Overview of a chemoresponse assay in ovarian cancer.

The objective of this review is to summarize recent scientific and medical literature regarding chemoresponse assays or chemotherapy sensitivity and resistance assays (CSRAs), specifically as applied to epithelial ovarian cancer. A total of sixty-seven articles, identified through PubMed using the key words "in vitro chemoresponse assay," "chemo sensitivity resistance assay," "ATP," "HDRA," "EDR," "MiCK," and "ChemoFx," were reviewed. Recent publications on marker validation, including relevant clinical trial designs, were also included. Recent CSRA research and clinical studies are outlined in this review. Published findings demonstrate benefits regarding patient outcome with respect to recent CSRAs. Specifically, analytical and clinical validations, as well as clinical utility and economic benefit, of the most common clinically used CSRA in the United States support its use to aid in making effective, individualized clinical treatment selections for patients with ovarian cancer.

What is the role of interval blood testing in the management of chemotherapy for gynecologic malignancies.

PURPOSE: To determine the safety of omitting routine interval laboratory assessments, dietary restrictions, and isolation precautions between cycles of chemotherapy for gynecologic malignancies. METHODS: Data were retrospectively obtained from the records of women receiving chemotherapy for gynecologic cancer from July 1999-June 2000. Routine nadir determinations were not performed between treatment cycles; social interaction was encouraged, and pathogen-free diet recommendations were not provided. RESULTS: Eighty women received 449 cycles of chemotherapy. Four (5%) patients developed neutropenic fevers, and one of these women succumbed to sepsis. Eighteen (22.5%) women had 29 cycles delayed due to persistent myelosuppression when the ensuing chemotherapy infusion was to be administered. Hematopoietic growth factors overcame these delays during subsequent cycles in all but two patients. CONCLUSION: Omitting scheduled interval laboratory monitoring, dietary restrictions, and isolation precautions between chemotherapy cycles is convenient for patients, likely cost-effective, and does not increase morbidity in the gynecologic oncology population.

Bartholin's gland carcinoma: a 15-year experience.

OBJECTIVE: Our objective was to review our experience with carcinoma of Bartholin's gland relative to treatment and oncologic outcome. METHODS: Patient names were collected from our vulvar cancer database for the period September 1985 to September 2000. The medical records were retrospectively reviewed, and data were abstracted relative to demographics, presenting symptoms, treatment, and oncologic outcome. RESULTS: We treated 12 women with Bartholin's gland carcinoma, and 11 patients are reported. Seven women presented with a painless vulvar mass, and 8 of 11 had initially been treated for an infectious process before referral to our institution. Squamous histology was most common, and the right gland was more frequently involved. Ten patients were treated with primary surgery, followed by adjuvant radiation in 7 for inadequate resection margins or lymphatic metastases. One patient was treated with primary chemoradiation. Stage I, II, III, IVA, and IVB disease was present in 3, 1, 4, 2, and 1 patient, respectively. Recurrence was suffered by 54.5% during a mean follow-up time of 73.5 months (median, 60; range, 8-180 months). Overall survival is 58.3% to date. CONCLUSIONS: Conventional therapy for Bartholin's gland carcinoma yielded a 67% 5-year survival. Seventy-one percent of women receiving adjuvant radiotherapy recurred despite this precaution. Work is needed to identify an effective systemic therapy and to better determine which patients may benefit from pelvic radiotherapy.

Accuracy of lymph node palpation to determine need for lymphadenectomy in gynecologic malignancies.

