Cochrane Canada Symposium 2012 Winnipeg, Manitoba May 2012

Cochrane Canada Symposium 2012  May 9-10, 2012

PROGRAM-AT-A-GLANCE

The 10th Annual Cochrane Canada Symposium Program-at-a-Glance is now available online! Click here to view the plenary sessions, workshops and oral presentations and start planning your schedule!

science news: Menopause clinicians support new advice on steroid use (Corticosteroids/glucocorticoids)

Menopause clinicians support new advice on steroid use

 (Corticosteroids/glucocorticoids)


.............Dr Tobie de Villiers, President of the International Menopause Society (IMS), commented, "Bone loss is a concern for all women around the age of menopause, and especially for the almost 5% of postmenopausal women worldwide who take oral glucocorticoid therapy. The IMS encourages women to be aware of this potentially dangerous side-effect of therapy and to discuss what precautions can be taken with their doctors."
Continuing, Dr de Villiers said "The ovaries stop producing estrogen around the time of the menopause, meaning that women find that the risk of bone loss and osteoporosis increases. This is already difficult for many women to cope with, so we need to be especially careful that the medicines which women take for other conditions don't actually harm women's bones. Glucocorticoids are important and valuable medicines, but like all medicines they have side effects and their use must be customised and monitored. Women, especially women after their menopause, need to be more aware of the possibility of this serious side-effect. These guidelines are aimed at allowing national organisations to develop effectively."

science report: Treating cancer as a chronic disease? (study of clear cell ovarian cancer....)

Treating cancer as a chronic disease?

ScienceDaily (Mar. 29, 2012) — New research from the Technion-Israel Institute of Technology Rappaport Faculty of Medicine and Research Institute and the Rambam Medical Center may lead to the development of new methods for controlling the growth of cancer, and perhaps lead to treatments that will transform cancer from a lethal disease to a chronic, manageable one, similar to AIDS.............

".......For this study, the team took cells from one woman's ovarian clear cell carcinoma and injected them either into or alongside the human stem cell-derived environment. "We noticed very early on, rather strikingly, that the human cancer cells grow more robustly when they are in the teratoma environment compared to any other means in which we grew them, such as in a mouse muscle or under the skin of a mouse," says Skorecki.

The scientists were able to tease out six different kinds of self-renewing cells, based on behavior -- how quickly they grow, how aggressive they are, how they differentiate -- and on their molecular profile. This was a previously unknown finding, that one tumor might have such a diversity of cells with crucial fundamental growth properties. Tzukerman explains that the growth of the cancer cell subpopulations can now be explained by their proximity to the human cell environment.

The researchers cloned and expanded the six distinct cell populations and injected them into the human stem cell teratomas. One key observation is that some cells, which were not self-replicating in any other model, became self-replicating when exposed to the human cells.
Skorecki said that while he wasn't surprised that the human environment affected the growth, he was in fact surprised by the magnitude of the effect: "We've known for years now that cancers are complex organs, but I didn't think the power of the human stem cell environment would be so robust, that it would make such a big difference in how the cells were grown."........

open access: Cone-beam computed tomography in hypofractionated stereotactic radiotherapy for brain metastases

Cone-beam computed tomography in hypofractionatedstereotactic radiotherapy for brain metastases

Conclusions
Hypofractionated stereotactic radiotherapy have the significant limitation of uncertainty in interfraction repeatability of the patient setup; image-guided radiotherapy using cone-beam computed tomography improves the accuracy of the treatment delivery reducing set-up uncertainty, giving the possibility of 3-dimensional anatomic informations in the treatment
position.

Journal of the American College of Surgeons - Mortality after Elective Colon Resection: The Search for Outcomes that Define Quality in Surgical Practice (blogger's note: or any other cancer surgeries)

Blogger's Opinion: or any other cancer surgeries for those 'deemed' not qualified with this issues having been widely debated over decades but left unresolved, it would be 'enticing' to detail the moral aspects of death ratios/unqualifed surgeons/outcomes (eg. in hindsight - those patients that should have been referred, but were not)

Journal of the American College of Surgeons - Mortality after Elective Colon Resection: The Search for Outcomes that Define Quality in Surgical Practice

Conclusions

Elective colon resection is a safe procedure in both teaching hospitals and nonteaching hospitals, with an impressively homogenous mean mortality rate of 1.56% in teaching hospitals, and 1.38% in nonteaching hospitals. We reject our original hypothesis because the data do not sufficiently discriminate to permit the use of death after elective colon resection as a differentiating quality measure; however, the data do identify individual poor performers. Poor performing institutions/surgeons should seek extramural guidance to improve their outcomes or discontinue performing such operations.

abstract: Insertion of an SVA element, a non-autonomous retrotransposon, in PMS2 intron 7 as a novel cause of Lynch syndrome.

Insertion of an SVA element, a non-autonomous retrotransposon, in PMS2 intron 7 as a novel cause of Lynch syndrome.:

Hum Mutat. 2012 Mar 27;


Abstract

Heterozygous germline mutations in the mismatch repair gene PMS2 predispose carriers for Lynch syndrome, an autosomal dominant predisposition to cancer. Here, we present a LINE-1-mediated retrotranspositional insertion in PMS2 as a novel mutation type for Lynch syndrome. This insertion, detected with Southern blot analysis in the genomic DNA of the patient, is characterized as a 2.2 kb long 5' truncated SVA_F element. The insertion is not detectable by current diagnostic testing limited to MLPA and direct Sanger sequencing on genomic DNA. The molecular nature of this insertion could only be resolved in RNA from cultured lymphocytes in which nonsense-mediated RNA decay was inhibited. Our report illustrates the technical problems encountered in the detection of this mutation type. Especially large heterozygous insertions will remain unnoticed because of preferential amplification of the smaller wild-type allele in genomic DNA, and are probably underreported in the mutation spectra of autosomal dominant disorders.

