Treatment of the Mayer-Rokitansky-Küster-Hauser syndrome with autologous in vitro cultured vaginal tissue: descriptive study of long-term results and patient outcomes.

OBJECTIVE: Evaluating sexual function and quality of life (QoL) in patients treated with a modified Abbé-McIndoe technique using in vitro cultured autologous vaginal mucosa. DESIGN: Descriptive study. SETTING: Policlinico Umberto I, Sapienza University of Rome. POPULATION: From 2006 to 2016, 39 women affected by Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) underwent vaginoplasty at our centre using a modified Abbé-McIndoe technique with in vitro cultured autologous vaginal tissue. METHODS: For each patient, vaginal tissue was obtained by full-thickness biopsy of the vaginal vestibule. Following enzymatic dissociation, cells were cultured for 2-3 weeks before the transplant. MAIN OUTCOME MEASURES: Each patient completed two validated questionnaires to quantify sexual function and QoL: the Female Sexual Function Index (FSFI), administered at 12, 36, and 60 months, and the Psychological General Well Being Index (PGWBI) administered at 0, 6, and 36 months after surgery. RESULTS: Twelve months after surgery, 29 patients were engaging in regular sexual activity. The FSFI test results showed a satisfactory sexual function compared to the general population, with median values of 25.85 (range 4.6-30.5) at 12 months, 27.2 (range 4.4-33.6) at 36 months, and 29.6 (range 23.9-33.6) at 60 months. The PGWBI questionnaire showed a median score of 420.5 (range 108-540) before surgery, and 459 (range 252-533) at the 60-month follow-up. CONCLUSIONS: Vaginoplasty performed with the use of autologous vaginal tissue, besides ensuring a long-term satisfying sex life, helps in achieving an improvement in QoL that is maintained over time. TWEETABLE ABSTRACT: Vaginoplasty using in vitro vaginal tissue ensures a satisfactory sexual function and improves quality of life.

Role of magnetic resonance imaging in fetuses with mild or moderate ventriculomegaly in the era of fetal neurosonography: systematic review and meta-analysis.

OBJECTIVES: To report the rate of additional central nervous system (CNS) anomalies detected exclusively on prenatal magnetic resonance imaging (MRI) in fetuses diagnosed with isolated mild or moderate ventriculomegaly (VM) on ultrasound, according to the type of ultrasound protocol adopted (dedicated neurosonography vs standard assessment of the fetal brain), and to explore whether the diagnostic performance of fetal MRI in detecting such anomalies is affected by gestational age at examination and laterality and degree of ventricular dilatation. METHODS: MEDLINE, EMBASE, CINAHL and Clinicaltrials.gov were searched for studies reporting on the prenatal MRI assessment of fetuses diagnosed with isolated mild or moderate VM (ventricular dilatation of 10-15 mm) on ultrasound. Additional anomalies detected only on MRI were classified as callosal, septal, posterior fossa, white matter, intraventricular hemorrhage, cortical, periventricular heterotopia, periventricular cysts or complex malformations. The rate of additional anomalies was compared between fetuses diagnosed on dedicated neurosonography, defined as a detailed assessment of the fetal brain, according to the International Society of Ultrasound in Obstetrics and Gynecology guidelines, and those diagnosed on standard fetal brain assessment. The rate of additional CNS anomalies missed on prenatal MRI and detected only at birth was calculated and compared between fetuses that had early (at or before 24 weeks' gestation) and those that had late (after 24 weeks) MRI. Subanalysis was performed according to the laterality (uni- vs bilateral) and degree (mild vs moderate, defined as ventricular dilatation of 10-12 and 13-15 mm, respectively) of ventricular dilatation. Whether MRI assessment led to a significant change in prenatal management was explored. Random-effects meta-analysis of proportions was used. RESULTS: Sixteen studies (1159 fetuses) were included in the systematic review. Overall, MRI detected an anomaly not identified on ultrasound in 10.0% (95% CI, 6.2-14.5%) of fetuses. However, when stratifying the analysis according to the type of ultrasound assessment, the rate of associated anomalies detected only on MRI was 5.0% (95% CI, 3.0-7.0%) when dedicated neurosonography was performed compared with 16.8% (95% CI, 8.3-27.6%) in cases that underwent a standard assessment of the fetal brain in the axial plane. The overall rate of an additional anomaly detected only at birth and missed on prenatal MRI was 0.9% (95% CI, 0.04-1.5%) (I2 , 0%). There was no difference in the rate of an associated anomaly detected only after birth when fetal MRI was carried out before, compared with after, 24 weeks of gestation (P = 0.265). The risk of detecting an associated CNS abnormality on MRI was higher in fetuses with moderate than in those with mild VM (odds ratio, 8.1 (95% CI, 2.3-29.0); P = 0.001), while there was no difference in those presenting with bilateral, compared with unilateral, dilatation (P = 0.333). Finally, a significant change in perinatal management, mainly termination of pregnancy owing to parental request, following MRI detection of an associated anomaly, was observed in 2.9% (95% CI, 0.01-9.8%) of fetuses undergoing dedicated neurosonography compared with 5.1% (95% CI, 3.2-7.5%) of those having standard assessment. CONCLUSIONS: In fetuses undergoing dedicated neurosonography, the rate of a CNS anomaly detected exclusively on MRI is lower than that reported previously. Early MRI has an excellent diagnostic performance in identifying additional CNS anomalies, although the findings from this review suggest that MRI performed in the third trimester may be associated with a better detection rate for some types of anomaly, such as cortical, white matter and intracranial hemorrhagic anomalies. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

