OVARIAN CANCER and US

Blog Archives: Nov 2004 - present

#ovariancancers



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Friday, September 30, 2016

(repeat) 25:24 min interview (Narod) Are women undergoing unnecessarily invasive cancer surgeries?



TVO.org

Ovarian Cancer Action - know the signs and symptoms - YouTube



YouTube 2:26 min (2014)

Disease extent at secondary cytoreductive surgery is predictive of progression-free and overall survival in advanced stage ovarian cancer



abstract: ....An NRG Oncology/Gynecologic Oncology Group study

Highlights

20% of suboptimal ovarian cancer patients had a pathologic CR at 2nd cytoreduction.
A pathologic CR at 2nd cytoreductive surgery is associated with improved PFS and OS.
A pathologic CR was not associated with known prognostic factors.

Abstract

Purpose

GOG 152 was a randomized trial of secondary cytoreductive surgery (SCS) in patients with suboptimal residual disease (residual tumor nodule > 1 cm in greatest diameter) following primary cytoreductive surgery for advanced stage ovarian cancer. The current analysis was undertaken to evaluate the impact of disease findings at SCS on progression-free survival (PFS) and overall survival (OS).

The impact of perioperative β blocker use on patient outcomes after primary cytoreductive surgery in high-grade epithelial ovarian carcinoma



Physiological condition or, more often "physiological conditions" is a term used in biology, biochemistry, and medicine. It refers to conditions of the external or internal milieu that may occur in nature for that organism or cell system, in contrast to artificial laboratory conditions.
Human physiology is the science of the mechanical, physical, and biochemical function of humans, and serves as the foundation of modern medicine. As a discipline, it connects science, medicine, and health, and creates a framework for understanding how the human body adapts to stresses, physical activity, and disease.
  ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
abstract:
The impact of perioperative β blocker use on patient outcomes after primary cytoreductive surgery in high-grade epithelial ovarian carcinoma 
  

Highlights

Stress is associated with poor prognosis in patients with solid tumors.
β blocker can lower down the physiologic stress response.
Use of perioperative β blocker after primary cytoreductive surgery for ovarian cancer associated with better overall survival

Abstract

Objective

To quantify the impact of perioperative β blocker use on survival after primary cytoreductive surgery for epithelial ovarian cancer.

Methods

We conducted a multi-center retrospective study of all women who underwent primary cytoreductive surgery for ovarian cancer (2000 − 2010). One institution had routinely used perioperative β blockers for patients “at risk” for coronary events. The other institution did not routinely use perioperative β blockers. Demographic, operative, and follow up data were collected. Cox proportional hazards models were used to assess the effect of β blockers on progression-free interval (PFI) as well as overall survival (OS).

Results

Out of 185 eligible patients, 70 received β blockers and 115 underwent cytoreductive surgery without perioperative β blockers. Both groups were similar in demographics. A history of hypertension was present more often in the β blocker group compared to the group that did not receive β blockers (22% and 6%, p = 0.002). PFI in β blocker group was greater at 18.2 vs. 15.8 months (p = 0.66). The OS in the β blocker group was significantly higher at 44.2 vs. 39.3 months (p = 0.01). In multivariate analysis, perioperative β blocker use was associated with significant improvement in OS (HR 0.68 (0.46–0.99); p = 0.046).

Conclusion

Our study showed an association between perioperative β blocker use and longer overall survival in patients undergoing primary ovarian cancer cytoreductive surgery. A prospective randomized clinical trial in this population would further validate these results.

Index: Sept 2016 Cancer Prevention Research



Cancer Prevention Research

2017 CADTH Symposium Travel Award Programs Criteria — Patient Group Representatives



2017 CADTH Symposium Travel Award Programs Criteria  Patient Group Representatives 
 

Patient group applicants must:

  • belong to a not-for-profit, patient-related organization, or a citizen’s group interested in health policy
  • submit a letter of recommendation from an executive member of the organization (e.g., President or Vice-President).

CADTH Symposium Travel Award Program for Students and Patient Group Representatives



CADTH.ca

About CADTH (what does the evidence say?)

Published on: September 29, 2016
Result type: News


CADTH is pleased to announce the 2017 CADTH Symposium Travel Award Program for students and patient group representatives.
Since 2007, CADTH has provided financial support toward conference-related costs for more than 190 student and patient group representatives as part of our commitment to making this important event accessible to all health care stakeholders.
This year, eligible students and patient group representatives can receive up to $1,500 to offset registration, travel, food, accommodation, and other conference-related expenses.

