Sunday, January 15, 2012
open access - JNCI: Finding Ovarian Cancer (correspondence in response to Lim et al.)
"For decades, investigators have sought a strategy for finding ovarian cancer early enough to reduce the risk of dying of ovarian cancer. In this issue of the Journal, Lim et al. (1) report on their study in which women answered a dozen simple questions such as whether they felt pelvic or abdominal pain in the recent past and, if so, when, how frequently, and how severely. Symptom indices like this are being promoted as easier or better ways to find ovarian cancer early, under the assumption that early therapy can achieve a better outcome than if the women wait until more or worse symptoms prompt them to see a physician. The study revealed that symptom indices as ovarian cancer screeners can be sensitive to the presence of cancer in the period between 3 and 14 months before clinical diagnosis......
financial media: (cryoablation) Tumor-Freezing Treatment Gives Ovarian Cancer Patients Extra Time: Presented at ISET 2012 - MarketWatch
"MIAMI BEACH, Fla., Jan 15, 2012 (BUSINESS WIRE) --
Killing tumors by freezing them through cryoablation can extend the
lives of women with ovarian cancer that has spread to other parts of the
body and is cost-effective, according to research being presented at the
4th annual Symposium on Clinical Interventional Oncology
(CIO), in collaboration with the International Symposium on Endovascular
Therapy (ISET).
The study included 21 patients whose tumors in the abdomen, liver, lung
and bone could not be removed surgically......."
FDA plans survey on direct-to-consumer drug ads -Modern Healthcare
Posted: January 15, 2012 - 1:00 pm ET
The Food and Drug Administration announced plans to survey doctors, nurse practitioners and physician assistants on their awareness and perception of direct-to-consumer prescription drug advertising. The agency is seeking comment on a proposed survey of 2,000 healthcare professionals, according to a notice scheduled to appear in the Federal Register (PDF).
Jan 15th: New Symptom Indices Offer No Gain in Ovarian Ca - in Oncology/Hematology, Ovarian Cancer from MedPage Today
Action Points
- Explain that two new ovarian cancer symptom indices offered little advantage over the current Goff Index.
- Point out that for all three indices, sensitivity was lower for data obtained from the general practitioner's notes and highest for those interviewed over the telephone, ant that the specificity was largely unchanged
"This sobering news follows hard on the heels of a large U.S. randomized trial finding no benefit, and indeed some harm, to women who were screened annually with a transvaginal ultrasound exam and a CA-125 blood test compared with a usual care control group," they wrote, referring to the NIH-sponsored Prostate, Lung, Colon, and Ovary (PLCO) screening program (JAMA 2011; 305:2295-2303).
They said one question the ovarian cancer community needs to answer is where it should focus its efforts: On the time between when a tumor is large enough to cause mild symptoms and when it is large enough to cause symptoms that prompt women to call a physician, or on a better understanding of disease etiology, leading to better prevention and therapy.
"These other research directions remain critical as the search continues for better ways to find ovarian cancer early," they said.
Primary source: Journal of the National Cancer Institute
Source reference: Lim AWW, et al. "Predictive value of symptoms for ovarian cancer: Comparison of symptoms reported by questionnaire, interview, and general practitioner notes" J Natl Cancer Inst 2012; 104: 1-11. Additional source: Journal of the National Cancer Institute Source reference: Hartge P, Speyer JL. "Finding Ovarian Cancer" J Natl Cancer Inst 2012; DOI: 10.1093/jnci/drj518. |
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Related Article(s): |
Medscape: Dermatologic Manifestations of Metastatic Carcinoma of the Skin
"Cutaneous metastasis is a rare occurrence but may be the presenting sign of a primary internal malignancy."
"The most common sources of cutaneous metastases in woman are the breasts (69%), the colon (9%), melanoma (5%), the ovaries (4%), and the lungs (4%). In men, they are the lungs (24%), the colon (19%), melanoma (13%), and the oral cavity (12%)."
New Articles -- EvidenceUpdates: A phase 3 trial of bevacizumab in ovarian cancer - abstract, reference + professional commentaries
also see linked reference:
Perren TJ, Swart AM, Pfisterer J, et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011 Dec 29;365(26):2484-96. (Original) PMID: 22204725
Saturday, January 14, 2012
PET/CT imaging in gynecologic malignancies: A critical overview of its clinical impact and our retrospective single center analysis 10.1016/j.critrevonc.2011.10.002 : Critical Reviews in Oncology
A growing body of evidence defines PET/CT as one of the most powerful tools for tumor, nodal and metastasis (TNM) cancer staging both in pre-treatment and in post treatment follow-up settings.
At any phase of cancer evaluation, detection of metastasis represents one of the most critical impediments to the cure of tumor; traditional diagnostic imaging modalities, such as computed tomography (CT), are frequently found to inadequately stage the tumor, based on subsequent outcomes.. ...
Highlights
► FDG-PET/CT is a valid instrument for the detection of recurrent or metastatic gynaecologic tumours.
