UPDATE: New Website Selling Miracle Mineral Solution Sodium Chlorite Solution Not Authorized for Oral Consumption by Humans

 Blogger's Note: the website is still active as of the date of this positing

UPDATE: New Website Selling Miracle Mineral Solution Sodium Chlorite Solution Not Authorized for Oral Consumption by Humans

Information Update
2012-74
May 18, 2012
For immediate release
OTTAWA - Further to our previous communications, Health Canada is advising Canadians that a new website has been identified selling "MMS", also known as Miracle Mineral Solution or Miracle Mineral Supplement. The website is http://www.buymms.biz
When new websites or retailers are identified, Health Canada will continue to update our current list of MMS products. Canadians are advised to monitor this list of affected products for any possible updates.
Health Canada continues to remind Canadians that there are no therapeutic products containing sodium chlorite authorized for oral consumption by humans. MMS may cause serious health problems that include poisoning, kidney failure and harm to red blood cells that reduces the ability of the blood to carry oxygen. Additional health problems may also include abdominal pain, nausea, vomiting, and diarrhoea.
Consumers should consult their health care practitioner if they have used or are using MMS products and report any adverse reaction to Health Canada.
Health Canada has notified distributors identified to date that the sale of sodium chlorite for human consumption is in contravention of the Food and Drugs Act. We have also requested that identified distributors remove product from the Canadian market. As such, this website (http://www.buymms.biz) may or may not be operational. (Blogger's Note: is active)

May 21 Webinar: Steps to Addressing Health Disparities

May 21 Webinar: Steps to Addressing Health Disparities:

Michelle Yeboah of FDA's Office of Minority Health tells how the agency is addressing health disparities among minority populations in America.

Google goes cancer: Researchers use search engine algorithm to find cancer biomarkers

Google goes cancer: Researchers use search engine algorithm to find cancer biomarkers:

The strategy used by Google to decide which pages are relevant for a search query can also be used to determine which proteins in a patient's cancer are relevant for the disease progression. Researchers from Dresden University of Technology, Germany, have used a modified version of Google's PageRank algorithm to rank about 20,000 proteins by their genetic relevance to the progression of pancreatic cancer. In their study, published in PLoS Computational Biology, they found seven proteins that can help to assess how aggressive a patient's tumor is and guide the clinician to decide if that patient should receive chemotherapy or not.
read more

Cancerworld.org: GrandRound - A second opinion, because there’s no second chance

 A second opinion, because there’s no second chance

Patients want the option of consulting a second doctor, and the evidence shows that, for a minority of them, treatment decisions have altered significantly as a result. But could granting every patient the legal right to a second opinion tie up precious resources as each one ‘shops around’ in search of the opinion they want to hear?.....

"The fear that many have about ‘upsetting’ their doctor should not be underestimated"


IN SHORT

• Women, especially breast cancer patients, are among the most likely to seek second opinions, probably because of the many different treatment options for breast cancer and its high visibility in the media.

• Computers networks are obvious second opinion enablers. The European Union’s e-Health

• action plan predicts that by 2008 the majority of European health organisations should have the technical capability to provide online teleconsultation services for second opinions and other needs.

• More than a quarter (29%) of US adults reported that they or a member of their family received a second medical opinion from a doctor in the past five years, according to a 2005 Harris Interactive survey. In 30% of these, the diagnosis differed from the original. Another Harris poll in 2006 found that 36% of US adults never get a second opinion and nearly one in ten (9%) ‘rarely or never understand’ their diagnosis.

• Australian researchers have found that ‘Googling’ symptoms on the Internet came up with the right diagnosis in 15 out of 26 cases (reported in the New England Journal of Medicine). At Duke University in the US, medical physicists are using a Google-like approach to compare mammograms with the most highly ranked images returned from a database.

Organisation of European Cancer Institutes (OECI): Mahasti Saghatchian: pioneering a quality mark for Europe's cancer centres

Mahasti Saghatchian: pioneering a quality mark for Europe's cancer centres - Cover Story -  Cancer World

Genetic Testing May Not Drive Up Health Costs - in Genetics, Genetic Testing from MedPage Today

Genetic Testing May Not Drive Up Health Costs - in Genetics, Genetic Testing from MedPage Today

Patient-Centered Outcomes Research Institute PCORI: What Is It? How Does It Work? The Director Explains

PCORI: What Is It? How Does It Work? The Director Explains

In this segment of Medscape One-on-One, Joseph Selby, MD, talks with Eli Adashi, MD, about his new role as head of the Patient-Centered Outcomes Research Institute, its mission, and how physicians might benefit from this institute created under the Affordable Care Act.

excerpt: 

"How Does PCORI Differ From the Cochrane Collaboration?

Dr. Adashi: A question you almost certainly have heard before and that some of our viewers almost certainly contemplated has to do with the distinction between PCORI and other undertakings, such as the Cochrane Collaboration and programs that engage in systematic reviews or meta-analysis of data. In what way does PCORI stand out to other efforts? Where is it unique and distinct?

Dr. Selby: I think the most striking difference is that we are a research funding institution. The Cochrane Collaboration collects, disseminates, and guides the creation of evidence syntheses. We will fund some evidence syntheses, but we'll also fund a lot of empirical research, including observational research and randomized comparisons. So, we are a funding institute of substantial size in distinction to, as you mentioned, the Cochrane Collaboration and several European organizations that synthesize data and go beyond synthesis to supporting policymaking.
The other distinguishing characteristic is that we don't make policy; we generate information....

Experts Report Little Certainty in Vitamin D’s Potential Benefits « news@JAMA

Experts Report Little Certainty in Vitamin D’s Potential Benefits « news@JAMA

Conclusions in the statement include the following:

• Topical or oral vitamin D may help treat psoriasis, but more evidence is needed to determine its efficacy in treating other skin disorders or preventing skin cancer.
• No strong evidence exists to support the theory that vitamin D supplements reduce the risk of type 2 diabetes or the metabolic syndrome.
• Clinical trial evidence does not support taking vitamin D supplements to lower cardiovascular disease risk.
• Observational studies linking vitamin D with reduced cancer incidence are strongest for colorectal cancer but weak or inconsistent for breast, prostate, and all cancers combined.

The statement will be published in the June issue of the Endocrine Society’s Endocrine Reviews.

The Disparity of Motivational Drivers in International Health Care Systems

OMICS Publishing Group | Full-text | The Disparity of Motivational Drivers in International Health Care Systems

Abstract

Healthcare systems are highly convoluted and nontransparent systems that face the immense challenge of disparaging economic and ethical drivers from each player in this complicated continuum. Economic slack is a critical obstacle that is generated through the misalignment of needed outcomes for each of these silos. Understanding the economic needs of each additional and overlapping player in the continuum is the first important step toward universal health care sustainability.

Editorial

".......Undeniably, some industrialized countries, particularly in Europe, are far closer to attaining sustainable, universal (timely) healthcare access than others and yet no country can claim perfection.....

