Expression of CD44, E-cadherin, and antimetastatic protein nm23-H1 in complete hydatidiform moles.

INTRODUCTION: There is scant information about the expression of CD44 and E-cadherin, two cell adhesion molecules, and the antimetastatic protein nm23-H1, in complete hydatidiform moles. We measured the expression of these markers to determine their usefulness in predicting the development of invasive disease. MATERIALS AND METHODS: We performed a retrospective study of 27 patients with complete hydatidiform moles, collecting clinical information including the patient's age, pre-evacuation hCG level, pathology, hCG monitoring, and the development of gestational trophoblastic neoplasia. Immunohistochemical staining for CD44, E-cadherin, and nm23-H1 was performed. CD44 expression was classified as positive or negative. For E-cadherin and nm23-H1, the intensity of expression was graded on a 0 to 3 scale. Chi-square or Fisher's exact testing was used to evaluate the relationship between these markers and the development of invasive disease. RESULTS: CD44 was expressed in 26% of cases. E-cadherin expression was 1+, 2+, and 3+in 8%, 33%, and 59% of cases, respectively. Nm23-H1 expression was 1+, 2+, and 3+in 4%, 11%, and 85% of cases. The risk of developing invasive disease did not correlate with the expression of CD44, E-cadherin, or nm23-H1. CONCLUSION: In this preliminary study, there is no relationship between CD44, E-cadherin, and nm23-H1 expression in complete hydatidiform moles and the risk of invasive disease. Other molecular markers predictive of invasive disease should be sought to limit hCG surveillance to those at risk.

Abnormal cervical cytology: a risk factor for endometrial cancer recurrence.

The objective of this study was to evaluate the relationship between cervical cytology, histologic type, and risk of endometrial cancer recurrence. We performed a retrospective study of patients undergoing surgery for endometrial carcinoma. Risk factors for recurrence including histology, tumor grade, nodal status, myometrial invasion, peritoneal washings, stage, and cervical cytology were assessed. Abnormal cervical cytology was defined as the presence of any endometrial cells on Pap smear. Papillary serous and clear cell carcinomas were considered high-risk histologies. Univariate and multivariate analyses of risk factors for recurrence were performed. Thirty-nine (9%) patients developed recurrent endometrial cancer. More patients with abnormal Pap smears recurred (12% versus 4%, P < 0.05). For endometrioid adenocarcinoma, abnormal cervical cytology occurred in 61% and 7% recurred, while with high-risk histologies, 84% had abnormal cervical cytology and 19% recurred (P < 0.05). Other significant predictors of recurrence on univariate analysis were myometrial invasion, nodal status, washings, stage, and histology. On multivariate analysis, only nodal status remained a significant predictor of recurrence. Abnormal cervical cytology is associated with increased risk of endometrial cancer recurrence. Abnormal cervical cytology occurs more frequently in high-risk histologies, which are known to have a higher risk of recurrence. On multivariate analysis, only nodal spread remains a significant predictor of recurrence.

CD44 expression in papillary serous endometrial carcinoma.

The objective of this paper is to evaluate the relationship between CD44 expression and the clinicopathologic features of papillary serous endometrial cancer. CD44 expression was assessed in 32 cases of papillary serous endometrial carcinoma by standard immunohistochemical staining techniques. Clinicopathologic features including myometrial invasion, nodal metastases, tumor spread, stage, and the shedding of malignant cells on cervical cytology were reviewed. The Chi-square test was used for statistical analysis. CD44 was not expressed in 81% of patients with papillary serous endometrial carcinoma. Malignant cells were seen on cervical cytology in 68% of all cases with significantly more in the CD44-negative group (78% vs. 33%, P 0.05). CD44 expression was not related to stage, myometrial invasion, nodal involvement, or intraperitoneal spread. We conclude that the cell adhesion molecule CD44 is expressed infrequently in papillary serous endometrial carcinoma. Shedding of malignant cells on cervical cytology is common in papillary serous endometrial cancer and occurs more frequently in CD44-negative cases. CD44 expression doesn't appear to be related to known prognostic features such as nodal metastases or stage. The biologic aggressiveness of this tumor type may, in part, be related to its lack of CD44 expression.

Changes in clinical measures of autonomic nervous system function related to cancer chemotherapy-induced nausea.

