Serum human epididymis protein 4 can be a useful tumor marker in the differential diagnosis of adnexal masses during pregnancy: a pilot study.

PURPOSE: The purpose of this study was to evaluate serum concentrations of human epididymis protein 4 (HE4) and cancer antigen 125 (CA 125) in healthy women and their pregnant counterparts to determine the influence of pregnancy on these biomarkers. MATERIALS AND METHODS: Serum concentrations of CA 125 and HE4 were measured in 27 healthy non-pregnant women and 26 healthy pregnant women in the first and second trimesters. RESULTS: Higher concentration of CA 125 was found in pregnants than in non-pregnant women (p = 0.002). There was no difference in CA 125 concentrations between first and second trimesters (p = 0.13). Serum HE4 concentration was not different in pregnant group compared to non-pregnant women (p = 0.510). Likewise, no difference was found in HE4 levels between the trimesters (p = 0.485). There was a positive correlation between increasing parity and CA 125 (p = 0.023), but not HE4 (p = 1.0). CONCLUSION: HE4 serum biomarker is unaffected by pregnancy status and may be useful for evaluation of doubtful pelvic masses in pregnancy. Contrarily, increased serum levels of CA 125 could yield increased number of false-positive results.

Complete remission of an endometrial carcinoma with bilateral multiple pulmonary and extrapelvic metastases treated by surgery and chemotherapy consisting of paclitaxel and carboplatin.

Successful management of a patient with endometrioid type, grade 2 endometrial carcinoma with bilateral multiple pulmonary and extrapelvic abdominal metastases has been reported. A 61-year-old woman with the preoperative diagnosis of stage IVB endometrial carcinoma underwent surgery followed by six cycles of chemotherapy consisting of paclitaxel (175 mg/m2) and carboplatin (area under curve 5). After the sixth course, there were no abnormal findings on chest and abdominal computed tomography. She has no evidence of disease recurrence 24 months after the induction of chemotherapy. Tumor markers are within normal limits. Endometrial carcinoma with pulmonary metastases, especially those with bilateral multiple pulmonary metastases associated with additional extrapulmonary spread can be successfully treated by extensive surgery followed by chemotherapy consisting of paclitaxel and carboplatin.

Endometrial carcinoma with laparotomy wound recurrence: complete remission following surgery and chemotherapy consisting of paclitaxel and carboplatin.

We present a patient with surgical stage I endometrial cancer who experienced laparotomy wound recurrence 4 years after primary treatment. She was treated successfully by complete surgical resection of recurrent tumors and chemotherapy. A 62-year-old white female with laparotomy wound recurrence of endometrial carcinoma with small-bowel involvement and concomitant subcutaneous metastasis in the abdominal wall underwent complete surgical resection of metastatic tumors followed by six cycles of chemotherapy consisting of paclitaxel (175 mg/m2) and carboplatin (area under the curve 5). Since 24 months after resection of recurrence, she has no evidence of disease recurrence. Endometrial carcinoma with laparotomy wound recurrences, especially those with concomitant metastases, can be successfully treated by complete surgical resection followed by chemotherapy consisting of paclitaxel and carboplatin.

Prevention of cyclophosphamide-induced ovarian damage by concomitant administration of GnRHa in mice: a dose-dependent relationship?

OBJECTIVE(S): This experimental study investigates the dose-related effects of cyclophosphamide (Cy) on primordial follicular reserve in young mice, and examines whether the concomitant administration of a gonadotropin-releasing hormone agonist (GnRHa) may protect gonadal reserve, even at different doses of Cy. METHODS: Forty sexually mature virginal Balb/c mice aged five to six weeks were administered different doses (0, 50, 75,100 mg/kg) of Cy. Another 40 animals were treated with increasing doses (0, 50, 75, 100 mg/kg) of Cy in combination with GnRHa. GnRHa treatment was initiated one week prior to chemotherapy and also continued after chemotherapy for one week. The ovaries were removed seven days after Cy administration and the total number of primordial follicles in both ovaries was counted. RESULTS: Primordial follicular destruction occurred at all levels of Cy exposure. There was a positive correlation between increasing doses of Cy and higher proportion of follicular loss (p < 0.0001). GnRHa was not able to protect against the chemotherapy-induced negative effect on primordial follicular count at low doses (50 mg/kg and 75 mg/kg). Mean +/- SD primordial follicle count in the 100 mg/kg Cy-treated group was significantly lower than in the 100 mg/kg Cy + GnRHa treatment group (73.9 +/- 33.1 vs 89 +/- 17.9, p = 0.047). CONCLUSION: Our data suggest a possible ovarian protective effect of GnRHa cotreatment only at high doses of Cy treatment. However, in spite of co-administration of GnRHa, loss of primordial follicular reserve occurred at all doses of Cy in mice.

