. This has caused confusion about why these protections are necessary, which is incredibly unfortunate.

For me, the fundamental question is, do patients want to be treated in hospitals where issues of quality and safety are examined and discussed by hospital staff on a daily basis, or in ones where they are not? If the answer to the question is “yes, safety and quality matter,” then it is critical to support this amendment. The OHA does, and so do individuals like patient safety expert Dr. Ross Baker from the University or Toronto, as do organizations like the Ontario Medical Association.

We have created a special webpage to explain the truth about the amendment, why it is necessary, and why we support it. You can access it at www.oha.com/thetruth. I encourage you to visit it to learn more."

Tom Closson

(OHA)

DOTmed.com - Mammography screening rate drops among younger women

Canary Foundation Issue 26 Newsletter May 2011

Insight Magazine (UK) Spring 2011 edition

Perspective: (U.S.) High-Risk Pools — Merely a Stopgap Reform | Health Policy and Reform

NCI Cancer Bulletin: (U.S.) FDA Approves Test to Identify Candidates for Breast Cancer Drug - Trastuzumab (Herceptin) - HER2 gene

FDA Approves Test to Identify Candidates for Breast Cancer Drug

The Food and Drug Administration (FDA) has approved a genetic test that doctors can use to help identify women with breast cancer who have extra copies of the HER2 gene and therefore may benefit from the drug trastuzumab (Herceptin).
Trastuzumab targets the protein made by the HER2 gene, which is located on chromosome 17. Approximately 25 percent of breast cancers have extra copies of the HER2 gene and produce higher levels of the HER2 protein. These tumors tend to grow faster and are more likely to recur than tumors that don’t overexpress HER2........cont'd

NCI Cancer Bulletin: Testing Dose-Dense Paclitaxel (Taxol) for Ovarian and Related Cancers - GOG-0262

"....Further bolstering evidence of dose-dense paclitaxel’s promise in ovarian cancer, the Japanese GOG conducted a phase III randomized clinical trial and showed that women receiving dose-dense therapy experienced statistically significantly longer progression-free survival and were more likely to be alive after 2 years....."

“Data from phase II studies show that dose-dense paclitaxel has activity in highly resistant ovarian cancer,” said Dr. Chan. “And the Japanese study has produced promising data, but there are differences in the prevailing ovarian cancer cell types, and possibly the genomic and toxicity profiles, of ovarian cancer in Asian compared with Western women. As such, these results need to be confirmed in other ethnicities before the dose-dense regimen can be considered the new standard of care.”

For More Information

See the lists of entry criteria and trial contact information or call the NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237). The toll-free call is confidential.

NCI Cancer Bulletin: Design Dilemma: The Debate over Using Placebos in Cancer Clinical Trials (reference to GOG 218 Avastin/Ovarian Cancer)

abstract: Editorial: Whole-Genome Sequencing, April 20, 2011 JAMA

Note: full access requires subscription ($$)

Whole-Genome Sequencing

Since this article does not have an abstract, we have provided the first 150 words of the full text.

KEYWORDS:
• EARLY DIAGNOSIS,
• GENETIC PREDISPOSITION TO DISEASE,
• GENOME, HUMAN,
• LEUKEMIA, MYELOID, ACUTE,
• LEUKEMIA, PROMYELOCYTIC, ACUTE,
• MUTATION,
• NEOPLASMS,
• ONCOGENE PROTEINS, FUSION,
• ONCOGENES,
• SEQUENCE ANALYSIS, DNA,
• TIME FACTORS,
• TP53 GENES,
• TP53 PROTEIN, HUMAN.

The past 60 years have witnessed remarkable progress in genetics and genomics from the description of the DNA double helix by Watson and Crick ¹ to the release of the first draft sequence of the human genome in 2001 ^{2, 3} and the successful completion of the human genome project in 2003. ⁴ From that time, there has been increasing hope and expectation that, as soon as the cost of sequencing the whole genome could become affordable, the promise of personalized medicine would be fulfilled.

No field of medicine has benefited more from advances in genomics and the application of genetic testing than oncology. These advances have had a substantial influence on cancer risk assessment, determination of prognosis, and choice of treatment. Clinical applications of novel genetic tools include sequencing and analysis of germline genomic rearrangements at key cancer genes like BRCA1, BRCA2, and TP53 ⁵; …

NCI Cancer Bulletin: Whole-Genome Sequencing Improves Cancer Diagnoses (including some good links eg Li-Fraumeni Syndrome, BRCA, Editorial)

Whole-Genome Sequencing Improves Cancer Diagnoses

Although whole-genome sequencing is not yet ready for routine clinical use, two studies show how the approach could improve the diagnosis and, potentially, the treatment of cancer. The reports, in the April 20 Journal of the American Medical Association, describe how researchers at Washington University School of Medicine in St. Louis and their colleagues used whole-genome sequencing to investigate the cases of two patients.
The first study focused on a 42-year-old woman who died from leukemia that was probably related to previous treatment for breast and ovarian cancers. The woman did not have a known family history of cancer, and tests for mutations in the breast cancer-associated genes BRCA1 and BRCA2 were negative. But a comparison of the genomes of her cancer cells and normal cells revealed a novel mutation in the TP53 gene that altered the function of the encoded protein. TP53 gene mutations have been implicated in a number of cancers, including some early-onset breast and ovarian cancers, as well as Li-Fraumeni syndrome.
The TP53 mutation does not appear to have been inherited from one of the patient’s parents. But because the mutation was seen in both normal and cancer cells, it had to have occurred very early in the patient’s life, possibly at conception. Thus, the mutation could have been present in her germline DNA and been passed on to her children, the researchers noted.
As specified by the study protocol, the researchers contacted the woman’s primary care physician, who then discussed the issue with the patient’s family members and encouraged them to seek genetic counseling. “Even though the patient died, her contribution to this study yielded new knowledge that might one day save the lives of her children,” study co-author Dan Koboldt of the Genome Institute at Washington University wrote in a post about the studies on his blog, MassGenomics.
The second study involved a 39-year-old woman with a form of acute myeloid leukemia (AML). A comparison of DNA from her tumor and normal cells revealed a fusion of two genes in her blood cells that was not detected through routine cytogenetic testing. The presence of this gene fusion is associated with good outcomes after chemotherapy. Consequently, the patient’s doctors recommended chemotherapy rather than stem cell transplantation, the treatment that had been indicated by the standard diagnostic testing results.
At the time of publication, the woman had been in remission for 15 months. The sequencing, analysis, and validation of the fusion gene were completed in just 7 weeks, which was quick enough that doctors could use the information to choose the most effective treatment for the patient, the researchers noted.
“These cases of personalized genomic medicine are just some of the first examples of what will likely be commonplace in the near future,” wrote the authors of an accompanying editorial.
“Clearly, the technology will no longer be the major impediment to widespread clinical use of these tools, and the main challenges will soon move to the clinical implementation and interpretation of genomic data,” the authors added.

