Limor Helpman

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.

Genito-Sensory Analysis in Women with Arousal and Orgasmic Dysfunction

INTRODUCTION Diagnosis and treatment of female sexual dysfunction (FSD) are currently based on subjective female reports and physical examination. The GenitoSensory Analyzer (GSA) is a quantitative sensory testing tool designed to quantify vibratory and thermal sensation in the vagina and clitoris in a reproducible manner, and may therefore contribute to the diagnosis and management of FSD. AIM To address the question of whether women with arousal and/or orgasmic sexual disorders have genital sensory abnormalities as measured by the GSA. MAIN OUTCOME MEASURES Thresholds for warm, cold, and vibratory sensation at predetermined points in the vaginal wall and clitoris. METHODS Female subjects complaining of arousal and/or orgasmic sexual disorders for more than 6 months were evaluated using a questionnaire based on the female sexual function index (FSFI). Women with a desire disorder, pain disorder, vulvar vestibulitis syndrome, or acute vaginal or/and introital infection were excluded. The GSA device measured thresholds for warm, cold, and vibratory sensation at predetermined points in the vaginal wall and clitoris. Eight measurements were obtained, and deviations from previously published normative values were identified. RESULTS Twenty-eight women (age 40.4 +/- 13 years) complaining of arousal and/or orgasmic FSD comprised the study cohort. Twenty-five of them (89%) had at least one pathologic genitor-sensory threshold on GSA testing and 19 (68%) had >3 pathologic thresholds. Pathologic GSA results were associated with lower arousal scores on the FSFI questionnaire, older age, and menopausal status. CONCLUSIONS Most of the study women had at least one genitor-sensory pathology on GSA testing, indicating a possible organic component in their disorder. Our findings support the incorporation of the GSA as a quantitative tool in the assessment and diagnosis of patients with FSD.

Neonatal respiratory morbidity after elective cesarean section

Objective. The objective of this study was to examine the rate of respiratory morbidity in neonates delivered by elective cesarean delivery (ECD) at term, with a definite confirmation of gestational age (GA) by 1st-trimester ultrasound. Methods. Consecutive women carrying a singleton pregnancy and undergoing ECD at term (>38 1/7 weeks), confirmed by 1st-trimester ultrasound, were included in the study group. Multiple gestations, cesarean section (CS) in labor, CS performed after rupture of membranes and induced deliveries were excluded. The control group included women with a singleton pregnancy at term (>38 1/7 weeks) who delivered spontaneously. This group of women was randomly selected during the study period. Results. The study group included 277 women delivered by ECD. The control group consisted of 311 women. Five newborns in the study group and none in the control group were admitted to the neonatal intensive care unit (NICU) due to respiratory disorders (p < 0.02). Excluding diabetic women did not change the results. On multivariate analysis, no other factors were found to independently influence the risk of respiratory complications. Conclusion. In our study, the rate of respiratory morbidity was found to be significantly higher in neonates delivered by ECD compared to those delivered vaginally. The fact that GA was confirmed by 1st-trimester ultrasound makes iatrogenic prematurity an unlikely sole cause for this excess morbidity.

Early adenocarcinoma of the cervix: Is radical vaginal trachelectomy safe?

OBJECTIVE Radical vaginal trachelectomy (RVT) is a revolutionary option for fertility preservation in young women with early cervical tumors. Several series have demonstrated outcomes comparable to radical hysterectomy (RH), but none has addressed the influence of histology. We evaluated the safety of RVT in adenocarcinomas. METHODS Data on surgically treated adenocarcinoma (AC) and squamous cell carcinoma (SCC) cases was taken from a centralized Toronto Cervical Cancer Database. Prognostically important tumor features, lymph node status, and the use of adjuvant therapies were compared. Adenocarcinoma cases treated with RVT were compared to AC cases treated with RH, and to SCC cases that had RVT. Recurrence-free survival was calculated from the date of surgery. Medians, proportions, and survival curves were compared with the Mann Whitney test, the Chi-square test, and the Log Rank test, respectively. RESULTS 74 patients with AC and 66 patients with SCC undergoing RVT, and 187 cases of AC undergoing RH were analyzed. Patients undergoing RVT were younger than patients having RH (31 vs. 40, p<0.001). Tumor characteristics were similar, but depth of invasion and the frequency of high grade lesions were higher in the RH group (5 mm vs. 3 mm, p<0.001; and 36% vs. 22%, p=0.04). Adjuvant treatment was given more frequently after RH (12% vs. 3%, p<0.05). There was no significant difference in recurrence-free survival between RH and RVT for AC, or between AC and SCC patients treated by RVT. CONCLUSIONS RVT is a safe alternative for early stage cervical adenocarcinoma in appropriately selected patients wishing to preserve fertility.