An alternative approach to identify women at risk for colorectal cancer. | 2012 ASCO Annual Meeting Abstracts

An alternative approach to identify women at risk for colorectal cancer. | 2012 ASCO Annual Meeting Abstracts

Abstract:
Background: 
Hereditary colorectal cancer (CRC) is preventable; however, identification of individuals at sufficiently high risk to warrant heightened surveillance is difficult. Lynch Syndrome (LS) is an inherited cancer syndrome due to germline mutation in a DNA mismatch repair gene. For women with LS, the lifetime risk of endometrial cancer (EC) is 64% and CRC is 54%. Fifty percent of women with LS will present with EC or ovarian cancer prior to CRC. Therefore, women with LS associated EC represent an ideal group for CRC prevention. The optimal method to identify women with LS associated EC is not known. The purpose of this study was to determine the utility of Amsterdam II and Society of Gynecologic Oncology (SGO) Criteria (modified Bethesda criteria that use EC as the sentinel cancer) in identifying women with LS associated EC. Our ultimate goal is to identify women at increased risk of CRC.


Our data suggest that classic clinical screening criteria are inadequate to detect patients with LS who present with EC, potentially missing up to 25% of these patients.

Gene	MLH1	MSH2	MSH6	PMS2	Total
Total number	14	27	11	7	59
Median age at diagnosis (range)	52 (42-79)	44 (33-81)	56 (31-76)	66 (45-87)	50 (31-87)
Diagnosis at greater than 50 years	7	8	9	6	30
FH CRC	3	16	4	3	26
Amsterdam criteria	3	13	0	1	17
SGO criteria	11	22	7	4	44

2012 ASCO Annual Meeting Abstracts (searchable)

2012 ASCO Annual Meeting Abstracts

Welcome to the 2012 ASCO Annual Meeting abstracts home. Abstracts published in the Annual Meeting Proceedings Part I will be available on this site at 6:00 PM EDT May 16, 2012. Plenary Abstracts, Late-Breaking Abstracts, and Clinical Review Abstracts (published in the Annual Meeting Proceedings Part II) will be available at 12:01 AM EDT on the date of their presentation at the 2012 ASCO Annual Meeting.

SEARCH    2012 Abstracts       Help EXPRESS PRINT    Abstracts by Meeting Track BROWSE    Abstracts by Meeting Track

paywalled: Lipid Profiles and Risk of Breast and Ovarian Cancer in the Swedish AMORIS Study

WIKI: Lipid metabolism refers to the processes that involve the intercourse and degradation of lipids.
The types of lipids involved include:

• Bile salts
• Cholesterols
• Eicosanoids
• Glycolipids
• Ketone bodies
• Fatty acids - see also fatty acid metabolism
• Phospholipids
• Sphingolipids
• Steroid - see also steroidogenesis
• Triacylglycerols (fats) - see also lipolysis and lipogenesis

                                                ~~~~~~~~~~~~~~~~~
Lipid Profiles and Risk of Breast and Ovarian Cancer in the Swedish AMORIS Study

Background: 

Obesity is a risk factor for breast (BCa) and ovarian cancer (OCa); the mechanisms of action are not completely understood. Perturbed lipid metabolism often accompanies obesity; we therefore ascertained the associations between lipid components and BCa and OCa risk in a prospective cohort study. 

Methods: 

234,494 women with baseline measurements of triglycerides (TG) and total cholesterol(TC) and glucose were selected from the AMORIS database. 27,394 had measurements of HDL,LDL, apolipoprotein (Apo) B and A-I. Associations between quartiles and dichotomized values of lipid components and BCa and OCa risk were analysed using Cox proportional hazard models.

Results: 

We identified 6,105 women diagnosed with BCa and 808 women diagnosed with OCa. A weak trend was observed between TG and BCa (HR: 1.01 (CI95% 0.94-1.09), 0.93 (0.86-1.00) 0.91 (0.84-0.99) 2nd 3rd and 4th quartiles; P = 0.01). No other associations between lipid components and risk of BCa or OCa showed statistical significance. 

Conclusions: 

A weak protective association was found between levels of TG and risk of BCa. 

Impact: An analysis including information on tumour characteristics of OCa and BCa may provide more insight in possible links between lipid metabolism and the risk of these cancers.

paywalled: CT diagnosis of intrasplenic metastasis from ovarian carcinoma

CT diagnosis of intrasplenic metastasis from ovarian carcinoma

 We concluded that CT can demonstrate intraparenchymal and infiltrative splenic metastasis in patients with ovarian cancer even in the absence of increased CA 125 levels.

Many US cancer survivors still lost in transition : The Lancet (U.S. / Canada....)

Many US cancer survivors still lost in transition : The Lancet

2012 CDC/NCI report - United States Cancer Statistics (USCS)

Cancer - NPCR - USCS - View Data Online

The 1999–2008 United States Cancer Statistics (USCS): Incidence and Mortality Web-based Report marks the tenth time that the Centers for Disease Control and Prevention (CDC) and the National Cancer Institute (NCI) have jointly produced official federal cancer incidence statistics for each state having high-quality cancer data. The report is produced in collaboration with the North American Association of Central Cancer Registries. This year's report features information on more than one million invasive cancer cases diagnosed during 2008 among residents of all 50 states, six metropolitan areas, and the District of Columbia. Incidence data are from CDC's National Program of Cancer Registries (NPCR) and NCI's Surveillance, Epidemiology and End Results (SEER) Program. Data from population-based central cancer registries in these states and metropolitan areas meet the selected criteria for inclusion in this report. The report also provides cancer mortality data collected and processed by CDC's National Center for Health Statistics (NCHS). Mortality statistics, based on records of deaths that occurred during 2008, are available for all 50 states and the District of Columbia. Report Highlights Cancer rates by race and ethnicity (all cancers combined) Cancer rates by state (all cancers combined) Cancer among men Cancer among women Racial or ethnic variations Geographic variations   United States Cancer Statistics (USCS) View Data Online 1999–2008 Cancer Incidence and Mortality Data This Web-based report includes the official federal statistics on cancer incidence from registries that have high-quality data and cancer mortality statistics for each year and 2004–2008 combined. It is produced by the Centers for Disease Control and Prevention (CDC) and the National Cancer Institute (NCI), in collaboration with the North American Association of Central Cancer Registries (NAACCR).

---------------------------- See Also • Help for new users • Contact information ----------------------------

Graphs Top Ten Cancers State vs. National Comparisons Selected Cancers Ranked by State      Maps The Interactive Cancer Atlas (InCA) shows USCS data from 1999–2008 in a dynamic format. Interactive Cancer Atlas (InCA)

Tables Cancer Types Grouped by Race and Ethnicity Cancers Grouped by State and Region Childhood Cancer Brain Cancers by Tumor Type  Cancer Data by State Use the dropdown menu to view cancer information for a selected state.