For Patient Group Representatives

  • It’s important that your voice is heard. If you work for a not-for-profit, patient-related organization, or a citizen’s organization interested in health policy, we invite you to apply for a travel award.

How to Apply

Step 1: Review the 2017 CADTH Symposium Travel Award Program Criteria
Step 2: Complete and submit the 2017 Travel Awards Application form to CADTH by December 9, 2016.
Travel award decisions will be made by the end of January 2017, and awards will be issued to successful applicants by the end of March 2017.
Reminder: The Abstract Submission Deadline for the 2017 CADTH Symposium is October 28, 2016.
If you have questions about the 2017 CADTH Symposium, or the Travel Award Program, please contact us at symposium@cadth.ca. We’re looking forward to seeing you in Ottawa in 2017.

Editorial (Canada): Physician and Government disconnect is becoming a chasm



CJS

Who truly represents the patient perspective?



Cancerworld

 “For some, having a patient on the panel simply means they can tick the     patient involvement box”

Wednesday, September 28, 2016

“Nothing about us without us”—patient partnership in medical conferences (open access)



The BMJ

 Key messages
  • Involving patients in medical conferences can help delegates to understand problems that matter most to patients and their caregivers
  • Involving patients can spark collaborations with patients in healthcare design, education, research, and clinical care improvements
  • Patient should be included in the creation of conference programmes and selection of speakers
  • Requirements of attending patients, such as facilities for self care and travel expenses, should be considered when planning conferences

The Agenda with Steve Paikin - YouTube (starting now) Dr Steven Narod



The Agenda with Steve Paikin - YouTube

 

The limited utility of currently available venous thromboembolism risk assessment tools in gyn oncology patients



abstract:
The limited utility of currently available venous thromboembolism risk assessment tools in gynecological oncology patients
 

Background

Use of risk assessment tools, such as the Caprini score or Rogers score, is recommended by national societies to stratify surgical patients by venous thromboembolism risk and guide prophylaxis. However, these tools were not developed in a gynecological oncology patient population, and their utility in this population is unknown.

Objective

The objective of the study was to examine the ability of both the Caprini and Rogers scores to stratify gynecological oncology patients by the risk of venous thromboembolism.

Study Design

Patients undergoing surgery for cervical, ovarian, uterine, vaginal, and vulvar cancers between 2008 and 2013 were identified from the National Surgical Quality Improvement Program Database using International Classification of Diseases, ninth revision, codes. The Caprini and Rogers scores were calculated for each patient based on the recorded demographic and procedure data. Venous thromboembolism events were recorded for 30 days postoperatively. Patients were categorized into risk groups based on the calculated Caprini and Rogers scores and the incidence of venous thromboembolism, and the 95% confidence interval was estimated for each of these groups. The relationship between the risk score and venous thromboembolism incidence was examined with Pearson’s correlation coefficient.

Results

Of 17,713 patients, 1.8% developed a venous thromboembolism. No patients were classified by the Caprini score as low risk, 0.1% were moderate risk, 3.0% were higher risk (score 4), and 96.9% were highest risk (score ≥5). The Caprini score groupings did not correlate with venous thromboembolism. The high-risk group had a paradoxically higher incidence of venous thromboembolism of 2.5% compared with the highest-risk group, 1.7% (P = .40). However, when the highest-risk group of the Caprini score was substratified, it was highly correlated with venous thromboembolism (R2 = 0.93). For the Rogers score, only 0.2% of patients were low risk (score <7), 36.9% were medium risk (score 7–10), and 63.0% were high risk (score >10). When the highest risk group of the Rogers score was substratified, it was also highly correlated with venous thromboembolism (R2 = 0.99).

