ScienceDirect.com - Gynecologic Oncology - Predictors of severe and febrile neutropenia during primary chemotherapy for ovarian cancer
Direct Link:
Thursday, May 17, 2012
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
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 surgeryResults
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.
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.
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.
The following pages summarize new and important cancer drug data released tonight by ASCO from research abstracts for its upcoming annual meeting.......
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......
Wednesday, May 16, 2012
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
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.
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:
|
A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z |
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.
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.:
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.
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.
IntroductionBenign 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.
paywalled - Unravelling the two entities of endometrioid ovarian cancer: A single center clinical experience
Unravelling the two entities of endometrioid ovarian cancer: A single center clinical experience
Abstract
Objective
Due
to the increasing prevalence of the benign condition, ovarian carcinoma
arising from endometriosis is emerging as a relevant clinical entity
with an unclear biological signature. We have investigated clinical and
histologic features of endometriosis-associated endometrioid ovarian
cancer using an institutional retrospective database.
Methods
Patients
diagnosed with endometrioid ovarian cancer at our institution were
divided into two groups according to the fulfillment or not of Sampson's
and Scott's criteria for the detection of endometriosis-associated
ovarian cancer. Clinical and histological data were reported and
compared. Survival analysis was obtained using the log-rank test in an
unadjusted Kaplan-Meier method. Multivariate analysis was performed
using the Cox proportional hazards regression model to establish
independent factors associated with endometriosis-associated
endometrioid ovarian cancer and to identify predictors of survival.
Results
Patients
with endometriosis-associated endometrioid ovarian cancer were
significantly younger, had a lower disease stage (77% vs 38%; p = 0.003), a less prevalent high grade tumor (38% vs 82%; p = 0.002)
and a higher prevalence of squamous and mucinous metaplasia.
The rate
of endometrial cancer diagnosis was significantly higher in women with
endometriosis-associated endometrioid ovarian cancer (33%) than in other
patients (11%) (p = 0.04) with a 92% concordance between
ovarian and endometrial histologic tumor grade. A significant difference
in survival rate could not be demonstrated between patients with or
without endometriosis.
Conclusions
The
analysis of a retrospective endometrioid ovarian cancer database may
allow to suggest a molecular, morphological and clinical parallelism
between endometrial and endometrioid ovarian cancer.
Highlights
►
Endometriosis-associated endometrioid ovarian tumors possess a
different biologic signature when compared to cancers not associated
with the disease.
► Clinical course and molecular alterations of type I and type II endometrial tumors are similar to those detected respectively in endometriosis-associated and non-associated endometrioid ovarian tumor.
► Clinical course and molecular alterations of type I and type II endometrial tumors are similar to those detected respectively in endometriosis-associated and non-associated endometrioid ovarian tumor.
Journal of Ovarian Research May 15th: Tubal ligation, hysterectomy and ovarian cancer: A meta-analysis
Blogger's Note: included in the study are references to hereditary ovarian cancer - BRCA's but not Lynch Syndrome
~~~~~~~~~~~~~~~
Journal of Ovarian Research Tubal ligation, hysterectomy and ovarian cancer: A meta-analysis
Introduction
Ovarian cancer is the fifth leading cause of cancer death in US women [1], yet primary prevention recommendations are limited. Gynecological surgeries including tubal ligation and hysterectomy may alter ovarian cancer risk by protecting the ovary from ascending carcinogens or damaging the utero-ovarian artery altering hormonal function. In addition, tubal ligation may increase immunity against the surface glycoprotein human mucin 1 (MUC1) [2-4]. While tubal ligation and hysterectomy generally have been found to be inversely associated with ovarian cancer, effect estimates vary between studies and little is
known about potential effect modifiers of these associations. Therefore, we conducted a meta-analysis of the association between ovarian cancer and tubal ligation as well as hysterectomy.
Results
......In secondary analyses, the association between tubal ligation and ovarian cancer risk was stronger for endometrioid tumors compared to serous tumors.
Conclusion
Observational epidemiologic evidence strongly supports that tubal ligation and hysterectomy
are associated with a decrease in the risk of ovarian cancer, by approximately 26-30%.