full free access: Levothyroxine dose & risk of fractures in older adults: nested case-control study -- Women's College Hospital Toronto study (hypothyroidism)

Note:
the study excluded thyroid cancer survivors but a quick scan does not indicate a search of the database/inclusion/exclusion of a prior/present history of other cancers with the exception of reference #44 prostate cancer

(eg. pre-menopausal longterm cancer survivours/longterm use of hypothydroism medications - comments/opinions welcome on this issue)

Also known as:  

Brand names
Eltroxin
Estre
Euthyrox
Levo-T
Levotabs
Levothroid
Levoxyl
Novothyrox
Synthroid
Thyrox
Unithroid  

Brand names of combination products
Thyrolar 1 (containing Thyroxine and Triiodothyronine) Thyrolar 1/2 (containing Thyroxine and Triiodothyronine) Thyrolar 1/4 (containing Thyroxine and Triiodothyronine) Thyrolar 2 (containing Thyroxine and Triiodothyronine) Thyrolar 3 (containing Thyroxine and Triiodothyronine)
 ```````````````````````````````````````````

Study cohort

Tory Silence On Medicare Pledge “Deafening” - Health Care Pledge Supported By All Parties, But One (Harper) note: finance minister Jim Flaherty a 'no response'

Tory Silence On Medicare Pledge “Deafening”
Health Care Pledge Supported By All Parties, But One

TORONTO ‐ Stephen Harper’s decision to refuse even the most basic commitment to Medicare has caused surprise and concern among Canadians who care about our health care system. Hundreds of local candidates representing the Liberal, New Democratic and Green Parties, and all three of their National Leaders, have given their support to the Health Care Protection Pledge, a commitment to sustain Medicare past the 2014 Health Accord negotiations. Stephen Harper is the only national leader who has chosen not to express support for our health care system, and all but two Conservative candidates have followed his lead, almost universally refusing to make a commitment to Medicare....cont'd

Canadian Doctors for Medicare - deadline to sign pledge to support Canadian health care system (re: federal election)

Sample Email To Federal Candidates

Dear ,
I am writing to ask that you make a commitment to our health care system and sign the Canadian Doctors for Medicare Health Care Protection Pledge.

The pledge was emailed to you last week and simply asks you to offer your commitment to protect our health care system. That commitment involves:

 Sustaining the Canada Health Act with all its protections and all five principles now and after the 2014 Health Accord and enforce it across Canada.
 Continuing to fund health care through Federal transfer payments tied to compliance with the Canada Health Act.

Please confirm your commitment to our health care system by signing the pledge and sending it to Canadian Doctors for Medicare by April 29th, 2011.

Canadian Doctors for Medicare will be publishing a list of candidates who signed, and who did not sign the pledge before voting day.

If you haven’t received the pledge, you can contact Canadian Doctors for Medicare at info@canadiandoctorsformedicare.ca or download a pledge form from their website www.canadiandoctorsformedicare.ca.
Sincerely,

....................................................

2011 Federal Candidates (separated by province/territory)
Alberta: AB_Federal_Candidates.pdf
British Columbia: BC_Federal_Candidates.pdf
Manitoba: MB_Federal_Candidates.pdf
New Brunswick: NB_Federal_Candidates.pdf
Newfoundland: NL_Federal_Candidates.pdf
Northwest Territories: NWT_Federal_Candidates.pdf
Nova Scotia: NS_Federal_Candidates.pdf
Nunavut: NU_Federal_Candidates.pdf
Prince Edward Island: PE_Federal_Candidates.pdf
Saskatchewan: SK_Federal_Candidates.pdf
Yukon: YK_Federal_Candidates.pdf

Target Ovarian Cancer Calls On DOH To Launch National Symptom Awareness Campaign As New NICE Guidance Stresses Importance Of Early Diagnosis, UK

Note: media story regarding new NICE guidelines for ovarian cancer

IMEDEX: Interactive Case: Ovarian Cancer: Front-Line Therapy in Patient with Inadequate Debulking Surgery

Note:  registration required (free), discusses Japanese trial with weekly Taxol and increased overall survival, GOG 262 ((see arms 1 & 2)  etc...

Interactive Case: Ovarian Cancer: Front-Line Therapy in Patient with Inadequate Debulking Surgery VIEW ACTIVITY Overview: Dr Bradley Monk very eloquently describes a case of newly diagnosed advanced ovarian cancer and reinforces the importance of debulking surgery and combination chemotherapy. Various therapeutic options and recent clinical trial data are discussed. Topics: • Small and large volume residual disease and treatment decision making • Standards and clinical trials • Role of antiangiogenic agents in ovarian cancer management

4/26/2011: full free access: Recent progress in the diagnosis and treatment of ovarian cancer -- Jelovac and Armstrong, 10.3322/caac.20113 -- CA: A Cancer Journal for Clinicians

Published online before print April 26, 2011, no registration req'd

April 2011: NICE Guidelines - Ovarian cancer: the recognition and initial management of ovarian cancer

The recognition and initial management of ovarian cancer

Description

This clinical guideline offers evidence-based advice on the care and early treatment of women with suspected or confirmed ovarian cancer.
This guidance updates and replaces recommendation 1.7.4 in Referral guidelines for suspected cancer (NICE clinical guideline 27; published 2005).

Guidance documents

• Full guideline PDF format  | MS Word format
• NICE guideline PDF format  | MS Word format
• Quick reference guide PDF format
• NICE guidance written for patients and carers PDF format  | MS Word format
• CG122 Ovarian cancer: guidance (web format)

Implementing this guidance

• Baseline assessment tool
• Clinical audit tool
• Clinical case scenarios
• Costing statement
• Slide set

• CG122 Ovarian cancer: GP podcast
• CG122 Ovarian cancer: SLR podcast

Other information

• Background information

About this guidance

Clinical guidelines CG122

Issued: April 2011
How this guidance was produced

Order printed copies of this guidance

This page was last updated: 27 April 2011

NICE Unable To Recommend Ovarian Cancer Drug In Final Guidance Due To Lack Of Appropriate Evidence (trabectedin (Yondelis)

reports available on line: Charity Intelligence Canada - Home

To receive a copy of our reports via email, contact info@charityintelligence.ca

website: Charity Intelligence Canada

Note: website includes background and financials:

Audited Financial Statements - Year Ending June 30, 2010

Audited Financial Statements - Year Ending June 30, 2009
Audited Financial Statements - Year Ending June 30, 2008

Also  »  Recommended Charities 2010

CTV Winnipeg- Too many deadly cancers go underfunded: report - CTV News

Charity Intelligence notes there are more than 200 forms of cancer, but the 10 forms that represent 70 per cent of Canadian cancer cases, deaths, potential years of life lost, and prevalence include:

• lung
• colorectal
• breast
• pancreatic
• non-Hodgkin lymphoma
• brain
• leukemia
• prostate
• ovarian
• stomach cancers

It also includes sarcoma, because it was the form of cancer that affected Terry Fox, who changed the face of cancer charity donations forever.

EvidenceUpdates - abstract/commentaries: Colonic stenting versus emergency surgery for acute left-sided malignant colonic obstruction: a multicentre r

 Note: this study was originally published in The Lancet and involved patients in 25 hospitals; the study pertained to left-sided colorectal cancers however may be appropriate/of interest to other cancer patient populations; commentaries are included from a variety of professions including gastroenterologist, oncologists...

 ------------------------------------------------------------------------------
BACKGROUND: Colonic stenting as a bridge to elective surgery is an alternative for emergency surgery in patients with acute malignant colonic obstruction, but its benefits are uncertain. We aimed to establish whether colonic stenting has better health outcomes than does emergency surgery.

Health-evidence Canada - website

Note: the benefit of this site is the combined link/abstract information plus professional commentaries; registration is free

About Us

This web site was originally created with funds from the Canadian Institutes of Health Research and is supported today in part by the National Collaborating Centre for Aboriginal Health (NCCAH), National Collaborating Centre for Environmental Health (NCCEH), National Collaborating Centre for Healthy Public Policy (NCCHPP), National Collaborating Centre for Infectious Diseases (NCCID), National Collaborating Centre for Methods and Tools (NCCMT), and the City of Hamilton Public Health Services Division.
The initial project, funded by the Canadian Institutes of Health Research, was conducted by Dr. Maureen Dobbins, Associate Professor, McMaster University (Ontario, Canada) to promote an ongoing environment of collaboration between the research community and the decision-making and practice setting. This site continues to achieve this goal with the City of Hamilton Public Health Services Division, by actively collaborating in ongoing research initiatives.
The ultimate goal of this site is to facilitate the adoption and implementation of effective policies/programs/interventions at the local and regional public health decision making levels across Canada.

To develop this web site, the research team worked to:

1. Identify, appraise, and make available methodologically-sound reviews of health promotion and public health interventions published from 1985 to the present
2. Conduct a comprehensive literature review and consult with 54 key practitioners in Canada to learn about how decisions are being made in these respective organizations, and to determine the best ways to summarize the results of reviews and disseminate findings
3. Consult with graphic design and marketing experts to assist with the preparation and marketing of dissemination material
4. Conduct 9 focus groups with practitioners to obtain their feedback on the dissemination strategy that was pilot tested in the fall of 2002 with Canadian decision makers, medical officers of health, public health managers and directors, health promotion mangers, and health policy makers at Canadian provincial and federal levels. A 2-page summary statements format was developed to synthesize the results of well-done systematic reviews and this summary format is being used to present the key findings of select reviews within the health-evidence.ca registry.
5. Identify public health and health promotion interventions that have not yet been systematically reviewed and begin to notify relevant funders of these gaps.
6. Evaluate knowledge transfer and exchange efforts on an ongoing basis and continue to work towards a national strategy for public health in Canada.

The Associated Press: Push to spur more drugs for deadly rare diseases

"There are treatments for just 200 of the roughly 7,000 rare diseases, illnesses that affect fewer than 200,000 people, often far, far fewer. Yet add those diseases together, and more than 20 million Americans have one." "A new International Rare Diseases Research Consortium is pushing for at least 200 more treatments by 2020, in part by pooling the work of far-flung scientists and families. Rather than starting from scratch, the Food and Drug Administration is pointing the way for manufacturers to "repurpose" old drugs for new use against rare diseases, publishing a list of those deemed particularly promising."

medical news: New Class of Cancer Drugs Could Work in Colon Cancers with Genetic Mutation (PARP inhibitors/MRE11 gene/Lynch Synrome))

15% of colorectal cancers have mutation that responds to PARP inhibitors

Newswise — ANN ARBOR, Mich. — A class of drugs that shows promise in breast and ovarian cancers with BRCA gene mutations could potentially benefit colorectal cancer patients with a different genetic mutation, a new study from the University of Michigan Comprehensive Cancer Center finds.

Working in cell lines from colorectal cancer patients, researchers found that a new class of drugs called PARP inhibitors worked against tumors with mutations in the MRE11 gene.

ongoing: Safety/Efficacy Study of a Drug to Reduce Thrombocytopenia in Patients Receiving Chemotherapy for Ovarian, FT or PC (Angiotensin 1-7)

Study of ABT-767 in Subjects With Breast Cancer 1 and Breast Cancer 2 (BRCA 1 and BRCA 2) Mutations and Solid Tumors or High Grade Serous Ovarian, Fallopian Tube, or Primary Peritoneal Cancer - Full Text View - ClinicalTrials.gov

Note: not yet recruiting

Estimated Enrollment:	50
Study Start Date:	April 2011
Estimated Study Completion Date:	March 2013

April 2011 index: Journal of Geriatric Oncology - Current Issue

example (abstract):

Volume 2, Issue 2, Pages 99-104 (April 2011)
Clinical aspects of the management of elderly women diagnosed with gynecologic malignancies: Treatment decisions and choices
The number of elderly women diagnosed with gynecologic cancer is increasing. This paper reviews the current trends in the management of elderly gynecologic cancer patients. Our goal is to identify critical issues that must be weighed when selecting treatment for elderly gynecologic oncology patients. As individuals continue to achieve longer lifespans, and the population of elderly women continues to grow, gynecologic oncologists will face new challenges regarding treatment. Due to minimal inclusion in randomized controlled trials and the influence of selection bias in many of the current studies, little evidence-based data is available regarding the most effective treatment options for this population. It is therefore unclear whether treatment should differ from that offered to younger populations, and if so under what circumstances. As of yet, there are no validated measures by which to determine tolerability and success of aggressive therapies for this population. Ultimately, each patient must be evaluated individually with regards to risk factors and prognosis, and therapy should not be withheld from elderly individuals solely on the basis of age alone.

