Rachel Kupets

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 Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice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.

Assessment of endometrial sampling as a predictor of final surgical pathology in endometrial cancer

Background:The histology and grade of endometrial cancer are important predictors of disease outcome and of the likelihood of nodal involvement. In most centres, however, surgical staging decisions are based on a preoperative biopsy. The objective of this study was to assess the concordance between the preoperative histology and that of the hysterectomy specimen in endometrial cancer.Methods:Patients treated for endometrial cancer during a 10-year period at a tertiary cancer centre were identified from a prospectively collected pathological database. All pathology reports were reviewed to confirm centralised reporting of the original sampling or biopsy specimens; patients whose biopsies were not reviewed by a dedicated gynaecological pathologist at the treating centre were excluded. Surgical pathology data including histology, grade, depth of myometrial invasion, cervical stromal involvement and lymphovascular space invasion (LVSI) as well as preoperative histology and grade were collected. Preoperative and final tumour cell type and grade were compared and the distribution of other high-risk features was analysed.Results:A total of 1329 consecutive patients were identified; 653 patients had a centrally reviewed epithelial endometrial cancer on their original biopsy, and are included in this study. Of 255 patients whose biopsies were read as grade 1 (G1) adenocarcinoma, 45 (18%) were upgraded to grade 2 (G2) on final pathology, 6 (2%) were upgraded to grade 3 (G3) and 5 (2%) were read as a non-endometrioid high-grade histology. Overall, of 255 tumours classified as G1 endometrioid cancers on biopsy, 74 (29%) were either found to be low-grade (G1–2) tumours with deep myometrial invasion, or were reclassified as high-grade cancers (G3 or non-endometrioid histologies) on final surgical pathology. Despite these shifts, we calculate that omitting surgical staging in preoperatively diagnosed G1 endometrioid cancers without deep myometrial invasion would result in missing nodal involvement in only 1% of cases.Conclusions:Preoperative endometrial sampling is only a modest predictor of surgical pathology features in endometrial cancer and may underestimate the risk of disease spread and recurrence. In spite of frequent shifts in postoperative vs preoperative histological assessment, the predicted rate of missed nodal metastases with a selective staging policy remains low.

Feasibility of same-day discharge after laparoscopic surgery in gynecologic oncology.

OBJECTIVE The purpose of this study is to evaluate whether same-day discharge after laparoscopic gynecologic oncology surgery is feasible and determines factors associated with admission. METHODS This retrospective cohort study included all patients consented for laparoscopy by two gynecologic oncologists at a tertiary care academic teaching hospital between January 2006 and June 2009. Procedures included those not typically discharged same-day, such as total laparoscopic simple or radical hysterectomies or radical trachelectomy +/- salpingo-oophorectomy +/- pelvic and para-aortic lymph node dissection +/- omentectomy. Those discharged same-day were compared to those admitted. Multivariate logistic regression analysis was done to determine factors associated with admission. RESULTS Three hundred three patients were included. 6.9% were converted to laparotomy. One hundred forty-seven (48.5%) had same-day discharge (median stay 295minutes). Among outpatients, 7 (4.8%) were readmitted within three weeks of surgery. Three patients (2%) could have avoided the ER or hospital admission had they been originally admitted postoperatively. No patients with same-day discharge had a major acute postoperative complication. Factors associated with admission include age (OR 1.76 for age 70years vs 50years, p=0.001), surgeon (OR 6.91, p<0.0001), conversion to laparotomy (p<0.0001), radical hysterectomy (OR 3.43, p=0.002), length of surgery (OR 2.94 for 4hours vs 2hours, p<0.0001), and surgery start time after 1PM (OR 3.77, p=0.0001). CONCLUSION Same-day discharge for laparoscopic gynecologic oncology surgery is feasible, with low morbidity and few readmissions within three weeks of surgery. Successful same-day discharge can increase by refining patient selection and operating room scheduling.

Initial Evaluation and Referral Guidelines for Management of Pelvic/Ovarian Masses

OBJECTIVES To optimize the management of adnexal masses and to assist primary care physicians and gynaecologists determine which patients presenting with an ovarian mass with a significant risk of malignancy should be considered for gynaecologic oncology referral and management. OPTIONS Laparoscopic evaluation, comprehensive surgical staging for early ovarian cancer, or tumour debulking for advanced stage ovarian cancer. OUTCOMES To optimize conservative versus operative management of women with possible ovarian malignancy and to optimize the involvement of gynaecologic oncologists in planning and delivery of treatment. EVIDENCE Published literature was retrieved through searches of PubMed or MEDLINE, CINAHL, and the Cochrane Library, using appropriate controlled vocabulary and key words. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. Grey (unpublished) literature was identified by searching the web sites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. RECOMMENDATIONS 1. Primary care physicians and gynaecologists should always consider the possibility of an underlying ovarian cancer in patients in any age group who present with an adnexal or ovarian mass. (II-2B) 2. Appropriate workup of a perimenopausal or postmenopausal woman presenting with an adnexal mass should include evaluation of symptoms and signs suggestive of malignancy, such as persistent pelvic/abdominal pain, urinary urgency/frequency, increased abdominal size/bloating, and difficulty eating. In addition, CA125 measurement should be considered. (II-2B) 3. Transvaginal or transabdominal ultrasound examination is recommended as part of the initial workup of a complex adnexal/ovarian mass. (II-2B) 4. Ultrasound reports should be standardized to include size and unilateral/bilateral location of the adnexal mass and its possible origin, thickness of septations, presence of excrescences and internal solid components, vascular flow distribution pattern, and presence or absence of ascites. This information is essential for calculating the risk of malignancy index II score to identify pelvic mass with high malignant potential. (IIIC) 5. Patients deemed to have a high risk of an underlying malignancy should be reviewed in consultation with a gynaecologic oncologist for assessment and optimal surgical management. (II-2B).

