Wylam Faught

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.

Prospective longitudinal study of ultrasound screening for endometrial abnormalities in women with breast cancer receiving tamoxifen

OBJECTIVE The goal of this work was to study the role of transvaginal ultrasonography (TVUS) together with colorflow Doppler imaging (CFDI) in the detection of significant endometrial abnormalities induced by tamoxifen. METHODS Over a 6-year period, 304 women on tamoxifen as adjuvant therapy for breast cancer were recruited into the current study. Standard demographic data as well as duration of tamoxifen use were collected. Patients were assessed at study entry and at yearly intervals with TVUS together with CFDI. All patients had an endometrial biopsy at the time of study entry, and repeat endometrial evaluations were done subsequently only if there were abnormal ultrasound findings or the presence of irregular vaginal bleeding. All ultrasonic characteristics and Doppler flow measurements were recorded. Descriptive statistics were used to describe the study group. Logistic regression was used to identify significant treatment- and ultrasound-related factors associated with the presence of significant uterine pathology. RESULTS One thousand and sixty-one ultrasound assessments were performed on 304 patients over a 6-year period. The mean age was 52.33 (range, 29-79). Seventy-two percent of the patients were postmenopausal at the time of breast cancer diagnosis. The median concentrations of estrogen and progesterone receptor were 75 and 73 fmol/L, respectively. Fifty-eight percent of the patients had received cytotoxic chemotherapy. The mean duration of tamoxifen use was 48.2 months. Thirty-two percent of the ultrasound examinations had associated significant uterine pathology defined as conditions that required further medical or surgical investigation and treatment. However, 80% of the abnormalities represented benign polyps. Six cases of primary endometrial cancer were detected. All cases presented with irregular bleeding. No recurrence of disease was detected at a median follow-up of 48 months. One case of metastatic breast cancer to the uterus was encountered. By setting the endometrial thickness cutoff at more than 9 mm to represent significant abnormality in this patient population, the sensitivity was 63.3%, specificity was 60.4%, positive predictive value was 43.3%, and negative predictive value was 77.5%. To detect endometrial cancer, the endometrial thickness cutoff at 9 mm had a positive predictive value of only 1.4%. Logistic regression analysis showed only endometrial thickness greater than 9 mm (OR 3.99, CI = 1.26-12.65, P = 0.018) and spiral artery pulsatility index measurement (OR 4.18, CI = 1.25-13.92, P = 0.02) to be associated with significant uterine abnormalities. CONCLUSIONS Routine sequential ultrasound surveillance in asymptomatic women on tamoxifen is not useful because of its low specificity and positive predictive value. A significant portion of screened asymptomatic women would need to undergo needless surgical evaluations of their endometrium if widespread use of ultrasound is implemented in this patient population.

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.

The Definition of Optimal Inguinal Femoral Nodal Dissection in the Management of Vulva Squamous Cell Carcinoma

ObjectivesTo reject the hypothesis that the number of nodes removed at time of surgical staging for vulva cancer is not an important prognostic factor.MethodsRetrospective chart reviews were carried out from 1980-2004 to identify patients with squamous cell vulva carcinoma treated with radical vulvectomy and bilateral inguinal femoral lymph node dissection. Patients’ demographics, disease characteristics, the number of lymph nodes removed at surgery, and standard oncologic outcomes were recorded. Cox proportional hazard models were built to model times to clinical progression and death using predictor variables of: age, tumor size and maximum depth of invasion, resection margin status, and total number of nodes removed.ResultsFifty-eight patients were identified. The median lesion size was 3.5 cm. The median depth of invasion was 7.5 mm. The 20th percentile for total number of lymph nodes removed was 10. Adjuvant radiation therapy was given in 31% of patients. At a median follow-up of 37 months, recurrence was observed in 17 patients (29.3%). Cox regressions showed the total number of nodes removed less than 10 to be the only significantly predictive of shorter time to first progression (HR = 12.88, 95% CI = 1.47-112.89, P = .021) and shorter disease specific survivals (HR = 11.41, 95% CI = 2.21-58.86, P = .004) (HR, hazard ratio; CI, confidence interval).ConclusionThe total number of nodes removed at time of surgical staging is an independent survival prognostic factor. A total of at least 10 nodes from a bilateral dissection can be used to define an optimal evaluation.

