Tandem duplication of chromosomal segments is common in ovarian and breast cancer genomes - McBride - 2012 - The Journal of Pathology - Wiley Online Library

Original Paper

Tandem duplication of chromosomal segments is common in ovarian and breast cancer genomes^†

1. David J McBride^1,‡,*, 
2. Dariush Etemadmoghadam^2,3,‡,*, 
3. Susanna L Cooke^1,4,‡,*, 
4. Kathryn Alsop^2,5, 
5. Joshy George^2,5, 
6. Adam Butler¹, 
7. Juok Cho¹,
8. Danushka Galappaththige¹, 
9. Chris Greenman¹, 
10. Karen D Howarth⁶, 
11. King W Lau¹, 
12. Charlotte K Ng⁴, 
13. Keiran Raine¹, 
14. Jon Teague¹, 
15. David C Wedge¹, 
16. Australian Ovarian Cancer Study Group², 
17. Xavier Caubit⁷, 
18. Michael R Stratton¹, 
19. James D Brenton⁴, 
20. Peter J Campbell¹, 
21. P Andrew Futreal^1,§, 
22. David DL Bowtell^2,5,8,§,*

Article first published online: 6 JUN 2012

Issue

The Journal of Pathology

Volume 227, Issue 4, pages 446–455, August 2012

http://onlinelibrary.wiley.com/doi/10.1002/path.4042/abstract;jsessionid=4DF2C7346B20F21CF48775015E8F1295.d03t04

Clinical experience of young patients with small cell ovarian carcinoma of the hypercalcemic type (OSCCHT)

http://www.sciencedirect.com/science/article/pii/S0301211512003533

[Intraoperative frozen sections in diseases of the female genital tract.]

[Intraoperative frozen sections in diseases of the female genital tract.]

http://www.ncbi.nlm.nih.gov/m/pubmed/22898883/

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ScienceDirect.com - European Journal of Obstetrics & Gynecology and Reproductive Biology - Ethical guidelines and the prevention of abuse in healthcare

http://www.sciencedirect.com/science/article/pii/S0301211512003375

Association for Molecular Pathology, et al. v. U.S. Patent and Trademark Office, et al. - Decision | American Civil Liberties Union (brca patent issue)

http://www.aclu.org/womens-rights/association-molecular-pathology-et-al-v-us-patent-and-trademark-office-et-al-decision

PHG Foundation | The challenges posed by direct-to-consumer genetic tests

Chemotherapy versus surgery for initial treatment in advanced ovarian epithelial cancer - Cochrane Review

Chemotherapy versus surgery for initial treatment in advanced ovarian epithelial cancer.

A

BACKGROUND: Epithelial ovarian cancer presents at an advanced stage in the majority of women. These women require surgery and chemotherapy for optimal treatment. Conventional treatment is to perform surgery first and then give chemotherapy. However, it is not yet clear whether there are any advantages to using chemotherapy before surgery.

OBJECTIVES: To assess whether there is an advantage to treating women with advanced epithelial ovarian cancer with chemotherapy before cytoreductive surgery (neoadjuvant chemotherapy (NACT)) compared with conventional treatment where chemotherapy follows maximal cytoreductive surgery.

SEARCH METHODS: For the original review we searched, the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, 2006), MEDLINE (Silver Platter, from 1966 to 1 Sept 2006), EMBASE via Ovid (from 1980 to 1 Sept 2006), CANCERLIT (from 1966 to 1 Sept 2006), PDQ (search for open and closed trials) and MetaRegister (most current search Sept 2006). For this update randomised controlled trials (RCTs) were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, 2011) and the Cochrane Gynaecological Cancer Specialised Register (2011), MEDLINE (August week 1, 2011), EMBASE (to week 31, 2011), PDQ (search for open and closed trials) and MetaRegister (August 2011).

SELECTION CRITERIA: RCTs of women with advanced epithelial ovarian cancer (Federation of International Gynaecologists and Obstetricians (FIGO) stage III/IV) who were randomly allocated to treatment groups that compared platinum-based chemotherapy before cytoreductive surgery with platinum-based chemotherapy following cytoreductive surgery.

DATA COLLECTION AND ANALYSIS: Data were extracted by two review authors independently, and the quality of included trials was assessed by two review authors independently.

MAIN RESULTS: One high-quality RCT met the inclusion criteria. This multicentre trial randomised 718 women with stage IIIc/IV ovarian cancer to NACT followed by interval debulking surgery (IDS) or primary debulking surgery (PDS) followed by chemotherapy. There were no significant differences between the study groups with regard to overall survival (OS) (670 women; HR 0.98; 95% CI 0.82 to 1.18) or progression-free survival (PFS) (670 women; HR 1.01; 95% CI 0.86 to 1.17).Significant differences occurred between the NACT and PDS groups with regard to some surgically related serious adverse effects (SAE grade 3/4) including haemorrhage (12 in NACT group vs 23 in PDS group; RR 0.50; 95% CI 0.25 to 0.99), venous thromboembolism (none in NACT group vs eight in PDS group; RR 0.06; 95% CI 0 to 0.98) and infection (five in NACT group vs 25 in PDS group; RR 0.19; 95% CI 0.07 to 0.50). Quality of life (QoL) was reported to be similar for the NACT and PDS groups.Three ongoing RCTs were also identified.

