Al Covens

Immunophenotyping of serous carcinoma of the female genital tract

To update the data on the expression of ‘mesothelioma markers’ by serous carcinomas of various sites we have studied cases from ovary (n=56), endometrium (n=37), fallopian tube (n=6), primary peritoneum (n=5) and cervix (n=3) using a panel of antibodies (WT1, P53, estrogen receptors, HER2/neu, D2-40, cytokeratin 5/6 and E-cadherin). Ovarian carcinomas demonstrated D2-40 and cytokeratin 5/6 immunoreactivity in 23.2 and 55.4% of cases, respectively. Endometrial carcinomas demonstrated D2-40 and cytokeratin 5/6 immunoreactivity in 43.2 and 37.8% of cases, respectively. D2-40 staining pattern was predominantly focal; however, strong reactivity was identified in 16.2% of endometrial and 10.7% of ovarian carcinomas. HER2/neu oncoprotein overexpression was demonstrated in 7 of 37 (18.9%) uterine serous carcinomas. In contrast, all the serous carcinomas of the other sites were HER2/neu negative. The proportion of positive cases was significantly different in ovarian vs endometrial carcinomas regarding WT1 (P=0.0458), estrogen receptors (P<0.001) reactivity and HER2/neu overexpression (P=0.0025). D2-40 and cytokeratin 5/6 are expressed in a considerable proportion of serous carcinomas and should be used cautiously in a ‘mesothelioma panel’ in situations where serous carcinoma is in the differential diagnosis. HER2/neu was exclusively overexpressed in serous carcinomas of endometrial origin.

Sentinel lymph node biopsy in vulvar cancer: Systematic review, meta-analysis and guideline recommendations.

OBJECTIVES Traditionally, treatment for early stage vulvar cancer has included removal of the primary tumor and inguinofemoral lymph node dissection (IFLD). Sentinel lymph node biopsy (SLNB) has been proposed as an alternative to IFLD for early stage vulvar cancer patients. The aim of this project was to systematically review and assess the potential for harms and benefits with the SLNB procedure in order to make recommendations regarding the adoption of the procedure, selection of patients and appropriate technique and procedures. METHODS A working group with expertise in gynecologic oncology and health research methodology was formed to lead the systematic review and process of guideline development. MEDLINE, Embase and The Cochrane Database of Systematic Reviews were searched for relevant articles published up to September 2014. Outcomes of interest included detection, false negative, complication and recurrence rates and indicators related to pathology. Meta-analyses were conducted where appropriate. RESULTS The evidence-base of a previously published health technology assessment was adopted. An additional search to update the HTAs evidence base located three systematic reviews, and eleven individual studies that met the inclusion criteria. According to a meta-analysis, per groin detection rate for SLNB using radiocolloid tracer and blue dye was 87% [82-92]. The false negative rate with SLNB was 6.4% [4.4-8.8], and the recurrence rates with SLNB and IFLD were 2.8% [1.5-4.4] and 1.4% [0.5-2.6], respectively. An internal and external review process elicited concerns about the necessity of performing this procedure in an appropriate organizational context. CONCLUSION SLNB is recommended for women with unifocal tumors<4 cm and clinically non-suspicious nodes in the groin, provided that specific infrastructure and human resource needs are met. Some recommendations for appropriate techniques and procedures are also provided.

Lymphovascular invasion is a significant predictor for distant recurrence in patients with early-stage endometrial endometrioid adenocarcinoma

To evaluate the value of lymphovascular invasion (LVI) in endometrial endometrioid adenocarcinoma (EEA) as a predictor for distant recurrence, we analyzed the histopathologic features of 513 consecutive cases of nonsurgically staged EEA limited to the uterus. Grade, myoinvasion, cervical involvement, and LVI were evaluated. With a median follow-up of 28 months (range, 2-144 months), 67 cases (13.1%) recurred, 37 (7.2%) had locoregional recurrence, and 30 (5.8%) developed distant recurrence. LVI was identified in 116 cases (22.6%) cases and was the only adverse histopathologic finding in 23 cases; 5 (22%) of the 23 recurred. Multivariate analysis demonstrated a significant association between any type of recurrence and cervical involvement (hazard ratio [HR], 2.760; 95% confidence interval [CI], 1.621-4.698) and LVI (HR, 2.717; CI, 1.568-4.707). Multivariate analysis revealed LVI as the only independent predictor for distant recurrence (HR, 2.841; CI, 1.282-6.297). Studies to examine the role of adjuvant systemic therapy in patients with early-stage disease should be considered.