PARP inhibition: A promising therapeutic target in ovarian cancer.

Ovarian cancer is burdened by the highest mortality rate among gynecological cancers. Gold standard is represented by the association of platinum-taxane -based chemotherapy and radical surgery. Despite several adjustments occurred in cytotoxic drug in last decades, most patients continue to relapse, and no significant enhancement has been reached in the overall survival. The development of drug resistance and the recurrence of disease have prompted the investigations of other targets that can be used in the treatment of ovarian cancers. Among such targets, polyadenosine diphosphate-ribose polymerase (PARP) represents a novel way to target specific patways involved in tumor growth. PARP accelerates the reaction of the polyADP-ribosylation of proteins implicated in DNA repair. PARP inhibitors have shown activity in cancers with BRCA mutations, with other deficient DNA repair genes or signaling pathways that modulate DNA repair, or in association with DNA damaging agents not involved in DNA repair dysfunction. A number of inhibitors for PARP has been developed, and such drugs are under investigation in clinical trials to identify their impact in the treatment of ovarian cancers. This review aims to summarize the recent researches and clinical progress on PARP inhibitors as novel target agents in ovarian cancer.

Management of hydrosalpinx before IVF: a literature review.

Hydrosalpinx has a detrimental effect on the outcome of in vitro fertilization (IVF). Surgical intervention such as salpingectomy or tubal occlusion before IVF improves the outcome of IVF, but these procedures are often contraindicated in women with dense pelvic adhesions. Thus, it is worthwhile to search minimally invasive alternative therapies. The main objective of this review is to assess and compare the value of all the therapeutic options for hydrosalpinx before IVF. The results of the following procedures were compared: the laparoscopic treatments (salpingectomy/proximal tubal occlusion), the hysteroscopic insertion of device achieving tubal occlusion, the tuberous sclerosis and the aspiration of hydrosalpingeal fluid at the time of IVF procedure. Laparoscopic surgical treatment should be considered for all women with hydrosalpinx before IVF. Whenever laparoscopy is not recommended, hysteroscopic insertion of device seems the most effective option for management of hydrosalpinx before IVF.

Postoperative administration of monophasic combined oral contraceptives after laparoscopic treatment of ovarian endometriomas: a prospective, randomized trial.