Internationally known expert in ovarian cancer to be honored at the ASCO Annual Meeting (Dr Robert F. Ozols)

Internationally known expert in ovarian cancer to be honored at the ASCO Annual Meeting

Pazopanib and Weekly Topotecan in Patients Recurrent Ovarian Cancer (TOPAZ) - Full Text View - ClinicalTrials.gov

Pazopanib and Weekly Topotecan in Patients Recurrent Ovarian Cancer (TOPAZ) - Full Text View - ClinicalTrials.gov

paywalled: Presence of a sarcomatous component outside the ovary is an adverse prognostic factor for primary ovarian malignant mixed mesodermal/mullerian tumors: a clinicopathologic study of 47 cases

Blogger's Note: also known by short form MMMT

Abstract

Primary ovarian malignant mixed mesodermal tumors are uncommon. There exist few data in the literature on the significance of the sarcomatous (sarcoma) component (SC) in these tumors. Here we investigated this aspect in 47 such tumors, with particular interest in whether the presence of SC outside the ovary confers a worse prognosis. .......................We advocate listing the specific extraovarian tumor component (SC and/or CC) in the pathology report for primary ovarian malignant mixed mesodermal tumors.

Gamma knife surgery for brain metastases from ovarian cancer.

Gamma knife surgery for brain metastases from ovarian cancer.


numerous tables including:

Table 1 Patient characteristics of 16 patients with 119 brain metastases

Conclusions

Brain metastases from ovarian cancer are rare, but their incidence is increasing as patient survival has been extended by successful platinum-based chemotherapy and improved imaging techniques have enabled the identification of smaller lesions. In our study, the median survival from brain metastases was 12.5 months, and the local control rate was 86.4 %. The KPS and total volume of brain metastases were important factors predictive of survival. Our results suggest that GKS is an acceptable therapy for brain metastases from ovarian cancer. 

Conflicts of interest  

None.

Open Access  

update March 15th Grants.gov - Find Grant Opportunities - Opportunity Synopsis

Grants.gov - Find Grant Opportunities - Opportunity Synopsis

The synopsis for this grant opportunity is detailed below, following this paragraph. This synopsis contains all of the updates to this document that have been posted as of 03/15/2012 . If updates have been made to the opportunity synopsis, update information is provided below the synopsis.....

News : Many Primary Care Docs Don't Know Long-Term Effects of Chemo: Survey

Blogger's Note: general/non-ovarian cancer specific


HON - News : Many Primary Care Docs Don't Know Long-Term Effects of Chemo: Survey


"....The findings highlight the need for more communication between the different doctors involved in a patient's care, one expert stressed.

The burden of that communication lies not only with doctors (oncologists and primary care physicians) but also with patients, said Dr. Stephanie Bernik, chief of surgical oncology at Lenox Hill Hospital in New York City.....

paywalled- Gynecologic Oncology - Response to: “Management of ovarian cancer has changed”

ScienceDirect.com - Gynecologic Oncology - Response to: “Management of ovarian cancer has changed”
 
In Press, Accepted Manuscript, Available online 15 May 2012
Joyce N. Barlin, Dennis S. Chi
 Close preview  |   Related articles  |  Related reference work articles    Abstract  - No abstract is available for this article.

paywalled - Gynecologic Oncology - Comparison of ERCC1/XPF genetic variation, mRNA and protein levels in women with advanced stage ovarian cancer treated with intraperitoneal platinum

ScienceDirect.com - Gynecologic Oncology - Comparison of ERCC1/XPF genetic variation, mRNA and protein levels in women with advanced stage ovarian cancer treated with intraperitoneal platinum

Abstract

Objective

Approximately 20% of patients receiving platinum-based chemotherapy for epithelial ovarian cancer (EOC) are refractory or develop early recurrence. Identifying these patients early could reduce treatment-associated morbidity and allow quicker transfer to more effective therapies. Much attention has focused on ERCC1 as a potential predictor of response to therapy because of its essential role in the repair of platinum-induced DNA damage. The purpose of this study was to accurately measure protein levels of ERCC1 and its essential binding partner XPF from patients with EOC treated with platinum-based therapy and determine if protein levels correlate with mRNA levels, patient genotypes or clinical outcomes.

Methods

ERCC1 and XPF mRNA and protein levels were measured in frozen EOC specimens from 41 patients receiving intraperitoneal platinum-based chemotherapy using reverse transcription polymerase chain reaction and western blots. Genotypes of common nucleotide polymorphisms were also analyzed. Patient outcomes included progression free (PFS) and overall survival (OS).

Results

Expression of ERCC1 and XPF were tightly correlated with one another at both the mRNA and protein level. However, the mRNA and protein levels of ERCC1 were not positively correlated. Likewise, none of the SNPs analyzed correlated with ERCC1 or XPF protein levels. There was an inverse correlation between mRNA levels and patient outcomes.

Conclusion

Neither genotype nor mRNA levels are predictive of protein expression. Despite this, low ERCC1 mRNA significantly correlated with improved PFS and OS.

paywalled - Gynecologic Oncology - Hormonal therapy for recurrent low-grade serous carcinoma of the ovary or peritoneum

ScienceDirect.com - Gynecologic Oncology - Hormonal therapy for recurrent low-grade serous carcinoma of the ovary or peritoneum

Objective

To determine whether hormonal therapies have efficacy in patients with recurrent low-grade serous carcinoma of the ovary or peritoneum.

Methods

We searched departmental databases for patients with histologically-confirmed, evaluable, recurrent low-grade serous ovarian or peritoneal carcinoma who received hormonal therapy at our institution between 1989 and 2009. We retrospectively reviewed patients' medical records for demographic, disease, hormonal therapy, and estrogen receptor and progesterone receptor expression data. We used the Response Evaluation Criteria in Solid Tumors version 1.1 to determine patients' responses to hormonal therapy. Because patients could have received more than one evaluable hormonal therapy regimen, we chose to define the outcome metric as “patient-regimens.” Median time to disease progression (TTP) and overall survival (OS) were also calculated. Regression analysis was also performed.

Results

We identified 64 patients with recurrent low-grade serous carcinoma of the ovary or peritoneum. Patients' median TTP and median OS were 7.4 and 78.2 months, respectively. Patients received 89 separate hormonal patient-regimens, which produced an overall response rate of 9% (6 complete responses and 2 partial responses). Sixty-one percent of the patient-regimens resulted in a progression-free survival duration of at least 6 months. Patient-regimens involving ER +/PR + disease produced a longer median TTP (8.9 months) than patient-regimens involving ER +/PR − disease did (6.2 months; p = 0.053). This difference approached but did not reach statistical significance.

Conclusions

Hormonal therapies have moderate anti-tumor activity in patients with recurrent low-grade serous carcinoma of the ovary or peritoneum. Further study to determine whether ER/PR expression status is a predictive biomarker for this rare cancer subtype is warranted.

paywalled - Gynecologic Oncology - A phase II study of a urokinase-derived peptide (A6) in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma: GOG

ScienceDirect.com - Gynecologic Oncology - A phase II study of a urokinase-derived peptide (A6) in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma: A Gynecologic Oncology Group study

Conclusion

A6 was well tolerated but had minimal activity in patients with persistent or recurrent EOC/FTC/PPC.

paywalled- Gynecologic Oncology - Economic impact of paclitaxel shortage in patients with newly diagnosed ovarian cancer ($8,699,872 monthly.

ScienceDirect.com - Gynecologic Oncology - Economic impact of paclitaxel shortage in patients with newly diagnosed ovarian cancer

Objective

To determine the potential economic impact of a paclitaxel drug shortage in patients with newly diagnosed, untreated ovarian cancer.

