media : Weak chemo treatments a 'national' problem: Ontario health minister

media

"A gap in the oversight of chemotherapy drug preparations that allowed watered-down cancer treatments to go undetected for a year is not unique to the province, Health Minister Deb Matthews says.
"This is not confined to Ontario. It's pretty clear that this is a national and, indeed, an international problem," Matthews said Wednesday........

Clinical Trial of a Supportive Care Team for Patients With Advanced Cancer

Abstract

Context

Encouraging use of hospice and minimizing the use of cure-oriented aggressive interventions that detract from quality of life in the last month of life are specific targets for improvement in cancer care.

Objectives

To evaluate the effect of an interdisciplinary cancer support team (CST) on quality of care and quality of life in patients with advanced cancers.

Methods

A nonrandomized clinical trial was conducted, comparing outcomes before and after the integration of an interdisciplinary CST in routine care of adults with Stage III or IV lung, gastrointestinal, or gynecologic cancer. In the control arm, patients (n = 332) received usual care; after the initiation of the intervention arm, eligible patients (n = 278) received the CST intervention. The intervention consisted of individualized care coordination, symptom management, education, psychosocial and spiritual supports, and advance care planning throughout the 15-month study period. Quality of end-of-life care was measured through an “aggressiveness of care” index. Health-related quality of life (HRQOL) was measured with the Functional Assessment of Cancer Therapy-General.

Results

There were no statistically significant differences between groups on specific indicators of quality of care. Surviving subjects with higher survival expectancy (who also reported better baseline quality of life) in the intervention arm had the greatest improvement in HRQOL scores, compared with the other three groupings of survival expectancy by treatment group (high vs. low by intervention vs. control) (P = 0.044).

Conclusion

Individually tailored supportive services from an interdisciplinary team are associated with improved HRQOL in some patients. This has implications for the potential benefits that can be accrued from providing intensive support to all patients, even those who may appear to be at less risk for distress. There also are important methodological considerations in using aggressiveness of care indices as a measure of quality of care.

paywalled: Letter: Integrated research efforts are needed to better understand how to reduce the proportion of patients with cancer who are diagnosed as emergencies

requires paid subscription

Genome-wide analysis of three-way interplay among gene expression, cancer cell invasion and anti-cancer compound sensitivity

 Blogger's Note: posted today is 2nd research article regarding the specifics of  Erlotinib and ovarian cancer (Hirte/McMaster)

open access

"Erlotinib was shown to be more sensitive in the doxorubicin-resistant human breast cancer cell lines and paclitaxel-resistant human ovarian cancer cell lines [51] and the sensitivity was positively correlated with EGFR expression. More references were provided in Additional file 1,
Supplementary information Text II."

Endometriosis and other efforts for women′s health

Endometriosis and other efforts for women′s health

Editors Message

You have free access to this content

At the end of the month of May, colleagues in the Nordic countries and some others from further afield gather for the fourth time to discuss endometriosis, a disease that may for many women spoil years of what should be the best time of life. We mark the Nordic congress in Turku by four contributions on endometriosis this month. On pp. 491–5 we have a Commentary from Christine Steenberg and colleagues in Oslo, Norway, on a problem that is receiving fresh attention, namely the debut of endometriosis at a young age and how this should be dealt with. The diagnosis is for a start not straightforward, because symptoms are not specific. Severe primary dysmenorrhea should be taken seriously, though, as should an additional family history of endometriosis [1]. Both have often been ignored in the past. The young girl who cannot go to school or work because of menstrual pain was given a couple of pain killers and told to just get up and go. Parents, teachers and doctors alike may have lacked knowledge and appreciation of a “hidden” disease. How views are changing in this respect is well covered in the Commentary, followed by a good discussion of what to do. Note the two tables in this article. Treatment options may be better than many realize. Early commencement of oral contraceptives must be regarded as a mainstay start-up therapy, even if research is needed to elucidate short- and long-term effects on the development of endometriosis [2]. We as gynecologists have much to contribute here to women′s health by alerting professionals and society to early endometriosis symptoms. In this we are helped by the patient associations who are our allies in this and will also join in at the Turku congress.

