In silico analysis and immunohistochemical characterization of NaPi2b protein expression in ovarian carcinoma with monoclonal antibody Mx35.

In silico analysis and immunohistochemical characterization of NaPi2b protein expression in ovarian carcinoma with monoclonal antibody Mx35.

Abstract
INTRODUCTION: Ovarian adenocarcinoma is frequently detected at the late stage, when therapy efficacy is limited and death occurs in up to 50% of the cases. A potential novel treatment for this disease is a monoclonal antibody that recognizes phosphate transporter sodium-dependent phosphate transporter protein 2b (NaPi2b).

MATERIALS AND METHODS: To better understand the expression of this protein in different histologic types of ovarian carcinomas, we immunostained 50 tumor samples with anti-NaPi2b monoclonal antibody MX35 and, in parallel, we assessed the expression of the gene encoding NaPi2b (SCL34A2) by in silico analysis of microarray data.

RESULTS: Both approaches detected higher expression of NaPi2b (SCL34A2) in ovarian carcinoma than in normal tissue. Moreover, a comprehensive analysis indicates that SCL34A2 is the only gene of the several phosphate transporters genes whose expression differentiates normal from carcinoma samples, suggesting it might exert a major role in ovarian carcinomas. Immunohistochemical and mRNA expression data have also shown that 2 histologic subtypes of ovarian carcinoma express particularly high levels of NaPi2b: serous and clear cell adenocarcinomas. Serous adenocarcinomas are the most frequent, contrasting with clear cell carcinomas, rare, and with worse prognosis.

CONCLUSION: This identification of subgroups of patients expressing NaPi2b may be important in selecting cohorts who most likely should be included in future clinical trials, as a recently generated humanized version of MX35 has been developed.

England: The Cancer Drugs Fund: Guidance to support operation of the Cancer Drugs Fund in 2012-13 : Department of Health - Publications

 Blogger's Note: this is primarily an administrative document, patient/consumer searches for specific drugs are not part of this guidance report

The Cancer Drugs Fund: Guidance to support operation of the Cancer Drugs Fund in 2012-13 : Department of Health - Publications

• Document type:
  Guidance
• Author:
  Department of Health
• Published date:
  23 April 2012
• Primary audience:
  Health and social care professionals
• Publication format:
  A4: electronic format only
• Gateway reference:
  17340
• Pages:
  14
• Supersedes/replaces:
  The Cancer Drugs Fund
• Copyright holder:
  Crown

This document provides guidance to support operation of the Cancer Drugs Fund in 2012-13. It replaces previous guidance for operation of the Cancer Drugs Fund in 2011/12. The Cancer Drugs Fund applies in England only.

• Download The Cancer Drugs Fund: Guidance to support operation of the Cancer Drugs Fund in 2012-13 (PDF, 123K)
• More about publications from the DH

Vitamin D testing – articles of interest : The Lancet

Vitamin D testing (see sidebar)

Other Articles of Interest

Review Vitamin D and multiple sclerosis

Articles Common genetic determinants of vitamin D insufficiency: a genome-wide association study

Research Letters 25-hydroxyvitamin D-1α-hydroxylase in normal and malignant colon tissue

Articles High-dose vitamin D3 during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial

Comment Genetic and environmental determinants of vitamin D status

Vitamin D testing – Authors' reply : The Lancet

Vitamin D testing – Authors' reply : The Lancet

Linked Articles

Correspondence Vitamin D testing :

Correspondence Vitamin D testing

Correspondence Vitamin D testing

Correspondence Vitamin D testing

Patient empowerment—who empowers whom? : The Lancet

Patient empowerment—who empowers whom? : The Lancet

The Lancet

 

"What is patient empowerment? Over 250 participants discussed this question at the first European Conference on Patient Empowerment, recently held in Copenhagen, Denmark, by the European Network on Patient Empowerment (ENOPE 2012). The conference was convened under the auspices of the Danish Presidency of the European Union (EU), and organised by the WHO Regional Office for Europe, Denmark's Ministry of Health, the Danish Committee for Health Education, the Caerum Foundation of Switzerland, and the English Expert Patient's group......

Cochrane: YourHealthNet - navigating effective treatments with systematic reviews

YourHealthNet - navigating effective treatments with systematic reviews

The parts of a Cochrane systematic review and the information they contain - learning to navigate a review

Cochrane systematic reviews

Cochrane systematic reviews are the major output of the international organisation The Cochrane Collaboration, and over 4,000 Cochrane reviews are available online on The Cochrane Library. Because Cochrane review authors carry out their research with scientific rigour and follow detailed guidelines Cochrane reviews are considered a high quality source of research evidence.

David Tovey from The Cochrane Collaboration talks about systematic reviews.   » Read a transcript or » Listen to David's comments » See screen shot... This is how a systematic review looks on The Cochrane Library.

Explore the parts of a Cochrane systematic review

Systematic reviews are a complex mix of process and product - they report on the process review authors undertook, and the conclusions authors came to about what they found. All Cochrane systematic reviews follow the same format and methods; they have the same content in the same sections. This ensures their transparency and rigour.....

Healthnewsreview: The limitations of – and explosion in the number of – observational studies

The limitations of – and explosion in the number of – observational studies:

In the Wall Street Journal, Gautam Naik has a thoughtful piece, “Analytical Trend Troubles Scientists,” hitting on the limitations of – and the explosion in the number of – observational studies.  Excerpts:

“While the gold standard of medical research is the randomly controlled experimental study, scientists have recently rushed to pursue observational studies, which are much easier, cheaper and quicker to do. Costs for a typical controlled trial can stretch high into the millions; observational studies can be performed for tens of thousands of dollars.
In an observational study there is no human intervention. Researchers simply observe what is happening during the course of events, or they analyze previously gathered data and draw conclusions. In an experimental study, such as a drug trial, investigators prompt some sort of change—by giving a drug to half the participants, say—and then make inferences.
But observational studies, researchers say, are especially prone to methodological and statistical biases that can render the results unreliable. Their findings are much less replicable than those drawn from controlled research. Worse, few of the flawed findings are spotted—or corrected—in the published literature.
“You can troll the data, slicing and dicing it any way you want,” says S. Stanley Young of the U.S. National Institute of Statistical Sciences. Consequently, “a great deal of irresponsible reporting of results is going on.”
Despite such concerns among researchers, observational studies have never been more popular.
Nearly 80,000 observational studies were published in the period 1990-2000 across all scientific fields, according to an analysis performed for The Wall Street Journal by Thomson Reuters. In the following period, 2001-2011, the number of studies more than tripled to 263,557, based on a search of Thomson Reuters Web of Science, an index of 11,600 peer-reviewed journals world-wide. The analysis likely doesn’t capture every observational study in the literature, but it does indicate a pattern of growth over time.
A vast array of claims made in medicine, public health and nutrition are based on observational studies, as are those about the environment, climate change and psychology.”