Medical management of ectopic pregnancy with extremely high beta-HCG levels: a case report.

We report the successful treatment of an unruptured ectopic pregnancy in a patient with extremely high beta-human chorionic gonadotropin concentrations. A 33-year-old woman, gravida 2, para 0, abortus 1, presented to our department due to menstrual delay. On transvaginal ultrasonography, she had an unruptured ectopic pregnancy (3.5 x 4.5 cm). Her initial beta-HCG concentration was 38,270 mIU/ml. The administration of methotrexate (50 mg/m2) was performed intramuscularly. Serum beta-HCG levels decreased > 15% between post-therapy days 4 (31,324 mIU/ml) and 7 (13,108 mIU/ml), and did not rise during the subsequent weekly controls. In selected cases with unruptured ectopic pregnancy and extremely high initial beta-HCG levels, medical management with a single-dose methotrexate regimen may be successful.

Thrombocytosis in gynecologic malignancies.

Recent studies have addressed the prevalence and prognostic impact of thrombocytosis in various gynecologic and non-gynecologic malignancies. Thrombocytosis appears to be of prognostic value in certain patients with gynecologic malignancies. In this survey we review the published data and attempt to analyze the prognostic implications of thrombocytosis in patients with gynecologic malignancies.

Insulin resistance and lipid profile in women with polycystic appearing ovaries: implications with regard to polycystic ovary syndrome.

The aim of this study was to investigate carbohydrate and lipid profiles in women with polycystic appearing ovaries (PCO) on ultrasound examination who did not fulfill the criteria for polycystic ovary syndrome (PCOS). We sonographically evaluated and biochemically diagnosed 35 patients with PCO, 31 women with PCOS and 23 healthy controls. We performed oral glucose tolerance tests (OGTT) and calculated the quantitative insulin sensitivity check index (QUICKI) and the homeostatic model assessment (HOMAIR) scores. Serum fasting insulin levels, 1-h insulin response, HOMAIR and QUICKI scores were significantly higher in the PCO and PCOS groups than in the controls. However, serum fasting glucose levels, fasting insulin levels, HOMAIR and QUICKI scores were similar in women with PCO and PCOS. In women with PCO, high-density lipoprotein (HDL) levels were higher, and very-low-density lipoprotein (VLDL) and triglyceride levels were lower compared with women with PCOS. Furthermore, insulin responses to OGTT, HOMAIR and QUICKI scores and lipid values correlated with serum androgen levels and body mass index (BMI) in PCO patients. In conclusion, women with PCO who do not fulfill the criteria for PCOS have abnormal insulin sensitivity and insulin resistance. The finding of similar insulin abnormalities in women with PCO to those in women with PCOS confirms that women with PCO have similar metabolic characteristics to those with PCOS.

Maternal serum levels of tumor necrosis factor-alpha and interleukin-2 receptor in threatened abortion: a comparison with normal and pathologic pregnancies.

OBJECTIVE: We evaluated tumor necrosis factor-alpha (TNF-alpha) and interleukin-2 (IL-2) receptor levels in patients with threatened abortion and compared the levels with normal and pathologic pregnancies. DESIGN: A prospective, nonrandomized, case-control study. SETTING: Academic research setting. PATIENT(S): Twenty-two patients with threatened abortion, 18 patients with pathologic pregnancies, 20 healthy pregnant women, and 20 nonpregnant women. INTERVENTION(S): Maternal serum TNF-alpha and IL-2 receptor levels were measured with a solid-phase, two-site chemiluminescent enzyme immunometric assay method. MAIN OUTCOME MEASURE(S): TNF-alpha and IL-2 receptor levels. RESULT(S): The mean +/- SEM maternal serum IL-2 receptor level for patients with threatened abortion was 481.3 +/- 35.7 U/mL, compared with 426.5 +/- 22.4 U/mL in the normal pregnant group. There was no statistically significant difference in the mean +/- SEM serum TNF-alpha level between the patients with threatened abortion and those with normal pregnancies (16.1 +/- 2.7 pg/mL vs. 10.9 +/- 0.8 pg/mL). The mean +/- SEM maternal serum IL-2 receptor level was significantly higher in patients with pathologic pregnancies than in those with normal pregnancies (506.2 +/- 27.6 U/mL vs. 426.5 +/- 22.4 U/mL). The mean +/- SEM maternal serum TNF-alpha level was significantly higher in patients with pathologic pregnancies than in those with threatened abortion (39.2 +/- 9.5 pg/mL vs. 16.1 +/- 2.7 pg/mL) and normal pregnancies (39.2 +/- 9.5 pg/mL vs. 10.9 +/- 0.8 pg/mL). CONCLUSION(S): In comparison with normal pregnancies, maternal serum IL-2 receptor and TNF-alpha levels were not significantly increased in patients with threatened abortion with good outcome.