Conclusion

Gynecological oncology patients score very high on current venous thromboembolism risk assessment models. The Caprini score is limited in its ability to discriminate relative venous thromboembolism risk among gynecological oncology patients because 97% are in the highest-risk category. Substratification of the highest-risk groups allows for relative venous thromboembolism risk stratification among gynecological oncology patients, suggesting that further evaluation of risk stratification is needed in gynecological oncology surgery.

open access: Metformin as an adjuvant treatment for cancer: a systematic review/meta-analysis (did not include ovarian cancer)



Blogger's Note: did not include ovarian cancer

open access



Our objective was to conduct a systematic review and meta-analysis of randomised and non-randomised studies to investigate the effect of metformin use compared with non-use on recurrence-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS) in adults who have potentially curable solid tumours.
  The majority of identified studies examined the effect of metformin in one of four tumour types: prostate, colorectal, breast and urothelial cancer, which, therefore, represent the main focus of this analysis. A summary of the main characteristics for studies of breast, colorectal and prostate cancer is presented in Table 1, and a table of study characteristics for other cancer types is presented in Table 2.
  1. Supplementary Data
 Meta-analyses have examined the role of metformin in the primary prevention of cancer, where it was found to significantly reduce overall cancer incidence; however, findings were inconsistent when individual tumour types were considered [1620]. Meta-analyses have also investigated the effect of metformin use across all stages of disease and have found that it reduces overall cancer mortality rates, but, again findings are conflicting for individual tumour types [2128], suggesting analyses are best conduced for individual tumour types separately.

Categorization of Cancer Survivors: Why We Need It (open access)



open access

In conclusion, proper categorization of persons now broadly defined as cancer survivors can provide support to risk-based survivorship care, new clinical and organizational approaches, and improved follow-up and surveillance recommendation and guidelines. Although dilemmas and differences in clinical approaches need to be addressed thoroughly in the shift toward accurate categorization of cancer survivors, we believe that the current lack of distinction among survivors negatively affects communication with our patients and families, patient adherence to clinical recommendations, and effectiveness of survivorship care in different delivery contexts. In contrast, the study and application of categories of survivorship might help us avoid the infliction of psychological burdens of over medicalization and potential social stigmatization on some of our patients and foster adequate follow-up, surveillance and global care for others.

Current South African clinical Practice in Debulking Surgery for Ovarian Cancer



abstract

 Conclusions: The progression of South African Gynaecological Oncologist towards more aggressive debulking surgery is following international trends, but many of the surgeons report a lack of experience in ultra-radical debulking surgery, especially in the upper abdomen.

Prevalence of Appendiceal Lesions in Appendicectomies Performed During Surgery for Mucinous Ovarian Tumors



abstract
 Prevalence of Appendiceal Lesions in Appendicectomies Performed During Surgery for Mucinous Ovarian Tumors: A Retrospective Study

Objectives: The aim of this study was to assess the frequency of appendiceal pathology in women undergoing surgery for mucinous ovarian neoplasm and to evaluate whether appendicectomy is necessary.
Methods: This single-institution retrospective study reviewed prevalence of appendiceal lesions in all patients operated on at our institution from 2002 to 2013 with the final diagnosis of mucinous tumor of the ovary. Clinicopathological data were analyzed.
Results: One hundred twenty-three cases were identified. These included 45 (37%) benign mucinous ovarian neoplasms, 63 (51%) borderline, and 11 (9%) invasive mucinous ovarian tumors. In addition, 4 (3%) cases of metastatic tumors to the ovary were also identified. Appendiceal pathology was found in association with all types of mucinous ovarian tumors (benign, borderline, and malignant). In 24% of cases, appendix was macroscopically abnormal at the time of the surgery, prompting the surgical removal. Regardless of the gross findings, microscopic abnormality in the appendix was seen in 24% of all cases. The prevalence of significant occult microscopic appendiceal pathology, that is, when the appendix was grossly normal, was 6%.
Conclusions: Given the prevalence of coexisting appendiceal pathology found in this study and the reported low rates of complications associated with the procedure, an appendicectomy is recommended in the management of all mucinous ovarian neoplasms.

Index: October 2016 International Journal of Gynecological Cancer



Current Issue

The Agenda | TVO.org Sept 28th: Cancer Treatments/Dr Steven Narod/Women's College Research institute



The Agenda | TVO.org
  Weeknights at 8 and 11 pm
 
Wed Sep 28

Cancer Treatments

The Agenda welcomes Dr. Steven Narod, senior scientist at Women's College Research Institute, to explain the best interventions for cancer.

 The Agenda is also available online anytime in audio and video podcast at iTunes, and streamed in our video player and on YouTube. Follow us on Twitter and Facebook.

