C.O. Granai

Utility of a novel serum tumor biomarker HE4 in patients with endometrioid adenocarcinoma of the uterus

OBJECTIVE Tumor markers with increased sensitivity and specificity for endometrial cancer are needed to help monitor response to therapy and to detect recurrent disease. Currently, the tumor maker CA125 is utilized in this role with limited value. The objectives of this study were to examine the levels of several novel tumor markers HE4, SMRP, CA72.4 and CA125 as potential markers in patients diagnosed with endometrioid adenocarcinoma of the uterus. METHODS Pre-operative serum samples from surgically staged patients with endometrioid adenocarcinoma of the uterus were analyzed for levels of HE4, SMRP, CA72-4 and CA125. Control samples were obtained from healthy postmenopausal women. Logistic regression models and receiver operating characteristic (ROC) curves were constructed for each tumor marker and for all combinations, with cross-validation analyses to obtain average sensitivities at set specificities of 90%, 95%, and 98%. RESULTS Serum samples from 156 healthy subjects and 171 patients with endometrial cancer (122 stage I, 17 stage II, 26 stage III, and 6 stage IV) were analyzed. At a 95% specificity, the sensitivities for differentiating between healthy subjects and all stages of cancer were 45.5% for HE4 and 24.6% for CA125. For stage I disease, HE4 yielded a 17.1% improvement in sensitivity compared with CA125. CONCLUSION HE4 is elevated in all stages of endometrial can100cer and is more sensitive in early-stage endometrial cancer compared to CA125. Further investigation of HE4 as a marker for early detection of recurrent endometrial cancer and monitoring response to therapy is warranted.

A 2-stage ovarian cancer screening strategy using the Risk of Ovarian Cancer Algorithm (ROCA) identifies early-stage incident cancers and demonstrates high positive predictive value

A 2‐stage ovarian cancer screening strategy was evaluated that incorporates change of carbohydrate antigen 125 (CA125) levels over time and age to estimate risk of ovarian cancer. Women with high‐risk scores were referred for transvaginal ultrasound (TVS).

Absence of estrogen and progesterone receptors in glassy cell carcinoma of the cervix

Objective To review available evidence about the effectiveness of alternative therapies for nausea and vomiting of pregnancy. Data Sources MEDLINE and 13 additional US and international data bases were searched in 1996–1997 for papers that described use of alternative medicine in the treatment of pregnancy and pregnancy complications, specifically those addressing nausea, vomiting, and hyperemesis. Bibliographies of retrieved papers were reviewed to identify additional sources. Methods of Study Selection All relevant English language clinical research papers were reviewed. Randomized clinical trials addressing specifically the use of nonpharmaceutical and nondietary interventions were chosen for detailed review. Tabulation, Integration, and Results Ten randomized trials studying the effects of acupressure, ginger, and pyridoxine on nausea and vomiting of pregnancy were reviewed. Evidence of beneficial effects was found for these three interventions, although the data on acupressure are equivocal. Insufficient evidence was found for the benefits of hypnosis. Other interventions have not been studied. Conclusion There is a dearth of research to support or to refute the efficacy of a number of common remedies for nausea and vomiting of pregnancy. The best-studied alter-native remedy is acupressure, which may afford relief to many women; ginger and vitamin B6 also may be beneficial.

Sex, Intimacy, and the Gynecologic Oncologist: Survey Results of the New England Association of Gynecologic Oncologists (NEAGO)

Abstract Sexuality is an important aspect of life and is often affected in patients diagnosed with cancer. For women, estimates of sexual dysfunction range from 40 to 100%. In light of these statistics, we were interested in determining the comfort level and practice of specialists in gynecologic oncology as it relates to taking a sexual history and addressing related concerns by conducting a survey of the New England Association of Gynecologic Oncologists (NEAGO). Our results show that although nearly all respondents felt comfortable addressing sexual problems in their patients, less than half took a sexual history in new patients and 80% did not feel there was sufficient time to devote to exploring sexual issues. The results of our survey suggest that aspects of sexual dysfunction in women with gynecologic cancer may be neglected by gynecologic oncology providers. This encourages cancer programs to develop formal resources for women with questions regarding sexuality following a diagnosis of cancer.

