Flow cytometric analysis of DNA content in cervical lesions.

Flow cytometry is used to screen gynaecologic specimens for Cervical Intraepithelial Neoplasia (CIN) and its precancerous lesions, possibly associated with human papilloma virus (HPV), in order to investigate the role of aneuploidy as a biological marker in HPV and CIN lesions. A total of 299 cervical samples was collected by scraping and the cellular DNA content was measured using the propidium iodide staining procedure. Two groups of patients were studied; a group of 142 negative controls for cytology and groups of patients assigned to mild, moderate or severe dysplasia, carcinoma in situ diagnosed by histologic classification according to the Papanicolaou staining technique. Pathological samples showing an alteration of the DNA index or perturbation of the cellular phase S compartment ranged from 6.4% to 41.9%. Our results confirm those obtained by other authors and suggest the hypothesis that aneuploidy is present with permanence of viral DNA in early stages of carcinogenesis, which can be used as a marker in the transition from benign to malignant cells. This work is of potential interest for the possible follow-up of patients having condyloma and could aid the early diagnosis of cervical carcinoma.

Cervical dilatation by sulprostone prior to vacuum aspiration for termination of early pregnancy.

In the period May 1983-October 1986 we treated 335 primigravidae requesting an abortion in the first trimester. They were given 500 micrograms sulprostone (16-phenoxy-omega-tetranor-PGE2-methylsulfonylamide) i.m. 12 to 14 hours before suction termination in order to obtain adequate and atraumatic cervical dilatation and thus reduce the possible risk of cervical incompetence and its consequences. The effects of this technique on the uterine cervix were compared with those obtained in 100 primigravidae after the insertion of laminaria to induce atraumatic cervical dilatation. We also evaluated the normal degree of cervical dilatation before any intervention in a control group of 100 primigravidae. The results obtained with sulprostone encourage the use of this drug to minimize cervical injury. The incidence of side-effects was not particularly high.

Anatomic correlates of ultrasound prenatal diagnosis of urinary tract abnormalities.

In 52 fetuses, in utero sonographic diagnosis of urinary tract malformations was correlated with their autoptic or surgical findings. 39 malformations were correctly diagnosed prenatally, although 5 other extrarenal-associated anomalies were not detected; 10 diagnoses were incomplete; in 3 cases the characteristics of malformations found at sonography turned out to be different at the post-mortem examination. The following factors impaired sonographic diagnoses: limited number of examinations, gestational age at the time of examination, nature of malformation and, above all, oligohydramnios (which is common in most urinary tract malformations). The correlations between renal malformations and karyotype anomalies are also discussed in relation to the higher incidence present in polymalformative syndromes.

Feto-placental haemodynamics in growth retardation: a pulsed Doppler study.

69 singleton pregnancies, with a diagnosis of intra-uterine growth retardation (IUGR) at ultrasound, were followed until delivery by pulsed Doppler evaluations in fetal thoracic descending aorta (DA) and umbilical artery (UA). Three haemodynamic groups were described according to flow characteristics expressed as the pulsatility index (PI) of the vessel under study. In each group the relative incidence of fetal distress, diagnosed according to CTG monitoring, was evaluated. Fetal distress occurred in 75% of the cases with a raised PI both in DA and UA, in 40% of the cases with a raised PI only in DA and in 21% of the cases with 'normal' PI values in both vessels. It can be said that Doppler flow measurements can be useful in defining the actual haemodynamic situation of the fetus with possible clarifications concerning its 'stressed' or 'distressed' condition and residual capacities to substain hypoxia.

Fetal echocardiography: the role of the screening procedure.

1841 pregnant women without any risk factor for heart malformation of the fetus underwent an echocardiographic screening at an average gestational age of 23 weeks. Seven cases of heart diseases were diagnosed (0.38%), of which one died in utero at 28 weeks and another one was interrupted. In four cases the karyotype was carried out prenatally, while in the remaining three it was performed only after birth. There were 11 false-negative (0.59%), mainly concerning anomalies of minor clinical significance. Within this group, two newborns with interatrial defect of the ostium secundum type appeared to be affected by trisomy 21. Therefore, the rate of congenital heart diseases in live births not at risk (0.86%) was in line with the data reported in paediatric literature. On the other hand, the association with chromosomal anomalies was surprisingly frequent (4 out of the 9 karyotypes performed were anomalous). Such finding should be verified by studying a larger non-selected population. However, a fetal karyotype should be offered, for its practical consequences, also in those cases of cardiac anomalies of lesser clinical significance.

