Napsin A as a marker of clear cell ovarian carcinoma

open access

Background

Clear cell carcinomas are aggressive tumors with a distinct biologic behaviour. In a genome-wide screening for genes involved in chemo-resistance, NAPA was over-expressed in cisplatin-resistant cells. The NAPA (protein) Napsin A was described to promote resistance to cisplatin by degradation of the tumor suppressor p53.

Methods

Totally 131 patients were included in this study all in FIGO-stages I-II; 16 were clear cell tumors which were compared with 40 Type I tumors and 75 type II tumors according to the markers Napsin A, p21, p53 and p27 and some clinical features. For detection of the markers tissue microarrays and immunohistochemistry were used.

Results

Positivity for Napsin A was detected in 12 (80%) out of the 15 clear cell tumors available for analysis compared with 3 (4%) out of the Type I and II tumors in one group (p < 0.001). Differences in p21 status, p53 status, and p21 + p53- status were striking when clear cell tumors were compared with Type I, Type II, and Type I and II tumors in one group, respectively. The p21 + p53-status was associated to positive staining of Napsin A (p = 0.0015) and clear cell morphology (p = 0.0003). In two separate multivariate logistic regression analyses with Napsin A as endpoint both clear cell carcinoma with OR = 153 (95% C.I. 21--1107); (p < 001) and p21 + p53- status with OR = 5.36 (95% C.I. 1.6-17.5); (p = 0.005) were independent predictive factors. ROC curves showed that AUC for Napsin A alone was 0.882, for p21 + p53- it was 0.720 and for p21 + p53-Napsin A + AUC was 0.795. Patients with clear cell tumors had lower (p = 0.013) BMI than Type I patients and were younger (p = 0.046) at diagnosis than Type II patients. Clear cell tumors had a higher frequency (p = 0.039) of capsule rupture at surgery than Type I and II tumors.

Conclusions

Positivity of Napsin A in an epithelial ovarian tumor might strengthen the morphological diagnosis of clear cell ovarian carcinoma in the process of differential diagnosis between clear cell ovarian tumors and other histological subtypes.

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

"...Our findings related to the clinico-pathological differences are supported by earlier studies[4,7,10] but results about the immunohistochemical profile for Napsin A is new. Clear cell carcinomas resembles Type I tumors based on relative genetic stability and

frequent presentation in stage I, but on the other hand, clear cell carcinoma is high grade at diagnosis. Furthermore, wild-type p53 is mostly present and mutations are uncommon in clear cell tumors contrary to Type II tumors, which are genetically unstable and have a highrequency of p53 mutations [10,11]. Ovarian clear cell carcinomas constitute a heterogeneous disease at the genomic level despite having similar histological

features. Previous data fromTan et al [11] has suggested that the pattern of genome-wide copy number aberrations may predict clinical outcome... 

Privacy and All That (sharing)

NEJM (requires paid subscription to view)

 

Perspective

Privacy and All That

"The two men had sat in neighboring chemotherapy chairs, swapping tales of side effects, antiemetics, their childhoods, religion. When one died, it affected the other profoundly. But there's no protocol for sharing information with patients about their fellow travelers."

Top 50 Concerns, Questions and Comments From Anesthesia Techs

Anesthesia Techs

Patient Portals Increase Access And Reduce Misinformation

Diagnostic Imaging

Already gaining popularity in health systems nationwide, patient portals could now play a more significant role in radiology by automatically structuring and combining radiology reports with related imaging studies. This integration would give patients greater access to helpful information about their health status.

In a study published in the November issue of the Journal of the American Medical Informatics Association, the University of California-Los Angeles developed as web-based patient portal for individuals with brain cancer.

Allowing patients to view their radiology reports makes sense even if patients can’t fully understand the studies, the authors wrote, because the patient interest is there.

“Even though radiology test results are one of the most difficult portions of the clinical record for lay people to understand, they are one of the most frequently accessed pieces of information via patient portals when available,” they wrote.

- See more at: http://www.diagnosticimaging.com/pacs-and-informatics/patient-portals-increase-access-and-reduce-misinformation#sthash.KubvbFbT.dpuf

 

Imaging informatics for consumer health: towards a radiology patient portal

Abstract

Objective With the increased routine use of advanced imaging in clinical diagnosis and treatment, it has become imperative to provide patients with a means to view and understand their imaging studies. We illustrate the feasibility of a patient portal that automatically structures and integrates radiology reports with corresponding imaging studies according to several information orientations tailored for the layperson.

Methods The imaging patient portal is composed of an image processing module for the creation of a timeline that illustrates the progression of disease, a natural language processing module to extract salient concepts from radiology reports (73% accuracy, F₁ score of 0.67), and an interactive user interface navigable by an imaging findings list. The portal was developed as a Java-based web application and is demonstrated for patients with brain cancer.

Results and discussion The system was exhibited at an international radiology conference to solicit feedback from a diverse group of healthcare professionals. There was wide support for educating patients about their imaging studies, and an appreciation for the informatics tools used to simplify images and reports for consumer interpretation. Primary concerns included the possibility of patients misunderstanding their results, as well as worries regarding accidental improper disclosure of medical information.

Conclusions Radiologic imaging composes a significant amount of the evidence used to make diagnostic and treatment decisions, yet there are few tools for explaining this information to patients. The proposed radiology patient portal provides a framework for organizing radiologic results into several information orientations to support patient education.

