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. 

The current uncoordinated, physician dependent organization of screening for individuals with Lynch syndrome in Canada is inadequate. Given the incidence and prevalence of these hereditary cancers and the clinical benefits of screening, there is a critical need to provide integrated health care and timely follow-up in a manner that facilitates navigation of and access to the health system"

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

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• 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. 

Surprisingly, the outcome did not confirm our initial hypothesis: the observed level of knowledge of persons who had undergone genetic counseling did not change with time.......... It seems that once they had been informed, the information was retained.........

New president of European Cancer Organisation, to Professor Cornelius van de Velde takes office (European Cancer Organisation) Professor Cornelius van de Velde

Cancer Barbie: Backers seeking bald doll to help sick kids come to terms with hair loss - NY Daily News

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

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:

• itochondrial Electron Transport Is the Cellular Target of the Oncology Drug Elesclomol Ronald K. Blackman, Kahlin Cheung-Ong, Marinella Gebbia, David A. Proia, Suqin He, Jane Kepros, Aurelie Jonneaux, Philippe Marchetti, Jerome Kluza, Patricia E. Rao, Yumiko Wada, Guri Giaever, Corey Nislow 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 Kartick C. Pramanik, Srinivas Reddy Boreddy, Sanjay K. Srivastava 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 Regina Berretta, Pablo Moscato . 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."

UConn researcher fabricated data (Resveratrol ) , investigation finds - BostonHerald.com

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

Kathy S.

Survivorship Conference 2012 - survivor advocate program deadline to apply January 23rd, 2012

Deadline extended for the 2012 Survivorship Research Conference and Survivor Advocate Program

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 6^th 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 23^rd, 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.

Emergence of CA125 Immunoreactivity in Recurrent or Metastatic Primary Ovarian Mucinous Neoplasms of the Intestinal Type : eClips Consult

DOTmed.com - Most patient harm events slip through hospital reporting systems (patient safety)

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.

Commentary including original article: Dissecting “PI3Kness”: The Complexity of Personalized Therapy for Ovarian Cancer

(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
Expiration Date:  Sept 13/2012

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...."

Correspondence/s: Breast-Cancer Screening — NEJM

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