Methods

A modified Markov state transition model with a 6 cycle time horizon compared two scenarios: (1) Standard treatment (STD): paclitaxel 175 mg/m2/carboplatin AUC 5 × 6 cycles; (2) Paclitaxel drug shortage (DS): docetaxel 75 mg/m2/carboplatin AUC 5 × 6 cycles. Adverse events, quality of life, and costs of chemotherapy, neuropathy, febrile neutropenia, and anemia were incorporated. Key assumptions: (1) Costs and consequences were assigned only to grade 2 + neuropathy, febrile neutropenia, and grade 3–4 anemia; (2) Grade 2 + neuropathy prompted a switch from paclitaxel/carboplatin to docetaxel/carboplatin or from docetaxel/carboplatin to carboplatin alone; (3) Febrile neutropenia resulted in inpatient hospitalization followed by G-CSF prophylaxis.

Results

The mean cost of 6 cycles of chemotherapy was $4939 in the STD and $16,107 in the DS scenario, for a cost difference of $11,168 per patient over 6 cycles of treatment. STD was the dominant strategy (less expensive and more effective than the drug shortage scenario). In sensitivity analysis, DS was more costly over a wide range of clinical estimates in each arm. A drug shortage that affects approximately 50% of women initiating chemotherapy is expected to impact 779 women and cost third party payers an additional $8,699,872 monthly.

Conclusions

Our model indicates that chemotherapy drug shortages can have a significant negative impact on the average cost of primary treatment for ovarian cancer and have the potential to negatively impact health system costs.

paywalled - Gynecologic Oncology - Predictors of severe and febrile neutropenia during primary chemotherapy for ovarian cancer

ScienceDirect.com - Gynecologic Oncology - Predictors of severe and febrile neutropenia during primary chemotherapy for ovarian cancer

Objective

To identify factors that increase the risk of neutropenic events in women with advanced ovarian carcinoma receiving initial chemotherapy.

Methods

Multi-center retrospective study of women with FIGO stage III–IV epithelial ovarian cancer treated postoperatively with multi-agent intravenous chemotherapy from 1995 to 2008. Outcomes were severe (SN; absolute neutrophil count [ANC] < 500/mm³) and febrile neutropenia (FN; ANC < 1000/mm³ and temperature > 38.1 °C). Cumulative risk of neutropenic events was estimated by Kaplan Meier method. Multivariate analysis was by Cox proportional hazard regression.

Results

Three hundred twenty-six patients met inclusion criteria. There were 251 SN events among 140 (43%) patients and 24 FN events among 22 (7%) patients. Univariate predictors of SN were body surface area < 2.0 m² (p = 0.03), body mass index (BMI) < 30 kg/m² (p < 0.01), Caucasian race (p < 0.01), treatment on research protocols (p < 0.01), non-carboplatin-containing regimens (p < 0.01), and planned relative dose intensity (RDI) > 85% of standard (p = 0.02). Women over age 60 were more likely to develop FN (p = 0.05). Multivariate predictors of SN were treatment on research protocols (hazard ratio [HR] 1.93; p < 0.01), Caucasian race (HR 2.13; p = 0.01), and planned RDI > 85% (HR 1.69; p = 0.05); predictors of FN were age > 60 (HR 2.84; p = 0.05) and non-carboplatin containing regimens (HR 4.06; p < 0.01).

Conclusion

While SN is fairly common, FN occurs infrequently in women with EOC undergoing taxane and platin-based chemotherapy and primary prophylactic growth factor support is not indicated. However, women older than 60 years of age receiving non-carboplatin containing regimens are at higher risk for FN and warrant closer surveillance.

paywalled - Gynecologic Oncology - Progression-free and overall survival of a modified outpatient regimen of primary intravenous/intraperitoneal paclitaxel and intraperitoneal cisplatin in ovarian, fallopian tube, and primary peritoneal cancer

ScienceDirect.com - Gynecologic Oncology - Progression-free and overall survival of a modified outpatient regimen of primary intravenous/intraperitoneal paclitaxel and intraperitoneal cisplatin in ovarian, fallopian tube, and primary peritoneal cancer

Highlights

► GOG 172 showed improved outcomes for optimally debulked ovarian carcinoma patients treated with IV/IP chemotherapy compared to IV chemotherapy.
► The regimen has not been widely accepted due to its inpatient administration, toxicity profile, and limited completion rate.
► A modified GOG 172 treatment regimen improved convenience, toxicity, and tolerability, with outcomes similar to those of GOG 172.

paywalled - Gynecologic Oncology - Impact of smoking on perioperative pulmonary and upper respiratory complications after laparoscopic gynecologic surgery

ScienceDirect.com - Gynecologic Oncology - Impact of smoking on perioperative pulmonary and upper respiratory complications after laparoscopic gynecologic surgery

Abstract

Objective

To determine the impact of smoking on the rate of pulmonary and upper respiratory complications following laparoscopic gynecologic surgery.

Methods

We retrospectively identified all patients who underwent laparoscopic gynecologic surgery at one institution between January 2000 and January 2009. Pulmonary and upper respiratory complications were defined as atelectasis, pneumonia, upper respiratory infection, acute respiratory failure, hypoxemia, pneumothorax, or pneumomediastinum occurring within 30 days after surgery

Results

Nine hundred three patients underwent attempt at laparoscopic surgery. Fifty-four were excluded because of conversion to laparotomy and 31 because of insufficient data. Of the 818 patients included, 356 (43%) had cancer. A total of 576 (70%) patients were never smokers, 156 (19%) were past smokers, and 86 (10%) were current smokers (smoked within 6 weeks before surgery). These three groups were similar with regard to median body mass index, operative time, and length of hospital stay. Compared to never and past smokers, current smokers were more likely to undergo high-complexity laparoscopic procedures (10.4%, 15.4%, and 19.8%, respectively; p = 0.015) and had younger median age 49 years, 51 years, and 46 years, respectively; p = 0.035. Nineteen (2.3%) patients experienced pulmonary complications — symptomatic atelectasis (n = 9), pneumonia (n = 5), acute respiratory failure (n = 2), hypoxemia (n = 1), pneumomediastinum (n = 1), and pneumothorax (n = 2). The rate of pulmonary complications was 2.1% (12 of 564 patients) in never smokers, 4.5% (7 of 156 patients) in past smokers, and zero in current smokers.

Conclusion

In this cohort, smoking history did not appear to impact postoperative pulmonary and upper respiratory complications. In smokers scheduled for operative procedures, laparoscopy should be considered when feasible.

paywalled: Current advances in the management of malignant germ cell and sex cord-stromal tumors of the ovary

Current advances in the management of malignant germ cell and sex cord-stromal tumors of the ovary:


Abstract | References

No abstract is available for this article.