Tumoral markers (CA 125--CEA) in the screening of ovarian cancer.

Ovarian cancer has high rate of mortality among malignant gynecologic tumors. Because of its aggressiveness and low rate of 5 year survival of patients treated, it is important to realise a screening program for its early diagnosis. Today, immunologic research is directed to the study of tumoral markers that allow us to detect the presence of still clinically silent ovarian neoplasms. Some tumoral markers such as CEA and CA 125 are available for post-surgical monitoring of patients treated for ovarian cancer. The Authors have carried out a study to evaluate the possibility of their use in the depistage of ovarian neoplastic pathology. A blood sample was taken for the evaluation of serum CEA and CA 125 in a series of 520 patients older than 45 years, who did not complain signs or symptoms of pelvic pathology. A pathologic value for CEA was considered higher than 7.3 ng/ml and for CA 125 greater than 37 U/ml. For CEA 2.5% (13 cases) presented pathologic values compared to 2.88% (15 cases) for CA 125. One third of cases (0.5%) with high levels of CEA had repeated blood samples. 3 of them had confirmed high levels of CEA but echotomography performed in these patients was negative for pathologic ovarian masses. 15 patients had CA 125 high levels. 3 out of 15 cases repeated the blood sample that resulted normal. On 11 of these cases an echotomography was also performed that diagnosed a uterine myomatosis in 4 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Frequency of cervico-vaginal infections (Trichomonas vaginalis; Chlamydia trachomatis -CHL-; herpes simplex virus -HSV-; human papilloma virus -HPV-) in cervical intraepithelial neoplasia.

The Authors have carried out a cyto-hystologic study on 533 cervical intraepithelial neoplasias (CIN) devoted to identifying the association frequency between cervical dysplastic lesions and cervico-vaginal infections caused by Trichomonas vaginalis, Chlamydia Trachomatis, Herpes Simplex virus and Human Papilloma virus. HPV lesions have revealed the pathology found more frequently in CIN lesions (33.2%) compared to 0.19% in the normal population, while the other infections have not shown significant differences between dysplastic lesions and normal control. In patients with CIN, the assumption of the estro-progestinic pill does not seem to contribute to the increase of frequency of cervico-vaginal infections.

Diagnostic validity of the Vabra Curettage. Compared study on 172 patients who underwent Vabra Curettage and the fractional curettage of the uterine cavity.

The authors report 172 cases of patients who had to undergo a curettage of the uterine cavity and an endometrial sampling with Vabra Curettage. In 80.8% of the cases, the histologic diagnosis of the material removed with Vabra Curettage was comparable with that of the uterine curettage. In 8.7% of the sampling, the histologic diagnosis of the tissue removed with the "suction technique" was easier. In 10.5% of the cases, the diagnosis was more reliable in the samplings taken away with uterine curettage. In this last group, nevertheless, the endometrial tissue removed with Vabra curettage allowed us to exclude the presence of an adenocarcinoma or of an atypical hyperplasia. Only in 1.2% of the specimens, the Vabra Curettage did not allow us to exclude an endometrial pathology (for lack of material). On account of the increased incidence of endometrial carcinoma, the tolerability of the method proposed, its low cost, the Authors advocate a large-scale use of this method for a prevention program directed at the high-risk population for this carcinoma.

Recurrence incidence in follow-up of patients affected by condylomatosis of the uterine cervix with VCE (viral cytopathic effect).