The article addresses the “hot area of medical research” – the search for biomarkers.

“The presence or absence of the biomarkers in a patient’s blood, some theorized, could indicate a higher or lower risk for heart disease—the biggest killer in the Western world.
Yet these biomarkers “are either completely worthless or there are only very small effects” in predicting heart disease, says John Ioannidis of Stanford University, who extensively analyzed two decades’ worth of biomarker research and published his findings in Circulation Research journal in March. Many of the studies, he found, were undermined by statistical biases, and many of the biomarkers showed very little predictive ability of heart disease.
His conclusion is widely upheld by other scientists: Just because two events are statistically associated in a study, it doesn’t mean that one necessarily sets off the other. What is merely suggestive can be mistaken as causal.
That partly explains why observational studies in general can be replicated only 20% of the time, versus 80% for large, well-designed randomly controlled trials, says Dr. Ioannidis. Dr. Young, meanwhile, pegs the replication rate for observational data at an even lower 5% to 10%.
Whatever the figure, it suggests that a lot more of these studies are getting published. Those papers can often trigger pointless follow-on research and affect real-world practices.”

But the story also appropriately points out the contribution obervational studies have made:

“Observational studies do have many valuable uses. They can offer early clues about what might be triggering a disease or health outcome. For example, it was data from observational trials that flagged the increased risk of heart attacks posed by the arthritis drug Vioxx. And it was observational data that helped researchers establish the link between smoking and lung cancer.”

I have written many times about the weakness of news stories that fail to point out the limitations of observational studies and – more specifically – stories that use causal language to describe the findings from observational studies that can “only” point to statistical associations.
News consumers and health care consumers need to better understand the limitations of all studies – including randomized clinical trials.

paywalled: Risk of Colonic Neoplasia After Proctectomy for Rectal Cancer in Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome)

abstract

Abstract

Objective: To define the neoplastic risk in the remaining colon after proctectomy for rectal cancer in patients with hereditary nonpolyposis colorectal cancer (HNPCC). (Lynch Syndrome)

Conclusions: Surgeons and patients need to be aware of substantial risk for metachronous neoplasia after proctectomy. Selection of operation should be individualized, but total proctocolectomy and ileoanal pouch should be strongly considered. If patients undergo proctectomy alone, close surveillance is mandatory.

Explaining High Health Care Spending in the United States: An International Comparison of Supply, Utilization, Prices, and Quality - The Commonwealth Fund

Blogger's Note: some interesting comparisons on a variety of comparables including in-hospital 30 day mortality rates, breast/cervical/colorectal cancer survival rates, diagnostic imaging; comparisons of countries:


Explaining High Health Care Spending in the United States: An International Comparison of Supply, Utilization, Prices, and Quality - The Commonwealth Fund

Overview

This analysis uses data from the Organization for Economic Cooperation and Development and other sources to compare health care spending, supply, utilization, prices, and quality in 13 industrialized countries: Australia, Canada, Denmark, France, Germany, Japan, the Netherlands, New Zealand, Norway, Sweden, Switzerland, the United Kingdom, and the United States......

paywalled: Evaluation of Society of Gynecologic Oncologists (SGO) Ovarian Cancer Quality Surgical Measures

Evaluation of Society of Gynecologic Oncologists (SGO) Ovarian Cancer Quality Surgical Measures: Publication year: 2012

Source: Gynecologic Oncology



Objectives
The Society of Gynecologic Oncologists has developed two measures to assess & improve the surgical care of patients with ovarian cancer (1) description of residual disease following cytoreduction and (2) adequacy of surgical staging. Our aim was to establish baseline surgeon compliance with these two measures.

Methods
A retrospective review of patients with ovarian, fallopian tube or peritoneal cancer undergoing surgery between 7/1/2006 and 7/1/2011 for the purposes of staging and/or cytoreduction was performed at the University of Washington and Geisinger Medical Center. Operative and pathology reports were reviewed to obtain information pertaining to stage, histology, residual disease after surgery and the extent of surgical staging.

Results 
537 cases were identified; 91% with ovarian cancer. 61% of patients had at least stage IIIC disease; 15% had recurrent disease and 16% had neoadjuvant therapy. For patients with stage I-IIIB disease, 74% had full surgical staging, 10% did not have full surgical staging but documented the reason for this in the operative report; 15% did not have full surgical staging, no reason was noted. 25% of all operative reports lacked documentation of residual disease with 40% documenting no gross residual disease, 18% with residual disease<1cm and 18% had suboptimal debulking with>1cm disease remaining. There was a statistically significant increase in appropriate documentation of amount of residual disease over time (p<0.001).

Conclusions
 Our study sets benchmarks for evaluation of documentation in gynecologic oncology centers. Improved documentation and staging will allow for equivalent standards of care across institutions.

paywalled Primary fallopian tube carcinoma risk in users of postmenopausal hormone therapy in Finland

Primary fallopian tube carcinoma risk in users of postmenopausal hormone therapy in Finland: Publication year: 2012

Source:Gynecologic Oncology

Objective Primary fallopian tube carcinoma (PFTC) is a rare malignancy and only sparse data exist on its possible association with postmenopausal hormone therapy (HT). We therefore studied this association in a nationwide cohort of Finnish HT users.

