open access: BMC Cancer - Predictive models for mutations in mismatch repair genes: implication for genetic counseling in developing countries (Lynch Syndrome)

 Background

Lynch syndrome (LS) is the most common form of inherited predisposition to colorectal cancer (CRC), accounting for 2–5% of all CRC. LS is an autosomal dominant disease characterized by mutations in the mismatch repair genes mutL homolog 1 (MLH1), mutS
homolog 2 (MSH2), postmeiotic segregation increased 1 (PMS1), post-meiotic segregation increased 2 (PMS2) and mutS homolog 6 (MSH6). Mutation risk prediction models can be incorporated into clinical practice, facilitating the decision-making process and identifying
individuals for molecular investigation. This is extremely important in countries with limited economic resources. This study aims to evaluate sensitivity and specificity of five predictive models for germline mutations in repair genes in a sample of individuals with suspected
Lynch syndrome.

"Lynch syndrome (LS) is the most common form of inherited predisposition to colorectal cancer (CRC), accounting for 2–5% of all CRC [1]. Colorectal cancer in LS differs from sporadic cases by an earlier age of diagnosis (mean age approximately 44 years), a predominance of proximally-sited colon cancers (60–70%) and an increased propensity to
synchronous or metachronous CRCs (25%) [2,3]. Individuals with LS have an 80% probability of developing CRC at 65 years, and they are at an elevated risk of developing a second primary CRC [4] as well as at an increased risk for extra-colonic malignancies, including endometrial, gastric, small bowel, urological tract, ovary, pancreas and brain cancer
[5]."

 Conclusions

The Barnetson, PREMM, MMRpro and Wijnen models present similar AUC. The AUC of the Myriad model is statistically inferior to the four other models. 

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

open access PLoS ONE: Health Risk or Resource? Gradual and Independent Association between Self-Rated Health and Mortality Persists Over 30 Years

Wiki:  
 Salutogenesis is a term coined by Aaron Antonovsky,^[1] a professor of medical sociology. The term describes an approach focusing on factors that support human health and well-being, rather than on factors that cause disease. More specifically, the "salutogenic model" is concerned with the relationship between health, stress, and coping.
Antonovsky's theories reject the "traditional medical-model dichotomy separating health and illness". He described the relationship as a continuous variable, what he called the "health-ease versus dis-ease continuum".^[1]

~~~~~~~~~~~~~~~~~~~~~~~~~~~~

 Background

Poor self-rated health (SRH) is associated with increased mortality. However, most studies only adjust for few health risk factors and/or do not analyse whether this association is consistent also for intermediate categories of SRH and for follow-up periods exceeding 5–10 years. This study examined whether the SRH-mortality association remained significant 30 years after assessment when adjusting for a wide range of known clinical, behavioural and socio-demographic risk factors.

Conclusions

SRH (self reported health) is a strong and “dose-dependent” predictor of mortality. The association was largely independent from covariates and remained significant after decades. This suggests that SRH provides relevant and sustained health information beyond classical risk factors or medical history and reflects salutogenetic rather than pathogenetic pathways.

Feb 9th: The Maze of PARP Inhibitors in Ovarian Cancer - Cancer Network

Blogger's Note:  full access, free subscription

Conclusion

"While consideration of chemoprevention with PARP inhibitors is on the horizon, many knowledge gaps exist regarding these agents. Although the trials in EOC provided some answers regarding the activity of PARP inhibitors, they raised many other questions. These questions may actually complicate the picture as newer agents in this drug class make their way to the clinical arena. A collaborative approach among the researchers is needed to systematically answer these questions so we are better equipped to provide effective treatment to the BRCA-deficient patients. It is noteworthy that The Cancer Genome Atlas Group analysis did reveal other commonly deregulated pathways in this disease—such as RB, RAS/PI3K, FOXM1, and NOTCH—that might provide future opportunities for therapeutic targeting while the story of the PARP inhibitors continues to unfold."