Surgical manual of the Korean Gynecologic Oncology Group: ovarian, tubal, and peritoneal cancers



open access:  Journal of Gynecologic Oncology

Millions of Canadians don't have to be told if health information breached



Health - CBC Investigation

  http://i.cbc.ca/1.3781045.1475002045!/fileImage/httpImage/image.jpg_gen/derivatives/original_620/mandatory-breach-notification2.jpg

Perioperative changes in serum CA125 levels: a prognostic factor for disease-specific survival in patients with ovarian cancer



open access

The objectives of the present study were to investigate the relationship between the postoperative decline in serum CA125 levels and the residual tumor volume after primary cytoreductive surgery in patients with advanced stage epithelial ovarian cancer, and to determine the value of perioperative changes in CA125 levels for predicting disease-specific survival.
(abstract) CONCLUSION:
The current study, although hampered by possible biases, suggests that the perioperative decline in serum CA125 is an early biomarker that predicts disease-specific survival in patients who underwent primary cytoreductive surgery for advanced stage EOC. If confirmed prospectively, the perioperative change in serum CA125 could be a better marker for residual tumor volume after primary cytoreductive surgery (and therewith disease-specific survival) than the surgeons' estimation of residual tumor volume.

Is pelvic inflammatory disease a risk factor for ovarian cancer?



abstract:
Is pelvic inflammatory disease a risk factor for ovarian cancer? | Cancer Epidemiology, Biomarkers & Prevention

Background: Pelvic inflammatory disease (PID) has been proposed as a risk factor for ovarian cancer. However, the existing literature on the association between PID and ovarian cancer risk is inconclusive and only few cohort studies have been conducted.
Methods: Using nationwide Danish registries, we conducted a population-based cohort study including all women from the birth cohorts 1940-1970 in Denmark during 1978-2012 (n=1,318,929) to investigate the association between PID and subsequent risk of epithelial ovarian cancer. Among women in the cohort, 81,281 women were diagnosed with PID and 5,356 women developed ovarian cancer during follow-up through 2012. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between PID and ovarian cancer, both overall and according to histotype.
Results: For ovarian cancer overall, we observed no association with PID (HR=1.05; 95% CI: 0.92-1.20). However, in histotype-specific analyses, we found a statistically significantly increased risk of serous ovarian cancer among women with PID (HR=1.19; 1.00-1.41; p=0.047). Conversely, PID was not convincingly associated with risk of any of the other histotypes of ovarian cancer.
Conclusion: PID was associated with a modestly increased risk of serous ovarian cancer, but not other histotypes.
Impact: Our results indicate that PID is not a strong risk factor for ovarian cancer. Whether PID is slightly associated with risk of serous ovarian cancer has to be confirmed in other studies.

The Status of PARP Inhibitors in Ovarian Cancer, Part 2



full text - open access:
The Status of Poly(Adenosine Diphosphate-Ribose) Polymerase (PARP) Inhibitors in Ovarian Cancer, Part 2: Extending the Scope Beyond Olaparib and BRCA1/2 Mutations
 Sept 2016

Abstract

Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors have shown clinical activity in epithelial ovarian cancer, leading both the US Food and Drug Administration (FDA) and the European Medicines Agency to approve olaparib for tumors characterized by BRCA1 and BRCA2 mutations. However, it is becoming increasingly evident that tumors that share molecular features with BRCA-mutant tumors-a concept known as BRCAness-also may exhibit defective homologous recombination DNA repair, and therefore will respond to PARP inhibition. A number of strategies have been proposed to identify BRCAness, including identifying defects in other genes that modulate homologous recombination and characterizing the mutational and transcriptional signatures of BRCAness. In addition to olaparib, a number of other PARP inhibitors are in clinical development. This article reviews the development of PARP inhibitors other than olaparib, and discusses the evidence for PARP inhibitors beyond BRCA1/2-mutant ovarian cancer.
 

Tuesday, September 27, 2016

Characteristics of Hospital Stays Involving Malnutrition (eg. postsurgical nonabsorption)



open access: Characteristics of Hospital Stays Involving Malnutrition

  The NIS includes obstetrics and gynecology, otolaryngology, orthopedic, cancer, pediatric, public, and academic medical hospitals.
Highlights
  • In 2013, there were nearly 2 million hospital inpatient stays involving malnutrition. The most common type was protein-calorie malnutrition (63.9 percent of all malnutrition stays), accounting for 4.5 percent of all inpatient stays and 9.1 percent of aggregate costs (nonmaternal and nonneonatal only).