Complementary and alternative medicine use among women receiving chemotherapy for ovarian cancer in 2 patient populations.

Objective The authors evaluated attitudes toward complementary and alternative medicine (CAM) use in 2 populations of women receiving chemotherapy for epithelial ovarian cancer (EOC). Methods Women with EOC currently being treated with chemotherapy at 2 tertiary cancer centers, in Canada and the United Kingdom, completed a self-administered questionnaire on attitudes and perceptions of CAM and types of CAM used within the previous month. Results One hundred ninety-two patients (94 from Canada, 98 from United Kingdom) completed the questionnaire. Overall, 85 women (44%) were identified as CAM users. Complementary and alternative medicine use was more common among Canadian women (52%) compared with women from the United Kingdom (37%), P = 0.02. Participants used 71 different types of CAM, the majority (61%) taking multiple CAM. The frequency of CAM use was the same in primary compared with recurrent disease. Eighty-nine percent of CAM users considered it important for their oncologist to be aware of CAM use. Canadian women, however, were less likely to inform their physician (Canada: 50%; United Kingdom: 81%), P = 0.02. Motivations for CAM use were the same in both populations including assist healing (60%), boost the immune system (57%), improve quality of life (48%), and relieve symptoms (45%). Thirteen percent thought CAM could cure cancer, whereas 17% thought it would prevent recurrence. Conclusions Complementary and alternative medicine use is common in women receiving chemotherapy for EOC. Increasingly, interactions between CAM and prescribed medication are being identified. Oncologists should be aware and actively inquire about CAM use. Although patterns of CAM use differed, the motivation for starting CAM was similar, highlighting the need to address supportive care in all patients.

Effect of treatment delay on survival in patients with cervical cancer: a historical cohort study.

Objective The objective of this study was to evaluate the effect of treatment delay on prognosis in patients with cervical cancer. Methods The study group of this historic cohort study comprised 321 patients newly diagnosed with cervical cancer between 1999 and 2010. Time from diagnosis to treatment was analyzed both as a continuous variable and as a categorical variable in 3 groups that differed in waiting time between diagnosis and treatment initiation: 30 days or less (group 1, n = 134), 30 to 45 days (group 2, n = 86), and more than 45 days (group 3, n = 101). Associations between waiting time group, patients’ characteristics, and disease outcome were investigated using t tests, analyses of variance and Cox regression analyses, Kaplan-Meier survival analysis, and log-rank (Mantel-Cox) tests. Results Time from diagnosis to treatment initiation, when analyzed as a continuous variable, was not a significant factor in survival. There were no between-group differences in age, smoking rate, marital status, gravidity, parity, tumor histology, or lymph node involvement. Early-stage disease and small tumor diameter were diagnosed most frequently in group 3. However, there was no significant between-group difference in 3-year survival rates (74.6%, 82.2%, and 80.8% in groups 1, 2, and 3, respectively; P = 0.38). On multivariate analysis, only stage, histology, and lymph node involvement were significant prognostic factors for survival. Before starting treatment, 28 patients underwent ovarian preservation procedures. Conclusions Longer waiting time from diagnosis to treatment was not associated with worse survival. Our findings imply that if patients desire fertility or ovarian preservation procedures before starting treatment, it is acceptable to allow time for them.

Safety of ovarian conservation and fertility preservation in advanced borderline ovarian tumors

OBJECTIVE To assess the impact of a fertility-sparing approach on disease recurrence in women with advanced borderline ovarian tumors. DESIGN Historic cohort study. SETTING A tertiary referral center for gynecological oncology patients and a university teaching hospital. PATIENT(S) Consecutive patients with advanced borderline ovarian tumors defined as stage IC and above, treated at a single institution during a span of 30 years. INTERVENTION(S) Data on surgical approach (e.g., fertility sparing, ovarian conserving) as well as histopathology, disease stage, CA-125 level, and use of chemotherapy were collected from the medical records, and their impact on disease recurrence was assessed. MAIN OUTCOME MEASURE(S) Recurrence-free interval. Its association with the type of surgery and with other clinical and pathological features was assessed using the Kaplan Meier and Cox proportional hazards methods. RESULT(S) Fifty-nine patients with advanced disease were identified. Median follow-up was 55.3 months. Mean age at diagnosis was 35 years. Most of the tumors (51, 84.4%) had serous histology. Twenty-seven patients (45.8%) developed recurrences and 6 (10%) died of their disease. Mean time to recurrence was 30.6 months. Of 44 women ≤40 years, 33 (75%) had a fertility-sparing procedure. Fertility preservation was not associated with disease recurrence. A total of 34 pregnancies and 26 live births were documented among 21 patients attempting conception. CONCLUSION(S) Borderline ovarian tumors carry a favorable prognosis, even at an advanced stage. Fertility preservation was not found to be associated with an increased risk of relapse in young patients with advanced disease, and may be reasonably considered.