Additional research is needed to determine whether the association between tubal ligation
and hysterectomy on ovarian cancer risk differs by individual, surgical, and tumor
characteristics.
pdf
What Did You Know, and When Did You Stop Knowing It? - Forbes
What Did You Know, and When Did You Stop Knowing It? - Forbes
Recently, a story (Analytical Trend Troubles Scientists) appeared in The Wall Street Journal that was critical of — what turns out to be — an increasingly common type of medical investigation: the observational study.
The WSJ story uses as its jumping-off point the (shocking? surprising?) discrepancy between two studies that both asked the same question and used the same data: does taking bisphosphonates (think Fosamax) increase your risk of stomach or throat cancer?
One study concluded that no, it does not significantly increase your cancer risk. The other said that yes, it does significantly increase said risk. ["Significantly" here means "probably", in the statistician's sense.] In neither case, though, did it find that your cancer risk would be particularly high: 0.1% vs 0.2% in 60/69-year-olds. So why the dustup?.....
DcR3 binds to ovarian cancer via heparan sulfate proteoglycans and modulates tumor cells response to platinum with corresponding alteration in the expression of BRCA1
DcR3 binds to ovarian cancer via heparan sulfateproteoglycans and modulates tumor cells response toplatinum with corresponding alteration in theexpression of BRCA1
Background
Overcoming platinum resistance is a major obstacle in the treatment of Epithelial Ovarian Cancer (EOC). In our previous work Decoy Receptor 3 (DcR3) was found to be related to platinum resistance. The major objective of this work was to define the cellular interaction of DcR3 with EOC and to explore its effects on platinum responsiveness.
Conclusions
Non-malignant cells contribute to the high levels of DcR3 in ovarian cancer. DcR3 binds readily to EOC cells via HSPGs and alter their responsiveness to platinum chemotherapy.The paradoxical responses seen were related to the expression pattern of HSPGs available on the cells surface to interact with. Although the mechanism behind this is not completely known alterations in DNA repair pathways including the expression of BRCA1 appear to be involved.
Tuesday, May 15, 2012
Inflammatory Breast Cancer: What We Know and What We Need to Learn
Inflammatory Breast Cancer: What We Know and What We Need to Learn:
Abstract
Purpose. We review the current status of multidisciplinary care for patients with inflammatory breast cancer (IBC) and discuss what further research is needed to advance the care of patients with this disease.
Design. We performed a comprehensive review of the English-language literature on IBC through computerized literature searches.
Results. Significant advances in imaging, including digital mammography, high-resolution ultrasonography with Doppler capabilities, magnetic resonance imaging, and positron emission tomography–computed tomography, have improved the diagnosis and staging of IBC. There are currently no established molecular criteria for distinguishing IBC from noninflammatory breast cancer. Such criteria would be helpful for the diagnosis and development of novel targeted therapies. Combinations of neoadjuvant systemic chemotherapy, surgery, and radiation therapy have led to an improved prognosis; however, the overall 5-year survival rate for patients with IBC remains very low (~30%). Sentinel lymph node biopsy and skin-sparing mastectomy are not recommended for patients with IBC.
Conclusion. Optimal management of IBC requires close coordination among medical, surgical, and radiation oncologists, as well as radiologists and pathologists. There is a need to identify molecular changes that define the pathogenesis of IBC to enable eradication of IBC with the use of IBC-specific targeted therapies.
paywalled: Sex Differences in Fertility-Related Information Received by Young Adult Cancer Survivors (ages 18-45 yrs/includes ovarian cancer))
Sex Differences in Fertility-Related Information Received by Young Adult Cancer Survivors [Treatment-Related Complications]:
Purpose
The aim was to investigate male and female cancer survivors' perception of fertility-related information and use of fertility preservation (FP) in connection with cancer treatment during reproductive age.
Conclusion
Our results show marked sex differences regarding the receipt of fertility-related information and use of FP. There is an urgent need to develop fertility-related information adapted to female patients with cancer to improve their opportunities to participate in informed decisions regarding their treatment and future reproductive ability.
paywalled: Potential Usefulness of Single Nucleotide Polymorphisms to Identify Persons at High Cancer Risk: An Evaluation of Seven Common Cancers [Statistics in Oncology]
Potential Usefulness of Single Nucleotide Polymorphisms to Identify Persons at High Cancer Risk: An Evaluation of Seven Common Cancers [Statistics in Oncology]:
Purpose
To estimate the likely number and predictive strength of cancer-associated single nucleotide polymorphisms (SNPs) that are yet to be discovered for seven common cancers.