AUTHORS' CONCLUSIONS: We consider the use of NACT in women with stage IIIc/IV ovarian cancer to be a reasonable alternative to PDS, particularly in bulky disease. With regard to selecting who will benefit from NACT, treatment should be tailored to the patient and should take into account resectability, age, histology, stage and performance status. These results cannot be generalised to women with stage IIIa and IIIb ovarian cancer; in these women, PDS is the standard. We await the results of three ongoing trials, which may change these conclusions.

http://www.ncbi.nlm.nih.gov/m/pubmed/22895947/

Issue 8, 2012 of The Cochrane Library is now available | The Cochrane Collaboration

Issue 8, 2012 of The Cochrane Library is now available

Issue 8, 2012 of The Cochrane Library is now available! New and updated reviews available on interventions for health-related quality of life for cancer survivors, weight loss and maintenance, and high blood pressure.

External link for more information: 

http://www.thecochranelibrary.com/view/0/index.html

Contributor's Information

Contributor's name: 

Cochrane Web Team

http://www.cochrane.org/news/tags/authors/issue-8-2012-cochrane-library-now-available

Revisiting the complexity of the ovaria - PubMed Mobile

Revisiting the complexity of the ovarian cancer microenvironment-clinical implications for treatment strategies.

Authors

Musrap N, Diamandis EP.

Journal

Mol Cancer Res. 2012 Aug 15. [Epub ahead of print]

Affiliation

University of Toronto.

Abstract

Epithelial ovarian cancer (EOC) is the leading cause of death among gynaecological malignancies in North American women. Given that EOC encompasses a broad class of tumors consisting of a variety of different histological and molecular subtypes, which generates genetically and etiologically distinct tumors, several challenges arise during treatment of patients with this disease. Overlaying this complexity is the contribution of supporting cells, particularly stromal components such as fibroblasts and immune infiltrates that collectively create a microenvironment that promotes and enhances cancer progression. A notable example is the induction of angiogenesis, which occurs through the secretion of pro-angiogenic factors by both tumor and tumor-associated cells. The recent development of angiogenic inhibitors targeting tumor vasculature, which have been shown to improve patient outcome when combined with standard therapy, has launched a paradigm shift on how cancer patients should be treated. It is evident that future clinical practices will focus on the incorporation of therapies that antagonize the pro-tumoral effects of such microenvironment contributors. Herein, an overview of the varying tumor-host interactions that influence tumor behaviour will be discussed, in addition to the recent efforts undertaken to target these interactions and their potential to revolutionize EOC patient care.

PMID

 22896662 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/m/pubmed/22896662/

Myriad Genetics' Q4 Revenues Rise 24 Percent; Ramp up of European Operations Continues | GenomeWeb

http://www.genomeweb.com/mdx/myriad-genetics-q4-revenues-rise-24-percent-ramp-european-operations-continues


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Women and Health Initiative: integrating needs and response : The Lancet

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The Promises and Challenges of Digital Imaging as Applied to Pathology: Dr. Ulysses G.J. Balis

http://www.youtube.com/watch?v=j1yh-Oak528&feature=youtube_gdata_player


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Myriad wins gene patent ruling from US appeals court

Myriad wins gene patent ruling from US appeals court

(Reuters) - A U.S. federal appeals court has once again affirmed the right of Myriad Genetics Inc to patent two genes linked to breast and ovarian cancer, after the U.S. Supreme Court told it to take another look at the hotly contested case.

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Mixed Endocervical Adenocarcinoma and High-grade Neuroendocrine Carcinoma of the Cervix With Ovarian Metastasis of the Former Component: A Report of 2 Cases

Mixed Endocervical Adenocarcinoma and High-grade Neuroendocrine Carcinoma of the Cervix With Ovarian Metastasis of the Former Component: A Report of 2 Cases

Endocervical adenocarcinomas (ECAs) uncommonly metastasize to the ovary; however, when they do they sometimes closely mimic a mucinous/endometrioid ovarian primary tumor. Here, 2 cases of mixed moderately differentiated ECA and high-grade cervical neuroendocrine carcinoma in which the ECA component metastasized to the ovary have been delineated and reported. In both cases, the primary tumor and the metastatic tumor were diffusely positive for p16 and high-risk human papillomavirus. Although similar to previously reported cases of adenocarcinoma in situ and invasive ECAs with ovarian involvement, none of the cases reported to date had concurrent neuroendocrine carcinoma with metastasis of the lower-grade component. In this respect, our cases are unique. The presence of lower uterine segment involvement in both cases and high-risk human papillomavirus positivity in the primary and metastatic tumors suggest a metastatic process, perhaps through transtubal spread, rather than independent primaries.

Chemo Resistance in Ovarian Cancer Has Genetic Basis - Cancer Network

cernetwork.com/ovarian-cancer/content/article/10165/2097235


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Appeals Court Affirms Isolated DNA Patents in Myriad Case | GenomeWeb

http://www.genomeweb.com/mdx/appeals-court-affirms-isolated-dna-patents-myriad-case


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Colon and Rectal Cancer: The Myth of 2 Beasts (mobile format)

http://www.medscape.com/viewarticle/768556?src=rss

Biologic rationale and clinical activity of mTOR inhibitors in gynecological cancer.

Biologic rationale and clinical activity of mTOR inhibitors in gynecological cancer.

Related Articles

Biologic rationale and clinical activity of mTOR inhibitors in gynecological cancer.

