Transforming growth factor-alpha levels in the serum and ascites of patients with advanced epithelial ovarian cancer.

A variety of cytokines have been identified to play a role in ovarian cancer. In this pilot study, we sought to determine whether transforming growth factor-alpha (TGF-alpha) was detectable in the serum and ascites of women with advanced stage epithelial ovarian cancer. TGF-alpha was measured using an enzyme-linked immunosorbent assay and was present in 18 of 25 control sera. Prior to treatment for stage III or IV epithelial ovarian cancer, 18 patients had undetectable serum levels of TGF-alpha, while 18 had values ranging from 10.6 to 531.7 pg/ml. The group with undetectable levels had a 6-month greater median survival; detectable TGF-alpha might be a negative prognostic indicator. In a separate group undergoing second-look laparotomy, differences in median TGF-alpha values versus controls and the primary study group approached significance. TGF-alpha was detected in significantly more control peritoneal fluid samples than in patient ascites. A larger study is warranted.

Metastatic placental site trophoblastic tumor.

Since our publication, which first defined the malignant potential of placental site trophoblastic tumor (PSTT), we have had a keen interest in this rare, unique entity. This histologic entity is noted by its monomorphic population of trophoblast-like cells which are classified as originating in the intermediate trophoblast. These cells contain hymman placental lactogen (HPL). This is in contrast to cytotrophoblastic and syncytiotrophblastic tissues as the histologic, cytologic and immunohistochemical stain characteristics are disparate. Its rarity and the wide spectrum of clinical behavior combined with the lack of sensitivity of serum levels of beta hCG in predicting disease recurrence and spread have lead to anecdotal reports outlining clinical management. Most discerning to the clinician is the high mortality of metastatic placental site trophoblastic tumor. At our institution, we have treated two patients with a metastatic disease with a successful conclusion. The durability of responses is 3 and 8 years. This report will present these patients in detail and define the important characteristics of successful treatment. The use of dose-intensive, multi-agent chemotherapy, early intervention when metastatic disease is discovered, imaging techniques to define disease spread, surgery for localized disease and the use of growth factors, most notably granulocyte colony-stimulating factor (G-CSF), are the fundamentals of clinical care of placental site trophoblastic tumor in patients with metastatic placental site trophoblastic tumor.

Do multiple measurements employing different ultrasonic techniques improve the accuracy of amniotic fluid volume assessment?

This investigation was undertaken to determine if the accuracy of the ultrasound assessment of abnormal amniotic fluid volume (oligohydramnios or polyhydramnios) is improved by employing multiple sonographic amniotic fluid measurements. Four ultrasound techniques consisting of the subjective assessment (ultrasonic visualization without measurement), largest vertical pocket, amniotic fluid index and 2-diameter pocket technique were performed followed by amniocentesis and dye-dilution confirmation of amniotic fluid volume in 66 singleton pregnancies. The ultrasound accuracy to detect abnormal amniotic fluid volume ranged from 61% with the largest vertical pocket to 70% with the 2-diameter pocket procedure used separately. Receiver operator characteristic curves demonstrated that combining the 4 ultrasonic measurements did not improve the accuracy of identifying amniotic fluid volumes.

Metastatic placental site trophoblastic tumor.

Since our publication, which first defined the malignant potential of placental site trophoblastic tumor (PSTT), we have had a keen interest in this rare, unique entity. This histologic entity is noted by its monomorphic population of trophoblast-like cells which are classified as originating in the intermediate trophoblast. These cells contain hymman placental lactogen (HPL). This is in contrast to cytotrophoblastic and syncytiotrophblastic tissues as the histologic, cytologic and immunohistochemical stain characteristics are disparate. Its rarity and the wide spectrum of clinical behavior combined with the lack of sensitivity of serum levels of beta hCG in predicting disease recurrence and spread have lead to anecdotal reports outlining clinical management. Most discerning to the clinician is the high mortality of metastatic placental site trophoblastic tumor. At our institution, we have treated two patients with a metastatic disease with a successful conclusion. The durability of responses is 3 and 8 years. This report will present these patients in detail and define the important characteristics of successful treatment. The use of dose-intensive, multi-agent chemotherapy, early intervention when metastatic disease is discovered, imaging techniques to define disease spread, surgery for localized disease and the use of growth factors, most notably granulocyte colony-stimulating factor (G-CSF), are the fundamentals of clinical care of placental site trophoblastic tumor in patients with metastatic placental site trophoblastic tumor.