Commentary: Accountable Care Organizations and Community Empowerment - — JAMA

Less apparent to the public during this period of historic change are the struggles occurring in US board rooms among hospital groups, specialty physicians, and primary care clinicians—debating quietly but intensely over how to form these ACOs, how to be accountable for care delivery, and how to divide anticipated savings derived from ACOs. However, in most of these settings, important constituencies—middle class and other working patients whose health and welfare are at stake—are not included in the discussions.......................The high and accelerating increases in the cost of health care and the limited roles of patients in decision making central to health and health care delivery are too real to ignore. Decision making by distal proxies such as elected legislators may no longer be enough to address the United States' mounting problems with health care, outcomes, and costs.

abstract: Health Outcomes After Stopping Conjugated Equine Estrogens Among Postmenopausal Women With Prior Hysterectomy — JAMA

Health Outcomes After Stopping Conjugated Equine Estrogens Among Postmenopausal Women With Prior Hysterectomy

A Randomized Controlled Trial

Abstract

Context 

The Women's Health Initiative Estrogen-Alone Trial was stopped early after a mean of 7.1 years of follow-up because of an increased risk of stroke and little likelihood of altering the balance of risk to benefit by the planned trial termination date. Postintervention health outcomes have not been reported. 

Objective 

To examine health outcomes associated with randomization to treatment with conjugated equine estrogens (CEE) among women with prior hysterectomy after a mean of 10.7 years of follow-up through August 2009. 

Design, Setting, and Participants 

The intervention phase was a double-blind, placebo-controlled, randomized clinical trial of 0.625 mg/d of CEE compared with placebo in 10 739 US postmenopausal women aged 50 to 79 years with prior hysterectomy. Follow-up continued after the planned trial completion date among 7645 surviving participants (78%) who provided written consent. 

Main Outcome Measures 

The primary outcomes were coronary heart disease (CHD) and invasive breast cancer. A global index of risks and benefits included these primary outcomes plus stroke, pulmonary embolism, colorectal cancer, hip fracture, and death. 

Results 

The postintervention risk (annualized rate) for CHD among women assigned to CEE was 0.64% compared with 0.67% in the placebo group (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.75-1.25), 0.26% vs 0.34%, respectively, for breast cancer (HR, 0.75; 95% CI, 0.51-1.09), and 1.47% vs 1.48%, respectively, for total mortality (HR, 1.00; 95% CI, 0.84-1.18). The risk of stroke was no longer elevated during the postintervention follow-up period and was 0.36% among women receiving CEE compared with 0.41% in the placebo group (HR, 0.89; 95% CI, 0.64-1.24), the risk of deep vein thrombosis was lower at 0.17% vs 0.27%, respectively (HR, 0.63; 95% CI, 0.41-0.98), and the risk of hip fracture did not differ significantly and was 0.36% vs 0.28%, respectively (HR, 1.27; 95% CI, 0.88-1.82). Over the entire follow-up, lower breast cancer incidence in the CEE group persisted and was 0.27% compared with 0.35% in the placebo group (HR, 0.77; 95% CI, 0.62-0.95). Health outcomes were more favorable for younger compared with older women for CHD (P = .05 for interaction), total myocardial infarction (P = .007 for interaction), colorectal cancer (P = .04 for interaction), total mortality (P = .04 for interaction), and global index of chronic diseases (P = .009 for interaction). 

Conclusions 

Among postmenopausal women with prior hysterectomy followed up for 10.7 years, CEE use for a median of 5.9 years was not associated with an increased or decreased risk of CHD, deep vein thrombosis, stroke, hip fracture, colorectal cancer, or total mortality. 

A decreased risk of breast cancer persisted. 

abstract: Familial Cancer - Mutation deep within an intron of MSH2 causes Lynch syndrome

"...thus highlighting the need for more extensive sequencing approaches in families where routine procedures fail to find a mutation."

abstract: Familial Cancer, A putative Lynch syndrome family carrying MSH2 and MSH6 variants of uncertain significance—functional analysis reveals the pathological one

Abstract

Inherited pathogenic mutations in the mismatch repair (MMR) genes, MSH2, MLH1, MSH6, and PMS2 predispose to Lynch syndrome (LS). However, the finding of a variant or variants of uncertain significance (VUS) in affected family members complicates the risk assessment. Here, we describe a putative LS family carrying VUS in both MSH2 (c.2768T>A, p.Val923Glu) and MSH6 (c.3563G>A, p.Ser1188Asn). Two colorectal cancer (CRC) patients were studied for mutations and identified as carriers of both variants. In spite of a relatively high mean age of cancer onset (59.5 years) in the family, many CRC patients and the tumor pathological data suggested that the missense variation in MSH2, the more common susceptibility gene in LS, would be the predisposing alteration. However, MSH2 VUS was surprisingly found to be MMR proficient in an in vitro MMR assay and a tolerant alteration in silico. By supplying evidence that instead of MSH2 p.Val923Glu the MSH6 p.Ser1188Asn variant is completely MMR-deficient, the present study confirms the previous findings, and suggests that MSH6 (c.3563G>A, p.Ser1188Asn) is the pathogenic mutation in the family. Moreover, our results strongly support the strategy to functionally assess all identified VUS before predictive gene testing and genetic counseling are offered to a family.

LOVD - An Open Source DNA variation database system (eg. genetic testing/unknown clinicial variant/s)

LOVD stands for Leiden Open (source) Variation Database.
LOVD's purpose : To provide a flexible, freely available tool for Gene-centered collection and display of DNA variations.

Mutalyzer

LOVD features integration with the Mutalyzer sequence variant nomenclature checker, allowing for direct nomenclature checking of sequence variants during the submission process.

If you are looking for a specific gene database, please check the list of gene variant databases at the HGVS site, in our list of LSDBs, or in the list of registered LOVD installations.

abstract: Calculator for ovarian carcinoma subtype prediction : Modern Pathology

Abstract:

With the emerging evidence that the five major ovarian carcinoma subtypes (high-grade serous, clear cell, endometrioid, mucinous, and low-grade serous) are distinct disease entities, management of ovarian carcinoma will become subtype specific in the future.

In an effort to improve diagnostic accuracy, we set out to determine if an immunohistochemical panel of molecular markers could reproduce consensus subtype assignment.

Immunohistochemical expression of 22 biomarkers were examined on tissue microarrays constructed from 322 archival ovarian carcinoma samples from the British Columbia Cancer Agency archives, for the period between 1984 and 2000, and an independent set of 242 cases of ovarian carcinoma from the Gynaecologic Tissue Bank at Vancouver General Hospital from 2001 to 2008. Nominal logistic regression was used to produce a subtype prediction model for each of these sets of cases. These models were then cross-validated against the other cohort, and then both models were further validated in an independent cohort of 81 ovarian carcinoma samples from five different centers.

Starting with data for 22 markers, full model fit, backwards, nominal logistic regression identified the same nine markers (CDKN2A, DKK1, HNF1B, MDM2, PGR, TFF3, TP53, VIM, WT1) as being most predictive of ovarian carcinoma subtype in both the archival and tumor bank cohorts. These models were able to predict subtype in the respective cohort in which they were developed with a high degree of sensitivity and specificity (κ statistics of 0.88±0.02 and 0.86±0.04, respectively).

When the models were cross-validated (ie using the model developed in one case series to predict subtype in the other series), the prediction equation's performances were reduced (κ statistics of 0.70±0.04 and 0.61±0.04, respectively) due to differences in frequency of expression of some biomarkers in the two case series. Both models were then validated on the independent series of 81 cases, with very good to excellent ability to predict subtype (κ=0.85±0.06 and 0.78±0.07, respectively).

A nine-marker immunohistochemical maker panel can be used to objectively support classification into one of the five major subtypes of ovarian carcinoma.

Observations: Electronic health records face human hurdles more than technological ones

abstract: Early detection of ovarian cancer - Early detection of ovarian cancer† If only we had a “Pap smear” for this disease

Abstract:

Primary care physicians are recognizing the symptoms of ovarian cancer and ordering the appropriate diagnostic tests. On the basis of the diverse behavior of epithelial cancers, the goal of screening technology should shift from diagnosing early stage to diagnosing low-volume disease.

abstract: Symptom burden in cancer survivors 1 year after diagnosis Cancer

CONCLUSIONS:

More than 1 in 4 cancer survivors had high symptom burden 1 year postdiagnosis, even after treatment termination. These results indicate a need for continued symptom monitoring and management in early post-treatment survivorship, especially for the underserved.

abstract: Cancer-related chronic pain - Cancer

CONCLUSIONS:

The authors extend the literature by showing that 20% of diverse cancer survivors had cancer-related CP, and 43% had experienced pain since diagnosis, revealing racial and sex disparities in cancer-related CP's incidence and impact on QOL. Having pain was related to poorer QOL in several domains and was more frequently experienced by women. Although black race was not related to pain prevalence, it was related to greater severity. This study reveals an unaddressed cancer survivorship research, clinical, and policy issue

press release U.S. - FDA Grants Orphan Drug Designation for Nektar's Investigational Drug, NKTR-102, for Treatment of Women with Ovarian Cancer (NKTR-102)

Nektar Therapeutics (Nasdaq: NKTR) today announced that the company's oncology drug candidate, NKTR-102, has been granted orphan drug status for the treatment of women with ovarian cancer by the U.S. Food and Drug Administration (FDA).




Nektar has a Phase 2 study ongoing for NKTR-102 that is enrolling approximately 125 patients with platinum-resistant ovarian cancer whose disease has progressed following treatment with pegylated liposomal doxorubicin (PLD) therapy.  In addition, Phase 3 planning is also underway for NKTR-102 in ovarian cancer.  For more information about clinical trials for NKTR-102, please visit the Nektar Therapeutics website.


NKTR-102 is an investigational agent and is not approved by the FDA, the European Medicines Agency (EMA) or other Health Authorities.

abstract: Pharmacokinetics and antitumor activity of patupilone combined with midazolam or omeprazole in patients with advanced cancer (inhibitors)

PURPOSE:
Patupilone is a novel microtubule-targeting cytotoxic agent with potential interaction with CYP3A4/CYP2C19 enzymes. Midazolam and omeprazole are primarily metabolized by CYP3A4 and CYP2C19, respectively. We evaluated the inhibitory effects of patupilone on the CYP3A4/CYP2C19 pathways.

METHODS:
This study had 2 parts: in an initial core phase, patients were randomly assigned to receive midazolam 4 mg or omeprazole 40 mg PO (days 1 and 29) and patupilone 10 mg/m(2) IV (days 8 and 29). Patients without progression continued patupilone every 3 weeks until disease progression or unacceptable toxicity (extension phase).

full free access: Docetaxel Distribution Following Intraperitoneal Administration in Mice Journal of Pharmacy & Pharmaceutical Sciences (technical)

Note: in mice (research); technical

abstract: Role of Minimally Invasive Surgery in Staging of Ovarian Cancer

Abstract

OPINION STATEMENT:
Since the introduction of laparoscopy and robotic surgery in gynecologic practice in the last several decades, use of these minimally invasive surgical techniques has increased dramatically. The role of minimally invasive surgical techniques continues to expand because they offer reduced intraoperative and postoperative complications, less intraoperative blood loss, and a shorter postoperative recovery. Despite initial concerns about the use of minimally invasive surgery in gynecologic oncology, this approach has been shown to be safe and effective in the management of uterine and cervical cancer, and minimally invasive surgical management of these malignancies is now commonplace. Concerns remain regarding the use of minimally invasive surgery for the staging and management of ovarian cancer, including concerns regarding the adequacy of abdominal exploration and staging with minimally invasive approaches compared to traditional laparotomy and the risks and implications of intra-operative tumor cyst rupture and port-site metastases. However, several case series, retrospective reviews, and case-control studies have demonstrated that minimally invasive surgery is both safe and effective for the staging of borderline ovarian tumors and early-stage epithelial ovarian cancer when performed by a trained gynecologic oncologist. Data to support the role of minimally invasive surgery for advanced epithelial ovarian cancer are scant and use of minimally invasive surgery in this setting is not recommended.