Methods
From the statistical power of published genome-wide association studies, we estimated the number of undetected susceptibility loci and the distribution of effect sizes for all cancers. Assuming a log-normal model for risks and multiplicative relative risks for SNPs, family history (FH), and known risk factors, we estimated the area under the receiver operating characteristic curve (AUC) and the proportion of patients with risks above risk thresholds for screening. From additional prevalence data, we estimated the positive predictive value and the ratio of non–patient cases to patient cases (false-positive ratio) for various risk thresholds.
Results
Age-specific discriminatory accuracy (AUC) for models including FH and foreseeable SNPs ranged from 0.575 for ovarian cancer to 0.694 for prostate cancer. The proportions of patients in the highest decile of population risk ranged from 16.2% for ovarian cancer to 29.4% for prostate cancer. The corresponding false-positive ratios were 241 for colorectal cancer, 610 for ovarian cancer, and 138 or 280 for breast cancer in women age 50 to 54 or 40 to 44 years, respectively.
Conclusion
Foreseeable common SNP discoveries may not permit identification of small subsets of patients that contain most cancers. Usefulness of screening could be diminished by many false positives. Additional strong risk factors are needed to improve risk discrimination.
Monday, May 14, 2012
Dr Rob Lamberts blog: Zen and the Art of Not Thinking Magically - Don't assume anything
Zen and the Art of Not Thinking Magically:
By Rob Lamberts, MD
Don’t assume anything.
Assumptions can kill. Assuming something regarding your own health care can cost you money, cause you pain, and yes, even kill you. Here’s my list of potentially harmful assumptions:
1. No news is good news
If you have a test done and don’t hear anything about the result, do not assume it is fine. This assumption kills people. I have too many patients with too much information flying at me every day for me to catch every important detail. Sometimes things are missed, but sometimes the results don’t come to our office. We have trained our patients to expect an email or letter with their results within a certain amount of time, so they sometimes call when the test results don’t come in. I tell them to do so in the clinical summary sheet I hand out at the end of each visit, but the assumption remains.
Always know what tests are being run, and always get the results of those tests (in writing, if possible).
2. The doctor will think I am stupid
I often have patients apologizing to me. They apologize when they have a “weird” symptom, when they “ask too many questions,” when they stop taking a medication due to side-effects, and when they are really, really worried about something. They seem afraid that I am going to roll my eyes and think of them as “one of those patients” – the kind that I complain about to my office staff.
I hate it when people apologize. Apologies assume there is some standard or expectation that a person is not meeting, and the only expectations that I have of my patients is:
a. they have or want to prevent medical problems
b. They want my help.
Why should I get mad at people for either of these things, as it is the job of a doctor to help people who need them. I know there are doctors out there who treat patients like bad kids or like they are morons, but those doctors are out of step with reality. They are the morons. I don’t apologize to the barber that my hair grew. I don’t apologize to my accountant for having tax questions. Understand your position as the paying customer; get what you paid for.
One warning on this one: viewing yourself as a customer cuts both ways. If you have the right to get what you pay for, the doctor has the right to be paid for what they give you. People often think docs should do what they do out of pure charity and kindness, which is wrong. I may expect the mechanic to be kind and charitable, but I should also expect to pay them for what they do. This means that expecting your doctor to spend 30 minutes with you and only charge you for a 5-minute visit is not fair to the doctor (or his wife and kids).
3. Doctors don’t want to be questioned
I hope I am not unusual in this, but I would rather have patients question what I do than to accept everything I say.
Patients’ questions help me in several ways. First, they let me know what I am not explaining well enough. I think people follow instructions better when they understand them, so if you don’t understand what I said, ask. Second, questions build my credibility. If I can explain the reason for my recommendations, I am more trusted. If I fear questions, then it looks like I am hiding something. Third, and most importantly, questions sometimes lead to better care. Sometimes patients ask me about something I haven’t considered. Sometimes the questions make me think things through and see my faulty logic. Sometimes questions make me look for information and learn something.
Good doctoring has a whole lot of teaching in it. Teaching is not a goal in itself, however; the goal is to get the person being taught to understand. If you don’t understand what’s being done, why you got a prescription, or what your diagnosis is, ask. If you wonder about another possible diagnosis, ask. If your doctor doesn’t like you asking questions, ask for a copy of your records and find another doctor.