Endometrial Endometrioid Adenocarcinoma A Pathologic Analysis of 827 Consecutive Cases

We reviewed 827 consecutive cases of pure endometrial endometrioid adenocarcinoma (EEA) treated by hysterectomy to update the distribution of pathologic features. Tumor grade (reported in a 2-tiered system), depth of myometrial invasion, presence of cervical involvement, lymphovascular invasion (LVI), and evidence of extrauterine disease were recorded.The median age at diagnosis was 62 years (range, 30-94 years). The tumor was high grade in 94 cases (11.4%), invaded into the outer half of the myometrium in 249 (30.1%), was positive for cervical involvement in 171 (20.7%), and was positive for LVI in 182 (22.0%). Lymph nodes (sampled in 85 cases) were positive in 13 (1.6%), and ovarian metastases were present in 15 cases (1.8%). High tumor grade was significantly associated with deep myometrial invasion (P > .0001), cervical involvement (P = .0065), and LVI (P > .0001).EEA manifests most commonly with low tumor grade and without deep myometrial invasion. High tumor grade is significantly associated with deep myometrial invasion, cervical involvement, and LVI.

Evaluation of Two Management Strategies for Preoperative Grade 1 Endometrial Cancer

OBJECTIVE: To compare the practices, adjuvant treatment, and outcomes of patients with preoperatively assessed grade 1 endometrioid endometrial cancer between two academic gynecologic oncology centers that use different treatment strategies. METHODS: A retrospective analysis was performed at Duke University Medical Center (Duke) and the Toronto Sunnybrook Regional Cancer Center (Sunnybrook) between 1991 and 2007. Patients at Duke generally underwent surgical staging unless intraoperative assessment identified a negligible risk of nodal disease. Patients at Sunnybrook generally did not undergo surgical staging. RESULTS: A total of 494 patients (272 from Duke and 222 from Sunnybrook were identified with preoperative, central-review–confirming, grade 1, endometrioid, endometrial cancer. Groups were similar in grade, final histology, type of hysterectomy, and length of hospital stay. Patients from Sunnybrook were older (aged 62 years compared with 59 years, P=.001) and were more likely to have capillary lymphatic space involvement (18.2% compared with 8.3%, P=.003) and cervical involvement (12.2% compared with 3.7%, P<.001). Approximately 2% of cases were upgraded to high grade on final specimen. Lymphadenectomy was performed on 49.4% of patients at Duke compared with 11.7% of patients at Sunnybrook. Overall 3-year survival was 96% at Duke and 96% at Sunnybrook (P=.217). Three-year recurrence-free survival was 96% at Duke and 95% at Sunnybrook (P=.327). CONCLUSION: Despite differences in practice and slight differences in patient populations, the recurrence-free and overall survival of women with preoperative centrally reviewed grade 1 endometrial cancer is excellent and without statistically significant difference between the two centers. LEVEL OF EVIDENCE: III

Cost-effectiveness of sentinel node biopsy and pathological ultrastaging in patients with early-stage cervical cancer

The objective of this study was to determine the cost‐effectiveness of radical hysterectomy (RH) and sentinel lymph node biopsy (SLNB) for the management of early‐stage cervical cancer (stage IA2‐IB1).