Individual cancer patients differ in their nausea/vomiting response to chemotherapy. It is not known why patients receiving the same chemotherapy have different severity of side effects. Several lines of research implicate the autonomic nervous system (ANS) in the development of chemotherapy-induced nausea. We examined the association between autonomic reactivity and the level of nausea experienced following chemotherapy in 20 patients with ovarian cancer treated with cisplatin or carboplatin who received the same antiemetic. We applied eight common non-invasive clinical tests of autonomic function prior to inpatient chemotherapy treatment, 2 h after treatment and again 24 h following treatment. Two hours after chemotherapy and before any nausea was reported by the patients, the nine patients who subsequently experienced high levels of nausea had a greater overall percentage of abnormal clinical ANS tests than the 11 patients who subsequently developed low levels of nausea (P < 0.01). Twenty-four hours after treatment, the overall number of abnormal autonomic tests remained non-significantly higher than at the pretreatment baseline for the high nausea group. Demographic and clinical characteristics were not related to chemotherapy-induced nausea in this sample. Autonomic reactivity appears to be related to the development of nausea following chemotherapy. Further investigation of ANS involvement in chemotherapy-induced nausea could increase understanding of nausea etiology and potentially lead to the prediction of susceptible patients.

Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer.

BACKGROUND: Intravenous platinum-based chemotherapy is the standard primary therapy for advanced ovarian cancer. We conducted a phase 3 trial to compare the effects of intraperitoneal and intravenous cisplatin on the survival of women with previously untreated, stage III, epithelial ovarian cancer. METHODS: The patients underwent an initial exploratory laparotomy and resection of all tumor masses larger than 2 cm. Within four weeks after surgery, six courses of intravenous cyclophosphamide (600 mg per square meter of body-surface area per course) plus either intraperitoneal cisplatin (100 mg per square meter) or intravenous cisplatin (100 mg per square meter) were administered at three-week intervals. RESULTS: Of 654 randomized patients, 546 were eligible for the study. The estimated median survival was significantly longer in the group receiving intraperitoneal cisplatin (49 months; 95 percent confidence interval, 42 to 56) than in the group receiving intravenous cisplatin (41 months; 95 percent confidence interval, 34 to 47). The risk of death was lower in the intraperitoneal group than in the intravenous group (hazard ratio, 0.76; 95 percent confidence interval, 0.61 to 0.96; P = 0.02). Moderate-to-severe tinnitus, clinical hearing loss, and neuromuscular toxic effects were significantly more frequent in the intravenous group. CONCLUSIONS: As compared with intravenous cisplatin, intraperitoneal cisplatin significantly improves survival and has significantly fewer toxic effects in patients with stage III ovarian cancer and residual tumor masses of 2 cm or less.

Cardiac spectral power reflects parasympathetic but not sympathetic nervous system activity in a clinical population.

The purpose of this short communication is to report our clinical findings regarding the use of the low frequency (LF, 0.02-0.15 Hz) and high frequency (HF, > 0.15 Hz) components of the spectral decomposition of heart-rate as indices of sympathetic (SNS) and parasympathetic nervous system (PNS) activity, respectively. Thirty-two females with histologically confirmed ovarian cancer, ranging in age from 46-72 years, participated in an autonomic assessment protocol consisting of a resting heart rate recording and several ANS function tests. The LF, HF and total power measures from the spectral decomposition were highly correlated with one another. In addition, the spectral components were most highly correlated with measures of PNS activity, i.e. standard deviation of heart rate at rest and the ratio of the six longest to the six shortest R-R intervals during deep breathing (E:I ratio). It is concluded, as other researchers have stated, that the use of the HF component of the HR spectrum as a measure of PNS activity is warranted, but caution must be used when interpreting the LF component.

Interstitial pregnancy complicated by rectal bleeding.

An interstitial pregnancy complicated by rectal bleeding is described. Despite modern imaging modalities, confounding features made preoperative diagnosis difficult. The pregnancy ruptured into the ileum. Ossified fetal skull bones and degenerated placental tissue were the only remains from the pregnancy.

Tamoxifen in platinum-refractory ovarian cancer: a Gynecologic Oncology Group Ancillary Report.