 

Medical News:Cancer Treatment OK During Pregnancy - in OB/Gyn, Pregnancy from MedPage Today

media: Fast-track testing helps to find ovarian cancer early (relates to Dove Report/see comment 'pelvic cancer')

Blogger's Note:

this media report relates directly to the Dove Report published (and commentary) in the Lancet Oncology Jan 17th;

search this blog and/or direct link  to the Lancet: http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2811%2970405-3/fulltext

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

" (Dr) Gilbert is also campaigning to change the name of ovarian cancer to "pelvic cancer."
Research over the last decade has shown that most cases of ovarian cancer don't actually begin in the ovaries at all, but in the fallopian tubes. Pre-cancerous cells grow in the tubes and then shed over the surface of the ovaries, where they cause tumours.
By the time the cancer is found in the ovaries, it's already advanced. She says the focus should be on finding the cancer in its earliest stage in the tubes.
"We, for so many years, [kept] looking at the wrong place," she told reporters Thursday.
"Put bluntly, we had the name wrong, the staging wrong, and the diagnostic testing wrong. It is no wonder we have lost so many lives to this disease.""

media: (re: Lancet report) Current trend is to preserve pregnancy in patients diagnosed with cervical or ovarian cancer

Blogger's Note: a slight bit more information

abstract: (cervical/ovarian) Gynaecological cancers in pregnancy : The Lancet

Blogger's Note: requires a subscription to view full paper $$$

open access: The Bangkok Statement on universal health coverage : The Lancet

"The theme of the Prince Mahidol Award Conference in Bangkok, Thailand on Jan 24—28, 2012, was Moving towards universal health coverage: health financing matters. At the close of the meeting, a 10-point declaration recognised universal health coverage (UHC) as fundamental to the right to health, and marked the commitment by more than 800 delegates to translate the rhetoric of UHC into better, more equitable health outcomes. Similar endorsements of UHC have been made before, including at the World Health Assembly in 2011. What makes the Bangkok Statement any more likely to hasten and widen the implementation of UHC?

One answer may be the power of the Prince Mahidol Award Conference and its sponsors to draw global health enthusiasts from a wide variety of disciplines and health systems. Delegates from 68 countries included donors and recipients of aid, managers and front-line health workers, ministers, economists, and consumers. From these many perspectives came the realisation that whether one seeks to provide access to health care for the 1 billion people who lack it, or to protect the 100 million people who end up in poverty every year as a result of medical costs, or to accelerate progress towards the Millennium Development Goals; UHC provides a common mechanism—and common cause. Simply put in a plenary by Peter Anyang' Nyong'o, Kenya's Minister for health services, “universal health coverage is fundamental to improving the lives of people.”.......

open access: Cancer treatment and care: a new and uneasy world : The Lancet

"......Thinking of the future, we sense oncological needs and expectations growing beyond what can be planned or provided for fairly. A drug like abiraterone, promising benefit in an area of evident clinical need, will have taken 20 years and substantial funds to develop. Early stage drug development is likely to have been undertaken by researchers with charitable or public funding, with the translational and clinical research by commercial entities leading, in abiraterone's case, to indelicate public haggling over how much 1 year of an average patient's life is reasonably worth....."

abstract: Prospective evaluation of molecular screening for Lynch syndrome in patients with endometrial cancer ≤ 70 years.

Blogger's Note: age >50 yrs will be at issue

Gynecol Oncol. 2012 Feb 1.

Abstract

OBJECTIVE:

Lynch syndrome (LS) is a hereditary syndrome that predisposes to multiple malignancies including endometrial cancer (EC). We aimed to evaluate a diagnostic strategy for LS based on routine analysis of microsatellite instability (MSI) and immunohistochemical (IHC) staining for mismatch repair (MMR) proteins in tumor tissue of all newly diagnosed EC patients ≤70years.

METHODS:

Consecutive EC patients ≤70years were included prospectively in eight Dutch centers. EC specimens were analyzed for MSI, IHC of four MMR proteins, MMR gene methylation status and BRAF-mutations. Tumors were classified as; 1) likely to be caused by LS, 2) sporadic MSI-H, or 3) microsatellite stable (MSS).