► Evidence corroborates FDG-PET/CT's role in ovarian cancer in monitoring response to chemotherapy.
► In uterine cervical carcinoma, FDG-PET/CT is more sensitive than MRI for detecting nodal metastases.
► Retrospective analysis of 116 patients showed FDG-PET/CT was principally useful in the setting of suspected recurrence.
► Evidence corroborates FDG-PET/CT's role in ovarian cancer in monitoring response to chemotherapy.
► In uterine cervical carcinoma, FDG-PET/CT is more sensitive than MRI for detecting nodal metastases.
► Retrospective analysis of 116 patients showed FDG-PET/CT was principally useful in the setting of suspected recurrence.
open access: Identifying women with suspected ovarian cancer in primary care: derivation and validation of algorithm | BMJ (note reference to recent NICE guidelines)
Objective
To derive and validate an algorithm to estimate the absolute risk of having ovarian cancer in women with and without symptoms.
Main outcome
The primary outcome was incident diagnosis of ovarian cancer recorded in the next two years.
Conclusion
The algorithm has good discrimination and calibration and, after independent validation in an external cohort, could potentially be used to identify those at highest risk of ovarian cancer to facilitate early referral and investigation. Further research is needed to assess how best to implement the algorithm, its cost effectiveness, and whether, on implementation, it has any impact on health outcomes.
.......As there are few established risk factors, targeted screening of asymptomatic patients at risk of developing ovarian cancer is unlikely to be cost effective at present (although further information is likely to become available when the UK ovarian cancer screening trial reports in 2015-6). The challenge presented by ovarian cancer, therefore, is to make the correct diagnosis as early as possible, despite the non-specific nature of symptoms and signs.4 This is particularly the case in primary care, where general practitioners need to differentiate those patients for whom further investigation is warranted from those who require reassurance or a “watch and wait” policy. Moreover, primary care clinicians need to decide which patients require urgent investigation or referral and which require routine tests or referral.........
Summary of key findings
We have developed and validated a new algorithm designed to estimate the absolute risk of having existing but as yet undiagnosed ovarian cancer based on a combination of symptoms and simple variables such as age and family history of ovarian cancer, which the patient is likely to know and which will increase the baseline absolute risk......................................................................................................................................
What is already known on this topic
- Ovarian cancer is the second most common gynaecological cancer and most women are diagnosed with late stage disease, which has a poor survival rate
- Earlier diagnosis could improve with more targeted investigation of symptomatic patients and increased public awareness of symptoms, which is a major challenge given the non-specific nature of some of the symptoms
What this study adds
- An algorithm based on simple clinical variables such as age, family history of ovarian cancer, anaemia, abdominal pain, abdominal distension, rectal bleeding, postmenopausal bleeding, appetite loss, and weight loss, which the patient is likely to know or which are routinely recorded in general practice computer systems, can estimate absolute risk of ovarian cancer in women with and without symptoms in primary care
- The algorithm could be integrated into general practice clinical computer systems and used to assess risk in women presenting with and without symptoms
Biomedcentral: open access - Biomarker robustness reveals the PDGF network as driving disease outcome in ovarian cancer patients in multiple studies
link: ABSTRACT and open text PDF
Background:
Ovarian cancer causes more deaths than any other gynecological cancer.
Identifying the molecular mechanisms that drive disease progress in ovarian cancer is a critical step in providing therapeutics, improving diagnostics, and affiliating clinical behavior with disease etiology. Identification of molecular interactions that stratify prognosis is key in
facilitating a clinical-molecular perspective.
Results:
The Cancer Genome Atlas has recently made available the molecular characteristics of more than 500 patients......
Blogger's Note: see also - The Cancer Genome Atlas completes detailed ovarian cancer analysis NCI Press Release (2011)
CONCLUSIONS
"..........Over the past few decades, different genes have been used, with greater or lesser success, as biomarkers for prognostics. In the work presented here, by performing genome-wide sequential
analyses across all genes and across all pathways, starting with TCGA and validating in two additional datasets, we saw how the single-gene approach fails to stratify patients robustly into prognostic groups.
"Our results demonstrate that pathway interactions are either associated with improved prognosis by "helping" the pathway counter the tumor, or with poor prognosis by "breaking down" the pathway's normal activity. Through better understanding of the pathway mechanisms and the interactions that undergo changes, we may find targets for new treatments. The fact that the pathway we identified did not correlate with age or tumor diameter and was found in all
three datasets strengthens the hypothesis that this pathway is a core mechanism of the disease."
Reported referral for genetic counseling or BRCA 1/2 testing among United States physicians: a vignette-based study.
Blogger's Note: in the absence of the full paper ($$$) conclusions should be viewed with caution (eg. detailed reasons, albeit summarized in the abstract...) because....the conclusion do not make sense.
Please post a message IF this paper is available elsewhere in open text publishing format.
BACKGROUND:
Genetic
counseling and testing is recommended for women at high but not average
risk of ovarian cancer. National estimates of physician adherence to
genetic counseling and testing recommendations are lacking.