  • Other malnutrition-related stays were for weight loss or failure to thrive (21.6 percent of all malnutrition stays), cachexia (8.3 percent), underweight (4.4 percent), postsurgical nonabsorption (1.7 percent), and nutritional neglect (0.1 percent).


  • Patients with malnutrition tended to be older (especially 85 years or older), black, and from low income and rural areas.


  • Compared with other types of malnutrition, in-hospital mortality was higher for stays with cachexia (11.7 percent died in the hospital) and protein-calorie malnutrition (8.4 percent)—4 to 5 times the in-hospital death rate of all nonmaternal, nonneonatal stays (2.4 percent).


  • Average hospital costs were higher for stays involving protein-calorie malnutrition ($25,200) and postsurgical nonabsorption ($23,000) than for other malnutrition stays.


  • Principal diagnoses varied by type of malnutrition: medical, surgical, or device complications were common for postsurgical nonabsorption; injuries and conditions due to external causes were common for nutritional neglect. Septicemia was common among all types of malnutrition.

Separating hope from hype in new cancer therapy 'revolution'



medical news

2016 Liz Tilberis Early Career Award Recipient - Hui Shen, PhD | Ovarian Cancer Research Fund



Hui Shen, PhD

 Ovarian Cancer Research Fund

Coffee and cancer risk: A meta-analysis of prospective observational studies



open access

Coffee is one of the most popular beverages worldwide, and it has been speculated to decrease the risk of many types of cancers. Coffee is a complex mixture of many biologically active components, some of which may have anti-tumor effects.

Ovarian cancer

Highest versus lowest intake: Nine cohort studies9,31,43,116,117,118,119,120,121 were included in the analysis (687017 samples) of the highest versus lowest intake of coffee and ovarian cancer. The study characteristics are presented (Stable 3a). The summary RR was 1.04 (95% CI = 0.90–1.20, P = 0.582) with low heterogeneity (I2 = 23.7%, P = 0.23) (Fig. 7B). The results suggest publication bias, with P = 0.02 for Begg’s test and P = 0.009 for Egger’s test. The summary RR was 0.96 (95% CI = 0.84–1.09) after Trim and fill analysis. The subgroup analysis indicated that there was no significant association between coffee intake and ovarian cancer risk in each subgroup. No factor could explain the source of heterogeneity through subgroup analysis (Stable 3b).

Editorial: Breast Density: More Than Meets the Eye



open access

Removing ovaries may not reduce breast cancer risk in women with BRCA1 mutations



Women's College Hospital (newsletter) 
 
Removal of the ovaries may not reduce the risk of breast cancer for women with BRCA1 mutations, researchers at Women’s College Hospital (WCH) found.
Women with BRCA1 and BRCA2 gene mutations are at high risk for both breast cancer and ovarian cancer. Removing the ovaries and fallopian tubes prevents ovarian cancer, but it has been unclear whether it also helps prevent breast cancer in women with BRCA mutations. Some earlier studies have suggested a significant risk reduction, while more recent research has found no benefit for breast cancer.
A new study led by Joanne Kotsopoulos, PhD, a scientist at the Women’s College Research Institute, compared breast cancer incidence in women with BRCA mutations based on whether or not they had had undergone oophorectomy (removal of the ovaries). The results suggest that the surgery may reduce breast cancer risk before age 50 for women with BRCA2 mutations, but not for women with BRCA1 mutations.
The prospective study included 3,722 women with BRCA mutations: 1,552 women who had undergone oophorectomy, and 2,170 who still had their ovaries. About 80 per cent of the study subjects had BRCA1 mutations, and about 20 per cent had BRCA2 mutations. The research team, including the study’s senior author Dr. Steven Narod, director of the familial cancer research group at WCH, followed the women for an average of 5.6 years, during which time 350 of them developed breast cancer.
Overall, there was no reduction in breast cancer risk associated with oophorectomy for women with BRCA mutations. However, when the results were analyzed by sub-groups, there was a protective effect against breast cancer before age 50 in women with BRCA2 mutations. The authors caution that this finding needs confirmation, given the very small number of women in one of the sub-groups.
Removal of the ovaries and fallopian tubes is still recommended for women with BRCA1 (at age 35) and BRCA2 (at age 40) mutations to protect against ovarian cancer.
The study (abstract) was published online in the Journal of the National Cancer Institute on Sept. 6, 2016.