Clinicopathologic variables predictive of residual dysplasia after cervical conization.

OBJECTIVE: To evaluate the clinicopathologic variables that are important for predicting residual dysplasia after cervical conization or the loop electroexcisional procedure. STUDY DESIGN: A retrospective review of 80 cases was performed on patients with squamous dysplasia in the conization specimen, endocervical curettage (ECC) performed immediately after resection, margin status reported by the pathologist and adequate postprocedure follow-up. RESULTS: Twelve patients had residual dysplasia. No case progressed to invasive carcinoma. A multivariate analysis was performed with presence or absence of residual dysplasia as the dependent variable and patient age, type of procedure (cold knife conization or loop excision), grade of dysplasia, margin status and ECC status as independent variables. Margin status was the strongest predictor of residual disease, followed by ECC status. Patient age had a minimal association with persistence. Of the 12 patients with residual dysplasia, 11 had a positive margin, and 8 had a positive ECC. Only 38% of patients with a positive margin had residual disease, but 67% with a positive margin and ECC had residual dysplasia. CONCLUSION: Margin status and ECC are useful in predicting residual dysplasia after conization.

Gynecologic reconstruction with a rectus abdominis myocutaneous flap: an update.

This series reports the outcomes and significant complications associated with the rectus myocutaneous flap when used for pelvic or inguinal reconstruction in patients with gynecologic cancers. Perioperative variables were retrospectively reviewed to identify social and medical risk factors as well as intraoperative and postoperative complications that predisposed to rectus flap failure. Fifteen patients with gynecologic malignancies underwent reconstructive procedures using a vertically oriented rectus abdominis myocutaneous flap for either vaginal (n = 14) or inguinal (n = 1) reconstruction. The patients' primary cancers were cervical (n = 11), rectal (n = 1), ovarian (n = 1), vulvar (n = 1), and vaginal (n = 1). The median age was 50 years. The median follow-up was 17 months. All flaps were mobilized in conjunction with a radical salvage operation. There were no cases of vaginal prolapse and no abdominal wound infections. However, 4 patients (27%) had major postoperative morbidity in this small series. There was one wound dehiscence and three episodes of necrosis of the subcutaneous and cutaneous portions of the flap. All 4 of these patients required additional operative intervention or debridement. Eleven patients had complete healing of the flap. The rectus abdominis myocutaneous flap is a valuable option for gynecologic reconstructive procedures. Perioperative strategies for improving flap viability include the identification of risk factors that may compromise flap perfusions such as prior abdominal incisions, peripheral vascular disease, and obesity. Meticulous surgical technique is required to preserve the vascular pedicle. These strategies may be useful in preoperative counseling, the perioperative evaluation, and the intraoperative management.

Prevention of postoperative adhesions by an antibody to vascular permeability factor/vascular endothelial growth factor in a murine model.

OBJECTIVE: Our purpose was to test the ability of an antiserum to vascular permeability factor/vascular endothelial growth factor to inhibit postoperative adhesion formation in a murine model. STUDY DESIGN: After a standardized peritoneal injury, 28 Balb/c mice were randomized and treated intraperitoneally with either vascular permeability factor antiserum (n = 14) or preimmune serum (n = 14) at the time of abdominal closure. Mice were killed on postoperative day 14, and the development of intraabdominal adhesions was determined. Adhesion scoring was based on an overall assessment of the extent, location, and type of adhesions present. Statistical analyses were performed with the Mann-Whitney and Fisher's exact tests. RESULTS: The mice treated with the vascular permeability factor antiserum had significantly lower adhesion scores than did the control group (mean +/- SD 1.5 +/- 0.9, median 1.0, vs control 2.5 +/- 0.7, median 3.0). When the groups were analyzed for the presence of grade 2 or 3 adhesions, the group treated with vascular permeability factor antiserum had a significantly lower incidence of advanced adhesions (38%, vs control 92%). CONCLUSION: This study demonstrates that the intraperitoneal administration of a neutralizing antiserum to vascular permeability factor/vascular endothelial growth factor limits postoperative adhesion formation. These observations, to the best of our knowledge, are the first to suggest a role for vascular permeability factor in the pathogenesis of adhesion formation.

Nonsurgical management strategies for the functional complications of ileocolonic continent urinary reservoirs.