Pretreatment hemoglobin, platelet count, and prognosis in endometrial carcinoma.

We analyzed whether a low pretreatment hemoglobin level is a prognostic factor in endometrial cancer and whether it is associated with thrombocytosis. Two hundred and twelve patients with endometrial cancer treated with surgery were reviewed. Data were analyzed with Pearson's chi-squared test, Fisher's exact test in contingency tables, the Mann-Whitney U-test, the Student's t-test, and Kaplan-Meier estimates. Multivariate analysis was performed with the log-rank test and the Cox proportional hazard model. Thirty-nine patients (18%) had a pretreatment hemoglobin value of < 12.0 g/dL. These 39 patients had significantly higher rates of nonendometrioid histology, high-grade tumors, myometrial invasion of > 50%, adnexal involvement, lymph-vascular space involvement, and advanced FIGO stage than patients with hemoglobin > or = 12.0 g/dL. The rate of thrombocytosis was significantly higher in patients with a low hemoglobin level (36% vs. 8%, P < 0.01). The overall 5-year survival rate of patients with low pretreatment hemoglobin was 59% compared with 89% for those with hemoglobin > or = 12 g/dL (P < 0.01). In the multivariate analysis age, thrombocytosis, nonendometrioid histology, high-grade histology, and advanced FIGO stage were significantly associated with a poor prognosis whereas adnexal involvement, lymph-vascular space involvement, low hemoglobin and myometrial invasion were not. These data indicate that low pretreatment hemoglobin is a prognostic factor in patients with endometrial cancer and that it is associated with thrombocytosis. Low hemoglobin was strongly associated with other unfavorable prognostic factors so that it was significant in the univariate but not the multivariate analysis.

Long-term survival in a patient with brain metastases preceding the diagnosis of endometrial cancer. Report of two cases and review of the literature.

Only five patients found to have brain metastasis preceding the diagnosis of endometrial cancer have been reported in the literature, and none of these survived beyond 38 months. The authors report on two patients with primary endometrial cancer who initially presented with cerebral metastasis. One of these patients died of disease 15 months after diagnosis. The other patient is still alive, with no evidence of disease, 171 months after she underwent radiosurgery for a solitary brain metastasis, aggressive cytoreductive abdominal and pelvic surgery, and doxorubicin-based chemotherapy. To the best of their knowledge, the authors believe that no similar observation has been made for any primary gynecological neoplasm, including endometrial, ovarian, or cervical cancer. This is the first report documenting that survival beyond one decade may be achieved after intensive multimodal therapy in selected patients in whom a solitary brain metastasis has been found before diagnosis of endometrial cancer. Aggressive therapy appears to be warranted in these patients.

Maternal serum tumor necrosis factor-alpha in patients with preterm labor.