Cancer Treat Rev. 2012 Oct;38(6):767-75

Authors: Diaz-Padilla I, Duran I, Clarke BA, Oza AM

Abstract

Advanced recurrent gynecological malignancies have a poor prognosis despite systemic treatment, which is usually cytotoxic chemotherapy. Responses are generally short-lived and more effective treatments are needed. Rationally designed molecularly targeted therapy is an emerging and important option in this setting. The mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase of the phosphatidylinositol-3-kinase (PI3K)/AKT signaling pathway with a critical role in controlling cancer cellular growth, metabolism and cell cycle progression. Aberrant PI3K-dependent signaling occurs frequently in a wide range of tumor types, including ovarian, endometrial and cervical cancer. Early clinical studies of first-generation mTOR inhibitors have shown promising clinical activity in endometrial cancer. However, the molecular basis of sensitivity and resistance to these agents remains largely unknown. In this review, we will update the clinical and biological data underlying the development of first generation mTOR inhibitors in the treatment of gynecological tumors. The role of potential new combination regimens with mTOR inhibitors in gynecological cancers will also be discussed.

PMID: 22381585 [PubMed - indexed for MEDLINE]

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Genetics, Inheritance and Strategies for Prevention in Populations at High Risk of Colorectal Cancer (CRC).

Genetics, Inheritance and Strategies for Prevention in Populations at High Risk of Colorectal Cancer (CRC).

Genetics, Inheritance and Strategies for Prevention in Populations at High Risk of Colorectal Cancer (CRC).

Recent Results Cancer Res. 2012;191:157-83

Authors: Burn J, Mathers J, Bishop DT

Abstract

Hereditary forms of colorectal cancer account for less than 5 % of colorectal cancer but attract disproportionate attention because they offer an opportunity for effective surgical prophylaxis, influence the health of the wider family and give insight into the critical pathways of carcinogenesis. Familial Adenomatous Polyposis (FAP) due to loss of the APC gene and Lynch syndrome or Hereditary Non-Polyposis Colon Cancer (HNPCC) due to breakdown in MisMatch Repair are the principal syndromes of broader interest and both have been the subject of chemoprevention trials. There has been a longstanding interest in non-steroidal anti inflammatories in FAP where trials have shown regression of polyps with the "pro drug"sulindac and the selective COX2 inhibitors though impact on long-term cancer risk is not confirmed. The CAPP1 trial focused on two interventions in a factorial design, aspirin and resistant starch or fermentable fibre. Resistant starch is not absorbed in the small intestine and undergoes colonic fermentation to short-chain fatty acids including butyrate which have anti-cancer effects. Polyposis registry clinicians across Europe recruited adolescents with FAP to receive aspirin (600 mg as 2 tablets/d) and/or 30 g as 2 sachets/d in a 1:1 blend of potato starch and high amylose maize starch [Hylon VII]) with placebo control for at least a year or until surgery before age 21. Fifty-nine percent (133/227) of recruits had a baseline and at least one other endoscopy. After a median of 17 months , the primary endpoint of a risk of an increased polyp number in the rectum and sigmoid colon was not significantly reduced in either treatment group with relative risks of 0.77 (aspirin; 95 % CI, 0.54-1.10;) and 1.05 (RS; 95 % CI, 0.73-1.49. The diameter of the largest polyp detected tended to be smaller in the aspirin arm. The planned subgroup analyses of patients who elected to continue on study for more than one year found a significant reduction in the size of the largest polyp in the aspirin versus non-aspirin group (p = 0.02), Mean crypt length decreased significantly over time on study in the two combined RS groups, compared with the two combined non-RS groups (p < 0.0001 for interaction), in a model of the interaction between intervention and time. In CAPP2, 1009 Lynch syndrome gene carriers were recruited from 43 international centres. 937 commenced intervention: 600mg enteric coated aspirin and/or 30grams of the resistant starch Novelose in a 2 by 2 factorial placebo controlled design. After a mean of 29 months, intervention, there was no evidence that either agent influenced ...

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http://m.prnewswire.com/news-releases/oncolytics-biotech-inc-completes-patient-enrollment-in-uk-phase-i-clinical-trial-investigating-reolysin-in-combination-with-cyclophosphamide-in-patients-with-advanced-malignances-166384116.html

Oncolytics Biotech® Inc. Completes Patient Enrollment in U.K. Phase I Clinical Trial Investigating REOLYSIN® in Combination with Cyclophosphamide in Patients with Advanced Malignances

CALGARY, Aug. 16, 2012 /PRNewswire/ - Oncolytics Biotech Inc. ("Oncolytics") (TSX:ONC) (NASDAQ:ONCY) today announced that it has completed patient enrollment in its U.K. Phase I clinical trial using intravenously-administered REOLYSIN in combination with cyclophosphamide in patients with advanced malignancies (REO 012).

"We are pleased to complete enrollment of this technical study examining cyclophosphamide's potential to modulate the immune system's response to REOLYSIN," said Dr. Matt Coffey, COO of Oncolytics. "Studies of this type help to advance our understanding of the interaction between the immune system and our product."

The primary objective of the open label, dose-escalating, non-randomized, 36-patient study is to determine the Minimum Effective Immunomodulatory Dose (MED) of cyclophosphamide necessary to obtain successful immune modulation. Secondary objectives of the trial include assessing the safety profile of the combination and gathering any evidence of antitumor activity.

Eligible patients include those who have been diagnosed with advanced or metastatic solid tumors, including pancreatic, lung and ovarian cancers that are refractory to standard therapy, or for which no standard curative therapy exists.

The principal investigators for the study are Dr. James Spicer of King's College, London, Dr. Johann de Bono and Dr. Kevin Harrington of the Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, London, and Professor Hardev Pandha of the Royal Surrey County Hospital NHS Trust, Surrey and Mount Alvernia Hospitals.