4. Standard care is the right care.
Much of what doctors do is based on, or at least consistent with science; but a lot of care goes on despite that science says otherwise. A group of physician organizations recently banded together and published the Choosing Wisely Campaign, a set of “things patients and physicians should question.” The groups urge doctors and patients to choose care that is:
- Supported by evidence
- Not duplicative of other tests or procedures already received
- Free from harm
- Truly necessary
- Getting an x-ray for people with uncomplicated back pain
- Using antibiotics for sinusitis lasting less than 7 days
- Routine EKG’s on average (lower-risk) people
- Routine screening stress-tests
- Use of anti-inflammatory drugs (NSAID’s) in people with high blood pressure, heart disease, kidney problems, or diabetes.
5. My doctors talk to each other
I am a primary care doctor, so I am supposed to be the hub of a patient’s care. If a patient of mine goes in the hospital, has surgery, sees a specialist, or goes to the emergency room, I am supposed to be notified. Unfortunately, this is probably not even true in of 50% of these situations. Even when patients ask specifically to have records sent to me, they often aren’t there.
Specialists also have this problem, often getting consults without a clear reason. Often this is a problem at the referring physician’s end, but we have had numerous specialists turn down offers to access our records. We have also offered access to our records by hospitalists and ER doctors, only to be been turned down. Many doctors prefer to give care with only information they gather. It is rare that any doctor has all of the information that may be helpful.
An exception to this is the integrated care system run by a hospital (usually), in which doctors all share medical records. Clearly the sharing of information in that setting is better than in my world, but being under the care of a hospital gives other disadvantages I will discuss later.
6. My doctor has accurate records
Not only do I not have much of the information that comes from other doctors, but the information I do have in my records are not always accurate. The biggest culprit in our office is old information that doesn’t get taken off. It takes a large amount of time to make sure a person’s records are accurate, and there are no insurance companies willing to pay for improved accuracy. So accuracy only happens when doctors take time away from reimbursed patient care and work to organize the records. Again, our office makes a valiant effort at keeping things accurate, but I have found that it takes a huge amount of time, planning, and energy to keep records updated.
I personally don’t think this will change until the patient becomes responsible to keep their own records. Nobody will ever care about a patient’s records as much as the patient does. In the mean-time, I recommend that you keep an updated list of your medications, surgeries, problems, and even your family/home situation and bring it with you to visits.
7. I will be notified when things are due
Are you due for a colonoscopy, thyroid lab tests, a follow-up CT scan, or a diabetic eye exam? Most people don’t know exactly when things are due, and many assume they will be notified when this is the case. Gastroenterologists do often call when the follow-up colonoscopy is due, and mammography facilities sometimes call for a follow-up, but these are exceptions to this rule. Doctors often say “repeat test in six months,” and then expect the patient to call to schedule after six months. Even patients coming into the office may not be reminded of overdue tests, mainly due to the disorganization of medical records (#3 above). If you think you might be due for something, ask. Even asking the question, “are there any tests or labs I am due to get done?” can help remind providers to check for these things. Remember, it is incredibly hard to keep records organize, so don’t assume your doctor’s office will act anything like Jiffy-Lube.
8. Hospitals care
The commercials boast of how local hospitals are “there for you when you need them most,” and “your advocate for your health.” This is horse hockey. The people in the hospital may be caring and kind. The doctors, nurses, and even administrators may want you to be healthy. But the hospital is a business which requires people to be sick and have lots of procedures done to be profitable. Most health care dollars are spent in hospitals, and many times those dollars do no good to the patient. I’ve seen end-stage cancer patients get heart catheterization, people with dementia spend weeks in the ICU, and countless other procedures are done with no benefit (other than income to the hospital).
Don’t be fooled. Your goal is to stay healthy and stay out of the hospital; your doing so is bad for the business of hospitals.
9. More is better
I have patients frequently asking for tests they don’t need. Shouldn’t people get yearly lab panels? Shouldn’t kids get their cholesterol checked? What about those screening mobile tests for carotid artery plaques or PAD? It’s hard to make my patients understand that in saying “no” to tests, I am being a better doctor. I talked about this in an earlier post, but it bears repeating. If someone has a high chance of having a condition, screening for it is useless (doing a strep test on someone with an obvious strep throat). If someone has a very low chance of having a condition, screening for it won’t reduce the risk (CA-125 screening for ovarian cancer, for example). Having more information is often not helpful, can lead to unnecessary worry or further testing, and costs a lot of money for no gain. I don’t want more information, I want the right information.