OBJECTIVE: To evaluate maternal serum tumor necrosis factor-alpha (TNF alpha) levels in patients with preterm labor without clinical signs of chorioamnionitis and to compare these with levels in nonlaboring controls. STUDY DESIGN: The study group consisted of 44 patients with a singleton pregnancy admitted to our department with the diagnosis of preterm labor between 26 and 36 weeks' gestation. The control group consisted of 25 healthy consecutive patients with a singleton pregnancy without preterm contractions who were seen for routine antenatal visits. Maternal serum TNF alpha was measured using a solid-phase, two-site chemiluminescent enzyme immunometric assay method, and levels were compared in patients with preterm labor and nonlaboring controls. RESULTS: The median maternal serum TNF alpha level for patients with preterm labor was 29.4 pg/mL (range, 12.3-173) as compared with 23 pg/mL (range, 11.9-62.7) in the control group (P = .031). Among 44 patients with preterm labor, 14 (32%) delivered within one week of admission. The median maternal serum TNF alpha level was significantly higher in patients who delivered within one week than in those who delivered after one week and controls (71.3 pg/mL [range, 28-173]) versus 22 pg/mL (range, 12.3-86) versus 23 pg/mL (range, 11.9-62.7) (P < .0001). CONCLUSION: TNF alpha was elevated in patients with preterm labor, suggesting a role for maternal serum TNF alpha in its initiation.

Persistent large choroid plexus cyst. A case report.

BACKGROUND: Prenatally diagnosed choroid plexus cysts regress or resolve spontaneously during pregnancy. A persistent large choroid plexus cyst with a prenatal diagnosis has not been reported previously. CASE: A 28-year-old, healthy primigravida was referred to our department at 32 weeks' gestation for a suspected fetal intracranial anomaly. Ultrasonography revealed a lateral ventricle 13 mm in width. The ventricle was dilated only in the atrium region. The choroid plexus was not distinct from the inner wall of the ventricle and did not fill the atrium of the lateral ventricle. The patient was followed with bi-weekly ultrasonography until delivery, and the left ventricular width increased from 13 to 17 mm. At 38 weeks' gestation the patient delivered a 3,350-g girl. Magnetic resonance imaging showed a 1.7 x 2.5 x 3.0-cm cyst in the left lateral ventricle. Follow-up magnetic resonance imaging scans at 6 and 11 months showed unchanged findings. Clinical and neurologic examinations at 11 months of age showed normal development. CONCLUSION: Although small (< 1 cm), postnatally persistent choroid plexus cysts are clinically insignificant variants of normal; the prognosis of large, persistent cysts (> or = 1 cm) is less clear. Long-term neurologic follow-up is mandatory for these neonates.

Does hysteroscopy facilitate tumor cell dissemination? Incidence of peritoneal cytology from patients with early stage endometrial carcinoma following dilatation and curettage (D & C) versus hysteroscopy and D & C.

BACKGROUND: In several case reports, distension and irrigation of the uterine cavity during fluid hysteroscopy was suspected to cause tumor cell dissemination into the abdominal cavity in patients with endometrial carcinoma. It was the aim of this study to compare the incidence of positive peritoneal cytology in patients who underwent dilatation and curettage (D & C) with or without previous hysteroscopy. METHODS: The authors conducted a multicentric, retrospective cohort analysis. One hundred thirteen consecutive patients with endometrial carcinoma treated between 1996 and 1997 were included. Endometrial carcinoma had to be limited to the inner half or less than the inner half of the myometrium (pathologic Stage IA,B). Positive peritoneal cytology was obtained during staging laparotomy. Patients underwent D & C either with or without prior diagnostic fluid hysteroscopy. No selection or randomization was applied to the two groups. Positive peritoneal cytology, defined as malignant or suspicious, was considered the primary statistical endpoint. RESULTS: Peritoneal cytology was suspicious or positive in 10 of 113 patients (9%). The presence of suspicious or positive peritoneal cytology was associated with a history of hysteroscopy (P = 0.04) but not with myometrial invasion (P = 0.57), histologic subtype (P = 1.00) or grade (r = 0.16, P = 0.10), or the time between D & C and staging laparotomy (r = 0.04, P = 0.66). CONCLUSIONS: Based on the limited extent of endometrial carcinoma in the current analysis, our data strongly suggest dissemination of endometrial carcinoma cells after fluid hysteroscopy. Determining whether a positive peritoneal cytology affects the prognoses of patients without further evidence of extrauterine disease will require longer follow-up.

Preoperative thrombocytosis is an independent prognostic factor in stage III and IV endometrial cancer.