 Conclusions: Findings from this large prospective study support a role of oophorectomy for the prevention of premenopausal breast cancer in BRCA2, but not BRCA1 mutation carriers. These findings warrant further evaluation.

Estimation of Heritability for Nine Common Cancers Using Data from Genome-Wide Association Studies in Chinese Population




polygenic inheritance

noun, Genetics.
1. the heredity of complex characters that are determined by a large number of genes, each one usually having a relatively small effect.
                         ~~~~~~~~~~~~~~~~~~~~~~~~~
abstract:
Estimation of Heritability for Nine Common Cancers Using Data from Genome-Wide Association Studies in Chinese Population

 The familial aggregation indicated the inheritance of cancer risk. Recent genome-wide association studies (GWAS) have identified a number of common single nucleotide polymorphisms (SNPs). Following heritability analyses have shown that SNPs could explain a moderate amount of variance for different cancer phenotypes among Caucasians. However, little information was available in Chinese population. We performed a genome-wide complex trait analysis (GCTA) for common cancers at nine anatomical sites in Chinese population (14,629 cancer cases vs. 17,554 controls) and estimated the heritability of these cancers based on the common SNPs. We found that common SNPs explained certain amount of heritability with significance for all nine cancer sites: gastric cancer (20.26%), esophageal squamous cell carcinoma (19.86%), colorectal cancer (16.30%), lung cancer (15.17%), and epithelial ovarian cancer (13.31%), and a similar heritability around 10% for Hepatitis B virus (HBV)-related hepatocellular carcinoma, prostate cancer, breast cancer and nasopharyngeal carcinoma. We found that nearly or less than 25% change was shown when removing the regions expanding 250kb or 500kb up and downwards of the GWAS-reported SNPs. We also found strong linear correlations between variance partitioned by each chromosome and chromosomal length only for lung cancer (R2=0.641, P=0.001) and esophageal squamous cell cancer (R2=0.633, P=0.002), which implied us the complex heterogeneity of cancers. These results indicate polygenic genetic architecture of the nine common cancers in Chinese population. Further efforts should be made to discover the hidden heritability of different cancer types among Chinese.

The challenge of fertility preservation in cancer patients II: a themed issue Oct 2016



The challenge of fertility preservation in cancer patients II: a themed issue of Future Oncology, Future Oncology, Future Medicine

 This issue includes reviews discussing the current state of the field in terms of ovarian health and fertility as well as providing future perspectives into potential treatments. The issue also presents novel research evaluating current techniques used to ensure optimum fertility preservation in the patients undergoing cancer treatment.
 In summary, this issue of Future Oncology highlights the importance of growth of the oncofertility field and the development of its future. We hope that the contents of the issue contribute to this integral field in supportive oncology.

Articles:

Commentary

Erectile dysfunction and infertility in male cancer patients: addressing unmet needs Jared L Moss, Mary Kate F Keeter, Robert E Brannigan, and Edward D Kim

Research Article

Should metaphase 1 and 2 stages oocytes be vitrified in the same time for fertility preservation? Christophe Sifer, Olivia Sellam-Chokron, Nathalie Sermondade, Isabelle Cedrin-Durnerin, Charlotte Sonigo, Charlène Herbemont, and Michael Grynberg

Special Report

Oncofertility in Japan: advances in research and the roles of oncofertility consortia Nao Suzuki

Perspective

Where are oncofertility and fertility preservation treatments heading in 2016? Miyuki Harada and Yutaka Osuga

Review

The artificial ovary: current status and future perspectives Christiani A Amorim and Ariella Shikanov

Seminars in Oncology (11 abstracts - familial/hereditary selected cancers)



abstracts
 Articles in Press

Monday, September 26, 2016

Cyclin A1 expression and paclitaxel resistance in human ovarian cancer cells



 se·nes·cence
səˈnesəns/ noun
Biology
noun: senescence
  1. the condition or process of deterioration with age.
    • loss of a cell's power of division and growth.
                      ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
abstract
 

Highlights

Elevated cyclin A1 expression is negatively associated with relapse time of ovarian cancer patients.
Ectopic expression of cyclin A1 in ovarian cancer cells suppresses paclitaxel-induced apoptosis.
However, cyclin A1-overexpression slows down cell proliferation and induces premature senescence.