OBJECTIVE: We sought to evaluate the efficacy of postoperative administration of monophasic, combined, low-dose oral contraceptives on endometrioma recurrence and on persistence-recurrence of associated pain symptoms after laparoscopic treatment of moderate-to-severe endometriosis. STUDY DESIGN: In a prospective, randomized trial 70 patients who were not attempting to conceive, aged 20 to 35 years, underwent laparoscopic excision of ovarian endometriomas, followed by either postoperative administration of low-dose cyclic oral contraceptives for 6 months or no treatment on the basis of a computer-generated sequence. At 3 and 6 months after surgery and then at 6-month intervals, both groups underwent ultrasonographic examination for possible evidence of endometrioma recurrence and for evaluation of the absence, persistence, or recurrence of pain symptoms. RESULTS: Two patients in the oral contraceptive group did not complete the study. After a mean follow-up of 22 months (range, 12-48 months), there were 2 (6.1%) endometrioma recurrences in the 33 patients who received postoperative oral contraceptives versus 1 (2.9%) recurrence in the 35 patients in the control group (not significant). The moderate-to-severe pain recurrence rate was 9.1% in the oral contraceptive group versus 17.1% in the control group (not significant). The mean time to recurrence of either symptoms or endometriomas was 18.2 months in the oral contraceptive group versus 12.7 months in the control group. The 12-month cumulative recurrence rate at life-table analysis was significantly lower for patients receiving oral contraceptives versus control subjects, whereas no significant difference was evident at 24 and 36 months. CONCLUSION: Postoperative administration of low-dose cyclic oral contraceptives does not significantly affect the long-term recurrence rate of endometriosis after surgical treatment. A delay in recurrence is evident at life-table analysis.

Erythropoietin addition to granulocyte colony-stimulating factor abrogates life-threatening neutropenia and increases peripheral-blood progenitor-cell mobilization after epirubicin, paclitaxel, and cisplatin combination chemotherapy: results of a randomized comparison.

PURPOSE AND METHODS: The ability of granulocyte colony-stimulating factor (G-CSF) plus erythropoietin (EPO) treatment was compared in a randomized fashion with that of G-CSF treatment alone in promoting hematologic recovery and peripheral-blood progenitor-cell (PBPC) mobilization in previously untreated patients with advanced ovarian cancer who underwent their first course of epirubicin, paclitaxel, and cisplatin (ETP) chemotherapy during a phase II study of intensive outpatient ETP chemotherapy followed by high-dose carboplatin, etoposide, and melphalan (CEM) late intensification with PBPC support. RESULTS: Comparative analysis of hematologic recovery of 50 randomized patients, after ETP chemotherapy, showed that life-threatening neutropenia occurred in 88% of the patients treated with G-CSF alone, whereas it occurred in only 4% of patients treated with G-CSF + EPO. Significantly different WBC and polymorphonuclear leukocyte (PMN) counts were observed in the two distinct arms on the day of WBC nadir (P <.0001 and P <.0001, respectively). Moreover, the addition of EPO to G-CSF increased PBPC mobilization and collection as compared with that in G-CSF-treated patients (P =.0009 and P =.0026, respectively), who required a significantly higher number of leukaphereses than G-CSF + EPO-treated patients (P =.0076) to obtain the planned minimum dose of PBPCs. Qualitative analysis by cloning assay of PBPCs collected in both arms revealed that G-CSF- and G-CSF + EPO-mobilized PBPCs have comparable in vitro functional properties. CONCLUSION: This randomized comparison revealed that EPO significantly increases most of the hematologic effect produced by G-CSF administration after chemotherapy. This biologic property of EPO translated in vivo into a global improvement of patients' hematologic status.

Cervical cancer response to neoadjuvant therapy: MR imaging assessment.

PURPOSE: To determine the accuracy of magnetic resonance (MR) imaging in evaluating the invasive cervical carcinoma response to concurrent chemotherapy and radiation therapy. MATERIALS AND METHODS: MR imaging was performed before and after concurrent chemotherapy and radiation therapy in 18 patients with locally invasive cervical carcinoma. Surgery followed neoadjuvant therapy in all patients. The presence of a lesion, signal intensity, zonal anatomy integrity, vaginal and parametrial invasion, and lymph node enlargement was determined. Posttreatment MR and histopathologic findings were correlated. RESULTS: Fourteen patients had histopathologic confirmation of MR findings: Twelve had true-negative and two had true-positive findings. (Two had microscopic neoplastic foci beyond the spatial resolution of MR images; these foci do not change surgical treatment planning and probably do not influence prognosis. Therefore, these two patients were considered to have complete response). Four patients had false-positive findings; the hyperintense lesion on posttreatment MR images was due to a tunnel cluster pattern (focal hyperplasia of the endocervical glands with inflammation) in three patients and necrosis in one patient, without any evidence of neoplastic tissue. Thirty-three of 36 parametrial halves and 67 of 72 vaginal fornices were correctly interpreted on posttreatment images. Involvement of three parametrial halves and five fornices was overestimated at MR, because edema or inflammation was not distinguishable from tumor. CONCLUSION: MR imaging is 78% accurate in evaluation of tumor response; in 22% of patients, however, benign conditions were not distinguishable from tumor.