 

This Guy’s Wife Got Cancer, So He Did Something Unforgettable The Free Thought Project

 Blogger's Note: thanks to FB for this, sad but real

The Free Thought Project

conference notice: 6th Familial Cancer Conference - Event - ESO

ESO

6th Familial Cancer Conference

05/06/2014 - 06/06/2014, Madrid, Spain

 

The combination of gemcitabine and carboplatin shows similar efficacy in the treatment of platinum-resistant and platinum-sensitive recurrent epithelial ovarian cancer patients

abstract

The aim of this study was to evaluate progression-free survival, overall survival (OS), response rate (RR), and clinical benefit in recurrent ovarian cancer patients treated with gemcitabine and carboplatin and to compare the outcome among platinum-resistant and platinum-sensitive patients. A retrospective study using the medical records of patients diagnosed and treated for recurrent epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma with gemcitabine and carboplatin from 2005 through 2012 at the Tel Aviv Sourasky Medical Center. The treatment regimen was carboplatin (area under the curve=5) administered on day 1 and gemcitabine 850 mg/m administered on days 1 and 8 in a 21-day cycle. Seventy patients with a median age of 57 years (range: 38-86) were included in the study. Most patients (94.3%) were initially diagnosed with stage III-IV disease and 44.3% had platinum-sensitive disease. Median progression-free survival in platinum-sensitive patients was 6.3 months [95% confidence interval (CI): 4.3-8.3] and 6.3 months (95% CI: 4.6-7.9) in platinum-resistant patients. Median overall survival was 15.8 months (95% CI: 13.6-18.1) in the platinum-sensitive patients and 18.4 months (95% CI: 10.0-27.8) in the platinum-resistant patients. Platinum-sensitive patients had a RR of 43.2% and platinum-resistant patients had a RR of 39.1%. The clinical benefit was 70.5% in platinum-sensitive patients and 65.2% in platinum-resistant patients. Overall treatment had a favorable safety profile. Gemcitabine and carboplatin demonstrate moderate toxicity with similar efficacy in both platinum-sensitive and platinum-resistant epithelial ovarian cancer, suggesting reversal of platinum resistance by gemcitabine.

 

Stereotactic radiosurgery in the treatment of brain metastases: The current evidence

open access

Introduction

According to conservative estimates about 8% of cancer patients will develop brain metastases,¹ which often cause the leading symptoms..... 

Destruction of the bladder by single dose Mitomycin C for low-stage transitional cell carcinoma (TCC) – avoidance, recognition, management and consent (Lynch syndrome patients note)

Blogger's Note: of interest to Lynch Syndrome patients with upper tract urothelial carcinoma (UTUC) and prophylaxis MMC to reduce the risk of bladder cancer after radical nephroureterectomy; note this study included bladder cancer patients

abstract

 Keywords:

• bladder perforation;
• intravesical mitomycin;
• consent;
• extravasation

Objectives

• To identify a cohort of patients under our care who have had significant and in some cases irreparable damage to their bladders after Mitomycin C (MMC) instillation.
• To highlight the importance of avoidance and recognition of bladder perforations during transurethral resection of bladder tumour (TURBT) and explore the issue of consent regarding MMC given the serious complications that may occur after its instillation.

Patients and Methods

• Patients referred to our tertiary centre for a second opinion to manage their complications after a suspected MMC leak was identified from the departmental database between January 2000 and December 2010.
• After collection of all the records, we established a cohort of six patients.
• All patients had their initial tumour resection elsewhere and were referred for specialist management thereafter. Details of the operating surgeon and cystoscopic findings were known only in half of the cases.
• Retrospective analysis of their notes including documentation from the referring centre was undertaken. This included a review of all the histology and imaging.

Results

• All patients had immediate severe pelvic pain on instillation of the MMC. Four of the six continue to have chronic pelvic pain.
• Two patients had urinary retention and three had severe lower urinary tract symptoms. One patient developed a frozen pelvis.
• Initial treatment was with an indwelling catheter for a period of 2–52 weeks to aid healing.
• Two patients had reconstructive surgery, one with success and the other with failure, as an intestinal patch failed to close the fistula and he continues with a catheter. One patient had an ileal conduit.
• No patient was warned of such complications.

Conclusions

• Although rare, prophylactic MMC can have devastating consequences.
• Patients should be aware of such major risks.
• Strong emphasis should be placed on the quality of the initial TURBT coupled with the judgement of an experienced surgeon before to MMC instillation. The real clinical benefit could be reviewed and intravesical MMC offered only to patients who have a good chance of benefit.

 

Patients Prefer to Insert NG Feeding Tubes Themselves: Study

medscape

Nov 2013 Scottish Intercollegiate Guidelines Network: Management of Epithelial Ovarian Cancer

open access


 Scottish Intercollegiate Guidelines Network

Management of epithelial ovarian cancer

A national clinical guideline

 

 

International Ovarian & Testicular Stromal Tumor Registry - Full Text View - ClinicalTrials.gov

Tumor Registry

Purpose

Rare tumors are understudied, yet have the potential to shed light on vast areas of cancer research. Ovarian sex cord-stromal tumors, rare tumors of childhood and young adulthood, have recently been found to be associated with a lung cancer of early childhood called pleuropulmonary blastoma (PPB). The cause of these ovarian tumors is unknown. DICER1 mutations are seen in the majority of children with PPB. Research shows DICER1 mutations are also seen in some patients with ovarian tumors. Like PPB, ovarian stromal tumors are highly curable when found in early stage; however, later forms of the disease are aggressive and often fatal. The International Ovarian Stromal Tumor Registry collects clinical and biologic data to understand why these tumors occur and how to treat them. Current work involves the study the role of DICER1 and miRNA expression in ovarian stromal tumors. Understanding the clinical history, predisposing factors and DICER1 and miRNA expression in these ovarian tumors of childhood will lead to targeted screening and risk stratification for evidence-based treatment and biologically rational therapies. These efforts will improve the lives of children by increasing survival and reducing late effects.

The specific goals of the International Ovarian and Testicular Stromal Tumor Registry are:

1. to understand risk factors by studying age, pathologic subtype, histopathologic features, tumor invasiveness, degree of differentiation, presence of metastasis
2. to collect information on personal and family history in order to refine the clinical characteristics of patients and families with and without germline DICER1 mutations and other genetic predisposing factors
3. to determine whether there is a pattern of gene expression or DNA alterations that correlate with predisposition to ovarian tumors, biologic behavior and clinical outcome
4. to determine optimal screening regimens
5. to use clinical data obtained through the Registry to refine treatment algorithms
6. to establish a collection of annotated biology specimens (tumor tissue and germline DNA) for future research

Condition
Ovarian Stromal Tumor Testicular Stromal Tumors Ovarian Small Cell Carcinoma

 

Can patient reported outcomes help identify the optimal outcome in palliative surgery?

abstract

Background

The purpose of this pilot study was to determine whether an open-ended questionnaire captures severe symptoms in cancer patients undergoing palliative surgical consultation that a structured, validated quality-of-life assessment does not capture.

