Alexandra Schepansky

Urine metabolite analysis offers potential early diagnosis of ovarian and breast cancers.

Purpose: Metabolomics is a new, rapidly expanding field dedicated to the global study of metabolites in biological systems. In this article metabolomics is applied to find urinary biomarkers for breast and ovarian cancer. Experimental Design: Urine samples were collected from early- and late-stage breast and ovarian cancer patients during presurgical examinations and randomly from females with no known cancer. After quantitatively measuring a set of metabolites using nuclear magnetic resonance spectroscopy, both univariate and multivariate statistical analyses were employed to determine significant differences. Results: Metabolic phenotypes of breast and ovarian cancers in comparison with normal urine and with each other revealed significance at Bonferroni-corrected significance levels resulting in unique metabolite patterns for breast and ovarian cancer. Intermediates of the tricarboxylic acid cycle and metabolites relating to energy metabolism, amino acids, and gut microbial metabolism were perturbed. Conclusions: The results presented here illustrate that urinary metabolomics may be useful for detecting early-stage breast and ovarian cancer. Clin Cancer Res; 16(23); 5835–41. ©2010 AACR.

Physical activity preferences of ovarian cancer survivors

Objective: Regular physical activity is positively associated with quality of life in ovarian cancer survivors, but no data exist on how best to promote activity in this population. This study investigated the interests and preferences of ovarian cancer survivors with regard to physical activity participation.

Physical activity in ovarian cancer survivors: associations with fatigue, sleep, and psychosocial functioning.

Purpose: Physical activity has been associated with better health-related outcomes in several cancer survivor groups but very few data exist for women with ovarian cancer. The purpose of this study was to investigate the associations between physical activity and health-related outcomes in ovarian cancer survivors and to examine any dose-response relationship. Patients and Methods: A cross-sectional postal survey of ovarian cancer survivors on and off treatment identified through the Alberta Cancer Registry was performed. Participants completed self-report measures of physical activity, cancer-related fatigue, peripheral neuropathy, depression, anxiety, and happiness, as well as demographic and medical variables. Results: A total of 359 ovarian cancer survivors participated (51.4% response rate) of whom 31.1% were meeting the public health physical activity guidelines of the Centers for Disease Control and Prevention. Those meeting guidelines reported significantly lower fatigue than those not meeting guidelines (mean difference, 7.1; 95% confidence interval, 5.5-8.8; d = 0.87; P < 0.001). Meeting guidelines was also significantly inversely associated with peripheral neuropathy, depression, anxiety, sleep latency, use of sleep medication, and daytime dysfunction and was positively associated with happiness, sleep quality, and sleep efficiency. There was no evidence of a dose-response relationship beyond meeting or not meeting the guidelines for any variables. Conclusions: Ovarian cancer survivors who were meeting physical activity guidelines reported more favorable outcomes of fatigue, peripheral neuropathy, sleep, and psychosocial functioning.

Atypical Squamous Cells—Cannot Exclude High-Grade Squamous Intraepithelial Lesion (ASC-H): A Result Not to Be Ignored

OBJECTIVE The objective of this study was to determine the risk of a clinically significant lesion associated with the diagnosis of atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H) on cervical cytology (Pap smear). METHODS This was a retrospective, observational, descriptive study. A computerized database containing cytologic and histologic information for the health region was used to identify women with a diagnosis of ASC-H on a Pap smear performed between January 1 and December 31, 2002. All pertinent pathology data (cytopathology, histopathology, and surgical specimens) were examined. Patients were excluded if they had a diagnosis of cervical cancer, adenocarcinoma in situ (AIS), or high-grade squamous intraepithelial lesion (HSIL) prior to the index Pap smear. RESULTS During the study period, 727 of 241 841 Pap smears (0.3%) were reported as ASC-H in 655 patients. Ninety-one patients had a previous diagnosis of cervical cancer, AIS, or HSIL and were excluded from analysis, and 12 patients on review did not have ASC-H. There were no follow-up data for 35 of the remaining 552 patients, leaving 517 patients in the study group. In this group, the rates of histologically proven cervical lesions were 2.9% (15/517) for cervical cancer, 1.7% (9/517) for AIS, and 65.6% (339/517) for HSIL. Women undergoing a procedure that included histological examination were more likely to have a significant lesion discovered. CONCLUSION The diagnosis of ASC-H on Pap smear is associated with an appreciable risk of clinically significant disease. Patients with an ASC-H Pap smear result should undergo timely colposcopic and histologic assessment to rule out HSIL, AIS, and cervical cancer.

Colposcopic management of abnormal cervical cytology and histology.

OBJECTIVE To provide a guideline for managing abnormal cytology results after screening for cervical cancer, to clarify the appropriate algorithms for follow-up after treatment, and to promote the best possible care for women while ensuring efficient use of available resources. OUTCOMES Women with abnormal cytology are at risk of developing cervical cancer; appropriate triage and treatment will reduce this risk. This guideline will facilitate implementation of common standards across Canada, moving away from the current trend of individual guidelines in each province and territory. EVIDENCE Published literature was retrieved through searches of PubMed or Medline, CINAHL, and The Cochrane Library in October 2008 using appropriate controlled vocabulary (e.g., colposcopy, cervical dysplasia) and key words (e.g., colposcopy management, CIN, AGC, cervical dysplasia, LEEP, LLETZ, HPV testing, cervical dysplasia triage). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated in the guideline to July 2012. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, and national and international medical specialty societies. Expert opinion from published peer-reviewed literature and evidence from clinical trials is summarized. Consensus opinion is outlined when evidence is insufficient. VALUES The quality of the evidence is rated using the criteria described by the Canadian Task Force on Preventive Health Care (Table 1). VALIDATION This guideline has been reviewed for accuracy from content experts in cytology, pathology, and cervical screening programs. Guideline content was also compared with similar documents from other organizations including the American Society for Colposcopy and Cervical Pathology, the British Society for Colposcopy and Cervical Pathology, and the European Cancer Network.