METHODS:
Using a vignette-based study, we surveyed 3200 United States family physicians, general internists, and obstetrician/gynecologists and received 1878 (62%) responses. The questionnaire included an annual examination vignette asking about genetic counseling and testing. The vignette varied patient age, race, insurance status, and ovarian cancer risk. Estimates of physician adherence to genetic counseling and testing recommendations were weighted to the United States primary care physician population.CONCLUSION:
Physicians reported that they would refer many average-risk women and would not refer many high-risk women for genetic counseling/testing. Intervention efforts, including promotion of accurate risk assessment, are needed.
Risks - When Too Much Vitamin D Is Too Much - NYTimes.com
references Johns Hopkins University study published in The American Journal of Cardiology.
Resveratrol Scientists React to Fraud Scandal
January 13, 2012 (New York, New York) — As the controversy over the research fraud allegations against Dr Dipak Das enter its third day, researchers, clinicians, and red-wine enthusiasts more generally are wondering just what the news means for the field of resveratrol research. At the very least, scientists told heartwire , plans for an international meeting scheduled for later this year have been turned upside down: Das was one of just eight international experts on the scientific committee for Resveratrol 2012.
Jan 2012: Faulty proteins may prove significant in identifying new treatments for ovarian cancer | e! Science News
Link: PLOS One published study
Objective
To define the BRCAness profile of sporadic ovarian carcinoma and determine whether BRCA1, PARP, FANCD2, PTEN, H2AX, ATM, and P53 protein expression correlates with response to treatment, disease recurrence, and recurrence-free survival.
"The study -- which was supported by the Sherie Hildreth Ovarian Cancer (SHOC) Foundation -- focused on proteins that are supposed to assist cells in repairing harmful breaks in DNA strands, a process called homologous recombination (HR). The malfunctioning of HR is not well understood in ovarian cancers where there is no family history of the disease. However, there is evidence that these proteins influence a patient's ability to respond to drugs and their survival rates after treatment."
abstract: Predictive Value of Symptoms for Ovarian Cancer: Comparison of Symptoms Reported by Questionnaire, Interview, and General Practitioner Notes
Background:Because of the poor survival outcomes associated with advanced ovarian cancer, early detection strategies are needed. Although several symptom indices have been described, their relationship with the potential lead time has been poorly documented.
Methods
Women aged 50–79 years who had newly diagnosed ovarian cancer (n = 194) and control subjects (n = 268) who attended ovarian cancer screening clinics were included in the analysis.
Conclusions
Previous estimates of index performance have been overly optimistic because they did not take into account the time required to make a diagnosis on the basis of testing in response to symptoms. In addition, the specificity of a symptom index is lower when based on a telephone interview vs questionnaire or GP notes. Thus, the clinical utility of a symptom index depends on precisely how it is used and how index-positive women are managed.
abstract: Genetic Counseling: Bias in the Reporting of Family History: Implications for Clinical Care
".....This is evident by the underreporting of paternal family histories of cancer, and also, though to a lesser extent, by degree (family relationship). These discrepancies in reporting family history of cancer imply we need to take more care in collecting accurate family histories and also in the clinical management of individuals in relation to hereditary risk"
abstract: Objectives: Published data are conflicting on the influence of cell type on prognosis in ovarian cancer. The recent separation of low-grade serous carcinoma as a distinctive cell type of ovarian cancer with an indolent behavior, in retrospect, suggests that survival in studies that have not separated this group may be inaccurate.
Blogger's Note: the focus of this abstract is serous cell type
Conclusions:
Low-grade serous carcinoma has a significantly better prognosis than high-grade serous carcinoma and also differs with regard to substage distribution and proportion of patients optimally debulked. Because of its excellent prognosis, failure to separate low-grade serous carcinomas, notwithstanding its infrequent occurrence, can change the results of survival analyses that do not make this separation.
Ovarian Endometrioid Adenocarcinoma: Incidence and Clinical Significance of the Morphologic and Immunohistochemical Markers of Mismatch Repair Protein Defects and Tumor Microsatellite Instability
"Ovarian cancer, particularly endometrioid (cell type)adenocarcinoma, is also associated with Lynch syndrome.....Overall, 10% of tumors had abnormal MMR protein status, defined as complete immunohistochemical loss of expression of MLH1, MSH2, MSH6, and/or PMS2.....Concurrent uterine tumor was present in 5/7 patients whose ovarian tumor had abnormal MMR/MSI.......Although abnormal MMR/MSI did not carry prognostic value in this study, it did predict the involvement of the uterus by the tumor. Thus, in patients with ovarian endometrioid adenocarcinoma who undergo uterus-sparing surgery, abnormal MMR/MSI should prompt further diagnostic evaluation of the endometrium for tumor."
Perspective: The clinical trial barriers: Nature Publishing Group (western medicine/Asian approaches)
"Western medicine depends on science to create and assess drugs at the molecular level. In Asia, there is a commonly held belief that there is an art to healing too, and that both art and science should cooperate to help eradicate illness and relieve suffering."