Methods

We prospectively used the Functional Assessment of Cancer Therapy–General (FACT-G) and an open-ended questionnaire to assess the symptoms of patients with incurable malignancies who underwent palliative surgical consultation at our institution between January 2011 and September 2012.

Results

Of the 69 patients enrolled, the most common indications for consultation were bowel obstruction (54%), jaundice (13%), wound problems (10%), and gastrointestinal bleeding (7%). Of the severe symptoms patients reported, 76% were identified with the FACT-G alone, 22% were identified with the open-ended questionnaire alone, and 2% were duplicate responses captured with both the FACT-G and open-ended questionnaire. The open-ended questionnaire captured 68 instances of severe symptoms in 47 patients that the FACT-G did not capture; of these symptoms, 52 were considered to be highly relevant to surgery and potential outcome measures.

Conclusions

An open-ended questionnaire can identify severe symptoms that a global quality of life survey cannot capture and could be used in conjunction with a global survey to reassess symptoms after palliative surgical consultation. 

Clinical Research in Surgical Oncology: An Analysis of ClinicalTrials.gov

abstract

Background

The objective of this study was to provide a descriptive analysis of registered clinical trials in surgical oncology at ClinicalTrials.gov.

Methods

Data was extracted from ClinicalTrials.gov using the following search engine criteria: “Cancer” as Condition, “Surgery OR Operation OR Resection” as Intervention, and Non-Industry sponsored. The search was limited to Canada and the United States and included trials registered from January 1, 2001 to January 1, 2011.

Results

Of 9,961 oncology trials, 1,049 (10.5 %) included any type of surgical intervention. Of these trials, 125 (11.9 %, 1.3 % of all oncology trials) assessed a surgical variable, 773 (73.7 %) assessed adjuvant/neoadjuvant therapies, and 151 (14.4 %) were observational studies. Of the trials assessing adjuvant therapies, systemic treatment (362 trials, 46.8 %) and multimodal therapy (129 trials, 16.7 %) comprised a large focus. Of the 125 trials where surgery was the intervention, 59 trials (47.2 %) focused on surgical techniques or devices, 45 trials (36.0 %) studied invasive diagnostic methods, and 21 trials (16.8 %) evaluated surgery versus no surgery. The majority of the 125 trials were nonrandomized (72, 57.6 %).

Conclusions

The number of registered surgical oncology trials is small in comparison to oncology trials as a whole. Clinical trials specifically designed to assess surgical interventions are vastly outnumbered by trials focusing on adjuvant therapies. Randomized surgical oncology trials account for <1 % of all registered cancer trials. Barriers to the design and implementation of randomized trials in surgical oncology need to be clarified in order to facilitate higher-level evidence in surgical decision-making.

 

Is it possible to diagnose malignancy from fluid in cystic ovarian tumors?

abstract

Objective

p53 gene mutations are frequently identified in ovarian cancer tissue. The aim of this study was to investigate whether wild type or mutated genomic DNA can be identified in ovarian cystic fluid specimens.

Study design

Forty-eight Japanese patients with cystic ovarian tumors (30 benign cysts, 8 borderline malignant tumors, and 10 cancers) were investigated. Cystic fluid and tumor tissue were obtained during surgery......

Conclusion

In cystic ovarian tumors, cystic fluid may provide informative material for molecular studies since it reflects the p53 status of tumor tissue in the cyst wall. This system might help to identify ovarian malignancy without resection of the tumor tissues.
 

DNA barcoding detects contamination and substitution in North American herbal products

open access

Conclusions:

Most of the herbal products tested were of poor quality, including considerable product substitution, contamination and use of fillers. These activities dilute the effectiveness of otherwise useful remedies, lowering the perceived value of all related products because of a lack of consumer confidence in them. We suggest that the herbal industry should embrace DNA barcoding for authenticating herbal products through testing of raw materials used in manufacturing products. The use of an SRM DNA herbal barcode library for testing bulk materials could

provide a method for best practices in the manufacturing of herbal products.This would provide consumers with safe, high quality herbal products.

Table 1 DNA barcode results listed for individual samples from blind testing of the 44 herbal products and 50 herbal

leaf samples representing 42 medicinal species of plan

Figure 3

DNA barcode results from blind testing of the 44 herbal products representing 12 companies (fillers, substitutions, contaminents, authentic)

 

Herbal Supplements Are Often Not What They Seem

NYTimes.com

Viewing Laboratory Test Results Online: Patients’ Actions and Reactions | Journal of Participatory Medicine

open access

Conclusion: This study demonstrates that patients who view their lab test results online overwhelmingly react with positive rather than negative emotions. The results also illustrate the influence of physician-patient prior communication on patients’ reactions and their followup actions. 

Table 3. Reactions when viewing test results online.

How to Pronounce Epithelial Ovarian Cancer - YouTube (english language)

youtube

How to help women with ovarian cancer advocate for their health- Make Guru

video

Dr. Birrer on Other Targets in Ovarian Cancer - video

 video

Dr. Thigpen on Ovarian Cancer Agents Not Approved by the FDA - video

 video

Duavee - Menopause: FDA OKs Drug to Treat Hot Flashes in Menopausal Women

medical news

Menopause - New Analysis Confirms Hormone Therapy Won't Prevent Disease After Menopause

medical news (read the whole article)

"...She noted that some doctors seem to have had a "misunderstanding" regarding the original WHI findings, and are reluctant to use hormone therapy even for hot flashes.... 