Isolated sentinel lymph node dissection with conservative management in patients with squamous cell carcinoma of the vulva: A prospective trial

OBJECTIVES Sentinel lymph node (SLN) dissections have a high sensitivity and negative predictive value for the detection of metastatic disease. The objective of this study was to examine the inguinal recurrence rate along with complication rates for patients undergoing inguinal SLN dissection alone for vulvar carcinoma. METHODS An IRB approved prospective study enrolled patients with biopsy proven squamous cell carcinoma of the vulva. Peritumoral injection of Tc-99 sulfur colloid and methylene blue dye was used to identify SLNs intraoperatively. Patients with SLNs negative for metastatic disease were followed clinically. Patients with metastasis detected in a SLN subsequently underwent a full groin node dissection followed by standard treatment protocols. RESULTS Thirty-six patients were enrolled onto study with 35 undergoing a SLN dissection. All SNL dissections were successful with a mean of 2 SLN obtained per groin. There were 24 patients with stage I disease, 8 stage II, 3 stage III and 1 stage IV. A total of 56 SLN dissections were performed with 4 patients found to have inguinal metastasis by SLN dissection. There were 31 patients with a total of 46 SLN dissections found to be negative for metastatic disease. The median follow-up has been 29 months (range 8 to 51) with 2 groin recurrences for a groin recurrence rate of 4.3% and a recurrence rate per patient of 6.4%. There have been no reports of groin breakdown, extremity cellulitis or lymphedema. CONCLUSIONS The recurrence rate for patients undergoing inguinal sentinel node dissection alone is low. These patients did not experience any complications as seen with complete groin node dissections. Sentinel lymph node dissection should be considered as an option for evaluation of inguinal nodes for metastatic disease.

Ovarian Cancer Associated with Testosterone Supplementation in a Female-to-Male Transsexual Patient

Ovarian cancer is the most fatal gynecologic malignancy. Women often present late and though median survival has improved, a majority of women will succumb to their disease. The incidence of ovarian cancer among female-to-male transsexuals is not known. We report only the second case of ovarian cancer in a female-to-male transsexual while on androgen supplementation therapy. Staining of his tumor for androgen receptors showed abundant expression. Androgen supplementation in this population may be associated with an increased risk of both ovarian cancer and of endometrial cancer. Consideration for bilateral salpingo-oophorectomy as part of gender reassignment surgery should be given, especially in this poorly studied group of patients whose overall risk of ovarian cancer remains unknown.

Malignant mixed mesodermal tumors of the ovary.

Objective To review the experience at Women & Infants Hospital and Hartford Hospital of patients with malignant mixed mesodermal tumors of the ovary, and to review the pertinent literature. Methods Fourteen cases of malignant mixed mesodermal tumors of the ovary at the two hospitals over a 5-year period were identified through their tumor registries. Demographic data, pathology, treatment, and survival rates were reviewed. Results The median survival of the patients in our series was 7 months, with 64% dead of disease in 1 year. A review of the pertinent literature indicated median survivals of 6–12 months, with more than 70% of the patients dead of disease at 1 year, despite treatment. Conclusion Further investigation is needed to determine the proper management for malignant mixed mesodermal tumors of the ovary. Meanwhile, current treatment strategies should recognize the present therapeutic limitations, so as not to diminish any further the quality of life for women with this malignancy.