In vitro effect of amifostine on haematopoietic progenitors exposed to carboplatin and non-alkylating antineoplastic drugs: haematoprotection acts as a drug-specific progenitor rescue.

We evaluated the protective ability of amifostine on peripheral blood mononuclear cell (PBMC)-derived colony-forming unit (CFU) and PB CD34+ cells which were previously exposed in vitro to etoposide, carboplatin, doxorubicin and taxotere. Amifostine pretreatment protected PBMC-derived CFU from the toxic effect of etoposide, carboplatin and taxotere. A significant detrimental effect was exerted by amifostine on the growth of doxorubicin-treated PBMC-derived CFU. Liquid cultures of PB CD34+ cells reproduced faithfully the effects observed on growth of PBMC-derived CFU and confirmed amifostine chemoprotection against etoposide and carboplatin with its detrimental effect on doxorubicin-treated progenitors. Combining the data of viable cell count, cytometric estimation of apoptosis, cell cycle and viable cell replication rate, we found that amifostine protects from etoposide and carboplatin toxicity mainly through a mechanism of cell rescue. Conversely, the detrimental effect of amifostine on the growth of doxorubicin-treated PB CD34+ cells is apparently due to an increased G2/M arrest. In conclusion, amifostine protects haematopoietic progenitors from etoposide, carboplatin and taxotere. Progenitor rescue is the mechanism through which amifostine reduced etoposide and carboplatin toxicity.

[Therapy of bacterial vaginosis. Prospective clinical study ot the efficacy and tolerability of quaternary ammonium salts vs. clindamycin]. / La terapia delle vaginosi batteriche. Studio clinico prospettico sull'efficacia e tollerabilità dei sali quaternari d'ammonio versus clindamicina.

BACKGROUND: To evaluate the efficacy and safety of intravaginal quaternary ammonium antimicrobial compounds (SQA) versus clindamycin 2% intravaginal cream (CL) in the treatment of bacterial vaginosis (VB). MATERIALS AND METHODS: One hundred-thirty-three patients affected by VB were enrolled in the study from January 1995 to October 1997. Patients were classified according to Amsel's criteria and/or to the indications of the Scandinavian Society of Bacterial Vaginosis. Twenty-three patients were initially excluded from the study, and 110 patients were randomized in two groups, SQA versus CL. Patients were reevaluated after 3 weeks, 3 months and 6 months from the end of therapy. The safety of treatment was also investigated. RESULTS: Of 110 patients, 59 were treated with SQA and 51 with CL. One hundred (90.9%) patients completed the therapy and were subjected to the first control after 3 weeks from the end of therapy. A significant reduction of most of the symptoms and all signs of VB was observed in the group treated with SQA. Similarly, a significant reduction of most of the symptoms (vaginal and urinary in particular) and all signs of VB was observed in the group treated with CL. The percentage of response was 86.7% for SQA group and 87.2% for CL group. Moreover, after 3 months from the end of therapy, 47.2% and 50% of the patients treated with SQA and CL, respectively, recurred, and after 6 months 78.5% and 75% of the patients recurred, respectively. CONCLUSIONS: SQA treatment conferred 86.7% of response after 3 weeks from the end of therapy, with poor side effects and a good compliance in good keeping with the results obtained with CL treatment.

Anti-proliferative activity of a new class of taxanes (14beta-hydroxy-10-deacetylbaccatin III derivatives) on multidrug-resistance-positive human cancer cells.

Paclitaxel, docetaxel and a series of new analogs synthesized from 14beta-hydroxy-10-deacetylbaccatin III (14-OH-DAB), a natural diterpene closely related to the core synthon of the 2 above prototypes, were tested in vitro for their growth-inhibitory activity on different human cancer cell lines, including some expressing the classic multidrug-resistant (MDR) phenotype (MCF-7 ADRr and CEM VBLr). The 14-OH-DAB derivatives showed enhanced anti-proliferative activity as compared to the parent compounds on the MDR-positive cancer cell lines. Particularly, IDN 5109 showed a 25- to 30-fold higher activity than paclitaxel. The fold change in activity between paclitaxel and analogs (IC50 paclitaxel/IC50 analogs) on the MDR-positive cell lines was calculated and a significant correlation observed. As far as the MDR-negative MDA-MB 231 cells are concerned, docetaxel and IDN 5109 exhibited a more potent activity than paclitaxel. On the basis of the data obtained on cell growth inhibition, we selected the most active compounds to study their effect on the cell cycle. Cell cycle analysis showed that all of the compounds tested were able to induce cell cycle block at G2/M in a concentration-dependent manner. The amount of cell block, measured as a G1/G2 ratio, was correlated significantly (p < 0.001) with apoptosis, as evaluated in the sub-G1 region (% of DNA fragmentation), thereby suggesting that the G2/M-blocked cells underwent apoptosis. To confirm the occurrence of apoptosis in this system, DNA gel agarose electrophoresis was performed and showed the typical ladder pattern.