Molecular Pathways: Estrogen Pathway in Colorectal Cancer

Blogger's Note: does not relate to Lynch Syndrome women; for those who have had an interest in and/or followed the WHI trial and subsequent analyses; when the initial WHI trial was publicized very little attention was paid to this particular aspect (eg. estrogen/hrt/risk reduction); debatable if and/or when 'we' will ever get to an analysis in affected Lynch Syndrome women (eg. low numbers etc.)

abstract

"Worldwide, colorectal cancer has a higher incidence rate in men than in women, suggesting a protective role for sex hormones in the development of the disease. Preclinical data support a role for estrogen and its receptors in the initiation and progression of colorectal cancer and establishes that protective effects of estrogen are exerted through ERβ. Hormone replacement therapy (HRT) in postmenopausal women as well as consumption of soy reduces the incidence of colorectal cancer. In the Women's Health Initiative trial, use of HRT in postmenopausal women reduced the risk of colon cancer by 56% [95% confidence interval (CI), 0.38–0.81; P = 0.003]. A recent meta-analysis showed that in women, consumption of soy reduced the risk of colon cancer by 21% (95% CI, 0.03–0.35; P = 0.026). In this review, using the preclinical data, we translate the findings in the clinical trials and observational studies to define the role of estrogen in the prevention of colorectal cancer. We hypothesize that sometime during the tumorigenesis process ERβ expression in colonocytes is lost and the estrogen ligand, HRT, or soy products, exerts its effects through preventing this loss. Thus, in the adenoma-to-carcinoma continuum, timing of HRT is a significant determinant of the observed benefit from this intervention. We further argue that the protective effects of estrogen are limited to certain molecular subtypes. Successful development of estrogen modulators for prevention of colorectal cancer depends on identification of susceptible colorectal cancer population(s). Thus, research to better understand the estrogen pathway is fundamental for clinical delivery of these agents."

 

Cancer Survivorship, a Unique and Growing Cohort in Medical Practice: Radiology Perspective

open access

Article Outline

• Abstract
• Pulmonary
• Genitourinary
• Musculoskeletal
• Gastrointestinal
• Monitoring for Recurrence
• Conclusions
• References

We will review the radiologic manifestation of the common consequences of cancer and its therapy. There are 2 general sequelae:

•Organ, tissue, or systemic damage related to therapy. Typically, this will include local scarring and inflammation due to surgery or radiation therapy. In addition, systemic therapy may cause inflammation, scarring, or necrosis in a broad range of target organs, including the lung, liver, kidneys, brain, and peripheral nerves.

•Emergence of a new cancer site: This will most frequently represent late-recurrence of the initial treated tumor. However, second primary cancers may result from the same underlying germline mutation that produces the original tumor (eg, ovarian cancer in BRCCA1 mutations) or as a result of mutagenic effects of radiation or chemotherapy.

 

Table. Summary of Some of the Available Imaging Modalities for Common Diagnoses in Oncologic Patients

Folcalin/Dexmethylphenidate: MedlinePlus Drug Information

Drug Information

Symcat Symptom Checker

free to try-registration not required

The impact of perioperative packed red blood cell transfusion on survival in epithelial ovarian cancer

abstract

OBJECTIVE:

Perioperative packed red blood cell transfusion (PRBCT) has been implicated as a negative prognostic marker in surgical oncology. There is a paucity of evidence on the impact of PRBCT on outcomes in epithelial ovarian cancer (EOC). We assessed whether PRBCT is an independent risk factor of recurrence and death from EOC.

METHODS:

Perioperative patient characteristics and process-of-care variables (defined by the National Surgical Quality Improvement Program) were retrospectively abstracted from 587 women who underwent primary EOC staging between January 2, 2003, and December 29, 2008. Associations with receipt of PRBCT were evaluated using univariate logistic regression models. The associations between receipt of PRBCT and disease-free survival and overall survival were evaluated using multivariable Cox proportional hazards models and using propensity score matching and stratification, respectively.

RESULTS:

The rate of PRBCT was 77.0%. The mean ± SD units transfused was 4.1 ± 3.1 U. In the univariate analysis, receipt of PRBCT was significantly associated with older age, advanced stage (≥IIIA), undergoing splenectomy, higher surgical complexity, serous histologic diagnosis, greater estimated blood loss, longer operating time, the presence of residual disease, and lower preoperative albumin and hemoglobin. Perioperative packed red blood cell transfusion was not associated with an increased risk for recurrence or death, in an analysis adjusting for other risk factors in a multivariable model or in an analysis using propensity score matching or stratification to control for differences between the patients with and without PRBCT.

CONCLUSIONS:

Perioperative packed red blood cell transfusion does not seem to be directly associated with recurrence and death in EOC. However, lower preoperative hemoglobin was associated with a higher risk for recurrence. The need for PRBCT seems to be a stronger prognostic indicator than the receipt of PRBCT.

 

ABO blood group and risk of epithelial ovarian cancer within the Ovarian Cancer Association

open access

" There are two important limitations in the current study. First, controls in the UKG study were not selected at the same time as the cases and may not represent the population that gave rise to the cases. However, in a sensitivity analysis excluding the UKG study populations, the association with the A blood group was largely unchanged (Supplemental Table 4), suggesting that the UKG controls are not a large source of bias. Second, the current study had limited power for the analysis of subgroups, such as potential differences by histologic type, particularly for the less common types, such as clear cell. However, although not statistically significant within all groups, the results were largely consistent among the three most common histologic types (serous, endometrioid, and mucinous). Further, with 5,233 cases and 6,838 controls, this is the largest study of the association between ABO blood group and ovarian cancer to date, with 80% power to detect a relative risk of 1.17 for the AB blood group, indicating that we had adequate power to detect modest associations with even the rarest blood group. Further, this study improves upon previous studies by using appropriate control groups as well as genotype-derived blood groups, which are less likely to suffer from misclassification compared to self-reported blood type. Additionally, the use of genotype-derived blood groups allowed a more detailed investigation of diplotypes rather than the simple blood groups previously investigated."

In summary, our findings for blood group are consistent with previous findings of increased ovarian cancer risk with blood group A. Although potentially due to chance, the finding that this association is limited to the A1/O diplotype should be confirmed in additional studies. Given that the A blood type is associated with a modest increase in ovarian cancer risk, further research into the biological mechanisms linking blood group with carcinogenesis is warranted. 