About Oncolytics Biotech Inc.

Oncolytics is a Calgary-based biotechnology company focused on the development of oncolytic viruses as potential cancer therapeutics. Oncolytics' clinical program includes a variety of human trials including a Phase III trial in head and neck cancers using REOLYSIN, its proprietary formulation of the human reovirus. For further information about Oncolytics, please visit: www.oncolyticsbiotech.com.

This press release contains forward-looking statements, within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements, including the Company's expectations related to the U.K. Phase I clinical trial with REOLYSIN in combination with cyclophosphamide , and the Company's belief as to the potential of REOLYSIN as a cancer therapeutic, involve known and unknown risks and uncertainties, which could cause the Company's actual results to differ materially from those in the forward-looking statements. Such risks and uncertainties include, among others, the availability of funds and resources to pursue research and development projects, the efficacy of REOLYSIN as a cancer treatment, the tolerability of REOLYSIN outside a controlled test, the success and timely completion of clinical studies and trials, the Company's ability to successfully commercialize REOLYSIN, uncertainties related to the research and development of pharmaceuticals and uncertainties related to the regulatory process. Investors should consult the Company's quarterly and annual filings with the Canadian and U.S. securities commissions for additional information on risks and uncertainties relating to the forward-looking statements. Investors are cautioned against placing undue reliance on forward-looking statements. The Company does not undertake to update these forward-looking statements, except as required by applicable laws.

SOURCE Oncolytics Biotech Inc.

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Universal health coverage achieved by Mexico in less than a decade

Is the controversy on breast cancer as part of the Lynch-related tumor spectrum still open?

Increased incidence of brain metastases in BRCA1-related ovarian cancers.

http://www.ncbi.nlm.nih.gov/m/pubmed/22889437/?i=5&from=ovarian%20cancer

Consumer awareness and attitudes about insurance discrimination post enactment of the Genetic Information Nondiscrimination Act.

http://www.ncbi.nlm.nih.gov/m/pubmed/22890887/?i=3&from=ovarian%20cancer

Kramer explains results of the PLCO trial « NCI Benchmarks

http://benchmarks.cancer.gov/2012/08/kramer-explains-results-of-the-plco-trial/

Delays Plague Breast and Ovarian Cancer Research – The Jewish Daily Forward

-research

Launching a 'social networking war' against cancer

http://medicalxpress.com/news/2012-08-social-networking-war-cancer.html

Pre-test genetic counseling increases cancer knowledge for BRCA patients - podcast

http://m.medicalxpress.com/news/2012-08-pre-test-genetic-cancer-knowledge-brca.html

CCR: Pre-invasive ovarian mucinous tumors are characterized by CDKN2A and RAS pathway aberrations.

http://m.clincancerres.aacrjournals.org/content/early/2012/08/11/1078-0432.CCR-12-1103


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Health News - Mechanisms of Acquired Chemoresistance in Ovarian Cancer Identified

-Ovarian-Cancer-Identified.html?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+healthnewshc%2FOxfp+%28Health+News+from+HealthCanal.com%29&utm_content=Google+Reader

JTM | open access | Correlation of pretreatment drug induced apoptosis in ovarian cancer cells with patient survival and clinical response (MiCK assay)

JTM | Abstract | Correlation of pretreatment drug induced apoptosis in ovarian cancer cells with patient survival and clinical response

Conclusion

The MiCK assay can predict the chemotherapy associated with better outcomes in ovarian cancer patients. This study quantifies outcome benefits on which a prospective randomized trial can be developed.

BMC Palliative Care | Full text | A national study of chaplaincy services and end-of-life outcomes

BMC Palliative Care | Full text | A national study of chaplaincy services and end-of-life outcomes

open access: Constitutive promoter methylation of BRCA1 and RAD51C in patients with familial ovarian cancer and early-onset sporadic breast cancer

Constitutive promoter methylation of BRCA1 and RAD51C in patients with familial ovarian cancer and early-onset sporadic breast cancer

Olanzapine for the Relief of Nausea in Patients With Advanced Cancer and Incomplete Bowel Obstruction | DocGuide

Olanzapine for the Relief of Nausea in Patients With Advanced Cancer and Incomplete Bowel Obstruction | DocGuide

Cancer Australia Connect - July 2012 issue (includes resources, guidelines....)

Untitled Document

doc2doc forum: Why are 25% of deaths not being properly recorded?

http://tinyurl.com/dxg6gvn

Forums  »  Open clinical  »  General clinical  »  Why are 25% of deaths not being properly recorded?

Taking Action Health Equity in Canada - Canadian Doctors for Medicare

TakingActionHealthEquity

Incidence and predictors of venous thromboembolism (VTE) among ambulatory high-risk cancer patients undergoing chemotherapy in the United States - Khorana - 2012 - Cancer - Wiley Online Library

Abstract

BACKGROUND:

Recent studies suggest that thromboprophylaxis is beneficial in preventing venous thromboembolism (VTE) in cancer outpatients, but this is not widely adopted because of incomplete understanding of the contemporary incidence of VTE and concerns about bleeding. Therefore, the authors examined the incidence and predictors of VTE in ambulatory patients with bladder, colorectal, lung, ovary, pancreas, or gastric cancers.

METHODS:

Data were extracted from a large health care claims database of commercially insured patients in the United States between 2004 and 2009. Demographic and clinical characteristics of the cancer cohort (N = 17,284) and an age/sex-matched, noncancer control cohort were evaluated. VTE incidence was recorded during a 3-month to 12-month follow-up period after the initiation of chemotherapy. Multivariate analyses were conducted to identify independent predictors of VTE and bleeding.