"For traditional Asian approaches to become integrated into modern medicine, we need to consider alternative inclusion and exclusion criteria for RCTs. We also need to review how outcomes are assessed. These concepts are neither new nor unproven. Both Western-style modern medicine and traditional Asian medicine aim to heal patients in a harmonized way and can be developed together into an integrated form of personalized medicine. Redesigning clinical trials will accelerate the blending of these two styles of healing, for the benefit of humankind."
Eighth retraction marks slide of lung cancer work (+breast cancer) | Reuters
"...."To a certain extent, what I'm worried about is that this may show aspects of how it is becoming increasingly difficult to check the scientific literature and how that difficulty stems at least in part from lack of immediate access to data but also lack of code and documentation," Baggerly told Reuters Health.
Given the highly technical nature of the work, it's not surprising that the flaws in the papers weren't caught before they were published, according to Baggerly.
"That's actually OK," he said. "It's not OK that it took so long for the challenges to be accepted once the research was questioned."
"The other thing that is not OK is the fact that it made it into guiding clinical trials," Baggerly added.
Brawley said the story "is a tragedy in a number of different ways.".....
abstract: Cancer and environment: Definitions and misconceptions - Environmental Research
Conclusions
Our findings emphasize the discrepancies in reporting environmental causation of cancer and the limits of inference in interpreting environmentally attributable risk estimates. Rather than achieving consensus on a single definition for the environment, we suggest the focus be on achieving transparency for any environmentally attributable risks.
Highlights
► We report definitions of the environment and attributable risk estimates over time.
► Definitions were categorized and assessed in relation to risk estimates.
► Reported environmentally attributable risk estimates ranged from 1% to 100%.
► There are limits of inference in interpreting environmentally attributable risks.
► The focus should be on transparency in the derivation of attributable risk estimates.
► Definitions were categorized and assessed in relation to risk estimates.
► Reported environmentally attributable risk estimates ranged from 1% to 100%.
► There are limits of inference in interpreting environmentally attributable risks.
► The focus should be on transparency in the derivation of attributable risk estimates.
abstract: Predictors of Long-Term Outcome from Intraperitoneal Radioimmunotherapy for Ovarian Cancer.
"A statistically significant improvement in progression-free survival (p≤0.05) was noted for less bulky disease and younger age. Administration of paclitaxel plus IFN, an immune response, and use of (90)Y showed a favorable nonsignificant trend. Dose escalation of radionuclide did not change risk of progression; thus, this therapy may have therapeutic efficacy at modest dose levels."
Friday, January 13, 2012
Adolescents And Young Adults: Bringing A Neglected Group Into Cancer Research – Health Affairs Blog (ages 7-18rs)
“A child is not a small adult,” but an adolescent is not a large child...."
"Consent and Assent in Children and AYA Cancer Patients
For most IRBs, informed consent can be granted by any prospective human subject over the age of 18. For minor patients under 7, consent is granted by the parents or guardians. What to do with patients between the ages of 7 and 18 (or with “intellectual ages” between 7 and 18) is less clear. While they are still minors and under the care of their parents or guardians, they are also independent human beings capable of judgments, particularly ones with which their parents or guardians may not agree. This is certainly the case when it comes to choosing their friends, making time for school work, selecting extracurricular activities, carefully operating a motor vehicle and experimenting with alcohol, drugs or sex....."
abstract: Whole-brain radiation therapy of brain metastasis.
Source
Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Princess Margaret Hospital, University of Toronto, Toronto, Ont., Canada.
Abstract
The purpose of this report was to review the role of whole brain radiotherapy (WBRT) in the management of brain metastases. In particular, we review the role of WBRT as a prophylactic therapy, and the role of surgery and stereotactic radiosurgery (SRS) with respect to WBRT, by discussing the relevant randomized controlled trials. WBRT is associated with toxicities and this may influence the decision to use WBRT and, therefore, we review both the acute side effects of WBRT and the moreserious late side effects of neurocognitive impairment and leukoencephalopathy. As patients are living longer with brain metastases the role of WBRT is moving forward; however, using modern radiation technology we may be able to reduce the morbidity of this therapy. We present an extreme case of re-re-treatment WBRT with hippocampal sparing and simultaneous integrated boosts to multiple lesions as one of the future directions under evaluation.abstract: Pancreatic cancer and a novel MSH2 germline alteration
CONCLUSIONS:
The MSH2 P349L may increase the risk for pancreatic cancer beyond the usual mutations in DNA mismatch repair genes; however, studies of additional families with the identical missense alteration are needed to confirm this initial impression.abstract: Incidence and predictors of positive and negative effects of BRCA1/2 genetic testing on familial relationships: a 3-year follow-up study
"....Reporting positive relationship effects was associated with older age, intolerance for uncertainty, cancer-specific distress, and more social support. Low education, positive attitude toward prophylactic mastectomy, and low social support increased the likelihood of negative effects.