Your Patient's Brain on Drugs -- Cancer Drugs: Cognitive Side Effects of Cancer Treatment

medscape

Peripheral Neuropathy in Ovarian Cancer - Dr Yi Pan

Peripheral Neuropathy in Ovarian Cancer - open access

Chemotherapy-induced peripheral neurotoxicity: A critical analysis

open access

Introduction

As a consequence of advances in cancer diagnosis and treatment, there are now an estimated 28 million cancer survivors worldwide.[1] As such, long-term quality of life is an increasingly important issue, with 67% of U.S. cancer patients surviving at 5 years. Addressing the long-term toxicities of cancer treatment is critical due to their potential impact on cancer survivorship.[2] Accordingly, there has been a gradual shift in focus toward postchemotherapy recovery and survivorship, with an awareness of the importance of the individual patient experience, patient-reported outcomes, and the long-term effects of treatment. Of particular importance is chemotherapy-induced peripheral neuropathy (CIPN), which can lead to permanent symptoms and disability in up to 40% of cancer survivors.[3] CIPN can be a significant disability following the treatment of many types of cancer, including breast, colorectal, testicular, and hematological malignancies, and have an impact on quality of life. As such, there is a critical need to understand pathophysiological mechanisms, optimize clinical assessment, and develop neuroprotective strategies to prevent neuropathy. This review will address the challenge of CIPN, highlighting treatment-related neuropathy caused by some of the most commonly used chemotherapeutic agents (such as taxanes, platinum compounds, vinca alkaloids, thalidomide, and bortezomib), and provide recommendations regarding assessment strategies, management, and follow-up.....


"The benefits of including direct patient evaluations include a more comprehensive and accurate assessment of CIPN, improved understanding of the impact of CIPN symptoms on the patient, and a better correlation of toxicity findings with functional outcomes."

 

Table 1. Chemotherapies Associated With Peripheral Neuropathy

Table 2. Assessment of CIPN Via Neuropathy Grading Scales

  

Table 3. Chemotherapy Dose and Duration as a Risk Factor for CIPN

Table 4. Current Clinical Trials in the Prevention and Treatment of CIPN

Table 5. CIPN Recommendations and Strategies 

Conclusions

CIPN remains a clinically significant and potentially serious side effect of cancer treatment, with increasing relevance to the millions of cancer survivors worldwide. The number of cancer survivors with disability due to CIPN is underreported, as the use of patient-reported outcomes and objective assessment tools typically reveal greater neurotoxicity than clinician assessment. Improved understanding concerning the pathophysiology underlying the development of CIPN and the diverse mechanisms across different chemotherapies seems crucial to the development of future neuroprotective strategies. Appropriate, standardized, and objective assessment tools combined with validated instruments that also document patient-reported symptoms will be necessary to identify the long-term impact of CIPN in cancer survivors. The dividend of improved cancer outcomes with advances in treatment may be compromised if we fail to develop approaches to minimize the chronic consequences of toxicities such as CIPN (Table 5).

 

The Retreatment of Carboplatin via High Dose Intraperitoneal Chemotherapy in Patients with a History of a Hypersensitivity Reaction

abstract

Purchase $35.95

---

"A hypersensitivity reaction (HSR) attributed to platinum-based chemotherapy is a relatively common occurrence. Hyperthermic intraperitoneal chemotherapy (HIPEC) potentially facilitates the safe retreatment of platinum therapy following this complication. We describe three ovarian cancer patients who were successfully retreated with carboplatin via HIPEC following an HSR."

 

Plasma miRNAs as Diagnostic and Prognostic Biomarkers for Ovarian Cancer

open access (technical)

"Carbohydrate antigen-125 (CA-125) is the most frequently used biomarker for ovarian cancer detection [4], but it is only elevated in approximately 50% of stage I EOCs and 70%–90% of advanced cases [5]. Hence, there is a critical need for novel biomarkers that are more sensitive and specific for detecting EOC when used alone or in combination with CA-125. Recently, microRNAs (miRNAs), a family of small regulatory RNAs, emerged as possible plasma markers for human disease, including cancer, because of their relative stability in the circulation [6]."

Background

Most (70%) epithelial ovarian cancers (EOCs) are diagnosed late. Non-invasive biomarkers that facilitate disease detection and predict outcome are needed. The microRNAs (miRNAs) represent a new class of biomarkers. This study was to identify and validate plasma miRNAs as biomarkers in EOC.

Methodology/Principal Findings

We evaluated plasma samples of 360 EOC patients and 200 healthy controls from two institutions.

Conclusions/Significance

Our findings indicate that plasma miR-205 and let-7f are biomarkers for ovarian cancer detection that complement CA-125; let-7f may be predictive of ovarian cancer prognosis.


 

Chemo Brain: A Decade of Evidence - Chemo Brain May Become Increasingly Common

A Decade of Evidence

Editor's Note: Cognitive dysfunction is a recognized entity that can occur in cancer patients treated with chemotherapy or radiotherapy. Medscape Oncology spoke with Jeffrey S. Wefel, PhD, Section Chief of Neuropsychology at MD Anderson Cancer Center, Houston, Texas, for an overview of what the evidence shows about the condition popularly known as "chemo brain.".....

• 3 Lines of Evidence Converge
• Chemotherapy Not the Sole Culprit
• Duration of Dysfunction Unknown
• Efforts to Determine Risk for Dysfunction
• Research Into Preventive Strategies

• References

 
 

Mind the Gap, NIH Seminar Series - Bridging the Gap Between Evidence and Practice

Mind the Gap

Bridging the Gap Between
Evidence and Practice

Medicine: Mind the Gap is a lecture series that explores issues at the intersection of research, evidence, and clinical practice—areas in which conventional wisdom may be contradicted by recent evidence. From the role of advocacy organizations in medical research and policy, to off-label drug use, to the effectiveness of continuing medical education, the seminar series will aim to engage the National Institutes of Health community in thought-provoking discussions to challenge what we think we know and to think critically about our role in today’s research environment.
 