OBJECTIVE: To assess the accuracy of intraoperative lymph node palpation for identifying lymph node metastasis in gynecologic malignancies. METHODS: We prospectively evaluated 126 women who had lymphadenectomies for staging of various gynecologic malignancies from August 1995 to June 1997. Surgeries were done by obstetrician-gynecologists with subspecialty certification in gynecologic oncology from the American Board of Obstetrics and Gynecology, who had practiced gynecologic oncology for at least 5 years. Data were collected on gynecologic oncologists' opinions of lymph node status by palpation. Nodes believed to be positive were sent separately. We recorded operating time for lymphadenectomies, and intraoperative and postoperative complications. RESULTS: Mean (range) patient age was 55 (18-83) years. Mean (range) operating time was 188 (85-435) minutes. The mean (range) lymphadenectomy time was 46 (5-150) minutes. The total number of lymph nodes dissected was 2138. One hundred seven of 2138 (5%) nodes were positive for malignancy. Thirty-eight of 107 (36%) positive lymph nodes were missed by palpation. Fifty-six of 2031 (3%) negative lymph nodes were selected as positive. Sixty-nine of 107 (64%) positive lymph nodes were identified correctly. Sensitivity and specificity of palpation were 72% and 81%, respectively. The positive and negative predictive values of lymph node palpation were 56% and 89%, respectively. CONCLUSION: Intraoperative lymph node palpation has low sensitivity and positive predictive value even when done by experienced board-certified gynecologic oncologists.

Innovations in the management of vulvar carcinoma.

Radical surgery has resulted in impressive cure rates in women with locally advanced vulvar carcinoma. Unfortunately, morbidity mostly related to inguinofemoral lymphadenectomy, is common. The present review discusses innovations in the management of vulvar disease with attempts to reduce attendant morbidity.

Surveillance of the endometrium in tamoxifen treated women.

There is much debate about the risks and benefits of tamoxifen, most specifically about the incidence of associated endometrial cancer. Nearly all of the published trials on the subject have been criticized for methodological flaws and various forms of bias, making resolution of this controversy difficult. There is a consensus, however, that tamoxifen results in an increased incidence of both premalignant and malignant lesions of the endometrium. As the indications for tamoxifen continue to broaden, a larger number of women will be subjected to the potential adverse effects of tamoxifen. Many techniques for screening patients on tamoxifen for the development of endometrial abnormalities have been suggested. None of these methods appears to be consistently clinically or cost effective. We have reviewed the literature on endometrial surveillance in tamoxifen treated women with a focus on the larger publications reported within the past year. From this, we have provided what we hope to be safe and cost-effective recommendations for the management of these patients.

Lymphatic mapping in gynecologic malignancies.

Gynecologic malignancies account for 15% of all cancer diagnosis in women. Primary lymphatic spread is well recognized in vulvar, cervical, uterine, and ovarian carcinomas. Vulvar carcinoma spreads locally to the inguinofemoral lymph nodes in a relatively predictable fashion similar to the local spread of breast carcinoma. Lymphatic mapping using radioactive colloid should provide adequate means to sample these nodal basins while attempting to reduce postoperative morbidity. Methods of vulvar lymphoscintigraphy are described.

Lateral microscopic extension of squamous cell carcinoma of the vulva.

PURPOSE: The aim of this study was to measure the radial occult microscopic spread of tumor in patients with invasive squamous cell carcinoma of the vulva. MATERIALS AND METHODS: In the operating room the gross tumor border was marked. The pathologist took a radial section in each quadrant and measured the distance of occult lateral spread of the tumor. RESULTS: From 7/01/93 to 6/30/96, 24 tumors from 21 patients were studied. The mean maximum tumor diameter was 3. 2 cm (0.5-7.0) and the mean depth of invasion was 9.1 mm (1.1-28.0). The gross and microscopic extent correlated in 20 tumors. Maximum lateral microscopic extent of the other 4 tumors was 3.5, 5 (to the margin), 10, and 16 mm. These 4 tumors were ulcerative and infiltrative and arose from or involved mucosa. CONCLUSION: The gross and microscopic periphery of most invasive squamous vulvar cancers are approximately the same. Ulcerative tumors with an infiltrative pattern of invasion which involve mucosal epithelium may be more likely to extend beyond what is grossly apparent. Measurement of the tumor-free margin should be included in future studies.

Detection of sentinel lymph nodes with lymphazurin in cervical, uterine, and vulvar malignancies.