RESULTS:

The mean age of the study population was 64 years, and 51% of patients were women. VTE occurred in 12.6% of the cancer cohort (n = 2170) over 12 months after the initiation of chemotherapy versus 1.4% of controls (n = 237; P < .0001); incidence ranged by cancer type from 19.2% (pancreatic cancer) to 8.2% (bladder cancer). Predictors of VTE included type of cancer, comorbidities (Charlson Comorbidity Index score or obesity), and commonly used specific antineoplastic or supportive care agents (cisplatin, bevacizumab, and erythropoietin).

CONCLUSIONS:

This large, contemporary, real-world analysis confirmed high rates of VTE in select patients with solid tumors and suggested that the incidence of VTE is high in the real-world setting. Awareness of the benefits of targeted thromboprophylaxis may result in a clinically significant reduction in the burden of VTE in this population. Cancer 2012. © 2012 American Cancer Society.

http://onlinelibrary.wiley.com/doi/10.1002/cncr.27772/abstract;jsessionid=48B8081B141F0857048BECC4CDB4F41D.d04t01

All-cause mortality and cancer incidence

http://www.ncbi.nlm.nih.gov/m/pubmed/22886909/

Roche’s Avastin may receive ovarian cancer recommendation from NICE if lower than approved dose is considered - FT.com

ADzHH

Social media in healthcare- a BMC Medicine twitter chat now on Storify!

Social media in healthcare- a BMC Medicine twitter chat now on Storify!

Following the publication of 'Medicine, morality and health care social media' in BMC Medicine, author Farris Timimi (Medical Director, Mayo Clinic Center for Social Media, @FarrisTimimi) and his colleague Lee Aase (Director, Mayo Clinic Center for Social Media, @LeeAase) joined BMC Medicine Editor Sabina Alam (@BMCMedicine) in a twitter chat to discuss the ideas raised in Timimi's commentary.

It was apparent there was consensus amongst the contributors of the twitter chat – social media should be used as a tool by healthcare providers to interact with patients. Some systems are already in place, but more work is required to develop the right kind of social media platforms, and perhaps more importantly, more physicians should be encouraged to learn how to use social media to engage with the general public. Whether the medical institutions should make this a requirement remains to be determined.

A summary of the discussion with a selection of the contributions can be viewed at Storify.

Following the success of this chat we are considering having more in the future. If you feel there are any topics that should be discussed please get in touch via email, or of course tweet at us ! (@BMCMedicine)

Patients with Lynch Syndrome Mismatch Repair Gene Mutations Are at Higher Risk for Not Only Upper Tract Urothelial Cancer but Also Bladder Cancer.

Patients with Lynch Syndrome Mismatch Repair Gene Mutations Are at Higher Risk for Not Only Upper Tract Urothelial Cancer but Also Bladder Cancer.

Patients with Lynch Syndrome Mismatch Repair Gene Mutations Are at Higher Risk for Not Only Upper Tract Urothelial Cancer but Also Bladder Cancer.

Eur Urol. 2012 Aug 2;

Authors: Skeldon SC, Semotiuk K, Aronson M, Holter S, Gallinger S, Pollett A, Kuk C, van Rhijn B, Bostrom P, Cohen Z, Fleshner NE, Jewett MA, Hanna S, Shariat SF, Van Der Kwast TH, Evans A, Catto J, Bapat B, Zlotta AR

Abstract

BACKGROUND: Lynch syndrome (LS), or hereditary nonpolyposis colorectal cancer, is caused by mutations in mismatch repair (MMR) genes. An increased risk for upper tract urothelial carcinoma (UTUC) has been described in this population; however, data regarding the risk for bladder cancer (BCa) are sparse. OBJECTIVE: To assess the risk of BCa in MMR mutation carriers and suggest screening and management recommendations. DESIGN, SETTING, AND PARTICIPANTS: Cancer data from 1980 to 2007 were obtained from the Familial Gastrointestinal Cancer Registry in Toronto for 321 persons with known MMR mutations: mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli) (MLH1); mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli) (MSH2); mutS homolog 6 (E. coli) (MSH6); and PMS2 postmeiotic segregation increased 2 (S. cerevisiae) (PMS2). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Standardized incidence ratios from the Ontario Cancer Registry, using the Surveillance Epidemiology and End Results public database, were used to compare cancer risk in patients with MMR mutations with the Canadian population. Microsatellite instability analysis and immunohistochemistry (IHC) of the MMR proteins were also performed and the results compared with matched sporadic bladder tumors. RESULTS AND LIMITATIONS: Eleven of 177 patients with MSH2 mutations (6.21%, p<0.001 compared with the Canadian population) were found to have BCa, compared with 3 of 129 patients with MLH1 mutations (2.32%, p>0.05). Of these 11 tumors, 81.8% lacked expression of MSH2 on IHC, compared with the matched sporadic cases, which all displayed normal expression of MSH2 and MLH1. The incidence of UTUC among MSH2 carriers was 3.95% (p<0.001), and all tumors were found to be deficient in MSH2 expression on IHC. Mutations in the intron 5 splice site and exon 7 of the MSH2 gene increased the risk of urothelial cancer. Limitations include possible inflated risk estimates due to ascertainment bias. CONCLUSIONS: LS patients with MSH2 mutations are at an increased risk for not only UTUC but also BCa and could be offered appropriate screening.

PMID: 22883484 [PubMed - as supplied by publisher]

[Ovarian cancer--modern approach to its origin and histogenesis].