Ontario Tumour Bank to supply samples to COEUR, a pan-Canadian ovarian cancer research project

press release

TORONTO, Nov. 1, 2013 /CNW/ - The Ontario Tumour Bank (OTB) will supply ovarian tumour samples to the Canadian Ovarian Cancer Experimental Unified Resource (COEUR) in an effort to further enhance ovarian cancer research in Canada, announced Dr. John Bartlett, Provincial Principal Investigator, OTB and Director of the Ontario Institute for Cancer Research's (OICR) Transformative Pathology Program.
"We are thrilled to be contributing these samples to COEUR and to be a part of such an innovative and exciting initiative to discover more about the causes of ovarian cancer and the best avenues for treatment," said Dr. Bartlett. "Through sharing and collaboration we are more likely to identify the best individualized treatment strategies to improve outcomes for patients with ovarian cancer."
The COEUR initiative, a project of the Terry Fox Research Institute, will establish a collection of ovarian cancer samples and clinical data from 2,000 women. Researchers will be provided with controlled access to the resources so they can perform biomarker studies with a particular focus on predicting response to therapy......

Letter: Renal risk stratification with the new oral anticoagulants (JULY 2013)

open access

"...Originally, the US Food and Drug Administration approved dabigatran (Pradaxa) at a dose of 150 mg orally twice daily in patients with a creatinine clearance of 15 to 30 mL/min/1.73 m². This dosing corresponded to the estimated glomerular filtration rate (eGFR) in patients with stage 4 chronic kidney disease, but this dosing is contraindicated in other guidelines worldwide (Canada, Europe, the United Kingdom, Japan, Australia, and New Zealand).² Not unexpectedly, 3,781 serious adverse effects were noted in the 2011 US postmarketing experience with dabigatran. These included death (542 cases), hemorrhage (2,367 cases), acute renal failure (291 cases), stroke (644 cases), and suspected liver failure (15 cases).³ Thirteen months after dabigatran’s approval in the United States, Boehringer Ingelheim changed the dosage and product guidelines.^2–4 The new dosage⁴ is 75 mg twice daily for patients with a creatinine clearance of 15 to 30 mL/min/1.73 m².

Therefore, I suggest a nephrologic “way out”⁵ when using the new oral anticoagulants to avoid the problems with dabigatran noted above......

 

Sleep disturbances in cancer patients: Underrecognized and undertreated

open access

"Depending on the methods used and populations studied, at least 30% and perhaps more than half of patients with cancer have insomnia (TABLE 1).^3,4,8–14 It is one of the most commonly reported complaints in this group,^15–17 and it occurs before, during, and after treatment of cancer."

Key points

Sleep disturbances, primarily insomnia, profoundly affect all aspects of quality of life.

Insomnia can be caused or worsened by a number of other conditions, such as pain, fatigue, depression, and anxiety, and these in turn can be worsened by insomnia. 

Cognitive-behavioral therapy is the treatment of choice for chronic insomnia. Underlying problems should be addressed.