RESULTS:

Tumor specimens of 179 patients (median age 61years, IQR 57-66) were analyzed. In our study 92% of included patients were over 50 years of age. Eleven EC patients were found likely to have LS (6%; 95% CI 3-11%), including 1 patient suspected of an MLH1, 2 of an MSH2, 6 of an MSH6 and 2 of a PMS2 gene defect. Germline mutation analyses revealed 7 MMR gene germline mutations. Ten patients likely to have LS (92%) were older than 50years. In addition, 31 sporadic MSI-H tumors with MLH1 promoter hypermethylation (17%; 95% CI 13-24%) were identified.

CONCLUSIONS:

Molecular screening for LS in patients with EC diagnosed≤70years, leads to identification of a profile likely to have LS in 6% of cases. New screening guidelines for LS are needed, including recommendations for EC patients older than 50years of age.

video: Serving on a Clinical Practice Guideline Panel | US Cochrane Center

Canary Foundation Early Detecton Symposium May 1st Palo Alto, California

JCO: Editorial - Ovarian Suppression for Prevention of Premature Menopause and Infertility: Empty Promise or Effective Therapy? (in Breast Cancer) see note/your comments?

Blogger's Note:  compared with other young cancer survivors??
                 ~~~~~~~~~~~~~

"Fertility and premature menopause are major concerns for young patients who are undergoing treatment for cancer. Young women with breast cancer face particular challenges when considering future fertility compared with other young cancer survivors.¹ The greatest concern is whether preservation of ovarian function and a subsequent pregnancy in a breast cancer survivor could increase the risk of recurrence, particularly in patients with hormone receptor–positive disease....."

See accompanying article on page 533

Their So-Called Journalism, or What I Saw at the Women’s Mags

Blogger's Note: not related to ovarian cancer but possibly of interest ) to our community of women authors, those who write about ovarian/cancers

Hypocritical oaths : Nature : Nature Publishing Group

Editorial: Full-text - The Use of Sedation in Palliative Care

"....Often pain and suffering make it difficult for patients themselves to participate, further reducing their autonomy and empowerment. Patients should be kept fully empowered by being thoroughly informed of all means available to reduce their symptoms and maximize their comfort at the earliest possible stage of their palliative care."

"Dying patients in palliative care settings deserve to have maximum control over their futures. This includes full disclosure on the use and effectiveness of sedation for palliative ends. Allowing patients more decision-making power in choosing various levels of sedation through to CDS would significantly improve the dying process while maintaining ethically sound practices as viewed by all parties concerned. Health care practitioners would not have to feel that they are hastening death. Patients would have greater control over their symptoms. Family members would not have to watch their loved ones endure dysteleological suffering. It is the best we can do when facing our finitude, and dying patients deserve our best."

Editorial: Full-text - For a Modern Concept of Palliative Care

"Unfortunately, in most countries hospice care addresses end-of-life care."

"....This late referral to palliative care is also in contrast with the classical definition of palliative care provided by WHO: “Palliative care is ….. applicable early in the course of illness, in conjunction with other therapies that are intended to prolong life, such as chemotherapy or radiation therapy, and includes those investigations needed to better understand and manage distressing clinical complications” [6]. "

open access: The tone of life on social networking sites | Pew Research Center's Internet & American Life Project (adult, also section on teens & SNS)

Blogger's Note: there is also a section on teen SNS

abstract: Palliative Medicine Fellowship: A Study of Resident Choices

Context

There are no data on the motives or characteristics of physicians choosing fellowship training in Hospice and Palliative Medicine (HPM).

Objectives

To understand more about the residents who choose HPM and what leads them to this decision.

Conclusion

Negative experiences with end-of-life care in residency, particularly in the intensive care unit, continue to be a factor in selection of HPM as a specialty. Many residents make their decision to enter the field and apply during Postgraduate Year 3. Most received negative comments about the choice. Fellows require a broad range of experience when selecting a fellowship program.

abstract: Survival for Ovarian Cancer in Europe: The across-country variation did not shrink in the past decade.

abstract: Does public disclosure of quality indicators influence hospitals' inclination to enhance results? (using Oesophageal resection as the example)

CONCLUSION:

Our results support the assumption that low-volume hospitals are inclined to adjust their numbers when, because outcomes are public, pressure to report a sufficient number is high. So, external verification of data is essential when this 'need to score' is high.