Conclusions The long-term, sequential use of EPT associates with an increased risk for PFTC. In absolute terms, 4 additional cases of PFTC would be detected in 10-year follow-up of 10,000 women who have used EPT for at least 5 years

Debate Over Who Should Be Allowed to Administer Anesthesia Moves to Courts - NYTimes.com

Debate Over Who Should Be Allowed to Administer Anesthesia Moves to Courts - NYTimes.com

Family history: Still relevant in the genomics era - Cleveland Clinic

Family history: Still relevant in the genomics era

 Key points

• The family history is an underused tool for predicting the risk of disease and for personalizing preventive care.
• Barriers to the appropriate collection and use of the family history include concerns over the reliability of patient reporting, a lack of time and reimbursement, and provider knowledge gaps.
• Use of family history to inform genetic testing for hereditary cancer syndromes has been shown to improve outcomes and may reduce overall health care costs.
• Future solutions need to focus on creating time-effective ways to collect and analyze the family history, and on developing innovative methods of educating medical providers at all levels of training as to how to apply the family history in clinical practice. 

Study Downplays Risk of CT Scans - MedicineNet

Blogger's Note: cancer patients know this; the concern is 'excess' or unnecessary scans (as indicated in the article)

Study Downplays Risk of CT Scans - MedicineNet

"More often than not, patients should be getting that CT scan because the risk of the underlying cause is higher than from radiation."

"...The findings were similar -- with deaths ranging from 2 percent to 33 percent -- in the more than 15,000 who got abdominal CTs. The researchers think 23 people in the entire group would have gotten cancer due to radiation exposure."

""In the patients getting 15 or more scans, all of them had pretty significant disease, where their expected mortality was likely to occur much sooner than the chances of the radiation-induced cancer taking effect," Zondervan said. In other words: Those who were the sickest, requiring the most CT scans, would probably die before any cancer caused by the CT radiation could start hurting them."

Medscape Oncologist Compensation Report: 2012 Results - U.S.

 Blogger's Note: not broken down specifically to the sub-specializtion of gyn/oncology, patients/public perceptions of physician's compensation/expenses, income demographics, time spent with patients, physician hours of work, satisfaction with profession.....

Medscape Oncologist Compensation Report: 2012 Results

Medscape: Breast Brachytherapy Takes a Hit (or Not)

Breast Brachytherapy Takes a Hit (or Not)

Medscape: Many Clinical Trials Unable to Supply High-Quality Evidence

Many Clinical Trials Unable to Supply High-Quality Evidence

 "Given the deficit in evidence to support key decisions in clinical practice guidelines…as well as concerns about insufficient numbers of volunteers for trials…the desire to provide high-quality evidence for medical decisions must include consideration of a comprehensive redesign of the clinical trial enterprise," they continue. Currently, less than 15% of major guideline recommendations are evidence-based, they write........

Women, Minorities More Likely to Leave Surgery Career Path

Women, Minorities More Likely to Leave Surgery Career Path


May 1, 2012 — Women and minority trainees in general surgery are more likely to fall short of board certification than their peers, according to a study published yesterday in the May issue of the Journal of the American College of Surgeons (JACS).......

HON - News : For Breast Cancer Care, Radiation of Whole Breast May Be Best (breast brachytherapy)

HON - News : For Breast Cancer Care, Radiation of Whole Breast May Be Best

JAMA Breast Cancer Study: Opposing View (breast brachytherapy)

JAMA Breast Cancer Study: Opposing View

paywalled: Epigenetic Resensitization to Platinum in Ovarian Cancer (low-dose decitabine/carboplatin)

Epigenetic Resensitization to Platinum in Ovarian Cancer
  
 "Together, the results of this study suggest that low-dose decitabine altered DNA methylation of genes and cancer pathways, restoring sensitivity to carboplatin in patients with heavily pretreated ovarian cancer and resulting in a high RR and prolonged PFS."

Abstract

Preclinical studies have shown that hypomethylating agents reverse platinum resistance in ovarian cancer. In this phase II clinical trial, based upon the results of our phase I dose defining study, we tested the clinical and biologic activity of low-dose decitabine administered before carboplatin in platinum-resistant ovarian cancer patients. Among 17 patients with heavily pretreated and platinum-resistant ovarian cancer, the regimen induced a 35% objective response rate

paywalled: Requirements to Assess Feasibility of Phase 0 Trials during Major Abdominal Surgery: Variability of PARP Activity

Requirements to Assess Feasibility of Phase 0 Trials during Major Abdominal Surgery: Variability of PARP Activity

Abstract

Purpose: The aim of this study was to evaluate the feasibility of phase 0 trials in the setting of a routine surgical procedure. Logistic considerations, tissue sampling and tissue handling, and variability of a biomarker during surgery, in here PARP, were evaluated. 

Experimental Design: Patients with highly suspicious or proven diagnosis of advanced ovarian cancer, planned for debulking surgery were asked to allow sequential tumor biopsies during surgery. Biopsies were frozen immediately and PARP activity was measured subsequently.

Conclusions: Conducting phase 0 trials during surgery seems to be feasible in terms of logistic considerations. In preparation of a phase 0 trial during surgery, a feasibility study like this should be conducted to rule out major interactions of the surgical intervention with respect to the targeted biomarker.

A Comprehensive Analysis of Human Gene Expression Profiles Identifies Stromal Immunoglobulin κ C as a Compatible Prognostic Marker in Human Solid Tumors

A Comprehensive Analysis of Human Gene Expression Profiles Identifies Stromal Immunoglobulin κ C as a Compatible Prognostic Marker in Human Solid Tumors

"No association was observed in ovarian cancer."

phase 1 - A Open-Label, Multiple Ascending Dose Study of DS-3078a, an Oral TORC1/2 Kinase Inhibitor, in Subjects With Advanced Solid Tumors or Lymphomas - Full Text View - ClinicalTrials.gov

A Open-Label, Multiple Ascending Dose Study of DS-3078a, an Oral TORC1/2 Kinase Inhibitor, in Subjects With Advanced Solid Tumors or Lymphomas - Full Text View - ClinicalTrials.gov

 This study is currently recruiting participants.

Verified April 2012 by Daiichi Sankyo Inc.