Drugs are often prescribed to help cancer patients sleep but should be used with caution, as there is limited information from clinical trials in this population. 

~~~~~~~~~~~~~

Many cancer patients don’t sleep well, for a variety of reasons. It is an important problem: not only does poor sleep worsen quality of life, it may affect prognosis. Moreover, treatment is available.

Yet many physicians caring for cancer patients do not ask about sleep problems, underestimating their impact or focusing on more urgent problems. Also, patients may not want to bring up the topic because they consider poor sleep to be unavoidable and untreatable and because they fear that reporting it may shift the focus of their treatment from trying to cure the cancer to easing its symptoms.

This practical review will help health care professionals avoid the common barriers to diagnosis and treatment of poor sleep in cancer patients. Because there are few data on other sleep disorders such as sleep apnea and restless leg syndrome, we will focus on the most common one in cancer patients—insomnia—and its effects on other symptoms and quality of life....

 

The effects of metformin on ovarian cancer

Blogger's Note: Metformin is a common drug used in diabetic patients

abstract

OBJECTIVE:

The potential therapeutic effects of metformin on several cancers were reported. However, the evidence of the effects of metformin on ovarian cancer is still limited and inconclusive. This systematic review and meta-analysis study aim to summarize the existing evidence of the therapeutic effects of metformin on ovarian cancer.

METHODS:

We performed systematic searches using electronic databases including PubMed and EMBASE until December 2012. Key words included "metformin" AND ("ovarian cancer" OR "ovary tumor"). All human studies assessing the effects of metformin on ovarian cancer were eligible for inclusion. All articles were reviewed independently by 2 authors with a standardized approach for the purpose of study, study design, patient characteristics, exposure, and outcomes. The data were pooled using a random-effects model.

RESULTS:

Of 190 studies retrieved, only 3 observational studies and 1 report of 2 randomized controlled trials were included. Among those studies, 2 reported the effects of metformin on survival outcomes of ovarian cancer, whereas the other 2 reported the effects of metformin on ovarian cancer prevention. The findings of studies reporting the effects on survival outcomes indicated that metformin may prolong overall, disease-specific, and progression-free survival in ovarian cancer patients. The results of studies reporting the effects of metformin on ovarian cancer prevention were meta-analyzed. It indicated that metformin tended to decrease occurrence of ovarian cancer among diabetic patients with the pooled odds ratio of 0.57 (95% confidence interval, 0.16-1.99).

CONCLUSIONS:

Our findings showed the potential therapeutic effects of metformin on survival outcomes of ovarian cancer and ovarian cancer prevention. However, most of the evidence was observational studies. There is a call for further well-conducted controlled clinical trials to confirm the effects of metformin on ovarian cancer survival and ovarian cancer prevention.

 

Ovarian cancer: sites of recurrence

abstract

INTRODUCTION:

Improved knowledge of recurrence sites after contemporary surgical management of ovarian cancer is needed.

MATERIAL AND METHODS:

We retrospectively reviewed consecutive patients managed for epithelial ovarian or tubal cancer with surgery and platinum-based chemotherapy between January 1, 2005, and December 31, 2009, in a tertiary teaching hospital. The site of first recurrence was recorded. Univariate analysis was performed to identify factors associated with site-specific recurrence. Overall survival and progression-free survival were computed using the Kaplan-Meier method, and log-rank tests were performed to assess the impact on survival of the variables of interest.

RESULTS:

Recurrences were noted in 3 (20%) of 15 International Federation of Gynecologists and Obstetricians stage I to IIa patients and 36 (62.1%) of 58 International Federation of Gynecologists and Obstetricians IIb to IV patients, and the median progression-free survival was 21.6 (2.5-71) and 19.3 (1.8-67.6) months, respectively. In the advanced-disease group, 75% of recurrences involved the peritoneum and 40% were confined to the peritoneum; peritoneal recurrences developed at both treated and untreated sites. Peritoneal recurrence was associated with greater initial peritoneal involvement (Sugarbaker score, 12.1 ± 8.2 vs 7.1 ± 7.4; P = 0.01) and residual postoperative tumor. Nodal recurrences were noted in 38% of all recurrences, usually in combination with peritoneal recurrence and in the abdominal territories. Isolated distant metastasis was a rare mode of recurrence (8%).

CONCLUSIONS:

The peritoneum is the main recurrence site in both early and advanced ovarian cancer. Initial disease spread and extent of surgery are associated with the recurrence risk. This article supports the view that more attention should be directed toward extensive treatment of the peritoneum.

 

 

Editorial: Multimorbidity and cancer outcomes: a need for more research

open access

....In this issue of Clinical Epidemiology, comprehensive data on the impact of comorbidity and survival in cancer patients are reported. These provide very important insight into the association between multimorbidity and cancer prognoses.
These analyses underscore the need for comprehensive, well-designed observational research on comorbidity and cancer. Findings from such types of research can be translated into clinical practice through development, testing, and implementation of intervention strategies designed to minimize the impact of comorbidity and the complications of cancer and its treatment. Such research is urgently needed since many cancer patients with multimorbidity have not benefitted from the recent advances in cancer treatment.

Secular, Spiritual, and Religious Existential Concerns of Women with Ovarian Cancer during Final Diagnostics and Start of Treatment

open access

 Conclusions

To involve patient resources has become a mantra in health care, including within the context of cancer treatment and care. However, while this approach might sound obviously correct, implementing it in daily clinical practice has proven to be difficult.

Hope and courage to face life represent significant personal resources that are created not only in the interplay between body and mind but also between patients and their healthcare professionals. The overall finding that it was not simply the women’s physical bodies but rather their whole lives that became impacted by the disease and treatment highlighted the importance of maintaining a professional engagement and holistic approach from the beginning of treatment—in particular during highly specialised fast-track clinical regimes.

The women dealt with their hope dialectically so that hope and despair could be presented simultaneously. Experiencing personal comfort and strength can reinforce hope, and we find it fair to conclude that the patients’ inner resources thus can be activated and strengthened by adjusted information of the disease and its treatment, psychosocial support, and physical care right from the commencement of the treatment modalities.....


6. Implications for Clinical Practise

Based on the findings presented in this paper we suggest the following.

(i)That person-centred care is trained and implemented in oncology settings.
(ii)That healthcare professionals focus also on the general health and everyday lives of the patients during treatment.
(iii)That physical comfort and well-being are seen, not as excessive luxury but as important tools to sustain and strengthen hope and courage to face life during treatment.
(iv)That communication and cooperation during transitions are further developed and prioritized.
(v)That supportive followup and rehabilitation are offered as an integrated part of the treatment for patients in need of it.(
vi)That patients are given the opportunity to develop, share, and adjust their narratives of illness during their treatment trajectory. 

Comorbidity and survival of Danish ovarian cancer patients from 2000-2011: a population based cohort study

open access