There is a critical need to find additional effective therapies in the management of ovarian cancer. A previously reported Gynecologic Oncology Group trial demonstrated that tamoxifen is an active drug when used in the salvage setting in this malignancy. Unfortunately, this original report did not specifically examine the utility of tamoxifen in patients with clinically defined platinum-refractory disease. In this reanalysis of the results of treatment of 102 evaluable patients entered into this multi-institutional trial, an objective response rate of 13% (95% confidence interval, 6.4-22.6%) was observed in patients with cisplatin-refractory ovarian cancer. The median response duration in this patient population was 4.4 months (range 1.2-9.2 months). Although the response rate is modest, this well-tolerated hormonal agent is a reasonable therapeutic option in selected patients with ovarian cancer when salvage therapy is to be considered. A possible role for this hormonal agent in other clinical settings in ovarian cancer will need to be defined through the conduct of carefully designed randomized clinical trials.

Use of thin-layer preparations for gynecologic smears with emphasis on the cytomorphology of high-grade intraepithelial lesions and carcinomas.

Thin-layer (TL) technology can improve the detection rate for squamous lesions of the uterine cervix. Studies to date have under-represented high grade lesions and malignancies. The present study utilized a patient population at high risk for such lesions in order to analyze the performance of TL procedures in this group, and in addition, to assess the similarities and differences in morphologic appearances of specimens prepared by the two methods. Conventional (CS) and thin-layer smears (TLS) were made in parallel from the same specimen. Each slide was examined in a blinded fashion. Diagnoses were compared and morphologic observations made. Two hundred fifty-nine cases were included, of which 32 (12%) were high grade dysplasias (11) or carcinomas (21). Thirty five (14%) were atypical or low grade dysplasias. There was exact correlation between Bethesda classification in 231 cases (89%). Of the 21 carcinomas identified, 19 (91%) were present on each preparation. Two cases of endometrial adenocarcinoma were missed on unsatisfactory or negative TLS. One case of squamous cell carcinoma was called high grade squamous intraepithelial lesion (HGSIL) on TLS while the CS was unsatisfactory. Three cases called atypical glandular cells (AGCUS) on TLS, and negative on CS, showed HGSIL (1) or no lesion (2) on follow-up. Morphologic features of low grade lesions were virtually identical on both preparations. Distinct features were noted on TLS in the high grade lesions. These included smaller appearing nuclear areas, less distinct nuclear chromatin, thicker three-dimensional groupings, and more isolated cells. Such findings were most pronounced in the glandular lesions. With training and experience, these features were easily identified in TL preparations, further documenting the utility of this procedure for use in routine practice.

Adrenal function following high-dose steroids in ovarian cancer patients.

PURPOSE: Steroid doses similar to those used to prevent paclitaxel-associated hypersensitivity reactions and cisplatin-induced nausea have been associated with hypothalamic-pituitary-adrenal (HPA) axis suppression. We assessed HPA function in patients receiving high-dose steroids as part of their chemotherapy regimen for epithelial ovarian cancer. PATIENTS AND METHODS: From January to July 1994, a cross-sectional study of HPA function was performed on patients receiving dexamethasone (DEX) as part of their paclitaxel and cisplatin chemotherapy regimen (n = 9). Patients received 20 mg of DEX orally, 6 and 12 hr prior to paclitaxel (135 mg/m2) and 10-20 mg intravenously before cisplatin (50-100 mg/m2). In addition, patients received approximately 12 mg/day of DEX orally for 4 days after their chemotherapy as an antiemetic. HPA integrity was evaluated by the administration of synthetic adrenocorticotropic hormone (ACTH). The ACTH stimulation test was performed 11-19 days after the completion of the course of DEX. Patients had fasting baseline cortisol levels drawn at approximately 0800 followed by a 25-unit intravenous injection of ACTH. Post-ACTH cortisol levels were repeated at 30 and 60 min. RESULTS: The mean (+/- SEM) fasting baseline level of cortisol was 12.4 +/- 2.3 micrograms/dl (normal, 7-23 micrograms/dl). At 30 min following ACTH administration, the mean cortisol level rose 17.1 micrograms to 29.5 +/- 1.8 micrograms/dl; at 60 min it rose 21.4 micrograms to 33.8 +/- 2.5 micrograms/dl [P < 0.001] (normal increase 9-39 micrograms). All patients demonstrated a sufficient increase in their plasma cortisol after ACTH stimulation, indicating normal HPA function on the days tested. However, there was a significant trend toward lower increases in plasma cortisol at 30 and 60 min as the interval from ACTH stimulation testing to the DEX regimen decreased (r = 0.986; P < 0.0001). The chemotherapy cycle number had no impact on cortisol response in the multivariate analysis. Based on multiple linear regression, HPA function may be suppressed for approximately 8 days, but up to 14 days from the start of this DEX regimen. CONCLUSION: Current steroid regimens prescribed with chemotherapy transiently decrease HPA function, but do not appear to inhibit the HPA axis long term. HPA function may be suppressed for approximately 8 days from the commencement of chemotherapy cycles involving DEX. Patients presenting within the first 8 days of a chemotherapy cycle using steroids with symptoms attributable to HPA suppression may benefit from HPA axis testing.