10. New is better
What about that new drug advertised on TV? What about the surgery done by robots? Should I take that antidepressant for pain? Do I have low-T? Should I go to the hospital with the brand new 200 gazillion dollar heart pavilion? Always look at advertising with a skeptical eye. The main reason businesses spend money on advertising is that they want to make more money when you use the thing they advertised. The 200 gazillion dollars for the heart pavilion has to come from somewhere. There’s a reason why you first heard of “low T” on television and not from your doctor: the company who wants to fix your T wants your money. Robotic surgery is surely cool, but it is also really expensive to buy that machine, and hospitals need you to want the “cool” surgery so they can pay for those machines.
Sometimes “new and improved” is a truthful boast, but usually it is a means into your wallet.
Rob Lamberts, MD, is a primary care physician practicing somewhere in the southeastern United States. He blogs regularly at More Musings (of a Distractible Kind). Where this post first appeared.
ESO: e-grandround May 24th: Biomarkers and candidate therapeutics in ovarian cancer pipeline
Biomarkers and candidate therapeutics in ovarian cancer pipeline
e-grandround
Biomarkers and candidate therapeutics in ovarian cancer pipeline CME accredited
e-grandround GR197 - 24 May 2012 - 18:15-19:00 CETExpert: Hani Gabra, Imperial College, London, United Kingdom
Discussant: Margaret Hutka, Royal Marsden Hospital, Sutton, United Kingdom
The live session starts in about 9 days
Access to the live session is open 15 minutes before the start of the session
Submit your question in advance
Access to the live session is open 15 minutes before the start of the session
An In Vitro Diagnostic Multivariate Index Assay (IVDMIA) for Ovarian Cancer: Harvesting the Power of Multiple Biomarkers (OVA1)
An In Vitro Diagnostic Multivariate Index Assay (IVDMIA) for Ovarian Cancer: Harvesting the Power of Multiple Biomarkers
Dr. Zhang is the inventor of the OVA1 algorithm, and as such is entitled to royalty payments from the sale of OVA1® through a license agreement between Johns Hopkins University and Vermillion, Inc.
Main Points
- The advantages of an in vitro diagnostic multivariate index assay (IVDMIA) in comparison to a single biomarker assay are based on the premise that the single-valued index, with its aggregated information from complementary biomarkers, will outperform each of its component biomarkers used individually.
- The ability of multivariate models to capture complex patterns in high-dimensional data also means that non-disease-related artifacts that happen to confound the samples used to train the models will also be captured.
- The inclusion of biomarkers in an IVDMIA requires that they are complementary, and that they collectively outperform a single marker with respect to the test’s intended use.
- OVA1® (Vermillion, Inc., Austin, TX) combines results from five tests—CA-125 II, prealbumin, apolipoprotein A-1, β2-microglobulin, and transferrin—into a single-valued index between 0 and 10; a higher value corresponds to a higher risk of malignancy.
- The addition of OVA1 to clinical assessment brings significant improvement in sensitivity. This is, however, at the cost of a reduced specificity. During the construction of the OVA1 multivariate model and the choice of cutoff values, a conscious decision was made to emphasize the need for a high sensitivity. This decision took into consideration the need to mitigate the safety concern of OVA1 with respect to its predefined intended use. Because OVA1 is to be used prior to the decision to refer to a specialist, a high sensitivity minimizes the risk of false-negative results for patients who actually have malignant diseases.
paywalled - Contraception - Reproductive factors in relation to ovarian cancer: a case–control study in Northern Vietnam
ScienceDirect.com - Contraception - Reproductive factors in relation to ovarian cancer: a case–control study in Northern Vietnam
Abstract
Background
Ovarian
cancer, one of the most common cancers in women and the most serious
gynecologic cancer, is known to be influenced by reproductive factors,
but these factors have not previously been examined in Vietnamese women.
PLoS ONE: European American Stratification in Ovarian Cancer Case Control Data: The Utility of Genome-Wide Data for Inferring Ancestry
Blogger's Note: interesting article includes migration of peoples from Europe to North America/s; ovarian cancer and genome
PLoS ONE: European American Stratification in Ovarian Cancer Case Control Data: The Utility of Genome-Wide Data for Inferring Ancestry
paywalled: Limited prognostic value of tissue protein expression levels of cyclin E in Danish ovarian cancer patients: from the Danish ‘MALOVA’ ovarian cancer study
Limited prognostic value of tissue protein expression levels of cyclin E in Danish ovarian cancer patients: from the Danish ‘MALOVA’ ovarian cancer study
The
primary objective of this study was to assess the expression of cyclin E
in tumour tissues from 661 patients with epithelial ovarian tumours.
