Familial cancer and genetic syndromes
Monday, September 17, 2012
Sunday, September 16, 2012
Risk of urothelial bladder cancer in Lynch syndrome is increased, in particular among MSH2 mutation carriers (2010)
J Med Genet. 2010 July; 47(7): 464–470.
Published online 2010 June 30. doi: 10.1136/jmg.2010.076992
PMCID: PMC2991077
Risk of urothelial bladder cancer in Lynch syndrome is increased, in particular among MSH2mutation carriers
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Meaningful Responses To ‘We-Know-the-Answer’ Syndrome
Blogger's Note: requires registration / free (Markman/ovarian cancer illustrated)
Meaningful Responses To 'We-Know-the-Answer' Syndrome
Critical thinking—like the phrase "evidence-based"—has become a rather overused mantra in clinical medicine. As an unfortunate result, this concept has lost much of its meaning and its impact on how we evaluate study results and ultimately consider their use in the non-trial setting.
If the link below does not open, please copy and past this link into your browser:
http://www.clinicaloncology.com/ViewArticle.aspx?d=Clinical+Trials&d_id=165&i=January+2012&i_id=808&a_id=20047
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Terry Fox runs being held across the country to raise money for cancer research
Terry Fox runs being held across the country to raise money for cancer research
Irene Preklet and Kris McCusker | Sun Sep 16, 8:22 AM
He's a Canadian hero known all around the world, and on Sunday thousands of people are lacing up to walk or run in his name. Terry Fox runs are being held across the country and the GTA, with the goal of continuing Terry's dream of raising money for cancer research. "What you ever you do you gotta do the best you can possibly do, and I'm going to give it everything I possibly can," Fox said. And that he did, as Fox ran his Marathon of Hope, inspiring people across a nation. Martha McLew, Ontario Director of the Terry Fox Foundation, says there are 17 runs in the GTA alone. "I think that when people come out to the Terry Fox run, they realize they are doing it for such a personal reason, they are doing it for a loved one, and to really thank Terry at the same time," McLew said. There is no per-registration needed and no mandatory fee. To find a run near you, click here.
http://www.680news.mobi/article.aspx?content_id=401999Human epididymis protein 4 (HE4) and Ovarian cancer prognosis.
Abstract
OBJECTIVE: A cohort study was conducted to evaluate whether preoperative plasma HE4 levels could predict the occurrence of death (primary endpoint) and progression (secondary endpoint) in women with ovarian cancer (OC).
METHODS: Between 1998 and 2006, we recruited 136 women newly diagnosed with OC of any FIGO stage at the University Hospital, CHUQ-L'Hôtel-Dieu de Québec, Canada. HE4 was measured using the Abbott's ARCHITECT HE4 assay. Dates of death were obtained by record linkage with the Québec mortality files. Progression was evaluated using the CA-125 or the RECIST criteria, as recommended by the Gynecology Cancer Intergroup. Adjusted hazard ratios (HR) of death and progression, as well as their 95% confidence intervals (CI), were estimated using the Cox proportional hazard regression model.
RESULTS: Preoperative levels of HE4 were strongly associated with all OC standard prognostic factors. HE4 levels increased significantly with age (p=0.02), FIGO stage (p<0.0001), grade (p=0.005), preoperative CA-125 levels (p<0.0001), and residual tumor (p<0.0001). HE4 levels above the median value (394 pmol/L) were significantly associated with mortality (HR=2.17; 95% CI: 1.42-3.32) and progression (HR=1.81; 95% CI: 1.21-2.72). After adjustment for the FIGO stage, which was the only factor significantly associated with prognosis in multivariate analyses, the association of HE4 with death remained statistically significant (HR=1.67; 95% CI: 1.08-2.59). However, the association with progression was no longer significant (HR=1.32; 95% CI: 0.87-1.99).
CONCLUSION: These results show that preoperative the plasma level of HE4 is a marker of OC aggressiveness and a predictor of death.
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Saturday, September 15, 2012
Objective evaluation of the alleviating effects of Goshajinkigan on peripheral neuropathy induced by paclitaxel/carboplatin therapy: A multicenter collaborative study.