Article Outline

• Introduction
• Malignant ovarian germ cell tumors
• • Molecular biology
  • Prognostic factors
  • Surgery
  • Adjuvant chemotherapy
• Ovarian sex cord-stromal tumors

paywalled: Incidence of and risk factors for postoperative ileus in women undergoing primary staging and debulking for epithelial ovarian carcinoma

Blogger's Note/Opinion: in ovarian cancer this issue is seemingly underreported; from a patient's perspective it  is underreported, abstract does not indicate expertize/impact/outcomes according to surgical skill/professional nor long term effects/in depth cause-related issues;


Medscape:  Ileus occurs from hypomotility (decreased motility)  of the gastrointestinal tract in the absence of mechanical bowel obstruction. Presumably, the muscle of the bowel wall is transiently impaired and fails to transport intestinal contents. This lack of coordinated propulsive action leads to the accumulation of gas and fluids within the bowel.....
                                       ~~~~~~~~~~~~~

Incidence of and risk factors for postoperative ileus in women undergoing primary staging and debulking for epithelial ovarian carcinoma:

Objective 
Thorough primary cytoreduction for epithelial ovarian carcinoma (EOC) improves survival. The incidence of postoperative ileus (POI) in these patients may be underreported because of varying POI definitions and the evolving, increasingly complex contemporary surgical approach to EOC. We sought to determine the current incidence of POI and its risk factors in women undergoing debulking and staging for EOC.

Methods 
We retrospectively identified the records of women who underwent primary staging and cytoreduction for EOC between 2003 and 2008. POI was defined as a surgeon's diagnosis of POI, return to nothing-by-mouth status, or reinsertion of a nasogastric tube. Perioperative patient characteristics and process-of-care variables were analyzed.

Results 
Among 587 women identified, the overall incidence of POI was 30.3% (25.9% without bowel resection, 38.5% with bowel resection; P =.002). Preoperative thrombocytosis, involvement of bowel mesentery with carcinoma, and perioperative red blood cell transfusion were independently associated with increased POI. Postoperative ibuprofen use was associated with decreased POI risk. Women with POI had a longer length of stay (median, 11 vs 6days) and increased time to recovery of the upper (7.5 vs 4days) and lower (4 vs 3days) gastrointestinal tract (P <.001 for each).

Conclusions 
The rate of POI is substantial among women undergoing staging and cytoreduction for EOC and is associated with increased length of stay. Modifiable risk factors may include transfusion and postoperative ibuprofen use. Alternative interventions to decrease POI are needed.

press release: In drug-approval race, US FDA ahead of Canada, Europe (range: 322-393 days)

In drug-approval race, US FDA ahead of Canada, Europe

Public release date: 16-May-2012

The U.S. Food and Drug Administration (FDA) generally approves drug therapies faster and earlier than its counterparts in Canada and Europe, according to a new study by Yale School of Medicine researchers. The study counters perceptions that the drug approval process in the United States is especially slow.

Led by second-year medical student Nicholas Downing and senior author Joseph S. Ross, M.D., assistant professor of internal medicine at Yale School of Medicine, the study will be published May 16 online by the New England Journal of Medicine.

Regulatory review represents the final step in the process of bringing new medical technologies from the lab to the bedside. Efficient regulatory review processes may enable patients to get access to promising new therapies sooner, while ensuring drug safety.
"The perception that the FDA is too slow implies that sick patients are waiting unnecessarily for regulators to complete their review of new drug applications," said Downing, who decided to conduct the study because there have been no recent comparisons of the FDA's regulatory review speed with those of regulating agencies in other countries.
Downing, Ross, and colleagues reviewed drug approval decisions of the FDA, the Canadian drug regulator, Health Canada, and the European Medicines Agency (EMA) between 2001 and 2010. They studied each regulator's database of drug approvals to identify novel therapeutics as well as the timing of key regulatory events, allowing regulatory review speed to be calculated. Canada and Europe were chosen as a comparison because they face similar pressures to approve new drugs quickly while ensuring they do not put patients at risk.

The team found that the median total time to review was 322 days at FDA, 366 days at EMA and 393 days at Health Canada.

"Among the subsample of drugs approved for all three regulators, the FDA's reviews were over three months faster than those of the EMA or Health Canada," said Downing. "The total review time at the FDA was faster than EMA, despite the FDA's far higher proportion of applications requiring multiple regulatory reviews."

Downing added that most new drug therapies were first approved for use in the U.S. "Examining novel drugs approved in multiple markets, we found that 64% of medicines approved in both the U.S. and in Europe were approved for U.S. patients first, and 86% of medicines approved in both the U.S. and Canada were also approved first in the U.S." he said.

###

Other authors on the study included Jenerius A. Aminawung, Nilay D. Shah, Joel B. Braunstein, and Harlan M. Krumholz.
The study was funded by the Pew Charitable Trusts.
Citation: New England Journal of Medicine, doi: 10.1056/NEJMoa1200223

Regulatory Review of Novel Therapeutics — Comparison of Three Regulatory Agencies — NEJM (U.S./Canada/Europe) note references to safety

Regulatory Review of Novel Therapeutics — Comparison of Three Regulatory Agencies — NEJM

"In conclusion, we found that among novel (new) therapeutics approved between 2001 and 2010, the FDA reviewed applications more quickly, on average, than did the EMA and Health Canada, and the vast majority of these novel therapeutics were first approved for use in the United States. Our findings contradict recent criticisms of the speed of review by the FDA and lead to questions about whether the speed of the review process is justified as an emphasis for PDUFA V, particularly since the FDA continues to outpace its European and Canadian peers."

Functional profiling of clear cell ovarian cancer. | 2012 ASCO Annual Meeting Abstracts

Functional profiling of clear cell ovarian cancer. | 2012 ASCO Annual Meeting Abstracts

Abstract:
Background: Clear cell ovarian cancer represents up to 15% of epithelial ovarian cancers. In comparison to other subtypes, clear cell ovarian carcinomas have a poorer prognosis and are relatively resistant to standard platinum based chemotherapy. Recently, loss of function mutations in the tumour suppressor gene ARID1A were identified in up to 50% of ovarian clear cell carcinomas. We have adopted an integral functional and molecular profiling approach as a route to identify new genetic dependencies and therapeutic targets for this disease.

Methods: Clear cell ovarian cancer cell lines were functionally profiled using high throughput screening with chemical and siRNA libraries. This has been integrated with molecular profiling data generated from exome and transcriptome sequencing to aid the discovery of novel targets.

Results: Using functional screens we have now identified critical gene dependencies and potential therapeutics in a series of clear cell ovarian cancer models. The comparison of functional viability profiles for models characterized by ARID1A loss of function mutations is now enabling an analysis of synthetic lethal effects that could be used to target clear cell ovarian cancers carrying these mutations.  

Conclusions: The work undertaken so far provides the framework for the discovery of therapeutic targets for clear cell ovarian cancer using an integrated approach. Revalidation of these preliminary results is now underway to characterize new genetic dependencies for this disease.

American Society of Clinical Oncology - ASCO - abstracts now available

American Society of Clinical Oncology - ASCO

ASCO '12 Abstract Dump: Cancer Stocks in Focus - TheStreet (financial)

ASCO '12 Abstract Dump: Cancer Stocks in Focus - TheStreet

.....While investors were flooded with new cancer drug data Wednesday, ASCO did hold back some of the some important and potentially stock-moving research for a more high-profile release at the meeting itself. 