Conclusion:Our findings do not support the belief that family relationships are frequently disrupted by BRCA1/2 testing."
abstract: What do we know about patients' perceptions of continuity of care? A meta-synthesis of qualitative studies
Abstract
Objective The increasing complexity in healthcare delivery might impede the achievement of continuity of care, being defined as ‘one patient experiencing care over time as coherent and linked’. This article aims to improve the knowledge on patients' perceptions of relational (RC), informational (IC) and management continuity (MC) across care levels.
Results The selected 25 studies most frequently investigated RC. Being attended to regularly and over time by one physician (RC) was valued by chronic ill patients, but balanced with convenient access by young patients (MC). Communication and information transfer across care settings as well as the gathering of holistic information about the patient were perceived to foster IC. Critical features for achieving MC were accessibility between care levels, individualized care and a smooth discharge process including the receipt of support. Patients further considered that their personal involvement was one facilitating element of continuity of care.
The impact of patient and public involvement on UK NHS health care: a systematic review
Study selection UK studies from 1997 to 2009 which included service user involvement in NHS healthcare services.
Conclusion There is a need for significant development of the PPI (Patient Public Involvement) evidence base particularly around guidance for the reporting of user activity and impact. The evidence base needs to be significantly strengthened to ensure the full impact of involving service users in NHS healthcare services is fully understood.
Analysis of Australian newspaper coverage of medication errors
Conclusion
Australian newspaper reporting of medication errors was relatively limited. Given the high prevalence of errors and the potential role consumers can play in identifying and preventing errors, there is a clear argument for increasing public awareness and understanding of issues relating to medication safety. Existing coverage of this issue is unrelated to research evidence. This suggests the need for patient safety researchers and advocacy groups to engage more strongly with the media as a strategy to increase the productive public discourse concerning medication errors and gain support for evidence-based interventions.
The Ann Arbor Chronicle | 2nd grade child dies of complications related to rare ovarian cancer
"At the opening of the Dec. 14, 2011 board meeting, board president Deb Mexicotte requested a moment of silence to acknowledge the recent loss of two students. Mariel Almendras, a second grader at Dicken, died of complications related to a rare ovarian cancer."
Uncertainty Over Use of GnRH Agonists in Breast Cancer (fertility preservation)
"One randomized trial is still ongoing — the Prevention of Early Menopause (POEMS), in women with hormone-receptor-negative breast cancer.
In view of the conflicting data, and while mature results from ongoing studies are awaited, the role of this treatment approach remains "uncertain," Dr. Partridge notes in her editorial.
Women...should not rely on GnRH agonist treatment.
"Given the current level of evidence, women who are interested in future fertility, and the providers who are assisting them in these often difficult decisions, should not rely on GnRH agonist treatment during chemotherapy for preservation of menstrual and ovarian function or fertility," she concludes."
media: Unleashing the genome in the bottle (Ion Torrent dna testing)
MORE STILL TO LEARN
"Another challenge is that although a person's genome doesn't change, its meaning will. As scientists uncover more DNA variants that protect against disease and variants that make it more likely, a genome sequence that meant one thing in 2012 will have a different meaning in 2013, not to mention 2020.A DNA variant that was once thought to be dangerous "might turn out to be benign if countered by another," says Greely. "Whose responsibility will it be to tell you that, years later?" DNA testing companies offer subscriptions that give customers regular updates like that."
CMAJ Editorial: Parking-centred health care
Blogger's Note:
the professional responses, in general, were not patient-friendly, rather system-friendly which indicates an ongoing disparity between those that give (care) and those that receive (care) and the public reality of the unrecognized, still, costs of healthcare.
Link to article - CMAJ
References
video: Patient Safety Advocates Talk About the Bureaucracy in Canadian Health Care - Leslie Worthington/Val Lee - Winnipeg
1) video: Sisters Leslie Worthington and Val Lee (Winnipeg)
The Patient Factor.com
2)The Patient Factor: Leslie Worthington "Her Father's Voice"
Thursday, January 12, 2012
Hereditary Cancer in Clinical Practice | Full text | Lynch syndrome: barriers to and facilitators of screening and disease management
Conclusions
Individuals with Lynch syndrome often encounter multiple barriers to and facilitators of disease management that go beyond the individual to the provider and health care system levels. The current organization and implementation of health care services are inadequate. A coordinated system of local services capable of providing integrated, efficient health care and follow-up, populated by providers with knowledge of hereditary cancer, is necessary to maintain optimal health.Table 1. Participant characteristics
"Importantly, Lynch syndrome has significant implications for public health policy [4]. The ultimate plan should be to provide resources that enable individuals in high risk families to develop a strong sense of resilience and maintain a balanced screening schedule. In particular, this cohort requires timely and appropriate health care services, including:
○ A critical mass of genetic counselors to provide timely services to high risk families
before, during and following genetic testing.
○ Service providers to coordinate and streamline diverse screening and treatment resources.
○ Health care providers, especially primary care physicians, informed about the risk
of cancer within families and reinforcing the importance of maintaining recommended
screening and initiating referrals to appropriate specialists.