First Received on April 26, 2012.   Last Updated on April 27, 2012   History of Changes

Medscape: Bevacizumab Benefits Patients With Recurrent Ovarian Cancer (bevacizumab plus carboplatin and gemcitabine followed by bevacizumab)

Bevacizumab Benefits Patients With Recurrent Ovarian Cancer

paywalled: Evaluation of prevalent and incident ovarian cancer co-morbidity : British Journal of Cancer

Access : Evaluation of prevalent and incident ovarian cancer co-morbidity : British Journal of Cancer

British Journal of Cancer , (1 May 2012) | doi:10.1038/bjc.2012.164

Evaluation of prevalent and incident ovarian cancer co-morbidity

Abstract

Background:

The peak in incidence of ovarian cancer occurs around 65 years and concurrent increasing risk by age for a number of diseases strongly influence treatment and prognosis. The aim was to explore prevalence and incidence of co-morbidity in ovarian cancer patients compared with the general population.

Methods:

The study population was patients with ovarian cancer in Sweden 1993–2006 (n=11 139) and five controls per case (n=55 687). Co-morbidity from 1987 to 2006 was obtained from the Swedish Patient Register. Prevalent data were analysed with logistic regression and incident data with Cox proportional hazards models.

Results:

Women developing ovarian cancer did not have higher overall morbidity than other women earlier than 3 months preceding cancer diagnosis. However, at time of diagnosis 11 of 13 prevalent diagnosis groups were more common among ovarian cancer patients compared with controls. The incidence of many common diagnoses was increased several years following the ovarian cancer and the most common diagnoses during the follow-up period were thromboembolism, haematologic and gastrointestinal complications.

Conclusion:

Women developing ovarian cancer do not have higher overall morbidity the years preceding cancer diagnosis. The incidence of many common diagnoses was increased several years following the ovarian cancer. It is crucial to consider time between co-morbidity and cancer diagnosis to understand and interpret associations.

Poll: Can Empathy Be Taught?

Poll: Can Empathy Be Taught?

press release: Risks of mixing drugs and herbal supplements: What doctors and patients need to know

Risks of mixing drugs and herbal supplements: What doctors and patients need to know

Next-generation 'epigenetic' cancer pill shown to be safe in phase I trial (CHR-3996)

Next-generation 'epigenetic' cancer pill shown to be safe in phase I trial

 " CHR-3996 was tested in 39 patients with a range of advanced cancers."

BMJ » Blog Archive » Chris Williams: When will we learn HOW to deliver healthcare?

 BMJ » Blog Archive » Chris Williams: When will we learn HOW to deliver healthcare?

Chris Williams is a medical student at the University of Liverpool, currently intercalating at the Liverpool School of Tropical Medicine for an MSc in Humanitarian studies.

paywalled: Conveying empathy to hospice family caregivers: Team responses to caregiver empathic communication

Conveying empathy to hospice family caregivers: Team responses to caregiver empathic communication: Publication year: 2012

Source: Patient Education and Counseling

Objective The goal of this study was to explore empathic communication opportunities presented by family caregivers and responses from interdisciplinary hospice team members.

Methods Empathic opportunities and hospice team responses were analyzed from bi-weekly web-based videoconferences between family caregivers and hospice teams. The authors coded the data using the Empathic Communication Coding System (ECCS) and identified themes within and among the coded data.

Results Data analysis identified 270 empathic opportunity-team response sequences. Caregivers expressed statements of emotion and decline most frequently. Two-thirds of the hospice team responses were implicit acknowledgments of caregiver statements and only one-third of the team responses were explicit recognitions of caregiver empathic opportunities.

Conclusion Although hospice team members frequently express emotional concerns with family caregivers during one-on-one visits, there is a need for more empathic communication during team meetings that involve caregivers.

Practice implications Hospice clinicians should devote more time to discussing emotional issues with patients and their families to enhance patient-centered hospice care. Further consideration should be given to training clinicians to empathize with patients and family caregivers.

press release: New surgical technique for removing inoperable tumors of the abdomen

New surgical technique for removing inoperable tumors of the abdomen

New surgical technique for removing inoperable tumors of the abdomen

Abdominal tumors involving both roots of the celiac and superior mesenteric artery (SMA) are deemed unresectable by conventional surgical methods, as removal would cause necrosis of the organs that are supplied by those blood vessels.

A case report published in the journal American Journal of Transplantation presents a novel surgical technique that enables surgeons to remove tumors that are unresectable by the usual surgical techniques.

Diamond Pet Foods Expands Voluntary Recall to Include Diamond Puppy Formula due to Possible Salmonella Contamination

Diamond Pet Foods Expands Voluntary Recall to Include Diamond Puppy Formula due to Possible Salmonella Contamination:

Diamond Pet Foods is expanding a voluntary recall to include Diamond Puppy Formula dry dog food. The company took this precautionary measure because sampling revealed Salmonella in the product.

Ovarian Cancer National Alliance Submits Comments to Government Regarding Ovarian Cancer Screening

Ovarian Cancer National Alliance Submits Comments to Government Regarding Ovarian Cancer Screening:

The Ovarian Cancer National Alliance submitted the following comments in response to the United States Preventive Service Task Force request for comments on draft recommendations for ovarian cancer screening.

Comments to USPSTF re:

Draft Reaffirmation Recommendation Statement

Screening for Ovarian Cancer: U.S. Preventive Services Task Force Reaffirmation Recommendation Statement