Long-term follow-up of vulvar cancer patients evaluated with sentinel lymph node biopsy alone

OBJECTIVE The objective of this study was to examine SLN evaluation alone in women with squamous cell carcinoma (SCC) of the vulva and evaluate the inguinal recurrence and complication rates. METHODS An IRB approved prospective study enrolled patients with SCC of the vulva. Peritumoral injection of Tc-99 sulfur colloid and blue dye was used to identify SLNs intraoperatively. Patients with negative SLN for metastasis were followed clinically without further treatment. Patients with metastasis to a SLN underwent full groin node dissection followed by standard treatment protocols. RESULTS A total of 73 women were enrolled onto protocol with 69 patients undergoing SLN dissection. Mean age was 66.9years (range: 29-91) with 47 stage I, 12 stage II, 9 stage III, 2 stage IV and 3 unstaged patients. SLN dissections were successful in 63 patients. Of the 111 groins evaluated with a SLN dissection 93% had a SLN identified with an average of 2 SLN per groin. There were 92 groins with negative SLN and 11 groins with positive SLN. 57 patients had negative SLN and underwent conservative management with the median follow-up of 58.3months. Three patients experienced groin recurrences (2 unilateral, 1 bilateral) for a recurrence rate of 5.2% (3/57). The complication rate for the inguinal incisions was 17.5% (1 cellulitis, 1 abscess, 2 lymphoceles, 5 lymphedema and leg pain). CONCLUSIONS Isolated SLN dissection alone has a low inguinal recurrence rate with decreased complications and should be considered as an option for women with SCC of the vulva.

The effects of a course in cadaver dissection on resident knowledge of pelvic anatomy: An experimental study

Objective To determine whether a course in cadaver dissection can significantly increase resident knowledge of pelvic anatomy beyond that of current educational practices. Methods Thirteen first-and second-year residents were randomly assigned to a cadaver dissection course (seven) or a control group (six). The dissection group performed dissections with instruction, using a dissection guide designed specifically for the course. The control group received study references on pelvic anatomy and protected study time. Each participant took a practical and written examination at the beginning and end of the study. Results The two groups did not differ statistically in their scores on the pre-test. Both groups improved on the posttest, but the dissection group scored nearly 50% higher on the test than did the controls. The two groups differed significantly on the post-test, adjusted for pre-test performance (P < .01). In their evaluation of the course, participants from the dissection group emphasized its educational value and urged that it be offered to residents as a regular part of their training. Conclusion Dissection of a human cadaver provides a valuable experience, allowing participants to gain a greater understanding of surgical anatomy and surgical procedures in a no-risk, unhurried setting. Residents who participated in a cadaver dissection course designed specifically for their needs showed a statistically significant increase in knowledge compared with those without this experience. Both objectively and subjectively, a cadaver dissection course is an excellent tool for instructing gynecology residents.

Addressing clinical trials: Can the Multidisciplinary Tumor Board improve participation? A study from an academic women's cancer program☆

OBJECTIVE The Tumor Board (TB) allows for an interdisciplinary approach to cancer treatment designed to encourage evidence-based treatment. However, its role in facilitating clinical trial participation has not been reported. We aimed to determine whether a prospective TB is an effective strategy for trial recruitment and to identify steps within the TB process that facilitate discussion of trial eligibility and optimize accrual. METHODS We conducted a retrospective cross-sectional analysis of women presented to Gynecologic Oncology TB between March and December 2008. Patient demographics, TB recommendations, and post-TB patient discussions were abstracted. These were compared to data derived from the Department of Oncology Research to determine research team awareness of eligible patients and confirm trial enrollment(s). Data analysis was completed with Chi-square test; risk ratios and confidence intervals were calculated as summary measures. RESULTS We reviewed 1213 case presentations involving 916 women. Overall, 358 TB recommendations (30%) identified eligible patients, of which enrollment consisted of 87 (24%) trials (6% therapeutic trials and 18% non-therapeutic trials). Compared to other types of TB recommendations, those involving trials were discussed less frequently at post-TB patient visits (79% vs. 44%). Documentation of trial discussion at the post-TB visit was more likely to result in trial participation, versus solely relying on the research staff to communicate enrollment eligibility with the treating team (RR 2.5, p=0.006). CONCLUSIONS Patients identified by the TB were 2.5-times as likely to enroll in a clinical trial, but trials were mentioned only 44% of the time. Interventions that facilitate trial discussions during post-TB meetings are needed to improve trial participation.