The link between endometriosis and a raised risk for hormone-dependent cancers later in life, not least ovarian cancer [3, 4], is another issue of women′s health which needs to be in the professional and public domain. The article by Anna-Sofia Melin and co-workers in Stockholm, Sweden (pp. 546–54), a well known group working on epidemiologic aspects of endometriosis, has from our side at AOGS been high-lighted by a press release, because we felt that this novel case-control study based on a whole population had an important message, namely that removal of endometriotic lesions has a protective effect against ovarian cancer. This knowledge is likely to affect clinical practice and the way endometriosis surgery should be conducted. The role of hormonal treatment, including oral contraception, is as yet less clear and a complex matter that calls for much more research. This is all discussed in an excellent fashion in this article, which certainly should be worth your attention.

Diagnostic accuracy of risk of malignancy index in predicting complete tumor removal at primary debulking surgery for ovarian cancer patients

Abstract

Ovarian cancer patients in whom complete tumor removal is impossible with primary debulking surgery (PDS) may benefit from neoadjuvant chemotherapy and interval debulking surgery. However, the task of performing a pre-operative evaluation of the feasibility of PDS is difficult. We aimed to investigate whether the risk of malignancy index (RMI) was a useful marker for this evaluation. RMI and surgical outcome were investigated in 164 patients, 49 of whom had no residual tumor after PDS. The receiver operating characteristic curve showed an area under the curve of 0.72 (confidence interval: 0.64–0.80). The possibility of complete tumor removal decreased with increasing RMI and there was a tendency towards higher RMI in patients with residual tumor after PDS, but no single cut-off value of RMI produced useful clinical predictive values. In conclusion, RMI alone is not an optimal method to determine whether complete tumor removal is possible with PDS.

Patient satisfaction with hospital stay does not reflect quality of surgical care

press release

Doing the Math on Resident Work Hours - NYTimes.com

NYTimes.com
 "....Now, two years after the 16-hour mandate was established, studies on the outcomes are being published, and the results reveal one thing.
Maybe we should have thought a little harder about the arithmetic........The problem? Trying to do the same amount of work in fewer hours.....

Profile of erlotinib and its potential in the treatment of advanced ovarian carcinoma

open access

The epidermal growth-factor receptor (EGFR) is overexpressed in the majority of epithelial ovarian cancers and promotes cell proliferation, migration and invasion, and angiogenesis, as well as resistance to apoptosis. This makes EGFR an attractive therapeutic target in this disease. A number of strategies to block EGFR activity have been developed, including small-molecular-weight tyrosine kinase inhibitors such as erlotinib. Erlotinib has been evaluated as a single agent in recurrent ovarian cancer, as well as in combination with chemotherapeutic agents in the first-line and recurrent settings, and in combination with the antiangiogenic agent bevacizumab in the recurrent setting, as well as in the maintenance setting after completion of first-line chemotherapy. Unfortunately, erlotinib has shown only minimal efficacy as a single agent, and it has not enhanced the effects of chemotherapy or bevacizumab when combined with these agents. Ongoing and future studies of erlotinib and other agents blocking EGFR will need to define mechanisms resulting in resistance to such interventions, and to validate biomarkers of response to identify patients most likely to benefit from such approaches......

 

Usefulness of epithelial cell adhesion molecule expression in the algorithmic approach to Lynch syndrome identification. Musulen E, Blanco I, Carrato C, Fernandez-Figueras MT, Pineda M, Capella G, Ariza A. Source Department of Pathology, Hospital Universitari Germans Trias i Pujol, C/ Ctra de Canyet s/n, 08916 Badalona, Barcelona, Spain. emusulen@hotmail.com Abstract Lynch syndrome (LS), the most frequent form of hereditary colorectal cancer syndrome, is caused by germ-line mutations in the mismatch repair system genes. Recently, a new mechanism involving the epithelial cell adhesion molecule (EPCAM)/TACSTD1 gene has been shown to be responsible in cases with abnormal MSH2 expression. Of interest, 3' exons deletions of the EPCAM gene, which is located upstream of MSH2 in chromosome 2, are associated with MSH2 promoter hypermethylation. EPCAM protein, expressed in epithelial tissues, is encoded by the EPCAM/TACSTD1 gene. Our study's aim was to explore EPCAM expression in colorectal carcinomas of MSH2-associated LS cases to evaluate the usefulness of EPCAM protein expression in the algorithm approach to LS population screening. We included a total of 19 MSH2-negative colorectal carcinomas from 14 different patients in whom we were able to perform a complete germ-line analysis. Nine patients showed a deleterious germ-line mutation that involved the MSH2 gene in 3 instances and the EPCAM gene exon 9 in 6 instances. All patients harboring the EPCAM mutation belonged to the same family. Of the 19 colorectal carcinomas, EPCAM expression loss was seen in only 5 tumors, all of them from patients showing a germ-line EPCAM deletion. Of interest, 6 tumors from 3 different patients carrying the same germ-line EPCAM deletion showed normal EPCAM expression. In conclusion, owing to the high specificity of EPCAM protein expression to identify LS patients carrying an EPCAM deletion, we recommend adding EPCAM immunohistochemistry to the LS diagnostic algorithm in MSH2-negative colorectal carcinoma.