Background

The development of intrinsic and acquired resistance to antineoplastic agents is a major obstacle to successful chemotherapy in ovarian cancers. Identification and characterisation of chemoresponse-associated biomarkers are of paramount importance for novel therapeutic development.

Methods

Global RNA expression profiles were obtained by high-throughput microarray analysis. Cell cycle, proliferation rate, and paclitaxel sensitivity of ovarian cancer cells harbouring cyclin A1-inducible expression construct were compared with and without tetracycline induction, as well as when the cyclin A1 expression was suppressed by short inhibiting RNA (siRNA). Cellular senescence was evaluated by β-galactosidase activity staining.

Results

Global RNA expression profiling and subsequent correlation studies of gene expression level and drug response has identified that elevated expression of cyclin A1 (CCNA1) was significantly associated with cellular resistance to paclitaxel, doxorubicin and 5-fluorouracil. The role of cyclin A1 in paclitaxel resistance was confirmed in ovarian cancer cells that harbour an inducible cyclin A1 expression construct, which showed reduced paclitaxel-mediated growth inhibition and apoptosis when cyclin A1 expression was induced, whereas downregulation of cyclin A1 expression in the same cell lines using cyclin A1-specific siRNAs sensitised the cells to paclitaxel toxicity. However, ovarian cancer cells with ectopic expression of cyclin A1 demonstrated slowdown of proliferation and senescence-associated β-galactosidase activity.

Conclusions

Our profiling and correlation studies have identified cyclin A1 as one chemoresistance-associated biomarker in ovarian cancer. The results of the characterisation studies suggest that cyclin A1 functions as an oncogene that controls proliferative and survival activities in tumourigenesis and chemoresistance of ovarian cancer.

Red Book Magazine: What Women Need to Know About Gynecologic Cancer - Cervical Cancer, Ovarian Cancer, HPV, and Uterine Cancer



What Women Need to Know About Gynecologic Cancer (Foundation for Women's Cancer)

Terry Fox (about/history) Canada's favorite hero (amongst many)



Blogger's Note: both parents have since passed away

Terry Fox 


September 1, 1980 – It was a dull day in Northern Ontario when Terry Fox ran his last miles.
He had started out strong that morning and felt confident. The road was lined with people shouting, “Don't give up, you can make it!” words that spurred him and lifted his spirits.
But after 18 miles he started coughing and felt a pain in his chest.
Terry knew how to cope with pain. He'd run through it as he always had before; he'd simply keep going until the pain went away.
For 3,339 miles, from St John's, Newfoundland, Canada's eastern most city on the shore of the Atlantic, he'd run through six provinces and now was two-thirds of the way home. He'd run close to a marathon a day, for 143 days. No mean achievement for an able-bodied runner, an extraordinary feat for an amputee.
Terry's left leg was strong and muscular. His right was a mere stump fitted with an artificial limb made of fibreglass and steel. He'd lost the leg to cancer when he was 18.
He was 22 now; curly haired, good-looking, sunburned. He was strong, wilful and stubborn. His run, the Marathon of Hope, as he called it, a quixotic adventure across Canada that defied logic and common sense, was his way of repaying a debt.
Terry believed that he had won his fight against cancer, and he wanted to raise money, $1 million perhaps, to fight the disease. There was a second, possibly more important purpose to his marathon; a man is not less because he has lost a leg, indeed, he may be more. Certainly, he showed there were no limits to what an amputee could do.
He changed people's attitude towards the disabled, and he showed that while cancer had claimed his leg, his spirit was unbreakable.
His Marathon of Hope had started as an improbable dream – two friends, one to drive the van, one to run, a ribbon of highway, and the sturdy belief that they could perform a miracle.

A study of motivations/expectations of patients seen in phase 1 oncology clinics - Roayl Marsden Hospital UK



 
 
 This study was previously presented at the American Society of Clinical Oncology Congress; June 3-7, 2016; Chicago, IL, Abstract no 10061
We thank the patients who participated in this study and their families, the Royal Marsden patient advocacy group, Debarati Goswami, and Kirsty Moran.
 