[Ovarian cancer--modern approach to its origin and histogenesis].

[Ovarian cancer--modern approach to its origin and histogenesis].

Abstract

Ovarian cancers (OC) belong to a heterogeneous group of pathologies and are traditionally classified with regard to histological type and degree of differentiation. OC was hypothesized to originate from ovarian surface epithelium (OSE) and inclusion cysts epithelium (IC). Unfortunately this theory was never supported by any clinical or molecular evidence linking carcinogenesis with OSE and was refuted. OC subtypes demonstrate morphologic features that resemble Müllerian duct-derived epithelia of the genital tract. Investigations of the HOX gene family Müllerian epithelial differentiation markers, confirmed the HOX genes expression in many subtypes of OC but not in OSE. The first step towards connecting OC origin with other than OSE genital tract structures were epidemiological observations indicating a minor OC risk after tubal ligation in women with the BRCA mutation. The first in situ carcinoma was found in the Fallopian tube fimbriae. Further research confirmed the same mechanism in sporadic OC. Endometriosis and endometrium cells may be a highly probable place of endometrioid OC initiation. Mucinous types share common futures with gastrointestinal tract cancers and there one needs to search for their precursors. Clear cell carcinoma may arise from glandular epithelium of endocervix or from endometrioid foci. The new classification of OC was proposed in 2004, suggesting to divide all OC into two types: I and II. Type II includes serous and endometrioid G3 subtypes, carcinosarcomas and undifferentiated OC. They are responsible for 75% of OC morbidity identified usually in FIGO stages Ill or IV, have poor prognosis and relapse early The remaining hystiotypes, with better prognosis and earlier FIGO stages at time of diagnosis, were classified as type I. Serous and endometrioid poorly differentiated ovarian cancers demonstrate mutation in TP53 gene (type II) and highly differentiated ones, generally in BRAS and KRAS genes (type I). The differences in molecular pathways also confirm different patterns of carcinogenesis of both OC types. Modern approach to OC histogenesis and origin emphasizes the necessity to verify OC screening, detection and treatment methods.

PMID: 22880466 [PubMed - in process]

Clear Cell Carcinoma of the Female Genital Tract (Not Everything Is as Clear as it Seems).

Clear Cell Carcinoma of the Female Genital Tract (Not Everything Is as Clear as it Seems).

Clear Cell Carcinoma of the Female Genital Tract (Not Everything Is as Clear as it Seems).

Adv Anat Pathol. 2012 Sep;19(5):296-312

Abstract

Clear cell carcinoma has a storied history in the female genital tract. From the initial designation of ovarian clear cell adenocarcinoma as "mesonephroma" to the linkage between vaginal clear cell carcinoma and diethylstilbestrol exposure in utero, gynecologic tract clear cell tumors have puzzled investigators, posed therapeutic dilemmas for oncologists, and otherwise presented major differential diagnostic challenges for pathologists. One of the most common errors in gynecologic pathology is misdiagnosis of clear cell carcinoma, on both frozen section and permanent section. Given the poor response to platinum-based chemotherapy for advanced-stage disease and increased risk of thromboembolism, accurate diagnosis of clear cell carcinoma is important in the female genital tract. This review (1) presents the clinical and pathologic features of female genital tract clear cell carcinomas; (2) highlights recent molecular developments; (3) identifies areas of potential diagnostic confusion; and (4) presents solutions for these diagnostic problems where they exist.

PMID: 22885379 [PubMed 

Beyond Office Hours: New App, Patient Portal, to Allow U-M Patients Mobile Access to Health Records

http://www.newswise.com/articles/view/592545/?sc=rsla&utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+NewswiseLatestNews+%28Newswise%3A+Latest+News%29&utm_content=Google+Reader

Empathy in Healthcare's a Waste, Unless It's a Strategic Focus - Forbes

nless-its-a-strategic-focus/

Quality of Life in Patients after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Is It Worth the Risk?

Quality of Life in Patients after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Is It Worth the Risk?

Abstract

Objective  

To investigate the course of health-related quality of life (HQL) over time in patients with peritoneal carcinomatosis (PC)
after complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

Methods  

Prospective, single-center, nonrandomized cohort study using the European Organization for Research and Treatment of Cancer
Quality of Life Questionnaire.

Results  

Ninety patients who underwent CRS and HIPEC for PC in our institution were enrolled in the study. Mean age was 56 years (range
27–77 years) (61 % female). Primary tumor was colorectal in 21 %, ovarian in 19 %, pseudomyxoma peritonei in 16 %, an appendix
tumor in 16 %, gastric cancer in 10 %, and peritoneal mesothelioma in 13 % of cases. Mean peritoneal carcinomatosis index
was 22 (range 2–39). Mean global health status score was 69 ± 25 preoperatively and 55 ± 20, 66 ± 22, 66 ± 23, 71 ± 23, and
78 ± 21 at months 1, 6, 12, 24, and 36, respectively. Physical and role function recovered significantly at 6 months and were
close to baseline at the 24-month measurement. Emotional function starting from a low baseline recovered to baseline by month
12. Cognitive and social function had slow recovery on follow-up. Fatigue, diarrhea, dyspnea, and sleep disturbance were symptoms
persistent at 6-month follow-up, improving later on in survivors.

Conclusions  

Survivors after CRS and HIPEC have postoperative quality of life similar to preoperatively, with most of the reduced elements
recovering after 6–12 months. We conclude that reduced quality of life of patients after CRS and HIPEC should not be used
as an argument to deny surgical therapy to these patients.