Urinary diversion with creation of a continent ileocolonic reservoir was performed in 25 patients with gynecological malignancies at our institution between September 1989 and September 1994. A retrospective review was conducted and cases were analyzed for functional complications associated with reservoir formation. Functional reservoir complications were defined as (1) difficulty with catheterization, (2) reservoir fistulae, (3) reservoir stones, and (4) ureteral stenosis. Management strategies and outcomes for these complications were determined. All patients had received prior pelvic radiation therapy. There was no surgical mortality. Median follow-up was 21 months, and 16 patients (64%) are currently alive. Fourteen of the patients (56%) had one or more complications attributable to a functional aspect of the continent reservoir. Two patients had difficulty with catheterization (8%), two patients had reservoir leak (8%), and one patient had reservoir stones (4%). Nonsurgical management strategies were used in these cases including balloon dilation of the ileocecal valve, stomal dilation, ureteral stenting, percutaneous nephrostomy, and endoscopic lithotripsy. All cases of catheterization problems, reservoir fistulae, and reservoir stones were resolved with nonoperative techniques. Thirteen of 50 ureters (26%) had some degree of stenosis. Percutaneous balloon dilation was utilized in nine cases of ureteral stenosis. Relief of stenosis was complete in five, partial in two, and not achieved in two of the cases. No patients required a reoperation for a reservoir complication. In conclusion, continent ileocolonic urinary diversion can be performed in patients previously treated with radiotherapy; however, functional reservoir problems may occur. Interventional radiology strategies are useful in managing many of these problems and reexploration can be successfully avoided.

Recurrent squamous cell carcinoma in a rectus abdominis neovagina.

The development of a carcinoma in a neovagina is rare. Most neovaginal neoplasias have been carcinomas in situ in the skin graft. To date, there has not been a report of a neovaginal carcinoma in a myocutaneous flap. This report is the first of a squamous cell carcinoma arising in a neovagina constructed from a rectus abdominis myocutaneous flap.

The utility of preoperative screening colonoscopy in gynecologic oncology.

The American Cancer Society (ACS) recommends that asymptomatic women, age 50 and over, undergo sigmoidoscopy every 3 to 5 years, after two negative yearly exams. Epidemiologic evidence suggests that women with gynecologic or breast cancers have an increased risk of developing colon cancer. It is unclear whether the ACS guidelines are applicable for women with a new diagnosis of gynecologic malignancy. This retrospective study was undertaken to assess the usefulness of preoperative colonoscopy in our gynecologic oncology patient population. Patients undergoing evaluation for a major operative procedure for known or suspected gynecologic malignancies were referred for colonoscopy at the discretion of their attending surgeon. Five hundred patients' charts were reviewed to identify 212 patients in whom preoperative colonoscopy was performed (the study group). In this group, 17 cases of colonic polyps, 5 cases of synchronous colon cancer, and 2 cases of cancer metastatic to the colon were discovered, representing 11% of the study group. Whereas 23% of the patients screened were less than 50 years of age, only two cases of polyps occurred in this age group, and no cases of cancer. Patients aged 70 or greater made up 28% of the study group, but accounted for 41% of the cases of polyps and 40% of the colon cancers. Twenty-nine percent of the study group had adenocarcinoma of the endometrium, representing 7 of 17 cases of polyps, 1 of 5 colon cancers, and 1 of 2 metastatic cancers. Although this retrospective study involved colonoscopy, the locations of the observed lesions were within the theoretic reach of a flexible sigmoidoscope in 75% of cases. We conclude that in the preoperative workup of gynecologic oncology patients, no colon screening is needed in the asymptomatic patient less than 50 years of age. ACS guidelines are appropriate for patients aged 50-70, but for those 70 or greater we would consider full colonoscopy.

A novel strategy using G-CSF to support EMA/CO for high-risk gestational trophoblastic disease.

EMA/CO (etoposide-methotrexate-actinomycin D and Cytoxan-Oncovin) is an effective and well-tolerated chemotherapy regimen for the treatment of high-risk gestational trophoblastic disease. However, it is associated with significant neutropenia often requiring dose reductions and treatment delays. We describe the use of granulocyte colony-stimulating factor (G-CSF) in three patients in order to maintain the treatment schedule. A subcutaneous injection of 5 micrograms/kg/day was administered on Days 3-6 and 9-14 of each chemotherapy cycle. No patients had any adverse effects and all received full chemotherapy doses without any treatment delay. The addition of G-CSF to the EMA/CO regimen may benefit patients by achieving dose intensity in the treatment of high-risk gestational trophoblastic disease.