Washington State University St Louis: DNA Sequencing Lays Foundation for Personalized Cancer Treatment

DNA Sequencing Lays Foundation for Personalized Cancer Treatment

Medicine Must Allow for Customization: A Lesson for Policy-Makers -- and Regulators - Forbes

Blogger's Note: Hartzband and Groopman article previously posted on blog, try searching blog "Forbes"

Medicine Must Allow for Customization: A Lesson for Policy-Makers -- and Regulators - Forbes

"As appealing as it is – as useful as it is – to imagine that there exists a gold-standard way to practice medicine, and a single-best way to approach most human ailments, the reality is considerably more complex and messy, as Hartzband and Groopman’s (continued) critique of so-called “best practices” makes clear.
The heart of their argument is this: “For patients and experts alike, there is a subjective core to every medical decision. The truth is that, despite many advances, much of medicine still exists in a gray zone where there is not one right answer. No one can say with certainty who will benefit by taking a certain drug and who will not. Nor can we say with certainty what impact a medical condition will have on someone’s life or how they might experience a treatment’s side effects. The path to maintaining or regaining health is not the same for everyone; our preferences really do matter.”
This resonates (see here and here), although I’ve also heard distinguished health policy proponents argue convincingly that even if experts can’t agree what is definitely “right,” there can definitely be agreement about a number of ways of practicing medicine that are clearly “wrong,” yet very common – so that while it may be harmful, and disingenuous, to insist upon a single algorithm or best approach, it could be helpful to at least provide clear guidance so that physicians would know to avoid certain therapeutic approaches.
Not only does Hartzband and Groopman’s argument have implications for the current healthcare debate, it also would seem to have significant implications for the way we view medical product regulation..........

AACR: Selumetinib Controlled Recurrent Low-grade Serous Ovarian Cancer

Selumetinib Controlled Recurrent Low-grade Serous Ovarian Cancer:

• Selumetinib controlled the disease in 81 percent of patients.
• Median progression-free survival was 11 months.
• Patients experienced minimal side effects.

CHICAGO — Selumetinib, a small-molecule MEK inhibitor, demonstrated the ability to control low-grade serous ovarian or peritoneal cancer, according to phase II study results presented at the AACR Annual Meeting 2012, held here March 31 – April 4.
The first line of defense against low-grade serous ovarian cancer is surgery, followed by cytotoxic chemotherapy. However, this is a slow-growing cancer and does not respond well to traditional chemotherapies, which target fast-growing cells.
Seeking a more rational treatment approach, Gynecologic Oncology Group (GOG) researchers led by John Farley, M.D., a professor at Creighton University School of Medicine at St. Joseph’s Hospital and Medical Center in Omaha, Neb., used selumetinib to target the MEK-1/2 protein kinase in the MAPK pathway, which is known to mutate in this form of cancer.
GOG researchers assigned 52 women to 100-mg doses of selumetinib orally twice daily in four-week cycles; 33 percent underwent 12 or more cycles. Prior to the study, 58 percent of patients had received three or more rounds of chemotherapy.
Selumetinib controlled the disease in 81 percent of patients. Specifically, eight patients had complete or partial responses to treatment, and 34 had stable disease. The median survival rate without cancer progression was 11 months, and 63 percent of patients had progression-free survival longer than six months. In addition, selumetinib was well tolerated, with three patients experiencing grade 4 adverse events.
“The results were striking,” said Farley. “Many of the patients in the study had received multiple rounds of chemotherapy and were running out of options. By using these tumors’ historical inherent molecular aberrations to select patients for a treatment that in theory could exploit these abnormalities, we took an important step toward individualized cancer therapies.”
In addition to studying the impact of selumetinib on this type of ovarian cancer, investigators were also interested in how patients with RAS/RAF mutations responded to the drug. The team analyzed the tumor DNA from 34 patients, 62 percent of whom had some form of RAS/RAF mutation. Ultimately, they found that RAS/RAF mutations had no impact on patient response.
The study was funded by the National Cancer Institute.

press release: Myriad Study Finds High Prevalence of Mutations in the PMS2 Gene (Lynch syndrome)

Myriad Study Finds High Prevalence of Mutations in the PMS2 Gene

"This study demonstrates the importance of the analyzing the PMS2 gene to fully comprehend a patient's Lynch syndrome status."

abstract: Clinical implications of pleural effusions in ovarian cancer.

Clinical implications of pleural effusions in ovarian cancer.:

Respirology. 2012 Mar 28;

Abstract

The pleural cavity constitutes the most frequent extra-abdominal metastatic site in ovarian carcinoma (OC). In patients with OC and pleural effusions, a positive fluid cytology is required for a stage IV diagnosis. Unfortunately, about 30% of malignant pleural effusions exhibit false negative cytological pleural fluid results. In those circumstances, exploratory video-assisted thoracoscopic surgery (VATS) serves as a diagnostic, staging and even therapeutic modality.