○ Clinical monitoring tools designed to evaluate the impact of predictive testing
and the ongoing psychosocial and behavioral adjustment to living in families with
hereditary cancer.
Hereditary Cancer in Clinical Practice |open access: Novel germline MSH2 mutation in Lynch syndrome patient surviving multiple cancers (ovarian cancer as first cancer)
Case report
Hereditary Cancer in Clinical Practice 2012, 10:1 doi:10.1186/1897-4287-10-1
Published: 10 January 2012
Abstract (provisional)
Lynch syndrome (LS) individuals are predisposed to a variety of cancers, most commonly colorectal, uterine, urinary tract, ovarian, small bowel, stomach and biliary tract cancers. The risk of extracolonic manifestations appears to be highest in MSH2 mutations carriers. We present a carrier case with a novel MSH2 gene mutation that clearly demonstrates the broad extent of LS phenotypic expression and highlights several important clinical aspects. Current evidence suggests that colorectal tumors from LS patients tend to have better prognoses than their sporadic counterparts, however survival benefits for other cancers encountered in LS are unclear.In this article we describe a family with a novel protein truncating mutation of c.2388delT in the MSH2 gene, particularly focusing on one individual carrier affected with multiple primary cancers who is surviving 25 years on. Our report of multiple primary tumors occurring in the 12-25 years interval might suggest these patients do not succumb to other extracolonic cancers, provided they are regularly followed-up.
The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.
"Firstly, the patient over time presented with five primary cancers (in different organs) all of them, except that of breast, typical for the tumor spectrum of LS. Early-stage ovarian mucinous carcinoma was the first manifestation of LS spectrum in the proband. The lifetime risk of ovarian cancer in Lynch syndrome is approximately 10-12% [12], with higher risks (36%) reported in MSH2 carriers [13]. Recent estimates of age-specific cumulative cancer risks in Lynch syndrome families suggest lower than published elsewhere ovarian cancers risk (24% ovarian cancer risk in MSH2) [14]. MMR-deficient ovarian cancers are biologically and clinically different from BRCA deficient cancers, the former overrepresented by non-serous histology types, early-stage and early-onset disease [12, 15]...."
Fertility Preservation Practices Among Ontario Oncologists (study - male/female patients?)
Blogger's Note: in absence of the full text. it is not obvious if the study included male patients
Abstract
This
study explores the attitudes, knowledge, and referring behaviors in
fertility preservation among Ontario physicians providing
adult cancer care.. ...... Seventy-four percent of the
physicians indicated that they rarely or never modified cancer treatment
due to concern about future fertility........ About 45% did not know where to refer female patients,
and 69.7% rarely ever made a fertility preservation
consultation referral for their female patients..........
Medical News: Gene Test Influences Cancer Treatment - in Meeting Coverage, AACR-IASLC from MedPage Today
Action Points
- This study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
- Use of guideline-recommended cancer therapy increased by more than 50% when oncologists included a tumor's gene expression profile in the decision-making process.
......"The changes that oncologists made in response to the test results weren't limited to the choice of chemotherapy," John Hornberger, MD, of Stanford University, said at the Joint Conference on the Molecular Origins of Lung Cancer.
"Some patients had surgery that initially wasn't planned and, in at least one case, the treating oncologist referred a patient to a different oncologist because the test showed the tissue of origin was different from what was indicated by pathology. Referrals to hospice also increased."..........
Access : Peutz Jeghers syndrome (PJS) and family planning: the attitude towards prenatal diagnosis and pre-implantation genetic diagnosis : European Journal of Human Genetics
"Peutz–Jeghers syndrome (PJS) is a hereditary disorder caused by LKB1 gene mutations, and is associated with considerable morbidity and decreased life expectancy. This study (median age of 44) was conducted to assess the attitude of PJS patients towards family planning, prenatal diagnosis (PND) and pregnancy termination, and pre-implantation genetic diagnosis (PGD)......."
open access: European Jnl Human Genetics - Permanence of the information given during oncogenetic counseling to persons at familial risk of breast/ovarian and/or colon cancer
"How long counselees retain the information given during their genetic consultation is of major importance. To address this issue, we conducted a survey among the 3500 families that have been offered genetic counseling at our Center since 1988........."
Discussion
"This prospective survey belongs to
the very few that studied the evolution of genetic knowledge of persons
with a cancer hereditary risk. The range of topics surveyed appeared
adequate to answer our questions. The 58%
response rate was rather good for a survey sent by mail.
Impact of surgeon volume on patient safety in laparoscopic gynecologic surgery: Gynecologic Oncology
Highlights
► Low volume surgeons experience increased perioperative laparoscopic complications
► Outcomes are improved in patients treated by medium and high-volume surgeons
► Outcomes are improved in patients treated by medium and high-volume surgeons
open access: Impact of using multiple causes of death codes to compute site-specific, death certificate-based cancer mortality statistics in the United States 10.1016/j.canep.2011.07.004 : Cancer Epidemiology | ScienceDirect.com
"Background: Cancer mortality statistics, an important indicator for monitoring cancer burden, are traditionally restricted to instances when cancer is determined to be the underlying cause of death (UCD) based on information recorded on standard certificates of death. This study's objective was to determine the impact of using multiple causes of death codes to compute site-specific cancer mortality statistics."