Published:	01 November 2013

Objective: To examine the prevalence of comorbidity among patients diagnosed with epithelial ovarian cancer in the Central Denmark Region and to study the impact of comorbidity on cancer survival over time.

Methods: We included women recorded with a first-time diagnosis of epithelial ovarian cancer in the Danish National Registry of Patients in the Central Denmark region between 2000 and 2011. We followed their survival through the Danish Civil Registration System. We estimated 1- and 5-year survival overall and stratified by Charlson Comorbidity Index score. We used Cox proportional hazard regression analyses to compute adjusted mortality rate ratios (MRRs) within different calendar time periods overall and by comorbidity level.

Results: We identified 1,540 patients. In 2000–2002, 25% of the newly diagnosed ovarian cancer patients had a comorbidity diagnosis compared with 35% in 2009–2011. Median age increased from 61 to 66 years. One-year overall survival changed from 73% (95% confidence interval [CI]: 69–78) in 2000–2002 to 69% (95% CI: 63–73) in 2009–2011, corresponding to an age- and comorbidity-adjusted MRR of 1.03 (95% CI: 0.79–1.36). Five-year survival changed only slightly during the study period, from 37% (95% CI: 32–42) in 2000–2002 to 39% (95% CI: 34–44) in 2009–2011. In patients with Charlson score ≥3, 1-year survival changed from 63% (95% CI: 35–81) in 2000–2002 to 41% (95% CI: 24–57) in 2003–2005 and thereafter stabilized. One-year survival changed from 56% (95% CI: 44–66) to 64% (95% CI: 53–74) in patients with Charlson score 1–2. Compared with Charlson score 0, adjusted 1-year MRRs for Charlson score ≥3 were 1.44 (95% CI: 0.62–3.36) in 2000–2002 and 2.11 (95% CI: 1.27-3.51) in 2009–2011, whereas adjusted 1-year MRRs for Charlson score 1–2 changed from 2.04 (95% CI: 1.33–3.14) in 2000–2002 to 1.09 (95% CI: 0.69–1.71) in 2009–2011.

Conclusion: Comorbidity increased among ovarian cancer patients over time and was associated with poor survival. One- and 5-year overall survivals changed only little and an expected decrease in survival, following increased prevalence of comorbidity and increasing age of patients, may have been counteracted by more aggressive surgery.
 

Identification of candidate circulating cisplatin-resistant biomarkers from epithelial ovarian carcinoma cell secretomes : British Journal of Cancer

Abstract

Background:

The majority of patients diagnosed with advanced epithelial ovarian carcinoma (EOC) relapse with resistant disease, and there are no biomarkers that possess clinical utility to identify or monitor these patients. This study aimed to identify secreted proteins (‘secretome’) collected from human EOC cell lines that differ in their inherent platinum sensitivity.

Methods:

Secreted proteins collected from conditioned medium from ovarian cancer cell lines that vary in their sensitivity to cisplatin were digested with trypsin and analysed by liquid chromatography-tandem mass spectrometry for peptide identification.

Results:

Of the 1688 proteins identified, 16 possessed significant differential abundances (P<0.05) between the platinum-resistant and -sensitive cell lines. A number of these were verified by immunoblot, including COL11A1, which was also found to be associated with worse progression-free survival (PFS; N=723) and overall survival (OS; N=1183) as assessed from publicly available transcript expression data from ovarian cancer tumour specimens.

Conclusion:

Secretome proteomics of EOC cells resulted in the identification of a novel candidate biomarker, COL11A1 (+search). The expression level of COL11A1 correlates to worse PFS and OS, and is predicted to reside in peripheral circulation making this an attractive candidate for validation in sera as a biomarker of cisplatin resistance and poor outcome.

 

A Study of ENMD-2076 in Ovarian Clear Cell Cancers - locations (not yet recruiting)

 ClinicalTrials.gov

Locations

United States, Pennsylvania
Fox Chase Cancer Center	Not yet recruiting
Philadelphia, Pennsylvania, United States, 19111-2497
Contact: Lainie Martin, M.D.     215-728-3889
Principal Investigator: Lainie Martin, M.D.
Canada, Alberta
Tom Baker Cancer Centre	Not yet recruiting
Calgary, Alberta, Canada, T2N 4N2
Contact: Prafull Ghatage, M.D.     403-521-3721
Principal Investigator: Prafull Ghatage, M.D.
Cross Cancer Institute	Not yet recruiting
Edmonton, Alberta, Canada, T6G 1Z2
Contact: Katia Tonkin, M.D.     780-432-8514
Principal Investigator: Katia Tonkin, M.D.
British Columbia Cancer Agency	Not yet recruiting
Vancouver, Alberta, Canada, V5Z 4E6
Contact: Anna Tinker, M.D.     604-877-6000
Canada, Ontario
Holger (Hal) Hirte	Not yet recruiting
Hamilton, Ontario, Canada, L8V 5C2
Contact: Holger (Hal) Hirte, M.D.     905-387-9495
Principal Investigator: Holger (Hal) Hirte, M.D.
London Regional Cancer Program	Not yet recruiting
London, Ontario, Canada, N6A 4L6
Contact: Stephen Welch, M.D.     519-685-8640
Principal Investigator: Stephen Welch, M.D.
Ottawa Regional Cancer Centre	Not yet recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: Johanne Weberpals, M.D.     519-737-8899 ext. 76462
Principal Investigator: Johanne Weberpals, M.D.
Princess Margaret Cancer Centre	Not yet recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Amit Oza, M.D.     416-946-2818
Principal Investigator: Amit Oza, M.D.

 

Search of: clear cell ovarian | Open Studies - List Results

Blogger's Note: this was a quick search which resulted in 28 responses (1 deleted as not relevant) - a FYI:

ClinicalTrials.gov

Rank	Status	Study
1	Not yet recruiting	Imaging Tumor Hypoxia With 18F-EF5 PET in Recurrent or Metastatic Clear Cell Ovarian Cancer
2	Recruiting	Temsirolimus, Carboplatin, and Paclitaxel as First-Line Therapy in Treating Patients With Newly Diagnosed Stage III or Stage IV Clear Cell Ovarian Cancer
3	Not yet recruiting	A Study of ENMD-2076 in Ovarian Clear Cell Cancers

EntreMed Commences Phase 2 Trial For ENMD-2076 In Ovarian Clear Cell Carcinomas - WSJ.com

WSJ.com

ROCKVILLE, Md., Oct. 31, 2013 /PRNewswire/ -- EntreMed, Inc. (NASDAQ: ENMD), a clinical-stage pharmaceutical company developing therapeutics for the treatment of a variety of cancers, announced today the commencement of a multi-center Phase 2 study entitled "Phase II Study of Oral ENMD-2076 Administered to Patients with Ovarian Clear Cell Carcinomas." The study is led by principal investigator Amit M. Oza, MD at Princess Margaret Cancer Centre in Toronto, Canada with participation of up to seven additional cancer centers in Canada and the United States. More information about the clinical trial can be found at www.clinicaltrials.gov.

Amit M. Oza, MD, principal investigator of the study, commented, "Ovarian clear cell carcinomas (OCCC) account for approximately 5-13% of all epithelial ovarian cancers and compared to other subtypes, are associated with poorer prognosis and can be resistant to conventional platinum-based chemotherapy. It presents a considerable clinical challenge and there is a need to develop new therapeutics in the management of this disease. ENMD-2076 has demonstrated single agent activity in tumor models of multiple cancers including ovarian cancer. In a recent Phase 2 trial where ENMD-2076 was administered to platinum-resistant recurrent ovarian cancer patients, some OCCC patients had prolonged disease control, suggesting that it may be effective in this subset of patients. We want to explore this further. The purpose of this study is to examine the response and PFS rates of ENMD-2076 in this difficult to treat patient population. We look forward to working closely with EntreMed and colleagues from other sites in this Phase 2 trial."

Ken K. Ren, Ph.D., EntreMed's Chief Executive Officer commented, "We are very pleased to have Dr. Oza lead this trial. Dr. Oza was a principal investigator in our Phase 2 study in platinum resistant ovarian cancer and has been instrumental in advancing our development program targeting this indication. The cumulative evidence has indicated the potential effectiveness of a combined anti-angiogenic and anti-Aurora A targeted approach in OCCC, and we believe ENMD-2076 presents strong clinical and scientific rationale for the treatment of this subset of patient population. This trial will provide us with more insight into the drug's clinical activities and its correlation with biomarkers."......