Key cancer drug data that remains under wrap include results from a phase III study of Johnson & Johnson's(JNJ_) Zytiga in "pre-chemo" prostate cancer patients; a phase III study of Bayer and Onyx's regorafenib in advanced gastrointestinal stromal tumors; several Roche/Genentech(RHHBY) studies, including Avastin in ovarian cancer and TDM-1 in breast cancer (partnered with Immunogen(IMGN_)); melanoma data from GlaxoSmithKline's(GSK_) targeted drug dabrefenib; and a new targeted PD-1 immunotherapy from Bristol-Myers Squibb(BMY_).
The following pages summarize new and important cancer drug data released tonight by ASCO from research abstracts for its upcoming annual meeting.......

Nine new breast cancer risk genes: Landscape of cancer genes and mutational processes in breast cancer complicated

Nine new breast cancer risk genes: Landscape of cancer genes and mutational processes in breast cancer complicated

Understanding: Sepsis (Blood Infection) Symptoms, Prognosis, Treatment, Causes - eMedicineHealth

Sepsis (Blood Infection) Symptoms, Prognosis, Treatment, Causes - eMedicineHealth

paywalled: Two-marker Combinations for Preoperative Discrimination of Benign and Malignant Ovarian Masses

Two-marker Combinations for Preoperative Discrimination of Benign and Malignant Ovarian Masses

Abstract

Background: 

When caring for patients with ovarian neoplasms, correct preoperative discrimination of benign and malignant disease is deemed vital. In this study, we tested serum biomarkers' alone and in combination, to achieve this aim.

Conclusion: 

A combination of CA-125 with HE4 could facilitate the identification of women at risk for ovarian cancer.

paywalled: Long-term results of screening with magnetic resonance imaging in women with BRCA mutations : British Journal of Cancer

Long-term results of screening with magnetic resonance imaging in women with BRCA mutations : British Journal of Cancer

Background: 

The addition of breast magnetic resonance imaging (MRI) to screening mammography for women with BRCA mutations significantly increases sensitivity, but there is little data on clinical outcomes. We report screening performance, cancer stage, distant recurrence rate, and breast cancer-specific mortality in our screening study.

Methods:

From 1997 to 2009, 496 women aged 25 to 65 years with a known BRCA1/2 mutation, of whom 380 had no previous cancer history, were enrolled in a prospective screening trial that included annual MRI and mammography.

Results:

In 1847 screening rounds, 57 cancers were identified (53 screen-detected, 1 interval, and 3 incidental at prophylactic mastectomy), of which 37 (65%) were invasive. Sensitivity of MRI vs mammography was 86% vs 19% over the entire study period (P<0.0001), but was 74% vs 35% from 1997 to 2002 (P=0.02) and 94% vs 9% from 2003 to 2009 (P<0.0001), respectively. The relative sensitivities of MRI and mammography did not differ by mutation, age, or invasive vs non-invasive disease. Of the incident cancers, 97% were Stage 0 or 1. Of 28 previously unaffected women diagnosed with invasive cancer, 1 BRCA1 mutation carrier died following relapse of a 3 cm, node-positive breast cancer diagnosed on her first screen at age 48 (annual breast cancer mortality rate=0.5%). Three patients died of other causes. None of the 24 survivors has had a distant recurrence at a median follow-up of 8.4 years since diagnosis.

Conclusion:

Magnetic resonance imaging surveillance of women with BRCA1/2 mutations will detect the majority of breast cancers at a very early stage. The absence of distant recurrences of incident cancers to date is encouraging. However, longer follow-up is needed to confirm the safety of breast surveillance.

media: Doctor-bashing’s not the cure for health-care costs

......the government has gone to war against the doctors again.....

 "Politicians and bureaucrats are always attracted to simple ways to control health-care spending. In the early 1990s, they decided the best way to control spending was to cut down on doctors. This brilliant idea resulted in a doctor shortage that has taken the past decade to fix......

Healthnewsreviews blog: The marketing of anemia drugs - a story we shouldn't forget (including comments)

The marketing of anemia drugs - a story we shouldn't forget

 "In an opinion piece on TheScientist.com, Daniel W. Coyne writes, “Amgen’s incomplete report on an early major trial of epoetin misled the medical community about the anemia drug’s risks and benefits—and helped make Amgen rich.”
In the book, “How We Do Harm,” Otis Brawley, MD, chief medical and scientific officer of the American Cancer Society, writes quite a bit about hemoglobin-building drugs.  He discusses:.....

FAQ: Adverse Events(search by drug name)

FAQ: Adverse Events

About Us

Adverse Events, Inc. (AEI) is a provider of up-to-the-minute, critical, potentially life-saving information regarding side effects associated with FDA-approved prescription medications. AEI has created a unique set of online tools that are optimized to provide un-paralleled access to adverse event information on over 4,000 drugs, in an easy to understand and navigate format. AEI’s tools give control over treatment plans back to patients and their doctors, while providing an immediate view of potential trends and problems in the drug industry to pharmaceutical, healthcare, insurers, financial institutions and media.
RxFilter™ is a proprietary 17-step data refinement process developed by AdverseEvents, Inc. that standardizes and normalizes the Federal Drug Administration (FDA) Adverse Events Reporting System (AERS) database. Combining complex computer algorithms with hands-on data analysis by highly trained researchers, the RxFilter process is the most thorough optimization procedure ever applied to the FDA's drug safety database. It accurately measures and tracks adverse events associated with medications reported to the FDA.

Top 10 Drugs with the Highest Number of Adverse Events Reported

Browse all by letter: example: Cisplatin    5,107 (number of adverse events reported)

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Oxaliplatin-related thrombocytopenia

Oxaliplatin-related thrombocytopenia

Oxaliplatin is a third generation platinum compound that inhibits DNA synthesis, mainly through intrastrandal cross-links in DNA. Most of the experience with the clinical use of this drug is derived from colorectal cancer but it is also used in other tumor types such as ovary, breast, liver and non-Hodgkin's lymphoma. Thrombocytopenia is a frequent toxicity seen during oxaliplatin treatment, occurring at any grade in up to 70 % of patients and leading to delays or even discontinuation of the chemotherapy. Although myelossupression is recognized as the main cause of oxaliplatin-related thrombocytopenia, new mechanisms for this side-effect have emerged, including splenic sequestration of platelets related to oxaliplatin-induced liver damage and immune thrombocytopenia. These new pathophysiology pathways have different clinical presentations and evolution and may need specific therapeutic maneuvers. This article attempts to review this topic and provides useful clinical information for the management of oxaliplatin-related thrombocytopenia...........

Seth's blog: Dedicating the merit

Dedicating the merit:

For an author, one of the nicest parts of the traditional book is the dedication page. The dedication is far more than an acknowledgement to someone who helped you write the book, it's a permanent signpost, a capstone to the work of a year or more.
Even if the person you've dedicated the book to can't read it, the writer benefits from the knowledge that a connection was made and that a memory was preserved.
Here's the thing: you can dedicate just about anything. A project, a meeting, a tweet. You don't have to tell anyone but yourself. This blog post, like all the posts before it, has a dedication page, at least in my head.
When you start creating for and in honor of those that have made a difference to you, your work changes.

paywalled: MR Imaging of Malignancies Arising in Endometriomas and Extraovarian Endometriosis

MR Imaging of Malignancies Arising in Endometr... [Radiographics. 2012] - PubMed - NCBI

Radiographics. 2012 May

Abstract: 

Cancers that arise in ovarian or extraovarian endometriosis are a distinct disease category with a histologic profile different from that of the more common epithelial ovarian cancers and with a better prognosis.