Table 1. Proportion of non-UCD cancer deaths by cancer site listed on the death certificate.
"There are a number of limitations to this analysis. For example, this analysis did not examine all causes of death retrospectively with regard to a cancer registry, and includes data from only three states within the United States; among those three states, the deaths eligible for this analysis do not reflect the full population of cancer deaths. Specifically, this analysis focused on cancer-related deaths and excluded cancer patients who died in another state, cancers diagnosed prior to 1993, individuals with multiple primaries, and death certificate and autopsy only deaths...."
Synta Pharmaceuticals and University of Toronto Researchers Elucidate Elesclomol Mechanism of Action Using Innovative Yeast-based Technology - MarketWatch
Elesclomol clinical trials on-going in acute myeloid leukemia and ovarian cancer-
"Synta Pharmaceuticals Corp. SNTA +0.67% -- A report published in the peer-reviewed journal PLoS ONE demonstrate how a novel yeast screening platform pioneered by researchers at the University of Toronto was used to elucidate the mechanism of action of elesclomol, a first-in-class drug that targets cancer cell metabolism and is currently being clinically developed by Synta Pharmaceuticals Corp. of Lexington, Massachusetts. Elesclomol is currently in clinical trials in both solid tumor and hematologic cancers, including a study in combination with paclitaxel in ovarian cancer and a single agent study in acute myeloid leukemia (AML) currently being conducted at Princess Margaret Hospital in Toronto....."
Blogger's Note: PLOS is an open access publisher; PLOS link - 3 publications:
Blogger's Note: PLOS is an open access publisher; PLOS link - 3 publications:
- itochondrial Electron Transport Is the Cellular Target of the Oncology Drug Elesclomol Drug Elesclomol Elesclomol Targets Mitochondrial ETC ... Mitochondrial Electron Transport Is the Cellular Target of the Oncology Drug Elesclomol ... Elesclomol is a first-in-class investigational drug PLoS ONE: Research Article, published 11 Jan 2012 10.1371/journal.pone.0029798
- Role of Mitochondrial Electron Transport Chain Complexes in Capsaicin Mediated Oxidative Stress Leading to Apoptosis in Pancreatic Cancer Cells agents such as Elesclomol or Trisenx are currently PLoS ONE: Research Article, published 25 May 2011 10.1371/journal.pone.0020151 Views: 1093Citations: Yes
- Cancer Biomarker Discovery: The Entropic Hallmark . Elesclomol) works by inducing apoptosis via a mechanism PLoS ONE: Research Article, published 18 Aug 2010 10.1371/journal.pone.0012262
Heat Biologics: Vaccine biotech Heat Bio lands $250K; plans trials for bladder, ovarian cancers
"Heat (Biologics) is in phase 2 clinical trials studying its vaccine candidate HS-110 to treat non-small cell lung cancer. The company plans to start additional clinical studies in bladder and ovarian cancer this year."
NEJM - interactive - (1812-2012) 200 years of medicine
Blogger's Note: interactive map adjusted to include: general medicine,surgery,obgyn and biology/science
http://nejm200.nejm.org/timeline/?emp=marcom
Survivorship Conference 2012 - survivor advocate program deadline to apply January 23rd, 2012
The National Cancer Institute’s Office of Cancer Survivorship, the American Cancer Society, LIVESTRONG, and the Centers for Disease Control and Prevention are bringing together researchers, clinicians, cancer survivors, advocates, program planners, policy-makers, and public health experts to present, discuss and disseminate groundbreaking cancer survivorship research. The 6th Biennial Cancer Survivorship Research Conference, entitled “Cancer Survivorship Research: Translating Science to Care,” will be held on June 14-16, 2012, at the Crystal Gateway Marriott in Arlington, Virginia.
The deadline for applications for the Survivor Advocate Program, which provides scholarships for up to 20 advocates to attend the conference, is extended to Monday, January 23rd, 2012. Advocates will learn first-hand about translating cancer survivorship advances from early-stage research to survivor care, interact with other advocate leaders and researchers, and develop tools to educate communities about key survivorship issues.
new open access journal Feb 2012 - Journal of Clinical Gynecology and Obstetrics
Journal of Clinical Gynecology and Obstetrics
ISSN 1927-1271 print, 1927-128X online.Journal of Clinical Gynecology and Obstetrics is a bimonthly, international, open access, peer-reviewed journal, publishes original contributions describing basic research and clinical investigation of gynecology and obstetrics, on the cellular, molecular, prevention, diagnosis, therapy and prognosis aspects.
Journal of Clinical Gynecology and Obstetrics is published both in print and online, it is an open access journal, all its contents are available online for free immediately after publication, this supports a greater global exchange of knowledge, meanwhile, the authors' new findings are disseminated faster and wider.
Journal of Clinical Gynecology and Obstetrics will be launched in February 2012.