Rates of risk-reducing surgery in Israeli BRCA1 and BRCA2 mutation carriers

The frequency of BRCA1 and BRCA2 mutations is higher in Israel than in almost all other countries. One strategy to reduce the burden of hereditary breast and ovarian cancers is to offer genetic testing followed by risk‐reducing surgery (mastectomy and salpingo‐oophorectomy) for mutation carriers. The extent to which Israeli women who carry mutations undergo these surgeries is not well characterized. Israeli women who are BRCA1 or BRCA2 mutation carriers and followed at a single high‐risk clinic were asked to complete a questionnaire detailing their clinical histories at the time of genetic results disclosure and a follow‐up questionnaire was completed 18 or more months thereafter. A total of 205 mutation carriers completed the questionnaires. Of 170 women with no cancer history, 84 (49%) had a risk‐reducing bilateral salpingo‐oophorectomy and 22 (13%) had a risk‐reducing mastectomy. Five of 35 (14.3%) women with breast cancer opted for contralateral mastectomy. Approximately one half of Israeli women with a BRCA1 or BRCA2 mutation opt for risk‐reducing oophorectomy, but the rate of risk‐reducing mastectomy is only 13%.

Abdominopelvic cytoreduction rates and recurrence sites in stage IV ovarian cancer: Is there a case for thoracic cytoreduction?

OBJECTIVE We report the rates of optimal abdominopelvic cytoreduction and the sites of recurrence in stage IV ovarian cancer patients, with particular attention to the potential impact of thoracic cytoreduction on treatment results in patients with intra-thoracic spread. METHODS A historic cohort study of all stage IV ovarian cancer patients diagnosed between 1994 and 2010 and underwent abdominopelvic cytoreductive surgery. Controls were stage IIIc patients. Statistical analyses included χ(2) test, Cox proportional hazards regression models and Kaplan-Meier curves with log-rank tests. RESULTS Group 1 included 76 stage IV patients, 55% with thoracic spread. Group 2 included 142 stage IIIc patients. Age, histology, primary peritoneal tumor and ascites rates were similar for the two groups. Respective rates of optimal abdominopelvic cytoreduction were 68% vs. 83.5% (p<0.05), median time to progression 5.3 vs. 12.3 months (p<0.01) and overall survival 27.2 vs. 46.1 months (p<0.01). Optimal cytoreduction and survival rates were similar for all group 1 patients regardless of spread location. Sites of recurrence in stage IV were abdomen (59.3%), thorax (6.8%), both (28.8%) or other (5.1%). The four patients with thoracic recurrence alone were all initially diagnosed with malignant pleural effusion. Three of them developed abdominal recurrence within 15‒6 months. CONCLUSIONS Optimal abdominopelvic cytoreduction was achievable in stage IV patients, although in significantly fewer patients than in stage IIIc. Sites of recurrence were rarely thorax alone, implying that thoracic debulking is likely to change the course of disease in only few patients and thus should be carefully individualized.

Bowel obstruction in recurrent gynecologic malignancies: Defining who will benefit from surgical intervention

AIM To define factors that could help select, in a cohort of gynecologic cancer patients with malignant gastro-intestinal obstruction, those most likely to benefit from palliative surgery. METHODS In this retrospective study of patients with malignant gastro-intestinal obstruction who underwent palliative surgery in our institute over 7 years, outcome measures were oral intake, chemotherapy, and 30-day, 60-day and overall survival. Based on Cox proportional-hazards regression models and Kaplan-Meier curves with log-rank tests, a prognostic score was developed to identify those most likely to benefit from surgery. RESULTS Sixty-eight palliative surgeries were performed in 62 patients with ovarian (69.1%), primary-peritoneal (8.8%), cervical (11.8%) or uterine (10.3%) malignancies. Procedures were colostomy (26.5%), ileostomy (39.7%), colonic stent (1.5%), gastrostomy (7.3%), gastroenterostomy (5.9%) and bypass/resection and anastomosis (19.1%). Eighteen patients died prior to discharge, within 3-81 days (median 25 days). The 30-day and 60-day mortality rates were 14.7% and 29.4%, respectively. Postoperative oral-intake and chemotherapy rates were 65% and 53%, respectively, with albumin level identified on multivariate analysis as the only significant predictor of both. Median postoperative survival was 106 days (3-1342). Bypass/resection and anastomosis was associated with improved survival. Ascites below 2 L, younger age, ovarian primary tumor, and higher blood albumin correlated with longer postoperative survival. A prognostic index based on these factors was found to identify patients with increased 30-day and 60-day mortality. CONCLUSIONS Our proposed prognostic index, based on age, primary tumor, albumin and ascites, might help select those gynecological cancer patients most likely to benefit from palliative surgery.