Objective evaluation of the alleviating effects of Goshajinkigan on peripheral neuropathy induced by paclitaxel/carboplatin therapy: A multicenter collaborative study.:
Exp Ther Med. 2012 Jan;3(1):60-65
Abstract
Paclitaxel/carboplatin chemotherapy for cancer (TC therapy) exhibits neurotoxicity and causes peripheral neuropathy at a high frequency, which is difficult to cope with. In this study, we investigated the efficacy of Goshajinkigan, a traditional Japanese herbal medicine, for TC therapy-induced peripheral neuropathy. The subjects included in our study were patients with ovarian or endometrial cancer who underwent TC therapy and developed peripheral neuropathy. The patients were randomly divided into Group A, comprising of 14 patients (vitamin B12 treatment), and Group B, comprising of 15 patients (vitamin B12 + Goshajinkigan treatment). The observation period was 6 weeks following treatment initiation, and the evaluation items were as follows: i) the current perception threshold (CPT value) of the peripheral nerve, ii) visual analogue scale for numbness, iii) National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 grade of neurotoxicity, and iv) a questionnaire on the subjective symptoms of peripheral neuropathy (functional assessment of cancer therapy-taxane). These were compared between the groups and no significant differences were noted in any item. However, CTCAE grade 3 neurotoxicity developed in 2 patients (14.3%) after 6 weeks of administration in Group A, whereas no neurotoxicity was observed in Group B. When the change in the frequency of abnormal CPT ratio at 6 weeks of administration from that before treatment was compared between the groups, the frequency of abnormal value was significantly lower in Group B than in Group A (p<0.05). This suggests that Goshajinkigan inhibits the progression of peripheral neuropathy.
PMID: 22969845 [PubMed - as supplied by publisher]
Evaluation of microsatellite instability in women with epithelial ovarian cancer.
Evaluation of microsatellite instability in women with epithelial ovarian cancer.:
Oncol Lett. 2012 Sep;4(3):556-560
Abstract
The function of microsatellite instability (MSI) and the optimal panel of markers for epithelial ovarian cancer (EOC) are not well established. This study aimed to use the National Cancer Institute (NCI) markers BAT25, BAT26, D2S123, D5S346 and D17S250 to evaluate MSI in patients with ovarian serous cystadenocarcinoma, compared with ovarian serous cystadenoma and normal ovaries. A total of 37 patients were divided into three groups, as follows: cystadenocarcinoma (n=13), cystadenoma (n=10) and normal ovaries (n=14). DNA was extracted with TRIzol and quantified by spectrophotometry. MSI was evaluated by polymerase chain reaction (PCR), and classified as high (MSI-H), low (MSI-L) or stable (MSS). FIGO staging was I/II in 23.1% and III/IV in 76.9% of the cystadenocarcinoma group. Polymorphisms were found using at least one marker in 32 women, and were observed with D2S123 (83.7%), D17S250 (81.1%), D5S346 (72.9%), BAT25 (21.6%) and BAT26 (16.2%) markers. In the cystadenocarcinoma group, BAT25, BAT26, D2S123, D5S346 and D17S250 markers were positive in 30.8, 76.9, 53.8, 69.2 and 69.2% of patients, respectively. The same markers were positive in 30, 50, 40, 60 and 30% of the cystadenoma group, and 50, 71.4, 71.4, 64.3 and 63.3% in the normal ovary group, respectively. MSI-H was present in 84.6, 60 and 78.6% of the cystadenocarcinoma, cystadenoma and normal patients, respectively. MSI-L was detected in 0, 30 and 7.1%, and MSS was identified in 15.4, 10 and 14.3% of the cystadenocarcinoma, cystadenoma and normal patients, respectively. The frequency of MSI in both benign epithelial ovarian neoplasms and in normal ovaries was high, as well as in EOC, with no statistically significant difference between the groups. This suggests that MSI may arise as a consequence of the ovulatory process, and not solely as a feature of malignant ovarian tumors.
PMID: 22970055 [PubMed - as supplied by publisher]
open access: Development of multiplexed bead-based immunoassays for the detection of early stage ovarian cancer using a combination of serum biomarkers.
Development of multiplexed bead-based immunoassays for the detection of early stage ovarian cancer using a combination of serum biomarkers.:
PLoS One. 2012;7(9):e44960
Abstract
CA125 as a biomarker of ovarian cancer is ineffective for the general population. The aim of this study was to evaluate multiplexed bead-based immunoassay of multiple ovarian cancer-associated biomarkers such as transthyretin and apolipoprotein A1, together with CA125, to improve the identification and evaluation of prognosis of ovarian cancer. We measured the serum levels of CA125, transthyretin, and apolipoprotein A1 from the serum of 61 healthy individuals, 84 patients with benign ovarian disease, and 118 patients with ovarian cancer using a multiplex liquid assay system, Luminex 100. The results were then analyzed according to healthy and/or benign versus ovarian cancer subjects. When CA125 was combined with the other biomarkers, the overall sensitivity and specificity were significantly improved in the ROC curve, which showed 95% and 97% sensitivity and specificity, respectively. At 95% specificity for all stages the sensitivity increased to 95.5% compared to 67% for CA125 alone. For stage I+II, the sensitivity increased from 30% for CA125 alone to 93.9%. For stage III+IV, the corresponding values were 96.5% and 91.6%, respectively. Also, the three biomarkers were sufficient for maximum separation between noncancer (healthy plus benign group) and stage I+II or all stages (I-IV) of disease. The new combination of transthyretin, and apolipoprotein A1 with CA125 improved both the sensitivity and the specificity of ovarian cancer diagnosis compared with those of individual biomarkers. These findings suggest the benefit of the combination of these markers for the diagnosis of ovarian cancer.