Transvaginal color Doppler ultrasonography in the presurgical characterization of adnexal masses.

The aim of our study was to evaluate flow-velocity waveforms from ovarian tumors with color Doppler, in order to test the predictivity of malignancy and to compare the Doppler technique with some morphological scoring systems. Color Doppler examination of ovarian neoplasms was performed in 122 patients within 2-3 days from surgery and, based on vascular characteristics and on Doppler resistance index, a "vascular" score was calculated. One hundred one women had benign and 21 had malignant tumors on histopathology. In all of the malignant lesions color Doppler was able to detect vascular patterns, whereas only 43% of the benign tumors showed recognizable vessels (P < 0.001). Malignant masses showed significantly greater vascular scores than those of benign tumors (P < 0.001). Doppler ultrasonography achieved better specificity and PPV when compared to morphological scores (96% vs 61-75% and 82% vs 35-48%). Color Doppler ultrasonography of ovarian tumors seems to be a reliable method in the presurgical characterization of ovarian neoplasms.

Antiproliferative effect of silybin on gynaecological malignancies: synergism with cisplatin and doxorubicin.

The aim of this study was to test the antiproliferative activity of silybin, a flavonoid, on human ovarian and breast cancer cell lines. Since flavonoids are thought to act through Type II oestrogen binding sites (Type II EBS), silybin binding to Type II EBS was also examined. Silybin, used in concentrations from 0.1 to 20 microM, exerted a dose-dependent growth inhibitory effect on OVCA 433, A2780 parental and drug-resistant ovarian cancer cells, and MCF-7 doxorubicin (DOX)-resistant breast cancer cells (IC50 = 4.8-24 microM). Both L and D diastereoisomers of silybin were effective in inhibiting A2780 WT cell growth (IC50 = 14 and 20 microM, respectively). Flow cytometry revealed that silybin decreased the percentage of cells in the S and G2-M phases of the cell cycle with a concomitant increase in cells in the G0-G1 phase. Silybin was able to compete with [3H]E2 for nuclear but not cytosolic Type II EBS. Its affinity parallels its efficacy in inhibiting cell proliferation. Furthermore, silybin (0.1 and 1 microM) potentiates the effect of cisplatin (CDDP) (0.1-1 micrograms/ml) in inhibiting A2780 WT and CDDP-resistant cell growth. Similar results were obtained on MCF-7 DOX-resistant cells when silybin (0.1 microM) was associated with doxorubicin (0.1-10 micrograms/ml). As assessed by the Berembaum isobole method, the effect of silybin-CDDP and silybin-DOX combinations results in a synergistic action. Using the 'stem cell assay' described by Hamburger and Salmon [Science 1977, 197, 461-463], we found that silybin exerted a dose-dependent inhibition of clonogenic efficiency of cells derived from three ovarian tumours (IC50 = 7.4, 4 and 6.4 microM, respectively). Since CDDP and DOX are the two most commonly used drugs for gynaecological tumours, the clinical application of silybin is currently under investigation in our institute.

The combination of erythropoietin and granulocyte colony-stimulating factor increases the rate of haemopoietic recovery with clinical benefit after peripheral blood progenitor cell transplantation.