BACKGROUND

To better inform clinical practice, this study was aimed at capturing patients' motivations for enrolling in phase 1 trials and at quantifying their expectations of the benefits, risks, and commitment associated with clinical trials and the impact of the initial consultation on their expectations.

METHODS

This was a single-center, prospective, quantitative study of newly referred adult patients considering their first phase 1 oncology trial. Participants completed questionnaires before they were seen and an abbreviated follow-up version after their consultation.
 

Patient Characteristics

Between September 2012 and March 2015, questionnaires were given to 402 prospective adult patients at their first attendance in the new patient phase 1 clinic of the Drug Development Unit. Ninety nine percent (n = 396) gave written consent to participate and completed the preclinic questionnaire; 301 patients returned the postclinic questionnaire (76%). The mean age was 57.4 years (standard deviation, 12.9 years); there was a slight preponderance of females (56.3%), and there was an even distribution of participants leaving formal education before and after the age of 17 years (46.2 vs 44.7%; Table 1). The commonest cancers were gastrointestinal, gynecological, and lung cancers, with their respective cancer specialists being the major primary referrers for 87.1% of the patients (Table 1).


Cancer site, No. (%)

Breast40 (10.1)
Gastrointestinal153 (38.6)
Gynecological66 (16.7)
Lung58 (14.6)
All others79 (19.9)              Total 396 (100.00)













Expectations may not match reality among cancer patients in some early phase clinical trials



Medical News

(new) Lynch Syndrome Community | Smart Patients



Lynch Syndrome Community | Smart Patients

Bowel injury in robotic gyn surgery: risk factors/management options



abstract:
Bowel injury in robotic gynecologic surgery: risk factors and management options. A systematic review
 

Objective

We sought to analyze the published literature on bowel injuries in patients undergoing gynecologic robotic surgery with the aim to determine its incidence, predisposing factors, and treatment options.

Data Sources

Studies included in this analysis were identified by searching PubMed Central, OVID Medline, EMBASE, Cochrane, and ClinicalTrials.gov databases. References for all studies were also reviewed. Time frame for data analysis spanned from November 2001 through December 2014.

Study Eligibility Criteria

All English-language studies reporting the incidence of bowel injury or complications during robotic gynecologic surgery were included. Studies with data duplication, not in English, case reports, or studies that did not explicitly define bowel injury incidence were excluded.

Study Appraisal and Synthesis Methods

The Guidelines for Meta-Analyses and Systematic Reviews of Observational Studies were used to complete the systematic review with the exception of scoring study quality and a single primary reviewer.

Results

In all, 370 full-text articles were reviewed and 144 met the inclusion criteria. There were 84 bowel injuries recorded in 13,444 patients for an incidence of 1 in 160 (0.62%; 95% confidence interval, 0.50–0.76%). There were no significant differences in incidence of bowel injury by procedure type. The anatomic location of injury, etiology, and management were rarely reported. Of the bowel injuries, 87% were recognized intraoperatively and the majority (58%) managed via a minimally invasive approach. Of 13,444 patients, 3 (0.02%) (95% confidence interval, 0.01–0.07%) died in the immediate postoperative period and no deaths were a result of a bowel injury.

Conclusion

The overall incidence of bowel injury in robotic-assisted gynecologic surgery is 1 in 160. When the location of bowel injuries were specified, they most commonly occurred in the colon and rectum and most were managed via a minimally invasive approach.

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Phase II study of Vigil® DNA engineered immunotherapy as maintenance in advanced stage ovarian cancer



abstract
 

Results

Forty-two patients were entered into trial, 31 received Vigil and 11 received standard of care. No ≥ Grade 3 toxicity related to product was observed. A marked induction of circulating activated T-cell population was observed against individual, pre-processed autologous tumor in the Vigil arm as compared to pre-Vigil baseline using IFNγ ELISPOT response (30/31 negative ELISPOT pre Vigil to 31/31 positive ELISPOT post Vigil, median 134 spots). Moreover, in correlation with ELISPOT response, RFS from time of procurement was improved (mean 826 days/median 604 days in the Vigil arm from mean 481 days/median 377 days in the control arm, p = 0.033).

Conclusion

In conjunction with the demonstrated safety, the high rate of induction of T-cell activation and correlation with improvement in RFS justify further Phase II/III assessment of Vigil.