(Dr's Monk/Vergote) CME - video - Imedex ELC : Best of the Day: 17th International Meeting of the European Society of Gynaecological Oncology (ESGO)
Discusses also OCEAN/GOG Avastin trials/PARP inhibitors ...
Release Date: Sept 13/2011
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| Expiration Date: Sept 13/2012 |
Wednesday, January 11, 2012
Online Tool to Guide Decisions for BRCA1/2 Mutation Carriers
1) abstract link:
Online Tool to Guide Decisions for BRCA1/2 Mutation Carriers
2) brca decision tool link:
History of cholelithiasis (gallstones) and cancer risk in a network of case-control studies.
Abstract
Background: We analyzed the relationship between cholelithiasis (gallstones) and cancer risk in a network of case–control studies conducted in Italy and Switzerland in 1982–2009.
Methods: The analyses included 1997 oropharyngeal, 917 esophageal, 999 gastric, 23 small intestinal, 3726 colorectal, 684 liver, 688 pancreatic, 1240 laryngeal, 6447 breast, 1458 endometrial, 2002 ovarian, 1582 prostate, 1125 renal cell, 741 bladder cancers, and 21 284 controls. The odds ratios (ORs) were estimated by multiple logistic regression models.
Results: The ORs for subjects with history of cholelithiasis compared with those without were significantly elevated for small intestinal (OR = 3.96), prostate (OR = 1.36), and kidney cancers (OR = 1.57). These positive associations were observed ≥10 years after diagnosis of cholelithiasis and were consistent across strata of age, sex, and body mass index. No relation was found with the other selected cancers. A meta-analysis including this and three other studies on the relation of cholelithiasis with small intestinal cancer gave a pooled relative risk of 2.35 [95% confidence interval (CI) 1.82–3.03].
Conclusion: In subjects with cholelithiasis, we showed an appreciably increased risk of small intestinal cancer and suggested a moderate increased risk of prostate and kidney cancers. We found no material association with the other cancers considered.
open access: Evidence for breast cancer as an integral part of Lynch Syndrome (MLH1/MSH2 - small study/review) - Genes, Chromosomes and Cancer
"...While early onset, right-sided CRC represents the hallmark cancer of Lynch syndrome (Lynch et al., 1993; Lynch and Smyrk, 1996; Aarnio et al., 1999), extracolonic cancers such as tumors of the stomach (Aarnio et al., 1997), upper urinary tract, small bowel (Rodriguez-Bigas et al., 1998), hepatobiliary tract, sebaceous gland (Muir-Torre variant of Lynch syndrome), and glioblastomas (Turcot variant; Hamilton et al., 1995) may occur in addition. Women from Lynch syndrome families are at a significantly increased risk for gynecologic malignancies, namely endometrial and ovarian carcinoma. In fact, the lifetime risk for endometrial (Watson et al., 1994; Aarnio et al., 1995; Aarnio et al., 1999) and ovarian cancers (Watson et al., 2001) is estimated at 30–60% and 12%, respectively, compared with 3 and 2%, respectively, in the general population. An elevated risk for breast cancer in Lynch syndrome has been suggested in several studies, but the issue remains controversial (Risinger et al., 1996; Scott et al., 2001; Vasen et al., 2001; Muller et al., 2002; de Leeuw et al., 2003; Oliveira Ferreira et al., 2004; Watson and Riley, 2005; Westenend et al., 2005; Blokhuis et al., 2008; Shanley et al., 2009)....."
Research Bought, Then Paid For - NYTimes.com
"THROUGH the National Institutes of Health, American taxpayers have long supported research directed at understanding and treating human disease. Since 2009, the results of that research have been available free of charge on the National Library of Medicine’s Web site, allowing the public (patients and physicians, students and teachers) to read about the discoveries their tax dollars paid for."
"But a bill introduced in the House of Representatives last month threatens to cripple this site. The Research Works Act would forbid the N.I.H. to require, as it now does, that its grantees provide copies of the papers they publish in peer-reviewed journals to the library. If the bill passes, to read the results of federally funded research, most Americans would have to buy access to individual articles at a cost of $15 or $30 apiece. In other words, taxpayers who already paid for the research would have to pay again to read the results...."
Bill Blocking NIH Public Access Policy Draws Fire - ScienceInsider
"A little-noticed proposal in Congress to block a federal policy requiring free access to biomedical research papers went big time today, adding fuel to a long-running debate in the blogosphere...."
New Bill Aims to Kill Open Access Publishing Policy | GenomeWeb Daily News | GenomeWeb
Blogger's Note: requires registration to view (free)
"NEW YORK (GenomeWeb News) – A new bill in the US House of Representatives that seeks to prevent federal agencies from requiring open-access publishing of government-funded research would effectively nullify a public access policy that the National Institutes of Health implemented in 2008....The White House has been collecting comments in response to a request for information on the subject, and will continue accepting them until tomorrow, Jan. 12."
collecting comments link as above:
Extended Deadline for Public Access and Digital Data RFIs
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