abstract: Case studies in the diagnosis and management of Peutz-Jeghers Syndrome (PJS) (ovarian sex cord tumors)

Abstract

Peutz-Jeghers syndrome (PJS) is a rare genetic disorder characterized by melanotic macules, gastrointestinal polyps and increased cancer risks. We discuss several common scenarios encountered in the diagnosis and management of PJS patients. If the diagnosis is unclear, all pathological material should be re-evaluated by an expert gastrointestinal pathologist. The PJS discussion email list-serve (patient managed) and the peutz-jeghers.com, geneclinics.org, stk11.com websites are useful resources for patients.

abstract: Breast and Ovarian Cancer: The Forgotten Paternal Contribution

Individuals with a paternal family history were found to have a different, and higher, pattern of risk estimates. No significant difference was seen between the type of referrals sent by general practitioners, oncologists, and gynecologists.

full free access: Phase ii/iii study of intraperitoneal chemotherapy after neoadjuvant chemotherapy for ovarian cancer: Canada

Note:

1) see Section 2.3 for study criteria (patient enrollment requirements);
2) .... acquisition of tumour specimens both before study therapy is started and after neoadjuvant chemotherapy has been received provides a unique opportunity for a correlative study of differing drug responses within the same patients.

Although the study is led by the ncic ctg, the protocol, the accompanying IP therapy guidelines, and a companion document intended to summarize and promote best practice in the administration of IP therapy are the result of a collaboration between the ncic ctg and the Society of Gynecologic Oncologists of Canada, with international partners in the United Kingdom (National Cancer Research Institute), Spain (Spanish Ovarian Cancer Research Group), and the United States (Southwest Oncology Group).

Abstract: (including full free text access):

abstract: Early Detection of Recurrent Ovarian Cancer in Patients with Low-Level Increases in Serum CA-125 Levels by PET/CT

Abstract

Purpose: Serum CA-125 has been shown to be a sensitive tumor marker of recurrent ovarian cancer. The goal of this study was to evaluate the use of 2-[F-18]fluoro-2-deoxy-d-glucose-positron emission tomography/computed tomography (FDG-PET/CT) in the early detection of recurrent ovarian cancer in patients with low-level increases in serum CA-125 levels.

abstract: A longitudinal investigation of (PTSD) posttraumatic stress disorder in patients with ovarian cancer

Abstract
INTRODUCTION:
Exposure to the aggressive and life-threatening nature of ovarian cancer and its treatment is potentially traumatic. However, little is known about the occurrence of posttraumatic stress disorder (PTSD) in these patients.

abstract: Ovarian cancer in the elderly: Impact of surgery on morbidity and survival (France)

Note: in this study 'elderly' =  70+ yrs

CONCLUSION:

Elderly ovarian cancer patients undergo less extensive surgery and have lower OS (overall survival) despite similar postoperative morbidity, optimal resection and DFS. OS decrease could be explained by difference in the management of recurrences.

Apr 2011: free full access - Recognition and initial management of ovarian cancer: summary of NICE guidance -- bmj.com

Note: guidelines include Carboplatin alone in high-risk early stage; IP for advanced stage ovarian cancer via clinical trial/s (which brings up the question as to the availability of trials??) Future research What is the relationship between the duration and frequency of symptoms in women with ovarian cancer before diagnosis, and the stage of disease at diagnosis and subsequent survival? What is the optimum threshold on the risk of malignancy index I (RMI I) that should be applied in secondary care to guide the management of women with suspected ovarian cancer? How does computed tomography compare with magnetic resonance imaging in accuracy of staging and prediction of optimal cytoreduction? Answering this will require large, multicentre case-control studies. What are the cost effectiveness and risks of systematic retroperitoneal lymphadenectomy in women whose ovarian cancer seems to be confined to the ovaries? Answering this will require a prospective randomised trial. What is the effectiveness of primary surgery in women with advanced ovarian cancer that cannot be fully excised?

free full access: Calcium supplements with/without vitamin D and risk of cardiovascular events: reanalysis of the Women’s Health Initiative - bmj.com (including responses)

Abstract/Conclusions:
Calcium supplements with or without vitamin D modestly increase the risk of cardiovascular events, especially myocardial infarction, a finding obscured in the WHI CaD Study by the widespread use of personal calcium supplements. A reassessment of the role of calcium supplements in osteoporosis management is warranted.

excerpt (from full text):

"...An important question that arises is whether co-administered calcium and vitamin D affects cardiovascular risk. The Women’s Health Initiative reported no adverse effect of calcium and vitamin D (1 g calcium/400 IU vitamin D daily) on any cardiovascular end point in their large (n=36 282), seven year, randomised, placebo controlled trial.3 4 However, 54% of the participants were taking personal (non-protocol) calcium supplements at randomisation and 47% were taking personal vitamin D supplements, effectively rendering this trial a comparison of higher dose and lower dose calcium and vitamin D for most of the participants.

Allowing clinical trial participants free access to the intervention being studied is unusual and has the potential to obscure both adverse and beneficial effects..."

press release- (OVA1 test) Vermillion to Host Conference Call to Present Company Update and Review Financial Results May 10th, 2011

BJC - Abstract - Predictors of contralateral breast cancer in BRCA1 and Predictors of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers (stage 1/11 breast cancer/mutation carriers)

Purpose:

The objective of this study was to estimate the risk of contralateral breast cancer in BRCA1 and BRCA2 carriers; and measure the extent to which host, family history, and cancer t

Conclusion:

The risk of contralateral breast cancer risk in BRCA mutation carriers declines with the age of diagnosis and increases with the number of first-degree relatives affected with breast cancer. Oophorectomy reduces the risk of contralateral breast cancer in young women with a BRCA mutation.

BJC - Abstract: Breast, ovarian, and endometrial malignancies in systemic lupus erythematosus: a meta-analysis

Results:

  The five studies included 47 325 SLE patients (42 171 females) observed for 282 553 patient years. There were 376 breast cancers, 66 endometrial cancers, and 44 ovarian cancers. The total number of cancers observed was less than that expected, with SIRs of 0.76 (95% CI: 0.69, 0.85) for breast cancer, 0.71 (95% CI: 0.55, 0.91) for endometrial cancer, and 0.66 (95% CI: 0.49, 0.90) for ovarian cancer.

Conclusions:

  Data strongly support a decreased risk of breast, ovarian, and endometrial cancers in SLE. This may be due to inherent differences in women in SLE (vs the general population) regarding endogenous oestrogen, other medications, and/or genetic make-up.

Oncology - Interpreting Clinical Trial Results - Clinical Options in Practice

Note: requires registration (free); worth reading

Oncology - Interpreting Clinical Trial Results

Authors: Maurie Markman, MD (More Info)

Released: 11/17/10

Last Reviewed: 12/1/10

(media) Regina: Pilot project tracks whether lab tests ordered by RQHR doctors are necessary (CA125)

Genetic variants associated with breast-cancer risk : The Lancet Oncology (Steven A Narod)

Note: register (free) to view

EpCAM expression in primary tumour tissues and metastases: an immunohistochemical analysis - Journal of Clinical Pathology

EpCAM expression in primary tumour tissues and metastases: an immunohistochemical analysis

"....Tumour tissues, such as primary and metastatic breast cancer, frequently overexpress EpCAM.2 Gastl and colleagues observed EpCAM overexpression in 35.6% of patients with invasive breast cancer, and this was associated with poor disease-free and overall survival.3 Moreover, our group has shown that survival decreases significantly with increasing amounts of EpCAM expression.4 EpCAM can be used as prognostic marker in node-positive and node-negative breast cancer.5 Furthermore, frequent and high-level EpCAM expression has been found in adenocarcinomas of the colon, stomach, pancreas and prostate.6 Most soft-tissue tumours and all lymphomas are EpCAM negative. EpCAM overexpression has been associated with a dismal prognosis in other tumour entities, such as gallbladder cancer,7 ovarian cancer8 and pancreatic cancer.9"

See also 
Table 3

EpCAM expression in genitourinary tract cancers (eg: ovarian, clear cell, mucinous...)

Conclusion
EpCAM expression was detected on adenocarcinomas of various primary sites. If EpCAM-specific antibodies are intended to be used in patients with cancer, we recommend prior immunohistochemical evaluation of EpCAM expression, particularly in patients with renal cell cancer, hepatocellular carcinoma, urothelial carcinoma, breast cancer and squamous cell carcinomas.

Apr 2011: Postherpetic Neuralgia: An Overview of the Pathophysiology, Presentation, and Management (shingles)

Postherpetic neuralgia (PHN) presents itself as a frustrating and fascinating subject within the realm of neuropathic pain. With herpes zoster (shingles) affecting roughly 3.4 per 1,000 people, and nearly .49 per 1,000 people developing PHN annually, the subject continues to be a prevalent dilemma in want of further study. Drs. Christopher Gharibo and Carolyn Kim explore the diagnosis, treatment and management of this complicated condition.

Download to read this article in PDF document:
Postherpetic Neuralgia: An Overview of the Pathophysiology, Presentation, and Management

This article is in PDF format and it requires Abobe Reader.

Apr 2011 Gastroenterology & Endoscopy News - Henry Lynch, MD, Delivers Keynote Address on Lynch Syndrome & Gary H. Hoffman, MD

Note: requires registration (free) to view, discusses sporadic cancer/s, BRAF mutation plus EPCAM mutations, treatment responses etc:

"EPCAM mutation carriers may have phenotypic features that differ from carriers of MSH2 mutations, namely, an almost exclusive expression of site-specific CRC and an absence of extracolonic cancers. “This is really new, and more information is needed on this,” he said".
"Of therapeutic interest, patients with MSI-high tumors may respond differently to chemotherapy."

 ----------------------------------------------------------------

"Henry Lynch, MD, Delivers Keynote Address on Lynch Syndrome

Doctor Who First Described the Syndrome Offers Guidance on Management of Inherited CRC

by Caroline Helwick

San Francisco—Microsatellite instability (MSI) is an important factor in the evaluation of Lynch syndrome colorectal cancer (CRC) and should be part of the workup of these patients, according to Henry Lynch, MD, who defined the syndrome and gave the keynote lecture at the 2011 American Society of Clinical Oncology Gastrointestinal Cancers Symposium....."

handbook (patient/consumer friendly) Australia: Understanding Genetic Tests for Lynch Syndrome - Information & Decision Aids

abstrract: A two-antibody mismatch repair protein immunohistochemistry screening approach for colorectal carcinomas, skin sebaceous tumors, and gynecologic tract carcinomas

Source

Department of Pathology, Stanford University, Stanford, CA, USA.

Abstract

Mismatch repair protein immunohistochemistry is a widely used method for detecting patients at risk for Lynch syndrome. Recent data suggest that a two-antibody panel approach using PMS2 and MSH6 is an effective screening protocol for colorectal carcinoma, but there are limited data concerning this approach for extraintestinal tumors.

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JNCI extract: Radiologists Urge FDA To Accept PET-Based Tumor Response Criteria in Clinical Trials

(U.S.) FDA Considers New Rules to Speed Up Confirmatory Trials of Cancer Drugs Granted Accelerated Approval

Spring 2011 Cure Magazine/website - "Take Our Poll' - chemobrain

Note: see very top of website page and click on 'take our poll' - a yes/no response
--------------------------------------------------------------
Take Our Poll

Do you believe you developed chemobrain due to cancer and/or treatment?

Search Sessions ASCO Advanced Planner annual meeting

Revisiting the Women’s Health Initiative Estrogen-Alone Trial - hcp.obgyn.net

Note: scroll to bottom for addition references

Towards fundamental research contribution in cancer survivorships | Patient's Section - defining life after cancer (physician response)

April 18th, 2011

Towards fundamental research contribution in cancer survivorships

We asked our Current Oncology Section Editors how they would define the term “life after cancer” and how that theme presents itself in their chosen fields. Below is a response from Dr. Michel L. Tremblay, Director of the Goodman Cancer Research Centre at McGill University: (cont'd)

abstract: Multidisciplinary Meeting on Male Breast Cancer: Summary and Research Recommendations

"...Therefore, the Breast International Group and North American Breast Cancer Group have joined efforts to develop an International Male Breast Cancer Program and to pool epidemiologic data, clinical information, and tumor specimens. This international collaboration will also facilitate the future planning of clinical trials that can address essential questions in the treatment of male breast cancer."