PMID: 22970327 [PubMed - in process]
Mucinous tumours of the ovary.
Mucinous tumours of the ovary.:
J Clin Pathol. 2012 Jul;65(7):580-4
Abstract
Mucinous epithelial ovarian cancers (mEOC) are a relatively rare subset of ovarian cancers. Despite a relatively favourable outcome in early disease, the more frequent advanced presentation is associated with poorer response to platinum/taxane chemotherapies, and poorer survival, compared to serous ovarian cancers. We consider some of the fundamental clinico-pathological and molecular features, and existing clinical trial data regarding mEOC. Underlying molecular differences, between mEOC and serous cancers may contribute to the observed clinical differences, including an increased prevalence of K-RAS mutations in mEOC, more in keeping with gastrointestinal tumours. This observation contributes to the rationale for a trial ("mEOC") investigating the use of "ovarian" versus "gastrointestinal" style chemotherapy. Looking to potential future approaches, we speculate upon the potential impact of emerging technologies on the future investigation and management of mEOC.
PMID: 22011449 [PubMed - indexed for MEDLINE]
Essays: Steven Lewis - Behavioural Economics Explains Why Ontario Doctors Are So Livid :: Longwoods.com
Behavioural Economics Explains Why Ontario Doctors Are So Livid :: Longwoods.com
Behavioural Economics Explains Why Ontario Doctors Are So Livid
Psychological outcomes of familial ovarian cancer screening: No evidence of long-term harm
Psychological outcomes of familial ovarian cancer screening: No evidence of long-term harm
View full text
Highlights
►
Abnormal results of familial ovarian cancer screening may raise women's
concerns in the short-term but not in the longer-term.
► Women receiving abnormal test results are more likely to withdraw from screening, primarily for salpingo-oophorectomy.
► Decision support is needed for women who are considering options for managing their risk of familial ovarian cancer.
► Women receiving abnormal test results are more likely to withdraw from screening, primarily for salpingo-oophorectomy.
► Decision support is needed for women who are considering options for managing their risk of familial ovarian cancer.
Abstract
Objectives
Ovarian
cancer screening for women at increased genetic risk in the UK involves
4-monthly CA125 tests and annual ultrasound, with further tests
prompted by an abnormal result. The study evaluated the longer-term
psychological and behavioural effects of frequent ovarian screening.
Methods
Women
completed T1 questionnaires before their first routine 4-monthly CA125
test, and T2 follow-up questionnaires one week after their result. Women
with abnormal results completed a further questionnaire one week after
return to routine screening (T3 primary end-point). T4 questionnaires
were sent at nine months. Measures included cancer distress, general
anxiety/depression, reassurance, and withdrawal from screening.
Results
A
total 1999 (62%) of 3224 women completed T1 questionnaires. T2
questionnaires were completed by 1384/1609 participants (86%): 1217
(89%) with normal results and 167/242 (69%) with abnormal results. T3
questionnaires were completed by 141/163 (87%) women, with 912/1173
(78%) completing T4 questionnaires. Analysis of covariance indicated
that, compared to women with normal results, women with abnormal results
reported moderate cancer distress (F = 27.47, p ≤ .001, η2 = 0.02)
one week after their abnormal result and were significantly more likely
to withdraw from screening (OR = 4.38, p ≤ .001). These effects were
not apparent at T3 or T4. The effect of screening result on general
anxiety/depression or overall reassurance was not significant.
Conclusions
Women
participating in frequent ovarian screening who are recalled for an
abnormal result may experience transient cancer-specific distress, which
may prompt reconsideration of risk management options. Health
professionals and policy makers may be reassured that frequent familial
ovarian screening does not cause sustained psychological harm.
Highlights
►
Abnormal results of familial ovarian cancer screening may raise women's
concerns in the short-term but not in the longer-term.
► Women receiving abnormal test results are more likely to withdraw from screening, primarily for salpingo-oophorectomy.
► Decision support is needed for women who are considering options for managing their risk of familial ovarian cancer.
► Women receiving abnormal test results are more likely to withdraw from screening, primarily for salpingo-oophorectomy.
► Decision support is needed for women who are considering options for managing their risk of familial ovarian cancer.
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