Systematic Reviews - Why prospective registration of systematic reviews makes sense

Abstract (provisional)

Prospective registration of systematic reviews promotes transparency, helps reduce potential for bias and serves to avoid unintended duplication of reviews. Registration offers advantages to many stakeholders in return for modest additional effort from the researchers registering their reviews.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

BioMed Central Blog : Systematic Reviews journal launches today

BioMed Central Blog : Systematic Reviews journal launches today

abstract: How valid are claims for synergy in published clinical studies?

Abstract

Background: Clinical trials evaluating drug combinations are often stimulated by claims of synergistic interactions in preclinical models. Overuse or misuse of the term synergy could lead to poorly designed clinical studies.

Conclusions: Synergy is cited frequently in phase I and phase II studies to justify the evaluation of a specific drug combination. Inappropriate methods for evaluation of synergy and poor assessment of therapeutic index have been used in most preclinical articles.

media: Is It Ever OK To Hug Your Doctor?

open access article: Human experiments: First, do harm : Nature News & Comment

Blogger's Note: a very good reminder on recognizing the actual 'end game' - the patients, obviously (not killing the patient in the process of a particular goal)


                                                                                
EVOLVING ETHICS
Sexually transmitted diseases (STDs) were a prime concern for health officials in the 1940s, and many medical studies — including the US experiments in Guatemala — used methods that would be considered unethical today. Although standards improved over the decades, clinical researchers continued to push the boundaries of acceptable science.....

UK survey - young adults - : When do life crises strike? Help us find out (online 20 min survey)

 When do life crises strike? Help us find out

17:45 7 February 2012

Being Human

Health

Jessica Griggs, careers editor

Psychologist Dan Levinson once remarked that he had never met anyone who had not gone through at least one major crisis during their adult life.
While films, sports-car cliches and personal experience may back up his comment, the questions of when and for whom crises occur have received little academic attention. Well, not for much longer.

Last year, New Scientist reported on the phenomenon of the quarter-life crisis; the re-evaluation and dramatic change of direction that sometimes occurs during early adulthood.

This was based on research carried out by researchers at the University of Greenwich who interviewed 50 young people about their emotional experiences during this time. The work established that the quarter-life crisis exists (as corroborated by the comments on our news story) but the sample wasn't large enough to determine how common it is or when it occurs.

Now, the innermost secrets of the crisis are to be laid bare. The Greenwich team are conducting an online survey of British adults which will probe the link between crisis episodes, age and life stage across a diverse group of adults.

The researchers are looking for adult volunteers to participate in the study. You can take part here (and be in with the chance of winning a cash prize for your efforts).

Stay tuned as New Scientist will exclusively report the findings later this year.
                      ~~~~~~~~~~~~~~

What does it involve and how long does it take?

The online questionnaire will involve approximately 20 minutes of your time.

You will be asked for the following information:
-    Age, job, income, marital status and number of children.
-    Crisis episodes and turning points in your adult life (if you are currently aged 25 or above)
-    Your marital satisfaction (if you are married)
-    Your sense of happiness, life satisfaction and wellbeing
-    Your sense of empathy

Who can participate?
In order to participate, you must be age 20 or over, have lived in the UK for the majority of your life since the age of 15 and be able to read and write English fluently.

Article: Friend or foe? Nature (PhD student)

"As a PhD student, learning to navigate the murky waters of collaboration and competition is pretty confusing........But many labs continue to jealously guard their progress and sacrifice paper quality for personal recognition. Should such egotism be acceptable in science, the main aims of which are, ideally, discovery and innovation, rather than accolades for its practitioners? As a young researcher, I am puzzled that a community reliant on integrity and transparency is tolerant of lies and misdirection in the publications race....."