As a patient advocacy organization dedicated to promoting the interests of women with ovarian cancer, the Ovarian Cancer National Alliance is pleased to provide comments on the Draft Screening Statement for Ovarian Cancer.
The United States Preventive Services Task Force is to be commended for reviewing the recent scientific publications regarding ovarian cancer screening. As the Task Force correctly noted, the latest studies confirm that the current blood and imaging tests are not useful for population based screening.
However, the Recommendation Statement does not specify that these tools are valid as part of the diagnostic protocol for women suspected of having ovarian cancer, due in large part to the presence of symptoms.
Further, the Task Force did not appear to use the results of studies that indicate more favorable results of using the CA-125 in tailored ways. For example, a study presented at the 2010 American Society of Clinical Oncology Annual Meeting had more than 3,000 post-menopausal women stratified into high, medium and low risk categories based on an algorithm. The women, based on risk, then had different follow up procedures. The practice followed in this study had a low false-positive rate.
While we are by no means arguing that the CA-125 and/or transvaginal ultrasound be recommended as appropriate screening tools, we urge the Task Force to consider all available information when making its recommendations.
We also request that the recommendation include language regarding the symptoms of ovarian cancer (bloating, difficulty eating/feeling full quickly, urinary frequency or urgency, abdominal pain). We encourage the Task Force to also note that if women have symptoms of the disease these screening recommendations do not apply. We suggest: These recommendations apply only to asymptomatic women at average risk (or instead of “at average risk”, “without any hereditary or family history that would put them at an elevated risk”.)
We thank the Committee for noting that this recommendation does not apply to high risk women, including those with a known genetic mutation that puts them at an increased risk of developing ovarian cancer.
About Ovarian Cancer
According to the American Cancer Society, approximately 21,000 American women are diagnosed with ovarian cancer each year, and approximately 15,000 women die from the disease annually. Ovarian cancer is the deadliest gynecologic cancer and the fifth leading cause of cancer death among women in America. Currently, more than half of the women diagnosed with ovarian cancer die within five years.
About the Ovarian Cancer National Alliance
The Ovarian Cancer National Alliance is a survivor-led national umbrella organization with state and local groups representing grassroots activists, women’s health advocates and health care professionals. The Ovarian Cancer National Alliance submits this testimony as a patient advocacy group dedicated to promoting the interests of women with ovarian cancer.

NIH grants $10.5 Million for Genome Explorations -The Burrill Report

NIH grants $10.5 Million for Genome Explorations -The Burrill Report:

The National Human Genome Research Institute, part of the National Institutes of Health, is awarding $10.5 million in ten grants to help researchers identify millions of genomic elements that play a role in determining what genes are expressed and at what levels in different cells. The multi-year grants are part of the Encyclopedia of DNA Elements project, or ENCODE, set up to provide scientists with a comprehensive catalog of functional genomic elements. The project's goal is to help explain the role that the genome plays in health and disease.

paywalled: Mucin 16 (cancer antigen 125) expression in human tissues and cell lines and correlation with clinical outcome in adenocarcinomas of the pancreas, esophagus, stomach, and colon

Mucin 16 (cancer antigen 125) expression in human... [Hum Pathol. 2012] - PubMed - NCBI

Hum Pathol. 2012 Apr 26

Mucin 16 (cancer antigen 125) expression in human tissues and cell lines and correlation with clinical outcome in adenocarcinomas of the pancreas, esophagus, stomach, and colon

Abstract

Mucin 16 (cancer antigen 125) is a cell surface glycoprotein that plays a role in promoting cancer cell growth in ovarian cancer. The aims of this study were to examine mucin 16 expression in a large number of digestive tract adenocarcinomas and precursors and to determine whether mucin 16 up-regulation is correlated with patient outcome.

Tissue microarrays were constructed using surgical resection tissues and included pancreatic (115 normal, 29 precursors, 200 pancreatic ductal adenocarcinomas), esophageal (86 normal, 104 precursors, 95 esophageal adenocarcinomas, 35 lymph node metastases), gastric (211 normal, 8 precursors, 119 gastric adenocarcinomas, 62 lymph node metastases), and colorectal (34 normal, 17 precursors, 39 colorectal adenocarcinomas) tissues. Mucin 16 was detected in 81.5%, 69.9%, 41.2%, and 64.1% of the pancreatic ductal adenocarcinomas, esophageal adenocarcinomas, gastric adenocarcinomas, and colorectal adenocarcinomas, respectively. Mucin 16 was seen in a subset of the precursors. On multivariate analysis, moderate/diffuse mucin 16 in pancreatic ductal adenocarcinomas was strongly associated with poor survival (P < .001), independent of other prognosis predictors. A similar trend was observed for esophageal adenocarcinomas (P = .160) and gastric adenocarcinomas (P = .080). Focal mucin 16 in colorectal adenocarcinomas was significantly correlated (P = .044) with a better patient outcome, when compared with mucin 16-negative cases. Using Western blot analysis, we found mucin 16 expression in 3 of 6 pancreatic ductal adenocarcinoma and 1 of 2 esophageal adenocarcinoma cell lines.

We conclude that most of the digestive tract adenocarcinomas and a subset of their precursors express mucin 16. Mucin 16 expression is an independent predictor of poor outcome in pancreatic ductal adenocarcinomas and potentially in esophageal adenocarcinomas and gastric adenocarcinomas. We propose that mucin 16 may function as a prognostic marker and therapeutic target in the future.

paywalled: Prevalence of mismatch repair-deficient crypt foci in Lynch syndrome: a pathological study : The Lancet Oncology

Prevalence of mismatch repair-deficient crypt foci in Lynch syndrome: a pathological study : The Lancet Oncology

Methods
"Resections done for small and large bowel cancer between January, 2002, and January, 2011, were retrieved. We systematically analysed non-tumorous mucosa from carriers of a Lynch syndrome mutation (set 1: ten patients) and control patients without Lynch syndrome (set 1: nine patients) for MMR protein expression (MLH1, MSH2, and EPCAM) with immunohistochemistry.....

May 1st (open access) Commentary including link to original paper: Lynch syndrome: new tales from the crypt : The Lancet Oncology

Blogger's Note: commentary focus is primarily on colorectal cancer:

Lynch syndrome: new tales from the crypt : The Lancet Oncology

"...Unfortunately, these lesions are too small and subtle to be relied upon clinically to suggest a diagnosis of Lynch syndrome. Importantly, the investigators acknowledge that, although they noted these lesions occurred frequently, most patients with Lynch syndrome will develop zero to two cancers, and typically only a few adenomatous polyps, through their lifetimes.5 Small bowel cancers occur in no more than 1—4% of patients with Lynch syndrome,6 yet that organ has one MMR-deficient crypt per 2 cm2 of mucosa. Obviously, most of these lesions do not develop into cancer. So, what happens to them?....."

"...The missing link in this work is the contrast between the large number of MMR-deficient crypts and the relatively small number of clinically relevant neoplasms in this disease. That said, this work is highly novel, underscores the differences between Lynch syndrome and sporadic colorectal cancers, and raises a fresh group of important questions to be addressed."