The frequent association of HPV lesions with cytological and/or hystological alterations of CIN in the uterine portio and in the lower genital tract suggests their possible role in the genesis of precancerous lesions of the cervix. In the systematic cytological screening, condylomatous lesions present an incidence varying from 0.52% to 1.5%. With the aim of verifying the incidence rate of condylomatosis of the portio, in the population of the women followed in the Colpocytological Service of obstetrics and gynaecology (Institute for Childhood of Trieste), the authors have performed a retrospective analysis on 17273 colpocytological examinations and have found 72 cases (0.41%) with cytological and/or histological evidence of viral-cytopathic effect produced by HPV. These patients have undergone various treatments of this pathology and have performed a follow-up. In some patients 12 cases, treated only with antiflogistic therapy or no therapy, 50% of these has shown a complete regression of viral infection in the first control after 4 months. In these patients, it is suggestive to suppose that a good immunological reactivity has brought the patient to recovery. For that, in their next work, the Authors will investigate the immunological responsiveness of patients affected by HPV lesions of the cervix.

Cervical intraepithelial neoplasia with conization: early complications and follow-up.

The authors made a review of the last 100 cases who underwent a conization of the cervix during the period 1980-1986. Cyto-histological evaluation was compatible in 78% of the cases with a cervical intraepithelial neoplasia of third degree and in 22% with a CIN of first and second degree. Early post-operative complications consisted of a hemorrhage in 3% of the cases, easily stopped with a vaginal packing. In 2% of the cases a risuture under general anaesthesia was required. In 1 case the stitches loosened and in another a urinary infection was present. Twenty-six patients underwent total hysterectomy after conization for different indications; only one patient had a relapse after six months as there was a moderate dysplasia localized in the vaginal vault. During the follow-up, 14 patient became pregnant. Among these, 5 underwent legal termination during the first trimester and 9 delivered at term without any complication. During these follow-up of 7 years in the older cases and 6 months in the more recent ones, 6 cases displayed a persistence of the disease after 3 months, (CIN of variable degree) and 2 cases relapsed at the second colpocytological control. These patients, according to the age and the presence of clinical indications, underwent total hysterectomy or diathermic coagulation with resolution of the disease. A relapsing invasive tumor was never observed.)

[Infection of Chlamydia trachomatis and dysplasia lesions of the cervix uteri (CIN)]. / Infezione da Chlamydia Trachomatis e lesioni displastiche della cervice uterina (CIN).

With the aim of evaluating the correlation between dysplastic lesions of the uterine cervix associated or not with condylomatosis and Chlamydia T. infection, we carried out a serological study of anti-Chlamydia species-specific antibodies and a direct and/or a cultural investigation on a sample of 320 women who performed a Pap-test. The serological examination showed positivity (titer greater than or equal to 1:32) in 49 control subjects (with negative cytology) (23.7%); in 27 cases (43.5%) with actual diagnosis of condylomatosis/CIN associated or not with condylomatosis and in 28 cases (54.9%) with previous diagnosis of condylomatosis/CIN associated or not with condylomatosis. The cultural investigation did not show any significant difference among the groups above mentioned. Finally, the frequency of positive cases for anti-Chlamydia antibodies was estimated for each grade of actual or previous CIN: a greater frequency of positivity was noted in cases with CIN 3 (75%).

[Conservative management of ectopic pregnancy]. / Il management conservativo della gravidanza ectopica.

BACKGROUND: The aim of this retrospective study was to analyze the safety and efficacy of the conservative approach in the management of ectopic pregnancy. METHODS: Thirty-five women with a tubal ectopic pregnancy, from 1990 to 1995, were subdivided into 2 treatment groups. Inclusion criteria were the following: tubal diameter < 3 cm, free fluid < 100 ml, no embryo heart activity, haemodynamic stability. Desire of future fertility and informed consent were requested. Eighteen women were treated with a single intramuscular injection of methotrexate, whereas in 17 cases expectant management was adopted. RESULTS: In the first group 2 cases required surgical treatment (resolution rate = 89%). In the second group no surgery was needed and spontaneous resolution was achieved in all cases (100%). In both groups the average resolution time was about 17 days. Serum hCG-beta levels were monitored daily until resolution. The initial hCG-beta value and its following trend seem to be the most important prognostic factors. CONCLUSIONS: More studies are indeed needed to establish the effect of conservative management on fertility after ectopic pregnancy.

[The indications for the management of fetuses with choroid plexus cysts]. / Indicazioni per il management dei feti portatori di cisti dei plessi corioidei.