Histologic and clinical significance of atypical glandular cells on pap smears

Objective: To determine the association between atypical glandular cells (AGC) on Pap smear and clinically significant histology, in a large health region. Methods: A cytologic database of over one million Pap smears was reviewed for a result of AGUS/AGC. Cytologic and histologic follow up was obtained to establish the presence of significant histology. Results: 456 patients available for follow up had AGUS/AGC cytology results (0.043% of all Pap smear results). 197(45.2%) patients had a clinically significant diagnosis including 40 with adenocarcinoma in situ (AIS) of the cervix and 48 with endometrial cancer. Conclusion: AGC on a Pap smear is frequently associated with a clinically significant diagnosis.

Epidemiology and investigations for suspected endometrial cancer.

OBJECTIVE To review the evidence relating to the epidemiology of endometrial cancer and its diagnostic workups. OPTIONS Women with possible endometrial cancer can undergo an endometrial evaluation by office biopsy, hysteroscopy, or dilatation and curettage. To assist in treatment planning, pelvic ultrasound, CT scan, or MRI may be considered. OUTCOMES The identification of optimal diagnostic tests to evaluate patients with possible endometrial cancer. EVIDENCE Published literature was retrieved through searches of PubMed, CINAHL, and The Cochrane Library, using appropriate controlled vocabulary (e.g., endometrial neoplasms) and key words (e.g., endometrium cancer, endometrial carcinoma). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated in the guideline to December 31, 2011. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, national and international medical specialty societies, and recent conference abstracts. VALUES The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table). BENEFITS, HARMS, AND COSTS This document is intended to guide the development of a standardized cost-effective investigation of patients with suspected endometrial cancer. VALIDATION The guideline was reviewed for accuracy by experts in pathology, radiation oncology, and medical oncology. Guideline content was also compared with relevant documents from the American Congress of Obstetricians and Gynecologists.

The role of surgery in endometrial cancer.

OBJECTIVE To review current practice and make recommendations for the management and treatment of endometrial cancer. OUTCOMES This guideline makes recommendations with respect to extended surgical staging, which provides important prognostic information and aids in determining the need for adjuvant treatments. EVIDENCE Published literature was retrieved through searches of PubMed, CINAHL, and The Cochrane Library, using appropriate controlled vocabulary (e.g., endometrial neoplasms) and key words (e.g., endometrium cancer, endometrial carcinoma). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated in the guideline to December 31, 2011. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, national and international medical specialty societies, and recent conference abstracts BENEFITS, HARMS, AND COSTS This guideline reviews the benefit of extended surgical staging compared with the potential harm of a limited surgery in grade 2 and 3 disease. VALUES The quality of evidence is rated and recommendations are made using the criteria described by the Canadian Task Force on Preventive Health Care (Table).

The Role of Adjuvant Therapy in Endometrial Cancer

OBJECTIVE To review the evidence relating to the use of adjuvant therapy after surgical treatment for endometrial cancer. OPTIONS Women with endometrial cancer can be given the option of receiving adjuvant radiotherapy and/or chemotherapy according to pathologic findings at time of surgery. OUTCOMES The outcomes measured are postoperative progression-free and overall survival in endometrial cancer patients. EVIDENCE Published literature was retrieved through searches of PubMed, CINAHL, and The Cochrane Library, using appropriate controlled vocabulary (e.g., endometrial neoplasms) and key words (e.g., endometrium cancer, endometrial carcinoma). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated in the guideline to December 31, 2011. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, national and international medical specialty societies, and recent conference abstracts. VALUES The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table). BENEFITS, HARMS, AND COSTS This guideline is intended to help standardize postoperative treatment of endometrial cancer and minimize undertreatment and overtreatment. VALIDATION The guideline was reviewed for accuracy by content experts in pathology, radiation oncology, and medical oncology. Guideline content was also compared with relevant documents from the American Congress of Obstetricians and Gynecologists.

Assessment of outcomes in surgically staged I/II endometrial adenocarcinoma patients treated with postoperative vaginal vault radiotherapy only.

Objective: To examine the efficacy of vaginal vault radiotherapy as adjuvant treatment for patients with high-grade, stage I/II endometrial adenocarcinoma who have been surgically staged. Methods: A retrospective chart review of 77 women between 1995 and 2006 with high-grade surgically staged I and II endometrial adenocarcinoma, who were treated with postoperative vaginal vault radiotherapy alone, was performed. The primary study end points were recurrence risk and sites of recurrence. The secondary end points were disease-free and overall survival. Kaplan-Meier estimates were calculated for overall and disease-free survival. Results: Seventy-seven women were identified and met inclusion criteria. Sixty-seven (87%) had grade 3 histologic features on final pathologic report. Forty-two patients (55%) were classified as stage IB, having superficial myometrial invasion; 21 (27%) were stage IC, with deep invasion; and 6 (8%) were stage II, involving the cervix. The median follow-up was 80 months (6.6 years). There were 10 recurrences (13.0%), of which 3 were local: 1 involving the vaginal apex; 1, the lower vagina and pelvic sidewall; and 1, the lower vagina. The 5-year recurrence risk was 11.2% and the 5-year survival probability 88.9%. Conclusions: It seems that for this cohort of 77 patients with surgically staged I and II grade 3 endometrial adenocarcinoma, adjuvant vaginal vault radiotherapy alone leads to acceptable recurrence rates and survival while minimizing morbidity.