Original paper - link/reference:

Kloor M, Huth C, Viogt AY, et al. Prevalence of mismatch repair-deficient crypt foci in Lynch syndrome: a pathological study. Lancet Oncol 201210.1016/S1470-2045(12)70109-2. published online May 1. 

UK media: 54% doctors support denying treatment to smokers and the obese until they quit or lose weight

54% doctors support denying treatment to smokers and the obese until they quit or lose weight

Ovarian Cancer and Us posts viewed per geographic locations: top 10 (April)

Blogger's Note: it's always interesting to see the demographic variations over time #1. United States

#2. Russia

#3. France

#4. Germany

#5. United Kingdom

#6. Canada

#7. China

#8. India

#9. Bulgaria

#10. Ireland

Ovarian Cancer and Us blog posts: top 10 viewed posts this month (April)

Top 10 most viewed posts this month (April):

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#2. Rivkin Center (Seattle) awards grant for cognitive...

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#5. PLoS ONE: Effect of Angiogenesis Inhibitor (Avasti...

#6. Medscape: Providers to Test Power of Apology in Ma...

#7. abstract: Low-Stage Ovarian Clear Cell Carcinoma: ...

#8. paywalled: Systematic review of progesterone use b...

#9. Malinda P. TEEL Obituary: View Malinda TEEL's Obit...

#10. Correspondence: Neoadjuvant Chemotherapy (ovarian ...

Ovarian Cancer and Us blog posts: top 10 most view in past 24hrs

Top 10 most viewed in past 24 hrs:

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financial news UK: Horizon lines up $multi-million...

(another) commentary: Endometriosis and ovarian ca...

EvidenceUpdates: Short-term effects of daily aspir...

paywalled: PET/CT scanning guided intensity-modula...

paywalled: Intrapleural paclitaxel for malignant p...

Endometriosis and ovarian cancer – Authors' reply ...

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paywalled: Is comprehensive surgical staging neede...

Journal of Experimental & Clinical Cancer Research...

Defining the Role of PET-CT in Staging Early Breast Cancer

Defining the Role of PET-CT in Staging Early Breast Cancer:

 Abstract
Introduction. Currently, there is a lack of data on the role of combined positron emission tomography–computed tomography (PET–CT) in the staging of early invasive primary breast cancer. We therefore evaluated the role of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG)-PET–CT in this patient population.
Methods. We prospectively recruited 70 consecutive patients (69 women, one man; mean age, 61.9 ± 8.1 years) with early primary breast cancer for staging with ¹⁸F-FDG-PET–CT. All PET–CT images were interpreted by two readers (independently of each other). A third reader adjudicated any discrepancies. All readers had ≥5 years of specific experience. Ethics board approval and informed consent were obtained.
Results. The mean clinical follow-up was 22.7 ± 12.6 months. The primary tumor was identified with PET–CT in 64 of 70 patients. Of the unidentified lesions, surgical pathology revealed two intraductal carcinomas, one invasive tubular carcinoma, and three invasive lobular carcinomas. Undiagnosed multifocal breast disease was shown in seven of 70 patients. PET–CT identified avid axillary lymph nodes in 19 of 70 patients, compared with 24 of 70 confirmed during surgery. There were four patients who were axillary node positive on PET but had no axillary disease at surgery.
Five patients were reported with avid metastases. Two of those patients were treated for metastatic disease (nodal, lung, and liver in one and bone metastases in the other) following further imaging and clinical assessment. In the other three patients, lesions (lung, n = 1; pleural, n = 1; paratrachael node, n = 1) were subsequently diagnosed as benign lesions.
Conclusion. Integrated ¹⁸F-FDG-PET–CT may have a role in staging patients presenting with early breast cancer.

The Incidence of Ovarian Cancer In Transgendered Individuals | The LGBT Cancer Project -- Out With Cancer

The Incidence of Ovarian Cancer In Transgendered Individuals | The LGBT Cancer Project -- Out With Cancer

".... The incidence of ovarian cancer in LGBT transgendered individuals must be closely monitored and aggressively treated if the cancer is detected in that population. Transgendered individuals who have undergone an operation changing their gender from their original sexual orientation of female to male are facing the additional obstacle of being diagnosed with ovarian....."

Amazon.com: Memoir of a Debulked Woman: Enduring Ovarian Cancer (9780393073256): Susan Gubar: Books

Amazon.com: Memoir of a Debulked Woman: Enduring Ovarian Cancer (9780393073256): Susan Gubar: Books

 Book Description

Publication Date: April 30, 2012 | ISBN-10: 0393073254 | ISBN-13: 978-0393073256 | Edition: 1

In this moving memoir, a renowned feminist scholar explores the physical and psychological ordeal of living with ovarian cancer.

Diagnosed with ovarian cancer in 2008, Susan Gubar underwent radical debulking surgery, an attempt to excise the cancer by removing part or all of many organs in the lower abdomen. Her memoir mines the deepest levels of anguish and devotion as she struggles to come to terms with her body’s betrayal and the frightful protocols of contemporary medicine. She finds solace in the abiding love of her husband, children, and friends while she searches for understanding in works of literature, visual art, and the testimonies of others who suffer with various forms of cancer.
Ovarian cancer remains an incurable disease for most of those diagnosed, even those lucky enough to find caring and skilled physicians. Memoir of a Debulked Woman is both a polemic against the ineffectual and injurious medical responses to which thousands of women are subjected and a meditation on the gifts of companionship, art, and literature that sustain people in need.

book reviews: New Perspectives From Cancer Patients - NYTimes.com

New Perspectives From Cancer Patients - NYTimes.com

".......That is Susan Gubar’s staggering, searing “Memoir of a Debulked Woman.” Ms. Gubar may not be a health professional, but as a noted feminist critic (she is an author of the influential 1970s classic “Madwoman in the Attic”), she has certainly spent a career immersed in the meaning and functions of the female body. In one of those inexplicably savage medical ironies, she was felled in her early 60s by the worst of the “female” diseases: ovarian cancer. As is common, it had spread throughout her abdomen by the time of diagnosis.