BACKGROUND: Identification of sentinel lymph nodes may allow prediction of metastatic disease in cancer patients. We did a prospective study to determine whether lymphazurin dye could identify sentinel lymph nodes in patients with cervical, uterine, and vulvar cancer. METHODS: In 33 patients having surgery for either uterine, cervical, or vulvar carcinoma, lymphazurin dye was injected into the respective organs before the tumor and node dissection began. Sentinel lymph nodes were identified and dissected in situ. RESULTS: The identification rate of sentinel lymph nodes was 0/8 (0%) for uterine cancer patients, 2/13 (15.4%) for cervical cancer patients, and 9/12 for vulvar cancer patients (75%). CONCLUSIONS: In a limited number of patients, lymphazurin day may be useful in identifying or assessing the sentinel nodes draining vulvar and cervical cancers. The role of this procedure in treatment planning for patients with gynecologic malignancies is yet to be determined.

Does ligation of the hypogastric artery at the time of radical hysterectomy and lymphadenectomy decrease blood loss? Results of a prospective randomized trial.

A prospective, randomized study of patients undergoing radical hysterectomy for gynecologic malignancies was undertaken from 10/95 to 11/96 to determine if ligation of the hypogastric arteries at the time of radical hysterectomy decreases blood loss. Patients were randomized to either ligation of the hypogastric artery (Group 1) or no ligation (Group 2) prior to a standard Piver type III radical hysterectomy. Surgeries were performed by Board certified gynecologic oncologists with gynecologic oncology fellows and/or OB/GYN residents. Patients were analyzed for demographic characteristics and intraoperative and postoperative parameters. Statistical analysis was performed with independent samples t-test, Mann-Whitney rank sum test, Chi square and Fisher exact test. Twenty-one patients were randomized to group 1 and 22 to group 2. Groups were similar with respect to demographics and preoperative parameters except for age. There were no differences among the groups with respect to intraoperative and postoperative parameters. The mean estimated blood loss for group 1 was 600 ml and 550 ml for group 2 (P = NS). Hypogastric artery ligation (HAL) at the time of radical hysterectomy for gynecologic malignancy does not reduce blood loss.

Endotoxin-induced atrial natriuretic factor release: in vivo and in vitro studies.

OBJECTIVE: We evaluated the effects of coliform endotoxin on the circulating levels of atrial natriuretic factor and renal function. To understand the direct effects of endotoxin in the release of atrial natriuretic factor by cardiac tissue, studies in isolated rat atria were performed. STUDY DESIGN: In vivo studies were used. Anesthetized dogs were studied, with one group receiving isotonic saline solution (n = 6) and the other group receiving 50 microg/kg of coliform endotoxin (n = 7) as a continuous infusion over a 4-hour period. Cardiovascular parameters, renal function, and circulating levels of atrial natriuretic factor were measured at specified time intervals. In another set of experiments with in vitro studies left atria from Sprague-Dawley rats were isolated and perfused. In the control group (n = 9) the standard Krebs perfusate was used. In the endotoxin group (n = 9) coliform endotoxin was added at a concentration of 250 microg/mL to the standard perfusate. Atrial pressure was used as an index of stretch, and atrial natriuretic factor was measured from the perfusate. RESULTS: Administration of endotoxin resulted in decreased blood pressure (P < .05) with a concomitant increase in heart rate. Renal artery flow, however, showed an increase (P < .05) initially followed by a return to its baseline value, with a sustained increase occurring in the saline solution control group. A significant (P < .05) and sustained increase in the circulating levels of atrial natriuretic factor after endotoxin infusion did not prevent the decrease in fractional sodium excretion (P < .05) and creatinine clearance despite an increase in the urinary output. Serum sodium, serum potassium, and osmolalities, however, remained relatively stable. The study pertaining to isolated atria showed that in the presence of low atrial pressures, addition of endotoxin had no significant effect on the release of atrial natriuretic factor. With the increase in atrial pressure atrial natriuretic factor release was significantly higher in the group directly exposed to endotoxin compared with the control group. CONCLUSIONS: These studies demonstrate that the slow infusion of coliform endotoxin results in increased circulating levels of atrial natriuretic factor. This increase is in part due to the direct effect of endotoxin on the heart as indicated by studies in isolated atria. Our data suggest that atrial natriuretic factor in endotoxemia acts in an integrative manner with other hormones on a variety of target organs to modulate cardiovascular function and fluid balance.