Paclitaxel-associated hypersensitivity reaction despite high-dose steroids and prolonged infusions.

The development of paclitaxel-containing chemotherapeutic regimens has been hindered by the frequent occurrence of allergic-type reactions to the drug or its diluent. Fortunately, current pretreatment regimens are associated with a reduced risk of major hypersensitivity reactions. However, there is still a group of patients that may experience these reactions from Taxol despite the use of prechemotherapy steroids and antihistamines. In a recent report, patients with prior reactions to Taxol were successfully retreated utilizing 24 hr of high-dose steroids and a very prolonged infusion regimen. We now report on two patients with major hypersensitivity reactions despite the use of this regimen. We conclude that not all Taxol-associated hypersensitivity reactions are preventable with current drug regimens. In addition, there is little evidence to support continued or exclusive use of the suggested rechallenge premedication schedule or the prolonged infusion rate.

Autonomic measures associated with chemotherapy-related nausea: techniques and issues.

Advances in antiemetic therapy for cancer patients have been hindered by a lack of understanding of the physiological mechanisms associated with nausea and their corresponding measurement techniques. Here we review conceptual and methodological issues involved in developing an autonomic frame of reference for nausea and outline two strategies for assessing autonomic function. A primarily research-oriented strategy uses heart rate, blood volume pulse, pallor, and skin temperature to assess autonomic activity and reactivity over 24 hr. Peak values of these measures relative to time of emesis, heart rate spectral analyses of autonomic activity, and analyses of the standard deviation of successive differences of beat-to-beat intervals were all associated with subsequent nausea. A primarily clinically oriented strategy assesses normal and abnormal results on eight common bedside clinical tests of autonomic function. The total number of abnormal tests was associated with subsequent nausea. A better understanding of chemotherapy side effect mechanisms is likely to result in less polypharmacy and more effective individualized treatment for cancer patients.

Failure of methotrexate treatment for term placenta percreta.

Placenta percreta is a severe condition associated with maternal morbidity and mortality even when surgery is performed electively. Methotrexate has been suggested as a possible treatment modality for adherent placenta to avoid catastrophic surgery. The purpose of this report is to present a case where the placenta was left in situ to avoid cystectomy at the time of cesarean section, with subsequent failure of treatment with methotrexate.

Echinomycin in recurrent and metastatic endometrial carcinoma. A phase II trial of the Gynecologic Oncology Group.

Twenty-one evaluable patients with recurrent or metastatic endometrial carcinoma were treated with 1,500 micrograms/m2 of echinomycin every 3 weeks. All patients had received prior chemotherapy. There was one complete response (5%), 95% confidence interval for response is 0.9-22.7%. The major toxicity was nausea and vomiting which was moderate to severe in 42% of patients. Myelosuppression was minimal. Echinomycin, in this dose and schedule, displays minimal activity in patients with advanced endometrial carcinoma who have had prior chemotherapy.

Presence of cytomegalovirus inclusion bodies in a recurrent ulcerative vaginal lesion.

Cytomegalovirus is present in the female lower genital tract with an incidence of 4% to 12%. Intracellular inclusion bodies, which constitute evidence of the presence of this organism, are noted on Papanicolaou smears or at direct biopsy. All previous reports regarding tissue diagnosis have involved the uterine cervix. We report an unusual case of a postmenopausal woman who was found to have recurrent symptomatic vaginal lesions; repeated biopsies of the lesion disclosed the presence of cytomegalovirus inclusion bodies.

Ultrasonographically guided subclavian vein catheterization in critical care obstetrics and gynecologic oncology.