BACKGROUND: To identify prognostic factors in stage III and IV endometrial cancer with special attention to pretreatment platelet count. MATERIALS AND METHODS: 59 patients with FIGO stage III or IV disease operated on between 1983 and 1993 were analyzed. Patients with preoperative thrombocytosis were compared with those without thrombocytosis. Prognostic factors were analyzed with a Cox proportional hazard model. RESULTS: With the exception of age, there were no significant differences between patients with or without thrombocytosis. At multivariate analysis, five-year disease-free survival was influenced significantly by FIGO stage (stage III vs stage IV; p = 0.009), thrombocytosis (p = 0.02) and cervical involvement (p = 0.024). Similarly, overall five-year survival was significantly influenced by stage (p < 0.001), cervical involvement (p = 0.005) and thrombocytosis (p = 0.01). Age, histology, grade, myometrial invasion, lymph-vascular space involvement or spread to adnexae were not significantly associated with survival. CONCLUSION: Thrombocytosis is an independent prognostic factor in stage III and IV endometrial cancer.

Impact of hysteroscopy on disease-free survival in clinically stage I endometrial cancer patients.

Recent data strongly suggest tumor cell dissemination of endometrial carcinoma cells in the course of fluid hysteroscopy. In patients who had endometrial cancer which was (except for peritoneal cytology) confined to the uterus, the disease-free survival (DFS) of 135 patients who underwent hysteroscopy prior to staging laparotomy was compared with the DFS of 127 patients without hysteroscopy. After a median follow-up of 23 months, 10 patients experienced tumor recurrence. Although there was a trend towards a higher incidence of positive peritoneal cytology at laparotomy in patients who underwent hysteroscopy, this difference did not achieve statistical significance (P = 0.47). For 5 years, the DFS was 92.4% in patients with hysteroscopy and 84.7% in patients without hysteroscopy before laparotomy (log-rank, P = 0.782). Our data therefore suggest a similar short-term DFS in endometrial cancer patients with and without hysteroscopy prior to laparotomy.

Parametrial spread in patients with endometrial carcinoma undergoing radical hysterectomy.

The objective of this paper is to study parametrial involvement in patients with endometrial carcinoma undergoing radical hysterectomy. We reviewed indications for surgery, pathology findings, and outcome of a series of 24 patients with endometrial carcinoma who underwent radical hysterectomy. The uterus, cervix and parametrial tissue were processed as step-serial sections. Histologically, 16 patients (67%) had carcinoma involving the cervix. Two of these patients (8%) had frank histologic parametrial involvement and four (17%) had disease extending to the transitional zone of the cervix. Parametrial involvement was continuous and seen only in patients with involvement of the cervical stroma. Six patients (25%) had pelvic node metastases. With a median follow-up of 53 months (range 2-140), four patients (17%) developed recurrences (all within 24 months). Twelve patients (50%), including one of the two with parametrial invasion, were free of disease for 5 years or longer. We conclude that direct parametrial extension can occur in locally advanced endometrial cancer. Radical hysterectomy with lymphadenectomy can be an adequate operation for such patients.

Numerical chromosomal aberrations of chromosome 1 and 7 in dysplastic cervical smears.

Cervical smears with Papanicolaou's staining (PAP) reveal only morphological characteristics of epithelial cells of the cervix uteri. Since chromosomal aberrations are known to play a role in malignant transition, we analyzed cervical smears for numerical changes of the chromosomes 1 and 7 with fluorescence in-situ hybridization to probe for a diagnostic value of these chromosomes in the characterization of cervical dysplasia. Cervical smears were collected from 21 patients with suspect histology of curettage or biopsy specimen, 14 of them having been subsequently graded as cervical intraepithelial neoplasia (CIN) III and 5 as CIN II. Nineteen normal cervical smears (PAP I-II) served as controls. Smears were hybridized with chromosomal enumeration probes for chromosome 1 and 7. Disomic cells (2 copies of chromosome 1 and 7) were decreased in the CIN II (63%) and CIN III group (57%) with respect to the control group (77%). Cells with 3 signals for chromosome 7 were significantly more frequent in the CIN III and the CIN II group than in the control group (6.7, 6.4 and 0.7%, respectively). Only the CIN II group (10%), but not CIN II (6%), showed a significant trisomy for chromosome 1 as compared with the controls (3.8%). A close correlation between the incidence of trisomy 1 or 7 and PAP grading was observed. PAP III-IIID smears with high trisomy 1 counts corresponded to CIN III histology, while all CIN II patients were PAP III-IIID with low incidence of trisomy 1. We conclude that trisomy of chromosome 7 is a feature of cervical dysplasia and seems to be an early event in dysplastic transition. In contrast, trisomy of chromosome 1 is observed only in high grade dysplasia and may be a marker for pre-malignant lesions.