The second was to evaluate whether cyclin E tissue expression levels
correlate with clinico-pathological parameters and prognosis of the
disease. Using tissue arrays (TA), we analysed the cyclin E expression
levels in tissues from 168 women with borderline ovarian tumours (BOT)
(147 stage I, 4 stage II, 17 stage III) and 493 Ovarian cancer (OC)
patients (127 stage I, 45 stage II, 276 stage III, 45 stage IV). Using a
10% cut-off level for cyclin E overexpression, 20% of the BOTs were
positive with a higher proportion of serous than mucinous tumours.
Sixty-two per cent of the OCs were positive for cyclin E expression with
the highest percentage found in clear cell carcinomas.
Results based on univariate and multivariate survival analyses with a 10% cut-off value showed that cyclin E had no independent prognostic value. In conclusion, we found cyclin E expression in tumour tissue to be of limited prognostic value to Danish OC patients.
Results based on univariate and multivariate survival analyses with a 10% cut-off value showed that cyclin E had no independent prognostic value. In conclusion, we found cyclin E expression in tumour tissue to be of limited prognostic value to Danish OC patients.
open access: original paper - Intra-operative frozen section analysis for suspected early-stage ovarian cancer: 11 years of Gateshead Cancer Centre experience - Cross - 2011 - BJOG: An International Journal of Obstetrics & Gynaecology - Wiley Online Library
Intra-operative frozen section analysis for suspected early-stage ovarian cancer: 11 years of Gateshead Cancer Centre experience - Cross - 2011 - BJOG: An International Journal of Obstetrics & Gynaecology - Wiley Online Library
Gynaecological oncology
Intra-operative frozen section analysis for suspected early-stage ovarian cancer: 11 years of Gateshead Cancer Centre experience
Article first published online: 6 SEP 2011
DOI: 10.1111/j.1471-0528.2011.03129.x
© 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG
Correspondence: re - Intra-operative frozen section analysis for suspected early-stage ovarian cancer - Twigg - 2012 - BJOG: An International Journal of Obstetrics & Gynaecology - Wiley Online Library
Intra-operative frozen section analysis for suspected early-stage ovarian cancer - Twigg - 2012 - BJOG: An International Journal of Obstetrics & Gynaecology
Correspondence
Sir,
We read with interest the article by Cross et al.1
on the use of intra-operative frozen section for suspected early
ovarian cancer. We would like to commend the authors for their work in
providing these data and we recognise the need for mechanisms that can
be used to address the National Institute for Health and Clinical
Excellence (NICE) Guidelines CG122, which recommend assessment of the
para-aortic lymph nodes in women with early ovarian cancer.2
However,
there are a number of areas of practice that we feel need to be
examined further before frozen section procedures can be used to alter
the management of women with suspected early-stage ovarian cancer.
First,
we are perplexed that the authors deemed it necessary to undertake
para-aortic lymphadenectomy for women with borderline ovarian tumours.
These are by nature an unpredictable class of tumour with mostly good
outcomes and little in the way of nonsurgical treatment options when
there is disseminated disease. Further, they are usually early-stage
tumours and so the utility of a para-aortic lymph node dissection is
questionable. If the authors had described the rate of disease in lymph
nodes and the difference in outcome this provided for the woman with
positive nodes their data would lend stronger support for more
widespread implementation.
Accepting this
and examining the authors data for ‘all comers’ (Table 1) we calculate
that 28.8% (415) of women had an appropriate para-aortic lymph node
dissection on the basis of the frozen section prediction, which
represents the real-world scenario for the gynaecological oncology
surgeon waiting in theatre for a frozen section analysis to be phoned
back.
If the authors changed their
protocol to only using dissection in women with malignancy on frozen
section, 63.8% (918) of women would appropriately not undergo a
para-aortic dissection. The total number of women correctly triaged by
frozen section analysis would be 92.6%. Of the remainder, 7% would not
undergo a para-aortic dissection that should and 0.35% would have a
dissection they do not need. Such a protocol change compares with the
authors’ figures who, when including a policy of para-aortic dissection
for borderline tumours on frozen section, overtreated 8% of the women
and undertreated 1.3%.
