Walter Gajewski

A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass

INTRODUCTION Patients diagnosed with epithelial ovarian cancer (EOC) have improved outcomes when cared for at centers experienced in the management of EOC. The objective of this trial was to validate a predictive model to assess the risk for EOC in women with a pelvic mass. METHODS Women diagnosed with a pelvic mass and scheduled to have surgery were enrolled on a multicenter prospective study. Preoperative serum levels of HE4 and CA125 were measured. Separate logistic regression algorithms for premenopausal and postmenopausal women were utilized to categorize patients into low and high risk groups for EOC. RESULTS Twelve sites enrolled 531 evaluable patients with 352 benign tumors, 129 EOC, 22 LMP tumors, 6 non EOC and 22 non ovarian cancers. The postmenopausal group contained 150 benign cases of which 112 were classified as low risk giving a specificity of 75.0% (95% CI 66.9-81.4), and 111 EOC and 6 LMP tumors of which 108 were classified as high risk giving a sensitivity of 92.3% (95% CI=85.9-96.4). The premenopausal group had 202 benign cases of which 151 were classified as low risk providing a specificity of 74.8% (95% CI=68.2-80.6), and 18 EOC and 16 LMP tumors of which 26 were classified as high risk, providing a sensitivity of 76.5% (95% CI=58.8-89.3). CONCLUSION An algorithm utilizing HE4 and CA125 successfully classified patients into high and low risk groups with 93.8% of EOC correctly classified as high risk. This model can be used to effectively triage patients to centers of excellence.

Evaluation of the Diagnostic Accuracy of the Risk of Ovarian Malignancy Algorithm in Women With a Pelvic Mass

OBJECTIVE: It is often difficult to distinguish a benign pelvic mass from a malignancy and tools to help referring physician are needed. The purpose of this study was to validate the Risk of Ovarian Malignancy Algorithm in women presenting with a pelvic mass. METHODS: This was a prospective, multicenter, blinded clinical trial that included women who presented to a gynecologist, a family practitioner, an internist, or a general surgeon with an adnexal mass. Serum HE4 and CA 125 were determined preoperatively. A Risk of Ovarian Malignancy Algorithm score was calculated and classified patients into high-risk and low-risk groups for having a malignancy. The sensitivity, specificity, negative predictive value, and positive predictive value of the Risk of Ovarian Malignancy Algorithm were estimated. RESULTS: A total of 472 patients were evaluated with 383 women diagnosed with benign disease and 89 women with a malignancy. The incidence of all cancers was 15% and 10% for ovarian cancer. In the postmenopausal group, a sensitivity of 92.3% and a specificity of 76.0% and for the premenopausal group the Risk of Ovarian Malignancy Algorithm had a sensitivity of 100% and specificity of 74.2% for detecting ovarian cancer. When considering all women together, the Risk of Ovarian Malignancy Algorithm had a sensitivity of 93.8%, a specificity of 74.9%, and a negative predictive value of 99.0%. CONCLUSION: The use of the serum biomarkers HE4 and CA 125 with the Risk of Ovarian Malignancy Algorithm has a high sensitivity for the prediction of ovarian cancer in women with a pelvic mass. These findings support the use of the Risk of Ovarian Malignancy Algorithm as a tool for the triage of women with an adnexal mass to gynecologic oncologists. LEVEL OF EVIDENCE: II

Sentinel node identification and the ability to detect metastatic tumor to inguinal lymph nodes in squamous cell cancer of the vulva

OBJECTIVES The goal of this study was to identify one or more inguinal sentinel nodes in patients with primary squamous cell carcinoma of the vulva and to determine the ability of the sentinel node to predict metastasis to the inguinal lymphatic basin. METHODS Techniques employing technetium-99m (Tc-99m) sulfur colloid and isosulfan blue dye were utilized to identify sentinel nodes in the inguinal lymphatic beds. Technetium-99m sulfur colloid was injected intradermally at the tumor margins 90-180 min preoperatively followed by a similar injection of isosulfan blue dye 5-10 min before the groin dissection. A handheld collimated gamma counter was employed to identify Tc-99m-labeled sentinel nodes. Lymphatic tracts that had taken up blue dye and their corresponding sentinel node were also identified and retrieved. A completion inguinal dissection was then performed. Each sentinel node was labeled as hot and blue, hot and nonblue, or cold and blue. The sentinel nodes were subjected to pathologic examination with step sections and nonsentinel nodes were evaluated in the standard fashion. RESULTS Twenty-one patients with a median age of 79 were entered onto protocol and a total of 31 inguinal node dissections were performed. A sentinel node was identified in 31/31 (100%) groin dissections with the use of Tc-99m. Isosulfan blue dye identified a sentinel node in 19/31 (61%) groin dissections. Surgical staging revealed 7 patients with stage I disease, 5 with stage II disease, 5 with stage III disease, and 4 with stage IV disease. Lymph nodes in 9 groin dissections were found to have metastatic disease, and in 4 of these dissections, the sentinel node was the only positive node. Lymph nodes in 22 groin dissections had no evidence of metastasis. No false-negative sentinel lymph nodes were obtained (sentinel node negative and a nonsentinel node positive). CONCLUSION Tc-99m sulfur colloid is superior to isosulfan blue dye in the detection of sentinel nodes in inguinal dissections of patients with vulvar cancer. A sentinel node dissection utilizing Tc-99m alone can identify a sentinel node in all inguinal dissections. Pathologic examination with step sections has shown the sentinel node to be an accurate predictor of metastatic disease to the inguinal nodal chain.

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.