Markman: KRAS Mutations in Ovarian Cancer -- Maybe Not

press release: Decoding cancer patients' genomes is powerful diagnostic tool (and potential treatments)

NBOCC News - April 2011 - National Breast and Ovarian Cancer Centre (NBOCC)

In this issue...

• National Breast and Ovarian Cancer Centre releases Reconciliation Action Plan
• Clinical practice guidelines for external review
• Promoting multidisciplinary care for all patients with cancer
• Shared care demonstration project update
• Virtual classrooms for rural health professionals caring for women with breast cancer
• NBOCC’s topic-specific clinical practice guidelines available in new online format
• Associate Professor John Buckingham
• New issue Clinical Update -Breast cancer: Issue 39

abstract: Familial Risks in Cancer of Unknown Primary: Tracking the Primary Sites

Conclusion:

The present data show that CUP is not a disease of random metastatic cancers but, instead, a disease of a defined set of cancers. The association of CUP with families of kidney, lung, and colorectal cancers suggests a marked genetic basis and shared metastatic mechanisms by many cancer types. Familial sites shared by CUP generally match those arising in tissue-of-origin determinations and, hence, suggest sites of origin for CUP. Mechanistic exploration of CUP may provide insight into defense against primary tumors and the metastatic process.

abstract: A putative Lynch syndrome family carrying MSH2 and MSH6 variants of uncertain significance—functional analysis reveals the pathogenic one (

Abstract

Inherited pathogenic mutations in the mismatch repair (MMR) genes, MSH2, MLH1, MSH6, and PMS2 predispose to Lynch syndrome (LS). However, the finding of a variant or variants of uncertain significance (VUS) in affected family members complicates the risk assessment. Here, we describe a putative LS family carrying VUS in both MSH2 (c.2768T>A, p.Val923Glu) and MSH6 (c.3563G>A, p.Ser1188Asn). Two colorectal cancer (CRC) patients were studied for mutations and identified as carriers of both variants. In spite of a relatively high mean age of cancer onset (59.5 years) in the family, many CRC patients and the tumor pathological data suggested that the missense variation in MSH2, the more common susceptibility gene in LS, would be the predisposing alteration. However, MSH2 VUS was surprisingly found to be MMR proficient in an in vitro MMR assay and a tolerant alteration in silico. By supplying evidence that instead of MSH2 p.Val923Glu the MSH6 p.Ser1188Asn variant is completely MMR-deficient, the present study confirms the previous findings, and suggests that MSH6 (c.3563G>A, p.Ser1188Asn) is the pathogenic mutation in the family. Moreover, our results strongly support the strategy to functionally assess all identified VUS before predictive gene testing and genetic counseling are offered to a family.

free full access: Understanding the Estrogen Receptor–Positive Breast Cancer Genome: Not Even the End of the Beginning

Ottawa press release: (drug GAP-107B8 / ascites) PharmaGap Sees Positive Results from In Vivo Ovarian Cancer Models at the Ottawa Hospital Research Institute

Note: in research  

OTTAWA, ONTARIO--(Marketwire - April 18, 2011) - PharmaGap Inc. (TSX VENTURE:GAP)(OTCBB:PHRGF) ("PharmaGap" or "the Company") today announced initial results from preclinical testing at the Ottawa Hospital Research Institute ("OHRI"). Initial results from this study are positive and provide evidence that a peptide formulation of PharmaGap's lead cancer drug GAP-107B8 administered via the intraperitoneal route can reduce tumour burden (19%) and significantly suppress ascites formation (73%) relative to controls. The test was undertaken at OHRI in collaboration with Dr. Barbara Vanderhyden. Dr. Vanderhyden, upon initial review of the data commented "The reduction in ascites volume is very interesting in its own right, because this is a notable cause of morbidity in women with ovarian cancer. There is currently no drug therapy that is effective against ovarian cancer-associated ascites accumulation. Paracentesis, the removal of abdominal ascites, is commonly used to alleviate symptoms and prolong survival of women with ovarian cancer.......

.........In this study two formulations of GAP-107B8 peptides were tested in an established intraperitoneal xenograft model in immune-deficient mice and evaluated for tumour burden and accumulation of malignant ascites (excess fluid containing cancer cells in the abdominal cavity). The cell line selected for testing (OCC-1 human ovarian cancer) is of a phenotype characterized by the production of peritoneal ascites with growth of multiple small solid tumours......

(adverse events) FDA: Safety Alerts for Human Medical Products > Axxent FlexiShield Mini by iCAD (formerly Xoft Inc.): Recall- Product May Shed Particles of Tungsten (breast)

RECOMMENDATION: Customers were instructed to stop using all units of the Flexishield Mini Catalog Number F5300 in their inventory and return them to the company. It is recommended that health care professionals inform the patient about the likelihood of post-operative tungsten particles in the breast and continue the imaging recommended in your clinical protocol for the full 5 years, unless otherwise directed by the patient’s treatment team. For the recalled lot numbers and additional recommendations please see the Recall Notice.
Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

• Complete and submit the report Online: www.fda.gov/MedWatch/report.htm

WebMD article: DNR Orders May Affect Surgical Outcomes (note: article source Archives of Surgery media release)

"If someone says, 'If my heart stops, I don't want it to be restarted,' that is one thing, but if they say something broad like, 'I don't want you to use extreme measures,' What do extreme measures mean? I think that is fuzzier," says Roman.
"It is important to have the conversation in more detail between physician and patient," says Roman. "So physicians can understand their patients' wishes better, and the patient understands the risks and outcomes better by knowing what to expect if certain things happen.".....

View Article Sources

SOURCES:
Roman, S. Archives of Surgery, April 18, 2011, advance online edition.
Clarence Braddock, MD, MPH, professor of medicine and associate dean for medical education, Stanford School of Medicine; director of clinical ethics, Stanford Center for Biomedical Ethics.
J. Randall Curtis, MD, MPH, section head of pulmonary and critical care medicine, Harborview Medical Center; professor of medicine, University of Washington, Seattle.
News release, American Medical Association.

abstract:
ONLINE FIRST
High Mortality in Surgical Patients With Do-Not-Resuscitate Orders
Analysis of 8256 Patients