Body mass predicts the survival of patients with new International Federation of Gynecology and Obstetrics Stage IB1 and IB2 cervical carcinoma treated with radical hysterectomy.

BACKGROUND: The authors evaluated the impact of body mass on survival and morbidity of patients with new International Federation of Gynecology and Obstetrics (FIGO) Stage IB1 and IB2 cervical carcinoma managed with radical hysterectomy. METHODS: Two hundred twenty-nine patients with Stage IB1 or IB2 cervical carcinoma treated with radical hysterectomy were studied in a multivariate logistic regression analysis. The body mass index (BMI) and the ponderal index (PI) were used as measures of body mass and were analyzed as predictors of recurrence, survival, and complications in light of the new staging system. RESULTS: Twenty-seven of 229 patients died of recurrent disease. A low BMI or a high PI were predictive of poor survival. Tumor greatest dimension, lymph node involvement, BMI, and PI were all independent predictors of survival (P=0.0006). The only independent predictor of complications was para-aortic lymph node dissection (P=0.0026). CONCLUSIONS: Cervical carcinoma patients with a low body mass, as indicated by a low BMI or a high PI, were found to have poor survival after undergoing radical hysterectomy. Additional predictors of poor survival included lymph node metastases and increased tumor size. BMI and PI are more important predictors of survival than the new FIGO Stages IB1 and IB2. Body mass is not predictive of complications.

A pilot study utilizing intraoperative lymphoscintigraphy for identification of the sentinel lymph nodes in vulvar cancer.

OBJECTIVE: To identify sentinel lymph nodes using intraoperative lymphoscintigraphy. METHODS: Technetium-99-labeled sulfur colloid was injected at the site of primary vulvar carcinoma. An intraoperative gamma counter was used to identify one or more sentinel lymph nodes. RESULTS: Ten patients underwent bilateral inguinal and femoral lymphadenectomy. The clinical stages are as follows: T1 in 6, T2 in 2, and T3 in 2. A total of four groins (3 patients) were positive for metastases. In one patient only the sentinel node was positive for disease. In a second patient, two unilateral nodes were positive for disease and both were identified with the gamma counter as sentinel nodes. In the third patient, a single sentinel node was positive for malignancy in each groin. Multiple nonsentinel lymph nodes were positive in each groin in this patient. In no case was the sentinel node negative when other nonsentinel nodes were positive. CONCLUSION: Intraoperative lymphoscintigraphy quantitatively identifies one or more sentinel lymph nodes. Since sentinel lymph nodes can be localized transcutaneously, this technique may be useful for selective lymphadenectomy. Larger patient accrual is necessary to verify this technique.

Management of gynecologic oncology patients with a preoperative deep vein thrombosis.

Our experience with gynecologic oncology patients presenting preoperatively with a deep vein femoral thrombosis is reported. Over a 3-year period data were collected on all patients at the University of South Florida (USF) requiring surgery for a known or suspected gynecologic cancer and having a concomitant active femoral venous thrombosis. Twelve such patients were managed. Management was divided among three options: heparinization, preoperative inferior vena cava (IVC) filter, and intraoperative IVC ligation. For two patients a filter could not be placed preoperatively due to tumor compression of the IVC. Both underwent IVC ligation intraoperatively. One of the two died intraoperatively, possibly related to pulmonary embolism. One of eight with a preoperative IVC filter had obvious clot propagation postoperatively, managed with heparin. One of two managed with heparin only had severe bleeding and heparin-associated thrombocytopenia (HAT) preoperatively. Based on our experience and a review of the literature, we recommend therapeutic heparinization and a preoperatively placed IVC filter for most preoperative gynecologic oncology patients with femoral deep venous thrombosis.

The clinical significance of calculated versus measured creatinine clearance in patients with gynecologic malignancy.