Phase III Randomized Trial of Weekly Cisplatin and Irradiation Versus Cisplatin and Tirapazamine and Irradiation in Stages IB2, IIA, IIB, IIIB, and IVA Cervical Carcinoma Limited to the Pelvis: A Gynecologic Oncology Group Study

PURPOSE This prospective, randomized phase III intergroup trial of the Gynecologic Oncology Group and National Cancer Institute of Canada Clinical Trials Group was designed to test the effectiveness and safety of adding the hypoxic cell sensitizer tirapazamine (TPZ) to standard cisplatin (CIS) chemoradiotherapy in locally advanced cervix cancer. PATIENTS AND METHODS Patients with locally advanced cervix cancer were randomly assigned to CIS chemoradiotherapy versus CIS/TPZ chemoradiotherapy. Primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS) and tolerability. RESULTS PFS was evaluable in 387 of 402 patients randomly assigned over 36 months, with enrollment ending in September 2009. Because of the lack of TPZ supply, the study did not reach its original target accrual goal. At median follow-up of 28.3 months, PFS and OS were similar in both arms. Three-year PFS for the TPZ/CIS/RT and CIS/RT arms were 63.0% and 64.4%, respectively (log-rank P = .7869). Three-year OS for the TPZ/CIS/RT and CIS/RT arms were 70.5% and 70.6%, respectively (log-rank P = .8333). A scheduled interim safety analysis led to a reduction in the starting dose for the TPZ/CIS arm, with resulting tolerance in both treatment arms. CONCLUSION TPZ/CIS chemoradiotherapy was not superior to CIS chemoradiotherapy in either PFS or OS, although definitive commentary was limited by an inadequate number of events (progression or death). TPZ/CIS chemoradiotherapy was tolerable at a modified starting dose.

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.

Videoconferencing for gynaecological cancer care: an international tumour board.

Sharing expertise between health-care staff is particularly important in the care of cancer patients, for whom treatment, even at its best, is not always effective, readily obvious or available. All relevant therapeutic options should be considered before deciding on cancer management. Self-evident though this may be, it is not always easy to do in practice, as it requires substantial collaboration1–4. Using videoconferencing, large, geographically dispersed groups can be convened and can function in realtime5–10. Case-specific discussions can occur with colleagues over great distances. In October 1998, we created an international tumour board (ITB) to improve the care of gynaecological cancer patients and to exchange medical knowledge between multidisciplinary groups in Providence, Rhode Island, USA, and in Safed, Israel. The ITB consists of doctors trained in cancer surgery, chemotherapy, radiation oncology, diagnostic radiology and tumour pathology, as well as nurses, nutritionists and oncology social workers. The prospective, focused, multidisciplinary process brings special insight and balance to the formulation of treatment recommendations. The establishment of such boards is difficult even in the largest medical institutions. ITB equipment

Using videoconferencing of a live surgery to teach about pelvic anatomy

No abstract available.

Combining clinical assessment and the Risk of Ovarian Malignancy Algorithm for the prediction of ovarian cancer

OBJECTIVES ACOG guidelines for the evaluation of women with a pelvic mass employ a combination of physical exam, imaging, and CA125 to guide physicians in the triage of women to gynecologic oncologists. We studied the use of ROMA with clinical assessment for cancer risk assessment in women with a pelvic mass. METHODS This was a prospective, multicenter trial evaluating women with a pelvic mass who had an initial clinical risk assessment (ICRA) performed by a generalist. ROMA scores were calculated and sensitivity, specificity, PPV and NPV were determined for ICRA and ICRA+ROMA. RESULTS A total of 461 women were entered into the study. There were 375 benign tumors, 48 EOC, 18 LMP tumors and 20 non-ovarian malignancies. For detection of ovarian cancer alone, ICRA had a sensitivity of 85.4%, a specificity of 84.3%, and a NPV of 97.8%. Adding ROMA to ICRA produced a significant improvement of 8.4% in sensitivity, achieving a sensitivity of 93.8% with a specificity of 67.2% and a NPV of 98.8%. Examination of all malignancies (ovarian & non-ovarian) provided a sensitivity of 89.7% for ROMA+ICRA in comparison to 77.9% for ICRA alone, a significant increase in sensitivity of 11.8%. The NPV also significantly increased from 95.5% to 97.3%. Overall, ROMA detected 13 additional malignancies missed by ICRA. CONCLUSIONS Adjunctive use of ROMA with clinical assessment improves the stratification of women with a pelvic mass into low and high risk groups for ovarian cancer. The combination is particularly effective in ruling out malignant disease.

Pathologic Evaluation of Inguinal Sentinel Lymph Nodes in Patients With Vulvar Cancer: A Comparison of Immunohistochemical Staining versus Ultrastaging With Hematoxylin and Eosin Staining

The authors identified 29 patients with squamous cell carcinoma of the vulva who had undergone inguinal sentinel lymph node dissection based on ultrastaging with hematoxylin and eosin staining. Isosulfan blue dye was used to identify sentinel nodes. After removal, each node was sectioned at 2-mm intervals for submission to histology. Two parallel slides were cut from each of 5 100-μm intervals in the section. One slide from each pair was stained with hematoxylin and eosin and subjected to ultrastaging. The parallel of each slide diagnosed as negative for micrometastases underwent immunohistochemical staining using a pancytokeratin cocktail AE1/AE3 (BioGenex Corp., San Ramon, CA), a streptavidin-biotin detection system, and AEC chromogen. They were then lightly counterstained with hematoxylin for review. In all, 107 sentinel lymph nodes were removed. Of these, 18 were diagnosed as positive and 89 were negative. The results of reevaluation of negative nodes with immunohistochemical staining of the parallel slide were negative in all 89 parallel slides. No differences in the detection of disease were seen between staining with hematoxylin and eosin and immunohistochemical staining.