 Lynch syndrome (LS), the most frequent form of hereditary colorectal cancer syndrome, is caused by germ-line mutations in the mismatch repair system genes. Recently, a new mechanism involving the epithelial cell adhesion molecule (EPCAM)/TACSTD1 gene has been shown to be responsible in cases with abnormal MSH2 expression. Of interest, 3' exons deletions of the EPCAM gene, which is located upstream of MSH2 in chromosome 2, are associated with MSH2 promoter hypermethylation. EPCAM protein, expressed in epithelial tissues, is encoded by the EPCAM/TACSTD1 gene. Our study's aim was to explore EPCAM expression in colorectal carcinomas of MSH2-associated LS cases to evaluate the usefulness of EPCAM protein expression in the algorithm approach to LS population screening. We included a total of 19 MSH2-negative colorectal carcinomas from 14 different patients in whom we were able to perform a complete germ-line analysis. Nine patients showed a deleterious germ-line mutation that involved the MSH2 gene in 3 instances and the EPCAM gene exon 9 in 6 instances. All patients harboring the EPCAM mutation belonged to the same family. Of the 19 colorectal carcinomas, EPCAM expression loss was seen in only 5 tumors, all of them from patients showing a germ-line EPCAM deletion. Of interest, 6 tumors from 3 different patients carrying the same germ-line EPCAM deletion showed normal EPCAM expression. In conclusion, owing to the high specificity of EPCAM protein expression to identify LS patients carrying an EPCAM deletion, we recommend adding EPCAM immunohistochemistry to the LS diagnostic algorithm in MSH2-negative colorectal carcinoma.

Body mass index and disease-specific mortality in an 80-year-old population at the 12-year follow-up

Abstract

Purchase $31.50

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Although many investigations examined the relationship between body mass index (BMI) and mortality, little is known about the possible associations between BMI and disease-specific mortality in very elderly people. Here we evaluated this association in an 80-year-old population. In 1998, 675 residents in Japan's Fukuoka Prefecture participated. They were followed up for 12 years after the baseline examination; 37 subjects (5.5%) were lost to follow-up. The subjects were divided into six groups by their BMI values: <19.5 (most-thin), 19.5 to <21.1 (relatively thin), 21.1 to <22.5 (thin/normal), 22.5 to <23.8 (normal/overweight), 23.8 to <26.0 (relatively obese), ≥26.0 (most-obese). The most-thin group had the highest mortality from all-causes, and from respiratory disease. The normal/overweight group had the lowest overall mortality among the six BMI groups. These associations were found in the men, but not in the women. The most-obese group did not have higher mortality from all-causes or cardiovascular disease compared to the normal/overweight group. Respiratory disease-related mortality was lowest in the most-obese group. No association was found between BMI group and mortality from cancer. In conclusion, in an 80-year-old Japanese population, mortality from all-causes or respiratory disease was highest in the most-lean group (BMI <19.5), and mortality from all-causes or cardiovascular disease was lowest in the group with BMI 22.5 to <23.8.

link (no abstract)

Nurs Educ Perspect.

Assessing baccalaureate nursing students' knowledge of ovarian cancer.

Loerzel VW.

Source

University of Central Florida, Orlando, USA. victoria.loerzel@ucf.edu

PMID:

23586207

[PubMed - in process]

Preclinical Antitumor Activity of Cabazitaxel, a Semi-Synthetic Taxane Active in Taxane-Resistant Tumors

 Blogger's Note: abstract does not reference ovarian cancer (note this is a preclinical study)

Abstract

Purpose: Taxanes are important chemotherapeutic agents with proven efficacy in human cancers, but their use is limited by resistance development. We report here the preclinical characteristics of cabazitaxel (XRP6258), a semisynthetic taxane developed to overcome taxane resistance. 

Experimental Design: Cabazitaxel effects on purified tubulin and on taxane-sensitive or chemotherapy-resistant tumor cells were evaluated in vitro. Antitumor activity and pharmacokinetics of intravenously administered cabazitaxel were assessed in tumor-bearing mice. 