Sentinel Lymph Node Biopsy in Vulvar Cancer: A Health Technology Assessment for the Canadian Health Care Context

OBJECTIVES Inguinofemoral lymphadenectomy for vulvar cancer is associated with a high incidence of groin wound complications and lymphedema. Sentinel lymph node biopsy (SLNB) is a morbidity-reducing alternative to lymphadenectomy. The objective of this health technology assessment was to determine the clinical effectiveness, cost-effectiveness, and organizational feasibility of SLNB in the Canadian health care system. METHODS A review of the English-language literature published from January 1992 to October 2011 was performed across five databases and six grey-literature sources. Predetermined eligibility criteria were used to select studies, and results in the clinical, economic, and organizational domains were summarized. Included studies were evaluated for methodologic quality using the Newcastle-Ottawa Scale. RESULTS Of 825 reports identified, 88 observational studies met the eligibility criteria. Overall study quality was poor, with a median Newcastle-Ottawa Scale score of 2 out of 9 stars. Across all studies, the detection rate of the sentinel lymph node was 82.2% per groin and the false-negative rate was 6.3%. The groin recurrence rate after negative SLNB was 3.6% compared with 4.3% after negative lymphadenectomy, and complications were reduced after SLNB. No economic evaluations were identified comparing SLNB to lymphadenectomy. Safe implementation of SLNB requires appropriate patient selection, detection technique, and attention to the learning curve. CONCLUSIONS Although study quality is poor, the available data suggest implementation of SLNB may be safe and feasible in Canadian centres with adequate procedural volumes, assuming that implementation includes careful patient selection, careful technique, and ongoing quality assessment. Cost-effectiveness has yet to be determined.

Treating vulvar cancer in the new millennium: Are patients receiving optimal care? ☆

OBJECTIVE The purpose of our study is to describe patterns of care of invasive vulvar carcinoma in the province of Ontario, Canada. Our ultimate goal is to improve vulvar cancer care by understanding variations in care and their impact on outcome. In this pilot study, we specifically evaluate the use of groin node dissection (GND). METHODS The provincial cancer registry was used to identify incident cases of vulvar carcinoma diagnosed between 1994 and 2003. These cases were linked to physician billings claims and hospital discharge records to identify treatment given in the first year after diagnosis. RESULTS The cohort included 978 women with vulvar carcinoma. 85% had at least one surgical procedure. 62% of these had a GND. GND was more likely in those who were treated by a gynecologic oncologist or who had less co-morbid illness. Approximately 25% received radiotherapy. CONCLUSION The rate of GND appears to be low. As proper management of the groins is critical for most patients with vulvar cancer, this observation raises concerns about the quality of treatment received by patients with vulvar carcinoma. Further investigation is required to verify the observations made in this hypothesis generating study.

Cervix Cancer Research Network (CCRN): Improving Access to Cervix Cancer Trials on a Global Scale

Abstract Eighty-seven percent of cervix cancer occurs in less-developed regions of the world, and there is up to an 18-fold difference in mortality rate for cervix cancer depending on the region of the world. The Cervix Cancer Research Network (CCRN) was founded through the Gynecologic Cancer InterGroup with the aim of improving access to clinical trials in cervix cancer worldwide, and in so doing improving standards of care. The CCRN recently held its first international educational symposium in Bangkok. Sixty-two participants attended from 16 different countries including Pakistan, India, Bangladesh, Thailand, Malaysia, Singapore, Philippines, Taiwan, China, Vietnam, Korea, Japan, Columbia, Brazil, Canada, and the United States. The focus of this symposium was to evaluate progress, to promote new clinical trials for the CCRN, and to provide education regarding the role of brachytherapy in the treatment of cervical cancer.

Cost-Efficiency of Robotic Surgery.

To the Editor: W commend Marino et al1 for their attempt at comparing the costs of laparoscopic and robot-assisted laparoscopic surgeries in gynecologic oncology. However, we respectfully disagree with the conclusive statements of the abstract. These statements are not supported by the data presented, and some are contrary to logical thinking. (1) Themain driver of additional costs is the fixed cost of the robot, which is not compensated by the lower hospital room costs.