Is venous thromboprophylaxis necessary in patients undergoing minimally invasive surgery for a gynecologic malignancy

OBJECTIVES Current recommendations for the use of venous thromboprophylaxis in patients undergoing minimally invasive surgery (MIS) for a gynecologic malignancy are derived from patients undergoing open surgery. Our objective was to determine the 30-day prevalence of symptomatic venous thromboembolism (VTE) after laparoscopic gynecologic oncology procedures in patients who received no thromboprophylaxis. METHODS Between January 2006 and September 2013, women who underwent MIS for endometrial, cervical or ovarian cancer at a single institution were included. Data on patient demographics, diagnosis, comorbidities, perioperative characteristics, use of thromboprophylaxis, and diagnosis of VTE were collected retrospectively. RESULTS Of the 419 patients who underwent MIS for a gynecologic cancer, 352 (84%) received no VTE prophylaxis. At least a total laparoscopic hysterectomy (simple or radical) or pelvic lymph node dissection was performed in 95% of these patients. The median length of surgery was 137 min and 95% of patients were discharged home within 1 day of surgery. The rate of VTE in the 352 untreated patients was 0.57% (1 pulmonary embolism and 1 deep vein thrombosis). There were no VTE diagnosed within 30 days of surgery in the 67 patients who received anticoagulant thromboprophylaxis. CONCLUSION The rate of VTE is low in patients undergoing minimally invasive surgery for a gynecologic malignancy despite no VTE prophylaxis. The benefits of routine use of VTE prophylaxis in this population are questionable.

Presumed previous human papillomavirus (HPV) related gynecological cancer in women diagnosed with anal cancer in the province of Ontario.

OBJECTIVE The oncogenic HPV subtypes responsible for gynecologic malignancies have also been implicated in the development of squamous cell cancer of the anus (SCAC). SCAC is more common in women, typically presenting at an older age than gynecologic cancers. The aim of this study was determine whether women diagnosed with anal cancer are more likely to have a history of HPV-related gynecological cancer as compared to a matched control group. METHODS We performed a population-based, case-control study at the Institute for Clinical Evaluative Sciences (ICES) which houses the administrative databases for all residents of the province of Ontario, Canada. All women diagnosed with SCAC between 1992 and 2005, identified using ICD-9 codes (154.2, 154.3, 154.8) for anatomic site and ICD-O codes (8070-8075, 8120, 8123, 8124) for histologic subtype, were included as cases. Up to 5 female controls, matched for age, socioeconomic status, health region and number of years enrolled in the provincial health plan, were selected for each case. The exposure of interest was previous HPV-related gynecologic cancer, specifically cervical cancer, vulvar cancer and vaginal cancer. Conditional logistic regression was performed to assess the relationship between this exposure and SCAC. RESULTS A total of 674 women with SCAC were identified whose median age was 61. Amongst the cases, there were 7 cervical, 3 vulvar and 1 vaginal cancers compared with 5 cervical, 0 vulvar and vaginal cancers in the 3264 controls. Previous HPV-related gynecological cancer (cervical, vaginal or vulvar cancer) was significantly associated with SCAC (OR: 10.5, 95% C.I.: 3.6 to 30.3). The median time between the diagnosis of anal cancer and previous cervical cancer was 20 years. CONCLUSIONS Previous HPV-related gynecological cancers are strongly associated with anal cancer and may occur decades before the anal cancer.

The association between cervical cancer screening and mortality from cervical cancer: A population based case–control study

OBJECTIVE To estimate the effect of cervical cancer screening on mortality from cervical cancer in women between the ages of 20 and 69 residing in Ontario by 5 year age groups. METHODS An Ontario population based case-control study of women between ages 20 and 69 was performed. Cases were women who were diagnosed with cervical cancer between January 1, 1998 and December 31, 2008 who died from cervical cancer within this period. Controls were women without a diagnosis of cervical cancer between January 1, 1998 and December 31, 2008 who were alive on the cases date of death. Exposure was defined as cervical cytology history. Conditional logistic regression was used to estimate the strength of association between mortality from cervical cancer and screening in 5 year incremental age intervals. RESULTS We identified 1052 cases and 10,494 controls. Less than 2.5% of women who died from cervical cancer were under the age of 30. Cervical cancer screening performed 3-36 months prior to the date of diagnosis was found to be protective of mortality from cervical cancer in women over the age of 30 (odds ratio=0.28-0.60; p<0.05 in all strata). In women under the age of 30 cervical cancer screening was not found to be protective of mortality from cervical cancer (odds ratio=1.58-2.43; non significant). CONCLUSION No association between cervical cancer screening and mortality from cervical cancer under the age of 30 was found. This could be due to there being a small or having no effect or due to the fact that mortality from cervical cancer under the age of 30 is extremely rare.

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.