Results: In vitro, cabazitaxel stabilized microtubules as effectively as docetaxel, but was ten-fold more potent than docetaxel in chemotherapy-resistant tumor cells (IC₅₀ ranges: cabazitaxel, 0.013-0.414 μM; docetaxel, 0.17-4.01 μM). The active concentrations of cabazitaxel in these cell lines were achieved easily and maintained for up to 96 hours in the tumors of mice bearing MA16/C tumors treated with cabazitaxel at 40 mg/kg. Cabazitaxel exhibited antitumor efficacy in a broad spectrum of murine and human tumors (melanoma B16, colon C51, C38, HCT 116 and HT-29, mammary MA17/A and MA16/C, pancreas P03 and MIA PaCa­2, prostate DU145, lung A549 and NCI-H460, gastric N87, head and neck SR475, and kidney Caki­1). Of particular note, cabazitaxel was active in tumors poorly sensitive or innately resistant to docetaxel (Lewis lung, pancreas P02, colon HCT­8, gastric GXF­209, mammary UISO BCA­1) or with acquired docetaxel resistance (melanoma B16/TXT). 

Conclusions: Cabazitaxel is as active as docetaxel in docetaxel-sensitive tumor models but is more potent than docetaxel in tumor models with innate or acquired resistance to taxanes and other chemotherapies. These studies were the basis for subsequent clinical evaluation.

Early telomere shortening and genomic instability in tubo-ovarian preneoplastic lesions (serous)

Abstract

Purpose: Genetic instability plays an important role in ovarian carcinogenesis. We investigated the level of telomere shortening and genomic instability in early and pre-invasive stages of ovarian cancer, serous tubal intraepithelial carcinoma (STIC) and tubo-ovarian dysplasia (TOD). 51 TOD from prophylactic salpingo-oophorectomies with BRCA 1 or 2 mutation, 12 STICs, 53 tubo-ovarian high grade serous carcinoma and 36 non-cancerous controls were laser-capture microdissected from formalin-fixed paraffin-embedded sections, analyzed by comparative genomic hybridization (array CGH) and for telomere length (using quantitative real-time polymerase chain reaction based on the Cawthon's method). TOD and STICs were defined by morphological scores and immunohistochemical expressions of p53, Ki67 and γH2AX.

Phase I Study of U3-1287, a Fully Human Anti-HER3 Monoclonal Antibody, in Patients With Advanced Solid Tumors

Abstract

Purpose:Human epidermal growth factor receptor 3 (HER3) is a key dimerization partner for other HER family members, and its expression is associated with poor prognosis. This first-in-human study of U3-1287 (NCT00730470), a fully human anti-HER3 monoclonal antibody, evaluated its safety, tolerability, and pharmacokinetics (PKs) in advanced solid tumor patients. 

Experimental Design: The study was conducted in 2 parts: part 1-sequential cohorts received escalating doses (0.3-20 mg/kg) of U3-1287 every 2 weeks (q2w), starting 3 weeks after the first dose; part 2-additional patients received 9, 14, or 20 mg/kg U3-1287 q2w, based on observed tolerability and PKs from part 1. Recommended phase II dose, adverse event (AE) rates, PKs, and tumor response were determined. Results: Fifty-seven patients (part 1: 26; part 2: 31) received U3-1287. As no dose-limiting toxicities were reported, the maximum tolerated dose was not reached. The maximum administered dose was 20 mg/kg q2w. The most frequent AEs related to U3-1287 were fatigue (21.1%), diarrhea (12.3%), nausea (10.5%), decreased appetite (7.0%), and dysgeusia (5.3%). No patient developed anti-U3-1287 antibodies. In these heavily pretreated patients, stable disease was maintained ≥ 9 weeks in 19.2% in part 1 and ≥ 10 weeks in 25.8% in part 2. 

Conclusions: U3-1287 treatment was well tolerated, and some evidence of disease stabilization was observed. PK data support U3-1287 dosing of 9 to 20 mg/kg every 2 to 3 weeks. Combination studies of U3-1287 are ongoing.

CBC: Watch Full Episode - Rate My Hospital - the fifth estate

Watch Full Episode - Rate My Hospital - the fifth estate

From the beginning of our lives to the end, Canadians place great trust in our hospitals - and a great deal of money. Canada's hospital budget is a staggering $56 billion a year, most of it spent on acute care hospitals. But what do we really know about the quality of care we get for all that money?