Cases like Ms. Gubar’s are usually first treated with the surgical removal of as much cancer as possible, along with all dispensable abdominal organs that are affected or at risk. This is the “debulking” of her title, and it is about as close to evisceration as civilians can experience. It became her focal metaphor for the experience of sudden dire illness, as all other interests drop away save “an overriding and offensive obsession with one’s own physical vulnerability.” On a less literary note, the procedure winds up bringing her almost more physical grief than the cancer itself.

Ms. Gubar moves back and forth between poet and patient, with the occasional sidestep into academic mode as she reviews writing by women affected with similar illness. It is a difficult and potentially cringe-making project.

But even the most skeptical and finicky reader — even the healthy reader, even the healthy male reader — will not put this book down. Some of its appeal comes from Ms. Gubar’s skill with textual analysis, and some from various appealing verbal shenanigans (has anyone else found and pondered the “mother” in chemotherapy, for instance?). Most gripping, though, is her frank, courageous account of life with a horrific postoperative infection in her large intestine that came to involve the buttock area....

video/text: Leftover ovarian tissue after surgery can cause serious complications | Medical Alert-media

Blogger's Note: short video; not specific to ovarian cancer but note absence of menopausal symptoms

Leftover ovarian tissue after surgery can cause serious complications | Medical Alert - WBAL Home

paywalled: Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women's Health Initiative randomised placebo-controlled trial : The Lancet Oncology

Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women's Health Initiative randomised placebo-controlled trial : The Lancet Oncology

 Interpretation

Our findings provide reassurance for women with hysterectomy seeking relief of climacteric symptoms in terms of the effects of oestrogen use for about 5 years on breast cancer incidence and mortality. However, our data do not support use of oestrogen for breast cancer risk reduction because any noted benefit probably does not apply to populations at increased risk of such cancer.

Lancet: [Cancer and Society] "A Monster Calls" (children's book)

[Cancer and Society] A Monster Calls:

The word “cancer” is not used once in A Monster Calls, but its influence is felt even before the first page. The story was conceived by children's author Siobhan Dowd, who died from breast cancer before being able to realise her vision. She did, however, leave behind the idea, the characters, and the beginning, from which Patrick Ness completed the story. The result is a harrowing and deeply engaging account of the heartbreaking effects that cancer has on the children of afflicted patients. It is by no means an easy tale to tell, but Ness's work has clearly resonated with young readers, whose votes awarded A Monster Calls the prestigious Red House Children's Book Award 2012.

Endometriosis and ovarian cancer – Authors' reply : The Lancet Oncology

Endometriosis and ovarian cancer – Authors' reply : The Lancet Oncology

"Both Vercellini and colleagues and Guo and colleagues raise concerns about screening, with which we agree. Our findings should not suggest to clinicians or the public that screening for ovarian cancer should be implemented for women with endometriosis. Rather, we hope that our work stimulates further research that can refine risk groups related to endometriosis on the basis of anatomical site, epidemiological risk factors, or molecular features. Vercellini and colleagues raise an interesting point about atypical endometriosis, but this diagnosis is not standardised or commonly used and can not be addressed in epidemiological studies.

..................Regardless, the attenuated associations remain statistically significant.

(another) commentary: Endometriosis and ovarian cancer : The Lancet Oncology

Endometriosis and ovarian cancer : The Lancet Oncology

correspondence: Endometriosis and ovarian cancer : The Lancet Oncology

Endometriosis and ovarian cancer : The Lancet Oncology

Commentary: Oestrogen and breast cancer: results from the WHI trial : The Lancet Oncology

Oestrogen and breast cancer: results from the WHI trial : The Lancet Oncology

"In The Lancet Oncology, the Women's Health Initiative (WHI) investigators report1 that receipt of conjugated equine oestrogen for a median of 5·9 years reduced the risk of invasive breast cancer by 23% compared with placebo (151 cases in 5310 women who received oestrogen vs 199 cases in 5429 controls; p=0·02). Women who did develop breast cancer after receipt of oestrogen had significantly reduced breast cancer-specific mortality (six deaths in the oestrogen group vs 16 deaths in controls; p=0·03) and all-cause mortality (30 deaths vs 50 deaths; p=0·04). This preventive effect occurred at all ages and continued beyond the period of oestrogen use, a carryover effect also noted in prevention trials of tamoxifen.2 ....Although modest, the WHI results are significant and raise important questions about their disparity with many observational studies and the mechanism of reported benefit with oestrogen therapy......

Chasing the greenback and the decline in scientific rigour : The Lancet Oncology

Chasing the greenback and the decline in scientific rigour : The Lancet Oncology

2012 Clinicopathological Features and Management of Cancers in Lynch Syndrome (easy to read)

Blogger's Note: nice, easy to read paper

Clinicopathological Features and Management of Cancers in Lynch Syndrome

Abstract
Lynch syndrome (LS) is characterized by an autosomal dominant inheritance of the early onset of colorectal cancer (CRC) and endometrial cancer, as well as increased risk for several other cancers including gastric, urinary tract, ovarian, small bowel, biliary tract, and brain tumors. The syndrome is due to a mutation in one of the four DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, or PMS2. The majority of LS patients and families can now be identified, and the underlying mutation detected using genetic diagnostics. Regular surveillance for CRC and endometrial cancer has proved beneficial for mutation carriers. However, screening for other tumors is also recommended even though experiences in the screening of these tumors is limited. Prophylactic colectomy, prophylactic hysterectomy, and bilateral salpingo-oophorectomy may be reasonable options for selected patients with LS. This paper describes the features and management of LS.

1. Introduction (The syndrome is due to a mutation in one of the four DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, or PMS2.)