abstract: (in mice) MEK1/2 Inhibitor Selumetinib (AZD6244) Inhibits Growth of Ovarian Clear Cell Carcinoma in a PEA-15–Dependent Manner in a Mouse Xenograft Model

Blogger's Note: in research (mice)

Abstract

Clear cell carcinoma (CCC) of the ovary tends to show resistance to standard chemotherapy, which results in poor survival for patients with CCC. Developing a novel therapeutic strategy is imperative to improve patient prognosis. Epidermal growth factor receptor (EGFR) is frequently expressed in epithelial ovarian cancer. One of the major downstream targets of the EGFR signaling cascade is extracellular signal–related kinase (ERK). PEA-15, a 15-kDa phosphoprotein, can sequester ERK in the cytoplasm. MEK1/2 plays a central role in integrating mitogenic signals into the ERK pathway. We tested the hypothesis that inhibition of the EGFR–ERK pathway suppresses tumorigenicity in CCC, and we investigated the role of PEA-15 in ERK-targeted therapy in CCC. We screened a panel of 4 CCC cell lines (RMG-I, SMOV-2, OVTOKO, and KOC-7c) and observed that the EGFR tyrosine kinase inhibitor erlotinib inhibited cell proliferation of EGFR-overexpressing CCC cell lines through partial dependence on the MEK/ERK pathway. Furthermore, erlotinib-sensitive cell lines were also sensitive to the MEK inhibitor selumetinib (AZD6244), which is under clinical development. Knockdown of PEA-15 expression resulted in reversal of selumetinib-sensitive cells to resistant cells, implying that PEA-15 contributes to selumetinib sensitivity. Both selumetinib and erlotinib significantly suppressed tumor growth (P < 0.0001) in a CCC xenograft model.  
However, selumetinib was better tolerated; erlotinib-treated mice exhibited significant toxic effects (marked weight loss and severe skin peeling) at high doses. Our findings indicate that the MEK–ERK pathway is a potential target for EGFR-overexpressing CCC and indicate that selumetinib and erlotinib are worth exploring as therapeutic agents for CCC. Mol Cancer Ther; 11(2); 360–9. ©2011 AACR

open access: American Society for Radiation Oncology - Radiotherapeutic and surgical management for newly diagnosed brain metastasis/es: An American Society for Radiation Oncology evidence-based guideline (2012)

Blogger's Note: 

search of the document = 0  'ovarian','ovary'

                                       ~~~~~~~~~~~

Radiotherapeutic and surgical management for newly diagnosed brain metastasis/es: An American Society for Radiation Oncology evidence-based guideline (2012) 

Read the guideline.

 This guideline provides guidance for patients and physicians regarding the following key clinical questions: What prognostic factors are important for assessing and managing patients with newly diagnosed brain metastases; for patients with single brain metastasis (excluding radiosensitive histologies such as small cell lung cancer, leukemia, lymphoma and germ cell tumor), does surgical resection and whole brain radiotherapy improve survival or brain control compared with whole brain radiotherapy alone or surgical resection alone; is survival or brain control different in selected patients with single brain metastasis (excluding radiosensitive histologies such as small cell lung cancer, leukemia, lymphoma and germ cell tumor) treated with surgery or radiosurgery; is there a survival or brain control difference in patients treated with WBRT and radiosurgery boost versus WBRT alone; is there a difference in survival, brain control or neurocognitive outcomes in patients treated with radiosurgery alone versus WBRT and radiosurgery; what is the role of comfort measures or palliative supportive care alone versus WBRT in patients with multiple brain metastases; what is the optimal WBRT dose fractionation schedule; what is the role of radiosensitizers with WBRT in the management of patients with brain metastases; and what is the role of chemotherapy and WBRT? 

Read the guideline.

(still) recruiting: Paclitaxel in Treating Patients With Ovarian Stromal Cancer - Full Text View - ClinicalTrials.gov (granulosa/sertoli-leydig, sex cord...)

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed ovarian stromal cancer not amenable to surgery
  • Granulosa cell tumor
  • Granulosa cell theca cell tumor
  • Sertoli-Leydig cell tumor (androblastoma)
  • Gynandroblastoma
  • Unclassified sex cord stromal tumor
  • Sex cord tumor with annular tubules
  • Steroid (lipid) cell tumor
• Recurrent disease after no more than 1 prior chemotherapy regimen
• Measurable disease
  • At least 1 cm in diameter