Measurement of creatinine clearance remains in convenient because of the need for 24-hour urine collection. Our study compared creatinine clearance calculated from serum creatinine (CC alpha) to measured creatinine clearance (MC alpha) using an unsupervised 8-hour urine collection at home. Forty-two women admitted to our gynecologic oncology service participated in this study. Twenty-six of these patients had cancer originating from the ovaries, 8 from the uterus, 7 from the cervix, and 1 from the fallopian tube. There were adequate data for 61 collections. MC alpha using unsupervised 8-hour urine collection at home correlated well with CC alpha. This calculated value may be sufficient to be used as a guide in evaluating renal function in patients with gynecologic malignancy. However, if it becomes necessary to measure creatinine clearance, our data suggest that an 8-hour collection may be used.

Massive pelvic hemorrhage during gynecologic cancer surgery: "pack and go back".

Over a 13-year period, intraabdominal packing has been used to control massive hemorrhage during surgery for gynecologic malignancy in six patients. Five patients had undergone total pelvic exenteration and one total abdominal hysterectomy with bilateral salpingo-oophorectomy for endometrial cancer. Massive hemorrhage was defined as infusion of more than 10 units of blood and replacement of more than one total blood volume. Tamponade was performed using continuous Kerlex rolls (Kendall Co., Boston, MA) in a bowel bag with directed pressure over the hemorrhaging site with abdominal closure. The packs were removed in 48 to 72 hr in the operating room, transabdominally in five patients and transvaginally in one. One postoperative death occurred within 8 hr of surgery. The packing was ultimately successful in the five remaining patients. In five of six patients, tumors were removed before the packing, whereas in one, the tumor was removed concurrently with the pack. In one patient, immediate repacking was required after pack removal, with ultimate hemostasis. Morbidity included "empty pelvis syndrome" in four patients, neuropathy in three (obturator in 1, sciatic in 2), and small bowel obstruction in one. In patients with severe intraoperative hemorrhage, intraabdominal packing has been successful as a mode of treatment.

Radical hysterectomy for stage IB1 vs IB2 carcinoma of the cervix: does the new staging system predict morbidity and survival?

Two hundred twenty-nine patients with Stage IB cervical cancer treated with radical hysterectomy were assigned to the new FIGO substages IB1 (n = 181) and IB2 (n = 48) based on clinical tumor diameter. Our purpose was to determine the impact of the new staging system for IB1 and IB2 cervical cancer on nodal status and survival. Additionally, we analyzed the morbidity of radical hysterectomy in light of the new staging system. The complications were similar between the two groups. Para-aortic lymphadenectomy was the only independent predictor of complications (P = 0.00026). Stage IB2 patients did have a significantly worse 5-year survival (72.8%) when compared with IB1 (90.0%) (P = 0.0265). Multivariate stepwise logistical regression analysis indicated that the new staging system did not have an independent impact on survival. Stage acts through nodal status in its impact on survival. Positive lymph nodes, tumor diameter, and Ponderal Index are all independent predictors of survival (P = 0.0001). Patients with Stage IB2 carcinoma of the cervix undergoing radical hysterectomy showed no significant increase in morbidity when compared with patients with Stage IB1 disease treated with the same procedure.

Intraoperative liver biopsy with the loop electrosurgical excision procedure in patients with gynecologic malignancies.

When patients with gynecologic malignancies undergo exploratory surgery, hepatic lesions suggestive of malignancy are occasionally encountered. In 18 patients undergoing laparotomy for gynecologic cancer, visible liver lesions suggestive of malignancy were biopsied with the loop electrosurgical excision procedure (LEEP). Hemostatic suture placement was required in 3 of these 18 patients, and in 15, hemostasis was achieved with electrocautery only. Three of the 18 biopsies (16.7%) were positive for malignancy. No intraoperative or postoperative complications were attributed to the liver biopsy. One patient required postoperative transfusion of 2 units packed red blood cells. A new technique is described using the LEEP to remove suspicious lesions during exploratory laparotomy in patients with gynecologic malignancies.