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.

Suprapubic or Urethral Catheter: What Is the Optimal Method of Bladder Drainage After Radical Hysterectomy?

BACKGROUND Lower urinary tract dysfunction is a common morbidity related to radical hysterectomy (RAH). Although transurethral catheterization (TUC) has traditionally been used for postoperative bladder drainage following RAH, suprapubic catheterization (SPC) is an alternative method that may be advantageous. OBJECTIVES To determine, by means of a retrospective cohort study, the incidence of urinary tract infection (UTI), duration of postoperative hospital stay, and time to trial of voiding in women catheterized suprapubically or transurethrally after RAH for early stage cervical cancer. METHODS Two hundred twelve patients who underwent RAH and staging for stage IA1 + LVS, 1A2, and 1B1 cancer of the cervix in Edmonton between 1996 and 2006 were included in the study. Three gynaecologic oncologists performed the surgeries. Operative, postoperative, and demographic data were extracted from patient records. Patients were catheterized either suprapubically (SPC group) or transurethrally (TUC group) according to the surgeons discretion. Comparative tests and multivariate regression analysis were used to compare outcome measures between the groups and to adjust for confounding variables. RESULTS The TUC group had a higher proportion of patients with UTI (27%) than the SPC group (6%) (P < 0.001). The SPC group had a shorter postoperative hospital stay (4.8 vs. 5.7 days; P < 0.001) and an earlier trial of voiding (2.7 vs. 4.4 days; P < 0. 001). Following regression analysis, statistically significant differences remained for UTI and time to initiation of a trial of voiding. CONCLUSION After RAH for early stage cervical cancer, suprapubic catheterization is associated with a lower rate of UTI and an earlier trial of voiding than transurethral catheterization.

Cervical Cancer During Pregnancy

Cervical cancer is one of the most devastating conditions that can complicate a pregnancy. Stage for stage, treatment for squamous cell cervical cancer is the same as that given in the non-pregnant patient. Radical surgery is the treatment of choice for the early stages of the disease. Although a planned delay in therapy may be considered for up to 20 weeks, for stages IA and IB1, it should be implemented cautiously and with the patients full awareness of the risks. If delay is considered for higher stages, the patient must be aware of the paucity of data to support this plan. Chemoradiation is the standard treatment for advanced cancer of the cervix. When acceptable fetal maturity has been reached, a classical Caesarean section is usually performed prior to definitive treatment.

Omental chemotherapy effects as a prognostic factor in ovarian cancer patients treated with neoadjuvant chemotherapy and delayed primary surgical debulking.

We sought to assess the prognostic significance of chemotherapy effect on upper abdominal metastatic disease. Retrospective chart reviews were carried out from 1997 to 2005 to identify ovarian cancer patients treated with neoadjuvant chemotherapy. Pathologic examinations of resected omental and ovarian tumors for the presence of chemotherapy effect were performed. Cox proportional hazard models were built to model time to progression and death by using predictor variables of age, tumor grade, amount and location of largest residual disease, and the presence of chemotherapy effects on resected tumors. Sixty-six patients with available slides and clinical information were identified. The presence of omental chemotherapy effects was observed in 58 patients (88%). Identified independent statistically significant predictors for progression-free survival included presence of omental chemotherapy effect (hazard ratio [HR], .38; 95% confidence interval [95% CI], .17–.89; P = .026) and suboptimal tumor residuals in upper abdominal location compared with pelvic location (HR, 2.41; 95% CI, 1.06–5.48; P = .035). The presence of omental chemotherapy effect was the only statistically significant predictor of disease specific survival (HR, .21; 95% CI, .068–.639; P = .006). The estimated median survival for the group with positive omental chemotherapy effect was 84.45 months (95% CI, 69.63–99.28). The corresponding statistic in patients with no observed response to chemotherapy was 31.15 months (95% CI, 21.84–40.47). Upper abdominal disease location and its response to chemotherapy were independent prognostic factors for progression-free survival. Aggressive upper abdominal debulking procedures are recommended to improve oncologic outcomes.