Because the malignant transformation of endometriomas is rarely associated with lymphadenopathy or peritoneal carcinomatosis, a high index of suspicion on the part of the radiologist is necessary to establish a timely diagnosis of endometriosis-related ovarian cancers and allow appropriate oncologic management. Although imaging is not currently performed for surveillance of endometriosis, magnetic resonance (MR) imaging is often performed when surgical treatment is under consideration................. For definitive diagnosis, histopathologic analysis is required.

paywalled: Treatment of Chemotherapy-Induced Anemia in Ovarian Cancer Patients: Does the Use of Erythropoiesis-Stimulating Agents Worsen Survival?

Treatment of Chemotherapy-Induced Anemia in Ovarian Cancer P... : International Journal of Gynecological Cancer

Abstract

Objective: 

Considering the paucity of data relating erythropoiesis-stimulating agent (ESA) use to ovarian cancer survival, our objective was to evaluate the effect of ESA as used for the treatment of chemotherapy-induced anemia (CIA) on survival in ovarian cancer patients.

Materials and Methods:  

A multi-institution retrospective chart review was performed on ovarian cancer patients. Data collection included patient demographic, surgicopathologic, chemotherapy, ESA, and survival data. Patients were stratified by ever-use of ESA and were compared using appropriate statistical methods.

Results: A total of 581 patients were eligible for analysis with 39% (n = 229) patients with ever-use of ESA (ESA-YES) and 61% (n = 352) never-use ESA (ESA-NO). Mean age was 60.4 years with most patients having stage IIIC (60%) of papillary serous histological diagnosis (64%) with an optimal cytoreduction (67%). Median follow-up for the cohort was 27 months. Both ESA-YES and ESA-NO groups were similar regarding age, body mass index, race, stage, histological diagnosis, and debulking status. Compared with the ESA-NO group, ESA-YES patients were significantly more likely to experience recurrence (56% vs 80%, P < 0.001) and death (46% vs 59%, P = 0.002). Kaplan-Meier curves demonstrated a significant reduction in progression-free survival for ESA-YES patients (16 vs 24 months, P < 0.001); however, overall survival was statistically similar between the 2 groups (38 vs 46 months, P = 0.10). When stratifying by ever experiencing a CIA, ESA-YES patients demonstrated a significantly worse progression-free survival (17 vs 24 months, P = 0.02) and overall survival (37 vs 146 months, P < 0.001).

Conclusions: 

Our data evaluating the use of ESA as a treatment of CIA in ovarian cancer patients are similar to reports in other tumor sites. Considering that patients who used ESA were more likely to experience recurrence and death and to have decreased survival, the use of ESA in ovarian cancer patients should be limited.

paywalled: Differential diagnosis of a pelvic mass: improved algorithms and novel biomarkers.

Differential diagnosis of a pelvic mass: improved algorithms and novel biomarkers.:


ABSTRACT:

More than 200,000 women undergo exploratory surgery for a pelvic mass in the United States each year and 13%-21% of pelvic lesions are found to be malignant. Individual reports and meta-analysis indicate better outcomes when cancer surgery is performed by gynecologic oncologists. Despite the advantages provided by more thorough staging and cytoreductive surgery, only 30%-50% of women with ovarian cancer are referred to surgeons with specialized training in the United States. Imaging, menopausal status and biomarkers can aid in distinguishing malignant from benign pelvic masses to inform decisions regarding appropriate referral. The risk of malignancy index (RMI) uses ultrasound, menopausal status and CA125 and has been utilized in the United Kingdom for two decades, providing sensitivity that has ranged from 71%-88% and specificity it from 97%-74% for identifying patients with malignant disease. Criteria have been established by the Society of Gynecology Oncology and American College of Obstetrics and Gynecology for referral to a gynecologic oncologist, but these have lower sensitivity and specificity than the RMI.

Recently, two new algorithms have been developed to identify women at sufficiently high risk to prompt referral to a specialized surgeon. The OVA1 multivariate index incorporates imaging, menopausal status, CA125 and four other proteomic biomarkers. Use of OVA1 provides 85%-96% sensitivity at 28%-40% specificity depending upon menopausal status. The negative predictive value for women judged to be at low risk is 94%-96%.

The risk of malignancy algorithm (ROMA) includes CA125, human epididymal protein 4 and menopausal status, but not imaging results.

paywalled: Intraperitoneal and intravenous chemotherapy in peritoneal carcinomatosis.

Intraperitoneal and intravenous chemotherapy in peritoneal carcinomatosis.:

Intraperitoneal and intravenous chemotherapy in peritoneal carcinomatosis.

Hepatogastroenterology. 2012 Jul-Aug

Abstract
Background/Aims:
We conducted a phase I trial of IP oxaliplatin and paclitaxel with IV paclitaxel and bevacizumab in patients with peritoneal carcinomatosis.

Methodology:
Patients received IV bevacizumab (2.5mg/kg) over 1 hour (day 1), then IV paclitaxel (110mg/m2) 24-hr-infusion (day 1) and IP oxaliplatin (25-40mg/m2) (day 2), and IP paclitaxel (30-60mg/m2) (day 8 from cycle 2 onwards). A '3+3' design was used.

Results:
Nineteen patients were treated (median age 60 years; 10 women, 9 men; median number of prior therapies 3). Primary tumors were colorectal (n=9), signet ring carcinoma (n=2), gastric (n=2), ovarian (n=2) and others (n=4). The maximum tolerated doses (MTD) of IP oxaliplatin and IP paclitaxel were 25mg/m2 and 60mg/ m2, respectively. Nine (47%) patients reported no toxicities >grade 2. Two patients receiving IP oxaliplatin 40mg/m2 and IP paclitaxel 60mg/m2 had dose limiting toxicities (DLT) of grade 3 diarrhea/dehydration and febrile neutropenia. Toxicities included abdominal pain (n=14), nausea (n=10) and constipation (n=7). Of 12 patients restaged at 2 months, 7 (58%) had stable disease (SD) including 2 (17%) who had SD for >4 months.

Conclusions: 
IP paclitaxel and IP oxaliplatin can be given safely at 60mg/m2 and 25mg/m2, respectively.

PMID: 22580643 [PubMed - in process]

paywalled: Recurrent and founder mutations in the PMS2 gene - Clinical Genetics

Recurrent and founder mutations in the PMS2 gene - Tomsic - Clinical Genetics

Germline mutations in PMS2 are associated with Lynch syndrome (LS), the most common known cause of hereditary colorectal cancer.

Mutation detection in PMS2 has been difficult due to the presence of several pseudogenes, but a custom-designed long-range PCR strategy now allows adequate mutation detection. Many mutations are unique. However some mutations are observed repeatedly, across individuals not known to be related, due to the mutation being either recurrent, arising multiple times de novo at hot spots for mutations, or of founder origin, having occurred once in an ancestor. Previously, we observed 36 distinct mutations in a sample of 61 independently ascertained Caucasian probands of mixed European background with PMS2 mutations.