Ovarian cancer: emerging molecular-targeted therapies June 2012

‘Real inequalities’ a threat to medicare’s mission, incoming CMA chief says - The Globe and Mail

From The Globe and Mail:
'Real inequalities' a threat to medicare's mission, incoming CMA chief 

National Guideline Clearinghouse | Identification of individuals at risk for Lynch syndrome using targeted evaluations and genetic testing: National Society of Genetic Counselors and the Collaborative Group of the Americas on Inherited Colorectal Cancer joint practice guideline.

Electronic health records: what does your signature signify?

Ovarian Cancer Clinical Trial: Patient Reported Symptoms in Ovarian Cancer (PRECISION) - ongoing

http://clinicaltrialsfeeds.org/clinical-trials/show/NCT01422265

Public funding for genomics: where does Canada stand?

Public funding for genomics: where does Canada stand?

After more than six years of funding exclusive projects in forestry and agriculture, Genome Canada has now announced a $67.5 million funding competition for large-scale genomics projects in human health, with focus on personalised medicine.ⁱ The human genomics community of this country understandably rejoiced at this long overdue announcement that gives them, for the first time in years, the means to compete internationally (http://www.genomecanada.ca/en/portfolio/research/2012-competition.aspx). Canada has been fairly generous in funding human-health related research but mostly through the Canadian Institutes of Health Research (CIHR) or the Canada Foundation for Innovation, neither of which has within its mandate to fund the type of specific multimillion-dollar project that is usually thought of as genomics. The typical CIHR grant, for example, rarely exceeds $1 million (200 000 over 5 years) in direct costs.

The elation over the announcement of this funding opportunity in late 2011 soon gave way to sober...

Postmenopausal hormone therapy and colorectal cancer risk by molecularly defined subtypes among older women

Postmenopausal hormone therapy and colorectal cancer risk by molecularly defined subtypes among older women

Background

Postmenopausal hormone (PMH) therapy may reduce colorectal cancer (CRC) risk, but existing data are inconclusive.

Objectives

To evaluate associations between PMH therapy and incident CRC, overall and by molecularly defined subtypes, in the population-based Iowa Women's Health Study of older women.

Methods

Exposure data were collected from Iowa Women's Health Study participants (55–69 years) at baseline (1986). Archived, paraffin-embedded tissue specimens for 553 CRC cases were collected and analysed to determine microsatellite instability (MSI-L/MSS or MSI-H), CpG island methylator phenotype (CIMP-negative or CIMP-positive) and BRAF mutation (BRAF-wildtype or BRAF-mutated) status. Multivariable Cox regression models were fit to estimate RRs and 95% CIs.

Results

PMH therapy (ever vs never use) was inversely associated with incident CRC overall (RR=0.82; 95% CI 0.72 to 0.93), with a significantly lower risk for MSI-L/MSS tumours (RR=0.75; 95% CI 0.60 to 0.94), and borderline significantly lower risks for CIMP-negative (RR=0.79; 95% CI 0.63 to 1.01) and BRAF-wildtype (RR=0.83; 95% CI 0.66 to 1.04) tumours. For PMH therapy >5 years, the subtype-specific risk estimates for MSI-L/MSS, CIMP-negative and BRAF-wildtype tumours were: RR=0.60, 95% CI 0.40 to 0.91; RR=0.68, 95% CI 0.45 to 1.03; and RR=0.70, 95% CI 0.47 to 1.05, respectively. PMH therapy was not significantly associated with the MSI-H, CIMP-positive or BRAF-mutated CRC subtypes.

Conclusions

In this prospective cohort study, PMH therapy was inversely associated with distinct molecularly defined CRC subtypes, which may be related to differential effects from oestrogen and/or progestin on heterogeneous pathways of colorectal carcinogenesis.

Sequential whole-body PET/MR scanner: concept, clinical use, and optimisation after two years in the clinic. The manufacturer’s perspective

Sequential whole-body PET/MR scanner: concept, clinical use, and optimisation after two years in the clinic. The manufacturer's perspective

Abstract  

PET and MRI are established clinical tools which provide complementary information, but clinical workflow limits widespread
clinical application of both modalities in combination. The two modalities are usually situated in different hospital departments
and operated and reported independently, and patients are referred for both scans, often consecutively. With the advent of
PET/MR as a new hybrid imaging modality there is now a possibility of addressing these concerns. There are two different design
philosophies for integrated PET/MR imaging—positioning PET inside the MRI magnet or in tandem, similar to PET/CT. The Ingenuity
TF PET/MR by Philips Healthcare is a sequential PET/MR tomograph combining state-of-the-art time-of-flight PET and high-field
MRI with parallel transmission capabilities. In this review article we describe the technology implemented in the system,
for example RF and magnetic shielding, MR-based attenuation correction, peculiarities in scatter correction, MR system optimisation,
and the philosophy behind its design. Furthermore, we provide an overview of how the system has been used during the last
two years, and expectations of how the use of PET/MR may continue in the years to come. On the basis of these observations
and experiences we discuss the utility of the system, clinical workflow and acquisition times, and possible ways of optimization.