The answer to
deciding which strategy one would wish to take up must come down to the
differences in outcome for these women, defined by morbidity and
mortality comparisons from overtreatment or undertreatment by surgery or
chemotherapy, respectively, and any subsequent influence this has on
overall survival. Unfortunately the authors do not provide this
information, and only allude to data in preparation that indicate their
ability to increase the stage of a woman’s disease. However, this figure
can be calculated from their data in Table 1 to equate to 82 women
(5.7%) who had a frozen section showing borderline disease but whose
final paraffin section report showed a malignancy. Until other centres
can validate their techniques and such practice can be shown to
translate into a survival benefit for women, it is unlikely that their
data will change surgical practice in women with early ovarian cancer.
References
- 1, , , , , , et al. Intra-operative frozen section analysis for suspected early-stage ovarian cancer: 11 years of Gateshead Cancer Centre experience. BJOG 2012;119:194–201.
- 2National Institute for Health and Clinical Excellence. The recognition and initial management of ovarian cancer. [http://www.nice.org.uk/CG122]. Accessed 20 January 2012.
Friday, May 11, 2012
paywalled: (re: juice plus) Gynecologic Oncology - A randomized parallel-group dietary study for stages II–IV ovarian cancer survivors
Blogger's Note: reference prior posting (juice plus) noting that the audio indicated that the study was done on those ovarian cancer survivours without active disease, not indicated in this abstract (defining cancer survivors?); as well, not indicated (needs confirmation) in the audio is that the study size was small at 51 patients
ScienceDirect.com - Gynecologic Oncology - A randomized parallel-group dietary study for stages II–IV ovarian cancer survivors
A randomized parallel-group dietary study for stages II–IV ovarian cancer survivors
- Received 29 September 2011. Accepted 15 November 2011. Available online 23 November 2011.
Abstract
Objective
Few
studies have examined the dietary habits of ovarian cancer survivors.
Therefore, we conducted a study to assess the feasibility and impact of
two dietary interventions for ovarian cancer survivors.
Methods
In
this randomized, parallel-group study, 51 women (mean age, 53 years)
diagnosed with stages II–IV ovarian cancer were recruited and randomly
assigned to a low fat, high fiber (LFHF) diet or a modified National
Cancer Institute diet supplemented with a soy-based beverage and
encapsulated fruit and vegetable juice concentrates (FVJCs). Changes in
clinical measures, serum carotenoid and tocopherol levels, dietary
intake, anthropometry, and health-related quality of life (HRQOL) were
assessed with paired t-tests.
Results
The
recruitment rate was 25%, and the retention rate was 75% at 6 months.
At baseline, 28% and 45% of women met guidelines for intake of fiber and
of fruits and vegetables, respectively. After 6 months, total serum
carotenoid levels and α- and β-carotene concentrations were
significantly increased in both groups (P < 0.01); however,
β-carotene concentrations were increased more in the FVJC group. Serum
β-cryptoxanthin levels, fiber intake (+ 5.2 g/day), and daily servings
of juice (+ 0.9 servings/day) and vegetables (+ 1.3 servings/day) were
all significantly increased in the LFHF group (all P < 0.05).
Serum levels of albumin, lutein and zeaxanthin, retinol, and retinyl
palmitate were significantly increased in the FVJC group (all P < 0.05). No changes in cancer antigen-125, anthropometry, or HRQOL were observed.
Conclusion
Overall,
this study supports the feasibility of designing dietary interventions
for stages II–IV ovarian cancer survivors and provides preliminary
evidence that a low fat high fiber diet and a diet supplemented with
encapsulated FVJC may increase phytonutrients in ovarian cancer
survivors.
Highlights
►
Many ovarian cancer survivors fail to meet current guidelines for
dietary intake.
► A low-fat diet supplemented with encapsulated fruit and vegetable juice concentrates can improve carotenoid levels.
► Encapsulated fruit and vegetable juice concentrates may help bridge the gap between what is consumed and what is needed.
► A low-fat diet supplemented with encapsulated fruit and vegetable juice concentrates can improve carotenoid levels.
► Encapsulated fruit and vegetable juice concentrates may help bridge the gap between what is consumed and what is needed.
Subscribe to:
Posts
(
Atom
)