Chemoprophylaxis with oral ciprofloxacin in ovarian cancer patients receiving taxol.

The purpose of this study was to review the clinical outcomes and cost of administration of a prophylactic antibiotic compared to G-CSF for the prevention of neutropenic morbidity associated with taxol. The study group was composed of 62 patients with ovarian cancer who received a 24-h infusion of a taxol-based regimen at doses less than or equal to 175 mg/m2 between June 1992 and April 1994. The records were retrospectively reviewed and the patients were grouped and analyzed according to the management of their myelosuppression. Group I patients (n = 29) were observed until their absolute neutrophil count (ANC) was less than 500/microliters and then were placed on ciprofloxacin 500 mg orally twice a day until their ANC was 1,000/microliters. Group II patients (n = 15) received G-CSF from Day 2 until the ANC was greater than 10,000/microliters beginning with their first cycle. Group III patients (n = 18) received their taxol regimen without either ciprofloxacin or G-CSF. Two hundred eighty-two taxol-based chemotherapy cycles were administered to these 62 patients. There was no statistically significant difference between the groups concerning disease status as measured by age, stage, performance status, dose intensity, or number of previous regimens. There were two episodes of febrile neutropenia in Group I and three episodes in Group II. Group III had 15 episodes of febrile neutropenia. The estimated cost of the different prophylactic regimens was $5,215.00 for Group I versus $104,000.00 for G-CSF in Group II. Within the three groups, there were 27 patients with an episode of febrile neutropenia (n = 20) or prolonged myelosuppression (n = 7) that were followed for an additional 104 taxol cycles. Twenty-four of these patients received G-CSF prophylaxis with intermittent ciprofloxacin and three received only ciprofloxacin. There were eight more episodes of febrile neutropenia in the patients receiving G-CSF. There were no additional febrile episodes on cycles prophylaxed with ciprofloxacin. There was no septic mortality. For patients receiving a 24 h infusion of taxol at doses less than 175 mg/m2, ciprofloxacin given through the ANC nadir may be effective in preventing febrile morbidity. A prospective randomized trial is underway to evaluate this approach.

Gray scale and color flow Doppler characterization of uterine tumors.

The aim of this study was to investigate gray scale and color flow characteristics of a group of patients with a suspected uterine pathologic condition. One hundred and twenty-two consecutive patients at the Women's Cancer Center, University of Minnesota, undergoing transvaginal sonography and color flow Doppler imaging for suspected uterine corpus abnormality made up the study group. After gray scale morphologic assessment, color flow Doppler imaging of the tumor and uterus was performed, including the ipsilateral uterine artery. Malignant tumors were confirmed pathologically in all 35 patients who had them. In comparing patients with benign versus malignant tumors, gray scale morphologic assessment confirmed that malignant uterine tumors (31 endometrial cancers and four sarcomas) were more likely to have a thickened echoic endometrium (P = < 0.0001), be enlarged (P = 0.004), to be retroverted (P = 0.02), and to lack a subendometrial halo (P < 0.0001). Patients with four benign and 13 malignant tumors demonstrated increased flow when assessed by CFD. The calculated sensitivity of increased color flow in predicting malignancy was 39%, with a specificity of 92%, a positive predictive value of 77%, and a negative predictive value of 71%. No difference existed between the benign and malignant groups for the systolic, diastolic, and mean velocities and for the calculated pulsatility index and resistive index in both sampled uterine and intramyometrial or tumor vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of placental management at cesarean delivery on operative blood loss.

OBJECTIVES: The effect of alternative methods of placental delivery at cesarean section on blood loss has not been reported. The hypothesis of this study was that spontaneous expulsion of the placenta would reduce operative blood loss, compared with that of manual extraction during cesarean delivery. STUDY DESIGN: We prospectively randomized and compared outcomes of 62 gravid women with manual (n = 31) or spontaneous (n = 31) placental delivery at cesarean section. Operative blood loss was measured directly. RESULTS: Blood loss measured at cesarean delivery was greater in the manually delivered group (967 +/- 248 ml) than in the spontaneously delivered group (666 +/- 271 ml, p < 0.0001). The incidence of postpartum endometritis was sevenfold greater in the manual than the spontaneous group (23% vs 3%, respectively; p < 0.05). CONCLUSIONS: We conclude that spontaneous expulsion of the placenta at cesarean delivery results in less operative blood loss and a lower incidence of postoperative endometritis.