In order to investigate the effects of erythropoietin (EPO) plus granulocyte colony-stimulating factor (G-CSF) administration after peripheral blood progenitor cell transplantation (PBPCT) we performed a phase I/II study in patients with high-risk cancer. 15 consecutive patients were treated wit recombinant human G-CSF (rhG-CSF) at the dose of 5 micrograms/kg subcutaneously (s.c.) every 24 h until day + 12 and with recombinant human EPO (rhEPO) at the dose of 150 IU/kg s.c. every 48 h until day + 11 following PBPCT. Their haemopoietic recovery was compared to that obtained in eight historic and control patients who did not receive any cytokines after PBPCT. No side-effects were observed during EPO plus G-CSF treatment and the treatment was not discontinued in any of the patients before completion of the treatment plan. The administration of EPO plus G-CSF after PBPCT produced a significant increase in the rate of white blood cell (WBC) (P = 0.0005), polymorphonuclear leucocyte (PMN) (P = 0.0005) and platelet (PLT) (P = 0.0105) recovery compared to the control group. The acceleration in haemopoietic recovery observed in the EPO plus G-CSF-treated patients produced a significant reduction of the days with WBC < 1 x 10(9)/l (P = 0.0009), PMN < 0.2 x 10(9)/l (P = 0.0030) and PMN < 0.5 x 10(9)/l (P = 0.0006). EPO plus G-CSF-treated patients required a significantly lower number of single donor PLT transfusions (P = 0.0142) and did not experience neutropenic fever, but historic control patients experienced fever > 38 degrees C for a median period of 4 d (0-12) with a medial period of parenteral antibiotic administration of 7.5 d (0-17). The length of the hospital stay was significantly shorter in the study group than in the historic control group (P = 0.0264). In conclusion, we can confirm that EPO plus G-CSF treatment is feasible and potentiates the haemopoietic recovery after PBPCT, thus simplifying the clinical management of cancer patients who undergo high-dose chemotherapy.

Epidermal growth factor receptors in placentae and fetal membranes from hypertension-complicated pregnancies.

Epidermal growth factor receptor concentrations (EGFR) in placentae and fetal membranes from 25 normal and 25 hypertension-complicated pregnancies were analysed by a radioreceptor technique. Higher EGFR concentrations were found in placentae from hypertension-complicated pregnancies than in those from normal pregnancies (median 125.0 fmol/mg protein, range: 33.4-190.7 versus median 50.3 fmol/mg protein, range 21.4-184.0) (P = 0.0002). EGFR concentrations were significantly lower in fetal membranes than in placental tissue, both in normal membranes (median 31.7, range 4.8-92.0 versus median 50.3, range 21.4-184.0) (P = 0.0004) and in hypertension-complicated pregnancies (median 65.0, range 16.8-125.0 versus median 125.0, range 33.4-190.7) (P = 0.0001). A statistically significant inverse correlation between EGFR concentrations and gestational age was found in placentae (r = 0.53, P = 0.0061) and fetal membranes (r = 0.56, P = 0.0032) from hypertension-complicated pregnancies. Multiple regression analyses demonstrated that hypertensive disease is more closely associated with EGFR concentrations than gestational age and fetal weight in placental tissue and fetal membranes. Our findings suggest that hypertensive disorders in pregnancy are associated with elevated EGFR concentrations in both the placenta and fetal membranes.

Combined use of CA 125 and CA 15-3 in patients with endometrial carcinoma.

Serum levels of CA 125 and CA 15-3 were measured in 148 patients with primary endometrial carcinoma. CA 125-positive levels were found in 33 and 22% of the cases using a cutoff of 35 and 65 U/ml, respectively. Thirty-five (24%) and 12 (8%) patients had CA 15-3 levels higher than 30 and 50 U/ml, respectively. Among 144 patients with clinical stage I-II, 17 (12%) had extrauterine disease. CA 125 (> 65 U/ml) and CA 15-3 titers (> 30 U/ml) were found in 59 and 47% of occult stage III with respect to 16 and 18% in stage I-II of disease, respectively (P = 0.0001 and P = 0.01). The combined use of CA 125 and CA 15-3 resulted in a reduction of false-positive results of CA 125 with an acceptable sensitivity of 41%. Low-risk patients (G1 and M0-M1 tumors) showed a CA 125 positivity (> 35 U/ml) of 10% with respect to 37% of high-risk patients (G2-G3 and M2 tumors) (P = 0.0026). CA 125 positivity (> 65 U/ml) was 22% in patients without metastatic lymph node involvement, compared to 58% of cases with histologically positive lymph nodes (P = 0.022). A similar trend, although not statistically significant, was found for CA 15-3. A good correlation was found between CA 125 and CA 15-3 serum levels and clinical course of disease during chemotherapy. A statistically significant relationship was demonstrated between CA 125 (> 65 U/ml) (P = 0.0027) and CA 15-3 positivity (CA 15-3 > 30 and 50 U/ml) (P = 0.0004 and P = 0.00025) and a shorter survival. Our data show that CA 125 and CA 15-3 may be used as predictors of extrauterine spread and in monitoring of chemotherapy response in endometrial cancer. Moreover, the presence of elevated levels of these antigens may identify a subset of patients with a particularly poor prognosis.