Eleven of these mutations were detected in more than one individual not known to be related and of these, six were detected more than twice. These six mutations accounted for 31 (51%) ostensibly unrelated probands. Here we performed genotyping and haplotype analysis in four mutations observed in multiple probands and found two (c.137G>T and exon 10 deletion) to be founder mutations, one (c.903G>T) a probable founder, and one (c.1A>G) where founder mutation status could not be evaluated. We discuss possible explanations for the frequent occurrence of founder mutations in PMS2.

paywalled: Mismatch repair analysis of inherited MSH2 and/or MSH6 variation pairs found in cancer patients - Kantelinen - Human Mutation - Wiley Online Library

Mismatch repair analysis of inherited MSH2 and/or MSH6 variation pairs found in cancer patients - Kantelinen - Human Mutation

Abstract

Mismatch repair (MMR) malfunction causes the accumulation of mismatches in the genome leading to genomic instability and cancer. The inactivation of an MMR gene (MSH2, MSH6, MLH1 or PMS2) with an inherited mutation causes Lynch syndrome (LS), a dominant susceptibility to cancer. MMR gene variants of uncertain significance (VUS) may be pathogenic mutations which cause LS, may result in moderately increased cancer risks, or may be harmless polymorphisms. Our study suggests that an inherited MMR VUS individually assessed as proficient may, however, in a pair with another MMR VUS found in the same colorectal cancer (CRC) patient have a concomitant contribution to the MMR deficiency. Here, eight pairs of MMR gene variants found in cancer patients were functionally analyzed in an in vitro MMR assay. Although the other pairs do not suggest a compound deficiency, the MSH2 VUS pair c.380A>G/c.982G>C (p.Asn127Ser/p.Ala328Pro), which nearly halves the repair capability of the wild type MSH2 protein, is presumed to increase the cancer risk considerably. Moreover, two MSH6 variants, c.1304T>C (p.Leu435Pro) and c.1754T>C (p.Leu585Pro), were shown to be MMR deficient. The role of one of the most frequently reported MMR gene VUS, MSH2 c.380A>G (p.Asn127Ser), is especially interesting, since its concomitant defect with another variant could finally explain its recurrent occurrence in CRC patients.

Increased Expression of PITX2 Transcription Factor Contributes to Ovarian Cancer Progression

PLOS Increased Expression of PITX2 Transcription Factor Contributes to Ovarian Cancer Progression:

Principal Findings
.....Clinicopathological correlation showed that the upregulated PITX2 was significantly associated with high-grade (P = 0.023) and clear cell subtype (P = 0.011) using Q-PCR and high-grade (P<0.001) ovarian cancer by IHC analysis. Functionally, enforced expression of PITX2 could promote ovarian cancer cell proliferation, anchorage-independent growth ability, migration/invasion and tumor growth in xenograft model mice. Moreover, enforced expression of PITX2 elevated the cell cycle regulatory proteins such as Cyclin-D1 and C-myc. Conversely, RNAi mediated knockdown of PITX2 in PITX2-high expressing ovarian cancer cells had the opposite effect.

Conclusion
Our findings suggest that the increased expression PITX2 is involved in ovarian cancer progression through promoting cell growth and cell migration/invasion. Thus, targeting PITX2 may serve as a potential therapeutic modality in the management of high-grade ovarian tumor.

paywalled: Recording patient preferences for end-of-life care as an incentivized quality indicator: What do general practice staff think?

Recording patient preferences for end-of-life care as an incentivized quality indicator: What do general practice staff think?:

Introduction: Since April 2009, indicators for the UK Quality and Outcomes Framework pilot have been developed and piloted across a nationally representative sample of practices. In October 2009 a single palliative care indicator was piloted for 6 months that looked at, ‘the percentage of patients on the palliative care register who have a preferred place to receive end-of-life care documented in the records’.

Aim: The aim of this study was to gain the views and experiences of general practice staff on whether the inclusion of a single incentivized indicator to record the preferred place to receive end-of-life care would improve the quality of palliative care. Any issues arising from its implementation in a pay-for-performance scheme were also explored.

Methods: Interviews took place with 57 members of staff in 24 practices: 21 GPs, 16 practice managers, 12 nurses and eight others (mostly information technology experts).

Results: The indicator was not deemed appropriate for incentivization due to concerns about incentivizing an isolated, single issue within a multi-faceted, multi-disciplinary and complex topic. Palliative care was seen to be too sensitive and patient specific to be amenable to population-level quality measurement. In implementation, the indicator would pose potential harm to patients who may be asked about their end-of-life care at an inappropriate time and by a member of staff who may not be best placed to address this sensitive topic.

Conclusions: The most appropriate time to ask a patient about end-of-life care is subjective and patient specific and therefore does not lend itself to an inflexible single indicator. Focusing on one isolated question simplifies and distracts from a multi-faceted and complex issue and may lead to patient harm.

American Society for Clinical Pathology: Molecular Testing in Colorectal Cancer (Lynch Syndrome/MLH1, MSH2, MSH6, PMS2/MSI-H/KRAS/BRAF.....)

Blogger's Note: focus (obviously) on colorectal cancer, however, the cancer spectrum of Lynch Syndrome is noted in this paper as well as the shortcomings of the Bethesda Guidelines

 Molecular Testing in Colorectal Cancer

Conclusion

In summary, current standard-of-care molecular testing of CRC is aimed at detecting Lynch syndrome and KRAS mutations. However, with recent rapid development of biological agents targeted against components of the EGFR signaling cascade in the treatment of CRCs, mutational analysis of the genes in the EGFR signaling pathway may become a standard of care for patients with CRC in the near future. Ideally, identifying molecular prognostic and predictive factors may allow us to identify high-risk patients with stage II CRC who will benefit from chemotherapy after surgery. In addition, this may allow us to determine patients’ eligibility for targeted biological therapies.

A benign multicystic peritoneal mesothelioma mimicking recurrence of ovarian borderline tumor: a case report

A benign multicystic peritoneal mesothelioma mimicking recurrence of ovarian borderline tumor: a case report:

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

 Introduction
Benign multicystic peritoneal mesothelioma (BMPM) is an extremely rare tumor that occurs mainly in women in their reproductive age. Its preoperative diagnosis and adequate treatment are quite difficult to attain.

Case presentation
The case was 23 years-old Japanese woman and had a history of right oophorectomy and left ovarian cystectomy for an ovarian tumor at 20 years of age. The left ovarian tumor had been histologically diagnosed as mucinous borderline tumor. Two years and 9 months after the initial operation, multiple cysts were found in the patient. Laparotomy was performed, and the uterus, left ovary, omentum, and pelvic lymph nodes were removed due to suspicion of recurrence of the borderline tumor. Histological examination, however, revealed that the cysts were not a recurrence of the borderline tumor but rather BMPM. There were no residual lesions, and the patient was followed up with ultrasonography. She remains free from recurrence 9 months after treatment.

Conclusion:
We report a case of BMPM mimicking recurrence of ovarian borderline tumor. BMPM should be suspected when a multicystic lesion is present in the pelvis as in the case presented here, especially in patients with previous abdominal surgery.