• Content Type Journal Article
• Category Review Article
• Pages 1-19
• DOI 10.1007/s10334-012-0330-y

• Journal Magnetic Resonance Materials in Physics, Biology and Medicine

Oncology imaging in the abdomen and pelvis: where cancer hides

Oncology imaging in the abdomen and pelvis: where cancer hides

Abstract  

As the incidence of cancer continues to increase, imaging will play an ever more important role in the detection, diagnosis,
staging, surveillance, and therapeutic monitoring of cancer. Diagnostic errors in the initial discovery of cancer or at follow-up
assessments can lead to missed opportunities for curative treatments or altering or reinitiating therapies, as well as adversely
impact clinical trials. Radiologists must have an understanding of cancer biology, treatments, and imaging appearance of therapeutic
effects and be mindful that metastatic disease can involve virtually any organ system. Knowledge of patient history and tumor
biology allows for optimizing imaging protocols. The majority of cancer imaging utilizes computed tomography, where contrast
enhancement characteristics of lesions can be exploited and detection of subtle lesions can involve manipulation of window
width and level settings, multiplanar reconstruction, and maximum intensity projections. For magnetic resonance imaging, diffusion-weighted
imaging can render lesions more conspicuous, improve characterization, and help assess therapeutic response. Positron emission
tomography with ¹⁸F-labeled fluorodeoxyglucose and sodium fluoride are invaluable in detecting occult existing and new cancerous lesions, characterizing
indeterminate lesions, and assessing treatment effects. The most common anatomic "hiding places" for cancer include metastases
to solid organs, such as the kidneys and pancreas, gastrointestinal tract, peritoneum and retroperitoneum, neural axis, muscular
body wall, and bones. Consistent work habits, employment of appropriate technologies, and particular attention to the above
anatomic areas can enhance detection, staging, and reassessments of these complex and often stealthy diseases, ensuring the
radiologists' integral role in the cancer care team.

• Journal Abdominal Imaging
• Online ISSN 1432-0509

Journal of Cancer Education - SpringerLink

http://www.springerlink.com/content/121578/


Sent from my iPhone

Dietary Lifestyle and Colorectal Cancer Onset, Recurrence, and Survival: Myth or Reality?

Dietary Lifestyle and Colorectal Cancer Onset, Recurrence, and Survival: Myth or Reality?

Abstract

Background and Purpose  

Interest in the possibility that diet might help to reduce the risk of colorectal cancer dates back to 1970 based on both
the large variation in rates of specific cancers in different countries and the impressive changes observed in the incidence
of cancer in migrants from low- to high-risk areas. Here, we report the state of art of literature data about this topic.

Methods  

Three sections have been separately considered: chemoprevention of first tumor onset, chemoprevention of recurrence after
surgery, and chemoprevention of polyp recurrence in the course of the follow-up of subjects with elevated risk. A particular
attention has been pointed to dietary factors and survival, whose relevance is showing a growing interest.

Results  

The relationship between diet and colorectal cancer has been extensively studied about the onset, sometimes with controversial
results. Its influence on recurrence and survival has been examined in only few studies.

Conclusions  

Literature data are convincing for a protective role on the onset of preneoplastic and neoplastic lesions for some foods such
as fibers, vitamin A and D, folic acid, calcium, antioxidants, and promising perspectives for some substances such as phyto-estrogens.
Less evidence-based data are available on the possibility to avoid the recurrence of the disease or to affect its mortality
with dietary habits. Future perspectives will be directed be not only to identify new dietary style able to prevent the onset
of neoplastic lesion of the colon but also to realize an effective chemoprevention.

• Content Type Journal Article
• Category Review Article
• Pages 1-11
• DOI 10.1007/s12029-012-9425-y

A prospective study of the feasibility and acceptability of a Web-based, electronic patient-reported outcomes system in assessing patient recovery after major gynecologic cancer surgery.

http://www.ncbi.nlm.nih.gov/m/pubmed/22871467/

Ovarian Cancer Biotargets of Cancer in Current Clinical Practice

Ovarian Cancer Biotargets of Cancer in Current Clinical Practice

In Biotargets of Cancer in Current Clinical Practice (2012), pp. 381-401, doi:10.1007/978-1-61779-615-9_14

Ovarian cancer is the fifth most common cancer in women and is the most lethal of all gynecologic cancers. Early-stage ovarian cancer is curable while women who are diagnosed with advanced ovarian cancer continue to have poor long-term survival due to recurrence of disease. Unfortunately, most women are diagnosed with advanced-stage disease. Early detection is a primary objective for clinicians and scientists, yet single modality (CA-125, transvaginal ultrasound) screening tests have been ineffective. More recent novel approaches combining modalities and utilizing serial serum sampling are being tested and hold great promise. In addition, the recent application of proteomics to this clinical question has the potential to identify new and important biotargets. Unfortunately, the majority of ovarian cancer patients have advanced-stage disease, and although most will die of their disease, their survival is quite heterogenous. The ability to stratify patients according to prognosis could help guide therapy. The current "gold standard" for prognosis uses patient, surgical, and tumor characteristics, yet these have the tendency to be notoriously inaccurate. This prognostic uncertainty and the drive to identify predictive factors by which we can select novel and targeted therapy have stimulated researchers to look beyond traditional markers and test and validate molecular and genomic biomarkers, which are anticipated to soon complement or even eclipse traditional factors clarifying prognosis and select treatments. For patients with advanced-stage disease, a multitude of prognostic factors have been characterized. While promising, none of these biotargets have been validated at present to be clinically useful. More recent application of genomic technologies is likely to yield clinically relevant signatures and/or biotargets which will provide the basis for personalization of care for these patients.
Jessica Oribabor, Allison Ambrosio, Cesar Castro, Michael Birrer

Environmentally Induced Epigenetic Transgenerational Inheritance of Ovarian Disease

"Environmentally Induced Epigenetic Transgenerational Inheritance of Ovarian Disease"