Effect of recombinant human interferon-alpha/2b on epidermal-growth-factor-, estrogen- and progesterone-receptor expression in primary cervical cancer.

The effects of a short period of in vivo systemic rh-IFN-alpha/2b treatment on epidermal-growth-factor(EGFR)-, estrogen(ER)- and progesterone(PR)-receptor content in 11 primary human cervical tumors was investigated by the radioreceptorial technique. EGFR levels were found to be significantly higher in cervical tumors after rh-IFN-alpha/2b treatment with respect to basal levels. In 2 cases, immunohistochemical and cytofluorimetric analysis showed that rh-IFN-alpha/2b treatment induces an increase in EGFR immunoreactivity and in the fraction of EGFR-positive cells. No difference in ER and PR levels in cervical tumors before and after rh-IFN-alpha/2b treatment was observed. Our results suggest that rh-IFN-alpha/2b up-regulates EGFR in primary human cervical tumors in vivo.

Interleukin-6 serum levels in patients with gynecological tumors.

Serum levels of IL-6 were evaluated in a large group of patients with benign or malignant gynecological tumors. The results obtained were correlated with the patients' clinicopathological features and follow-up data. Using a highly sensitive immunoenzymatic method for the evaluation of serum IL-6 levels, we observed that > 95% of normal healthy women exhibited values within the range of 1.9-6 pg/ml. Using a cut-off of 6 pg/ml, elevated levels of serum IL-6 were found in 53% of 45 patients with primary epithelial ovarian cancer and less frequently in patients with endometrial and cervical cancer (37% and 10% respectively). Elevated levels of IL-6 were occasionally seen in patients with benign disease. IL-6 serum levels appeared to be less sensitive than CA 125 in ovarian cancer diagnosis. In cancer patients, increased IL-6 serum levels were related to the presence of the tumor since all post-operative patients exhibited a marked decrease. In patients with advanced ovarian cancer post-operative levels of IL-6 correlated with residual disease. Very high levels of IL-6 were observed in the ascitic fluid of 9 ovarian cancer patients, but IL-6 mRNA was not detected in tumor cells. This suggests that the increased production of IL-6 observed in ovarian cancer is reactive. Higher levels of IL-6 were found in patients unresponsive to chemotherapy, as compared with responsive ones. Univariate analysis of survival data suggests that increased IL-6 serum levels correlate with negative prognosis.

Immunosuppressive acidic protein (IAP) and squamous cell carcinoma antigen (SCC) in patients with cervical cancer.

Immunosuppressive acidic protein (IAP) and squamous cell carcinoma (SCC) serum levels were assayed in a group of 63 primary cervical cancer patients. IAP serum levels were significantly higher in cancer patients (median, 630 micrograms/ml; range, 290-1150) than in controls (median, 290 micrograms/ml; range, 135-775) (P < 0.01). The percentage of IAP-positive (> 613 micrograms/ml) cases was 50.7%. SCC serum levels were found to be above 2.5 ng/ml in 73% of cervical cancer patients, and in 6% of controls. A statistically significant correlation was observed between IAP and SCC levels in cancer patients (r = 0.35, P < 0.004). When IAP and SCC were considered together the overall sensitivity was 87.3% and an improvement of both predictive value of negative test and accuracy without any significant reduction of predictive value of positive test was found. IAP status correlated with metastatic lymph node involvement. A statistically significant association between a shorter survival and high serum LAP levels was observed. The 24-month overall survival (OS) was 92% for IAP- cases with respect to 65% for IAP+ cases (P = 0.036). In the univariate analysis, advanced stage of disease, clinical parametrial involvement, and lymph node involvement were also associated with poor survival. In the multivariate analysis IAP status showed a statistically significant association with poor survival (P = 0.049), together with lymph node involvement (P = 0.007) and advanced stage of disease (P = 0.008).