Choroid plexus cysts (CPC) in the fetus are still the subject of considerable debate in the literature. Because of their association with aneuploidy, and especially with trisomy 18, of which they are an ultrasonographic marker, the detection of fetal CPC now poses the problem of how these cases should be managed, since most occur in young women (there being no correlation between CPC and age), and since the incidence among the general population is fairly high (around 1%). With the aim of contributing further to the debate, a retrospective study was performed of all cases of fetal CPC diagnosed in our Centre between January 1984 and August 1994, together with a review of the relevant literature. There were 95 cases of fetal CPC with complete neonatal and necroptic data available. These cases included women recruited in the course of routine screening for congenital malformations carried out in our Centre at 14 and 21 weeks gestation, women referred to us from other Centres, and women recruited in the course of amniocentesis indicated for those aged over 35. In all cases in which fetal CPC was detected, a careful ultrasonographic examination was performed to exclude the presence of even the smallest morphologic anomaly. Whenever the fetus was found to have an anomaly karyotyping was done. If the CPC was not associated with any morphologic anomaly, karyotyping was proposed only to those women at risk of aneuploidy because of their age. There were 11 cases of trisomy 18, all of which presented morphologic anomalies associated with CPC. Some of these anomalies where "minor", however, and therefore difficult to assess even when a careful ultrasonographic examination was performed by an experienced operator (Intra ventricular septal defect, single umbilical artery). In 2 cases, CPC was associated with trisomy 21. Both women were aged over 35. All the other cases of CPC not associated with morphologic anomaly were normal on postnatal examination. From a meta-analysis of the literature, two distinct management protocols emerge for the problem of "isolated CPC detected at ultrasonographic examination". One group of authors recommends karyotyping for all women with fetal CPC, considering the presence of CPC in itself a risk factor for aneuploidy. The second group, to which we ourselves belong, believes it is sufficient to perform a careful ultrasonographic examination so as to exclude the presence of other morphologic anomalies associated with the CPC. Karyotyping should be proposed only to women at risk of aneuploidy because of their age (> 35). A review of the biggest series reported in the literature shows that, of a total of 1670 fetuses with CPC, 94 were trisomy 18. None of the cases of CPC "in isolation" emerged as being associated with this aneuploidy. However, numerous cases of trisomy 18 have been described in which CPC is associated with "minor" morphologic anomalies in the fetus which may be difficult to detect. It is therefore essential to perform a careful ultrasonographic examination in all cases of CPC, preferably in a Centre with specialist knowledge of ultrasonography. If this option is not available, then karyotyping of all women with fetal CPC is clearly advisable.

A case of prune-belly syndrome: prenatal diagnostic problems.

The authors discuss a case of "Prune-belly syndrome" which could be diagnosed prenatally thanks to echography; they stress the importance of echographic controls since the first gestational weeks to better recognize pathological findings, and describe their attempts to drain the megavesica. However these attempts could not reverse the ominous prognosis.

The clinical significance of absent or reverse end-diastolic flow in the fetal aorta and umbilical artery.

The clinical utility of Doppler blood flow investigations of the fetal and fetoplacental vessels is still under debate as far as timing of the delivery is concerned. However, in cases of absent or reverse end-diastolic flow, fetal compromise is usually very severe. As a consequence, we have investigated the possibility of using this information as a guide to obstetrical management. Altogether, 32 fetuses with absent or reverse end-diastolic flow in the fetal descending aorta and/or umbilical artery were studied. Reverse flow was observed in 11 cases and absence of end-diastolic flow in 21 cases. The two groups are considered separately. No significant difference was found in the mean gestational age at delivery. However, a highly significant difference was found in the mean birth weight and perinatal mortality rate. All the cases of perinatal mortality were encountered in the group presenting with reverse flow (mortality rate, 63.6%). All the live fetuses were delivered by Cesarean section and no neonatal mortality was observed in this group. Two cases of handicap were observed, one in each group. In our experience, reverse flow indicates the necessity for immediate delivery if no other clinical contraindications are present. Absence of end-diastolic flow can be observed for longer periods without adverse outcome. Absence of end-diastolic flow always precedes the appearance of fetal distress. Therefore, we believe that, after exclusion of conditions such as fetal abnormalities or extreme prematurity, a planned delivery should be considered.