Serum HE4 vs CA-125 for Ovarian Cancer Diagnosis

Medscape

Treatment of malignant ascites with a combination of chemotherapy drugs and intraperitoneal perfusion of verapamil

Abstract

“Information is Information”: A public perspective on incidental findings in clinical and research genome-based testing

Abstract

Background

The potential for genomic incidental findings is increasing with the use of genome-based testing. At the same time approaches to clinical decision making are shifting to shared decision-making models involving both the healthcare community and the public. The public's voice has been nearly absent in discussions on managing incidental findings.

Methods

We conducted 9 focus groups and 9 interviews (N=63) with a broad cross-section of lay public groups to elucidate public viewpoints on incidental findings that could occur as a result of genome-based testing in clinical and research situations. Data were analyzed using qualitative content analysis.

Results

Participants wanted incidental findings disclosed to them whether or not these were clinical or research findings. Participants used different terms to define and describe incidental findings; they wanted to know that incidental findings are possible and be given a choice to learn about them. Personal utility was an important reason for disclosure, and participants believed that managing information is a shared responsibility between professionals and themselves.

Conclusion

Broad public input is needed in order to understand and incorporate the public's perspective on management of incidental findings as disclosure guidelines and policies are developed in clinical and research settings.

An International Study on New DNA Variants that Increases the Risk for Breast,Prostate and Ovarian Cancers

press release

".....These results show the enormous complexity of cancer. One example would be hereditary breast cancer, which correlates in most cases with mutations in the BRCA1 and BRCA2 genes. These tumours, however, could be explained by the accumulation of multiple mutations in genes that when appearing alone slightly increase the risk of developing cancer. “These genes would explain why many families have these types of hereditary cancers without the presence of mutations in the BRCA genes,” clarifies Benítez.....

Supreme Court gene patent decision could affect every patient

media

Proteomic analyses of serous and endometrioid epithelial ovarian cancers: cases studies :molecular insights of a possible histological etiology of serous ovarian cancer - Longuespée - PROTEOMICS - Clinical Applications - Wiley Online Library

Abstract

Purpose

Epithelial ovarian carcinogenesis may occur de novo on the surface of ovarian mesothelial epithelial cells or from cells originating in other organs. Foreign müllerian cell intrusion into the ovarian environment has been hypothesized to explain the latter scenario. In this study, MALDI mass spectrometry (MS) profiling technology was used to provide molecular insights regarding these potentially different mechanisms

Experimental design

Using MALDI MS profiling, the molecular disease signatures were established in their molecular context. MALDI MS profiling was used on serous and endometrioid cancer biopsies to investigate cases of epithelial ovarian cancer. We then applied bioinformatic methods and identification strategies on the LC-MS/MS analyses of extracts from digested FFPE tissues. Extracts from selected regions (i.e., serous ovarian adenocarcinoma, fallopian tube serous adenocarcinoma, endometrioid ovarian cancer, benign endometrium and benign ovarian tissues) were performed, and peptide digests were subjected to LC-MS/MS analysis.

Results

Comparison of the proteins identified from benign endometrium or three ovarian cancer types (i.e., serous ovarian adenocarcinoma, endometrioid ovarian adenocarcinoma and serous fallopian tube adenocarcinoma) provided new evidence of a possible correlation between the fallopian tubes and serous ovarian adenocarcinoma. Here, we propose a workflow consisting of the comparison of multiple tissues in their anatomical context in an individual patient.

Conclusion and clinical relevance

The present study provides new insights into the molecular similarities between these two tissues and an assessment of highly specific markers for an individualized patient diagnosis and care.

Colleen's Dream | Supporting Ovarian Cancer ResearchColleen's Dream | Supporting Ovarian Cancer Research

Colleen's Dream

Angiosarcoma originating from an ovarian mature teratoma, a rare disease with complex treatment modalities

open access

Highlights

► Ovarian angiosarcomas are rare and clinically aggressive neoplasms.
► In addition to surgery, taxol is the most studied adjuvant chemotherapy. ► Anti-angiogenic therapies can be considered as an option.

Hospitals Profit From Surgical Errors, Study Finds - NYTimes.com

NYTimes.com

"...... Dr. Barry Rosenberg, an author and a managing director of Boston Consulting, said the study came about because his firm was working with Texas Health Resources to find ways to reduce its hospitals’ surgical complication rates, which, at 5.3 percent, were in line with those reported by similar hospitals. Part of that work involved analyzing the costs, and he said the team was stunned to realize that lowering the complication rates would actually cost the hospital money.

“We said, ‘Whoa, we’re working our tails off trying to lower complications, and the prize we’re going to get is a reduction in profits,’ ” Dr. Rosenberg said in an interview.......