Invasive hemodynamic monitoring has become an integral part of intensive care management. Whereas the pulmonary artery catheter is the mainstay for determination of the hemodynamic profile and differentiation between cardiogenic and noncardiogenic forms of pulmonary edema, immediate central venous access in itself is of importance in rapid volume replacement in cases complicated by severe hypovolemia. Central venous catheters are also the preferred route of administration of total parenteral nutrition to patients with cancer. We present our experience with real-time ultrasonographic guidance during subclavian vein catheterization in critical care obstetrics and gynecologic oncology.

Computed tomography of leiomyomatosis peritonealis disseminata with malignant transformation.

Malignant transformation of leiomyomatosis peritonealis disseminata is a very rare occurrence, reported twice previously. We report the third case and present the computed tomography findings associated with the development of this unusual pathologic condition.

Diagnoses after laparotomy for a mass in the pelvic area in women.

The management and outcome of 80 women with an undiagnosed pelvic mass who were referred to the Gynecologic Oncology Division at the University of Rochester during a one year period were reviewed. All patients underwent an exploratory laparotomy for definitive diagnosis. We correlated the final diagnosis with the results of preoperative evaluation and intraoperative assessment. Of the 80 patients, 48 were diagnosed with malignant disease. Of patients with carcinoma, 32 had carcinoma of the ovaries, two had other gynecologic malignancies, ten had nongynecologic malignancies and four had synchronous gynecologic and nongynecologic carcinomas. Carcinoma of the colon and rectum was the most common nongynecologic carcinoma; other malignant diseases were found in the endometrium, vagina, colon and rectum and the breast as well as lymphoma. Preoperative roentgenographic examinations and colonoscopy only had a sensitivity of 38 percent in detecting primary carcinoma of the colon and rectum. Ultrasound of the pelvic region and computed tomographic scan of the abdomen did not improve prediction of malignant disease in the patient population. Serum CA 125 was elevated in 26 of 37 patients with a carcinoma; however, it was elevated with relatively equal frequency in carcinomas of the ovaries and colon and rectum. Intraoperative frozen section accurately identified the primary site of the disease in 90 percent of the patients. However, in the presence of a tumor in the ovaries, carcinomatosis and a tumor in the colon, the results of frozen section were erroneous in four of six patients. Because preoperative assessment seems to be of limited value in excluding nongynecologic lesions, we recommend that pelvic surgeons be prepared to manage operatively a variety of malignant disease or have appropriate consultation available at laparotomy.

Recurrent stage I endometrial adenocarcinoma in the nonirradiated patient: preliminary results of surgical "staging".

Recurrent endometrial carcinoma, even when clinically confined to the vagina or pelvis, is associated with poor survival. Pelvic radiotherapy for patients with localized recurrences who have not been previously irradiated has not been highly effective. Our hypothesis was that local salvage therapy fails because a significant number of patients have occult, subclinical distant metastases at the time of relapse. In order to accurately assess disease status at the time of the recurrence, we prospectively evaluated eight patients with recurrent disease limited to the vagina/pelvis by physical examination, routine laboratory tests, and radiologic imaging. All patients underwent a "staging" procedure which included laparotomy, selective pelvic/periaortic lymphadenectomy, peritoneal biopsies, and washings. Three (37.5%) of eight patients had upper abdominal disease found at laparotomy (95% confidence interval 0.11 to 0.71). Presence of subclinical metastases was associated with larger tumor size (> or = 2 cm) and elevated serum CA 125 antigen levels. Treatment was modified in three patients according to the results of surgical staging. One patient was treated with chemotherapy while two patients received whole-abdominal radiation in addition to pelvic fields. Seven of eight patients are alive 21 to 61 months following salvage therapy. Three (43%) of seven patients treated with radiotherapy suffered nonneoplastic bowel obstruction requiring laparotomy at 3, 6, and 15 weeks following completion of radiation therapy. Since 37.5% of patients with recurrent endometrial carcinoma clinically confined to the pelvis had occult upper abdominal disease, surgical reassessment may be warranted, especially in those with elevated serum CA 125 levels or large tumors. Our limited sample size precludes any definitive conclusions regarding our data. Further research will determine the frequency of subclinical metastases and the value of serum CA 125 levels in assessing disease status.