2. Genetic Characteristics of Lynch Syndrome
3. Identification of Lynch Syndrome
4. Tumor Spectrum of Lynch Syndrome
5. Colorectal Cancer (>MLH1 and MSH2; <MSH6;)
6. Endometrial Cancer (MSH6 mutations are at higher risk)
7. Gastric Cancer (seems to be not different between different mutations)
8. Uroepithelial and Kidney Cancers (predominately MSH2)
9. Other Tumors

• 9.1. Ovarian Cancer        Ovarian cancer has been shown to occur in excess in LS. Two Finnish studies [5, 45] have shown a lifetime risk for ovarian cancer in LS ranging between 9% and 12% compared to 1.3% in the general population. Recently, Watson et al. [6] reported a lifetime risk of 7% in a large series from four LS research centers. They also found that MSH2 family members had nearly twice the incidence rate observed in MLH1 family members, and the highest risk period for ovarian cancer was from age 40 to 55 years. Ovarian cancer in LS seems to have a better prognosis than that in the general population or in BRCA1/2 mutation carriers [59]. Information currently available is too limited to assess whether screening for ovarian cancer in LS mutation carriers has any advantages.

• 9.2. Carcinomas of the Biliary Tract and Pancreas (duodenum/jejunum)
• 9.3. Brain Tumors (higher in MSH2 than in MLH1)

10. Conclusions

 (ovarian) reference: 
59.  E. M. Grindedal, L. Renkonen-Sinisalo, H. Vasen et al., “Survival in women with MMR mutations and ovarian cancer: a multicentre study in Lynch syndrome kindreds,” Journal of Medical Genetics, vol. 47, no. 2, pp. 99–102, 2010. View at Publisher · View at Google Scholar · View at Scopus

$8.68M in early researcher awards announced in Ontario | Laboratory Product News

$8.68M in early researcher awards announced in Ontario | Laboratory Product News

 UNIVERSITY OF WATERLOO

Project title: Rational design of novel surface active compound for improving non-viral DNA transfection efficiencies. Lead researcher: Dr Shawn Wettig. Gene therapy uses DNA to treat disease. While it shows great promise, creating a delivery system to deliver DNA to specific areas in the body is a challenge. Dr Wettig is working to develop delivery systems, starting with one for ovarian cancer, the leading cause of death among gynecological cancers.

paywalled: Hematological Toxicity After Robotic Stereotactic Body Radiosurgery for Treatment of Metastatic Gynecologic Malignancies

Hematological Toxicity After Robotic Stereotactic Body Radiosurgery for Treatment of Metastatic Gynecologic Malignancies

published online 30 April 2012.

Corrected Proof

• Abstract

Purpose

To evaluate hematological toxicity after robotic stereotactic body radiosurgery (SBRT) for treatment of women with metastatic abdominopelvic gynecologic malignancies.

Methods and Materials

A total of 61 women with stage IV gynecologic malignancies treated with abdominopelvic SBRT were analyzed after ablative radiation (2400 cGy/3 divided consecutive daily doses) delivered by a robotic-armed Cyberknife SBRT system. Abdominopelvic bone marrow was identified using computed tomography-guided contouring. Fatigue and hematologic toxicities were graded by retrospective assignment of common toxicity criteria for adverse events (version 4.0). Bone marrow volume receiving 1000 cGy (V10) was tested for association with post-therapy (median 32 days [25%-75% quartile, 28-45 days]) white- or red-cell counts, hemoglobin levels, and platelet counts as marrow toxicity surrogates.

Results

In all, 61 women undergoing abdominopelvic SBRT had a median bone marrow V10 of 2% (25%-75% quartile: 0%-8%). Fifty-seven (93%) of 61 women had received at least 1 pre-SBRT marrow-taxing chemotherapy regimen for metastatic disease. Bone marrow V10 did not associate with hematological adverse events. In all, 15 grade 2 (25%) and 2 grade 3 (3%) fatigue symptoms were self-reported among the 61 women within the first 10 days post-therapy, with fatigue resolved spontaneously in all 17 women by 30 days post-therapy. Neutropenia was not observed. Three (5%) women had a grade 1 drop in hemoglobin level to <10.0 g/dL. Single grade 1, 2, and 3 thrombocytopenias were documented in 3 women.

Conclusions

Abdominopelvic SBRT provided ablative radiation dose to cancer targets without increased bone marrow toxicity. Abdominopelvic SBRT for metastatic gynecologic malignancies warrants further study.

Journal of Experimental & Clinical Cancer Research | Abstract | Circulating microRNAs in cancer: origin, function and application

Journal of Experimental & Clinical Cancer Research | Abstract | Circulating microRNAs in cancer: origin, function and application

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

  Review

Circulating microRNAs in cancer: origin, function and application

Journal of Experimental & Clinical Cancer Research 2012, 31:38 doi:10.1186/1756-9966-31-38


Published: 30 April 2012

Abstract (provisional)

MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression at the posttranscriptional level. The dysregulation of miRNAs has been linked to a series of diseases, including various types of cancer. Since their discovery in the circulation of cancer patients, there has been a steady increase in the study of circulating miRNAs as stable, non-invasive biomarkers. However, the origin and function of circulating miRNAs has not been systematically elucidated. In this review, we summarize the discovery of circulating miRNAs and their potential as biomarkers. We further emphasize their possible origin and function. Finally, we discuss the application and existing questions surrounding circulating miRNAs in cancer diagnostics. Although several challenges remain to be concerned, circulating miRNAs could be useful, non-invasive biomarkers for cancer diagnosis.

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

Biomarkers in the circulation

"Circulating biomarkers undoubtedly play an increasingly significant role in clinicalapplications such as disease diagnostics, monitoring therapeutic effect and predicting recurrence in cancer patients. The currently used fluid-based biomarkers are primarily proteins, such as alpha-fetoprotein (AFP) [8], chromogranin A (CgA) [9], nuclear matrix
protein 22 (NMP 22) [10], carbohydrate antigen 125 (CA 125) [11]; enzymes, such as prostate specific antigen (PSA) [12]; and human chorionic gonadotropin (hCG) [13]. While these biomarkers provide an opportunity to analyze tumors comprehensively in an invasive
way, low sensitivity and specificity limit their clinical application. For example, serum levels of AFP are often elevated in hepatocellular carcinoma (HCC); however, this is also the case in germ cell tumors, gastric, biliary and pancreatic cancers.......

 reference/cited (google):

23. Resnick KE, Alder H, Hagan JP, Richardson DL, Croce CM, Cohn DE: The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform. Gynecol Oncol 2009, 112:55–59.