[Role of Doppler velocimetry of uterine arteries and ambulatory blood pressure monitoring in detecting pregnancies at risk for preeclampsia]. / Ruolo della Doppler flussimetria delle arterie uterine e del monitoraggio in continuo della pressione arteriosa nell'individuazione di soggetti a rischio per lo sviluppo di preeclampsia.

AIM: The aim of this study is to evaluate the performance of ambulatory blood pressure monitoring (ABPM) in association with Doppler velocimetry of uterine arteries in the detection of preeclampsia (PE). METHODS: In a prospective study, 22 patients at risk for the development of PE have been en-rolled: 17 were nulliparous women with increased resistances in uterine arteries at 24 weeks and 5 had an obstetric history of PE. All patients were tested with ABPM and uterine arteries Doppler velocimetry. A resistance index (RI) higher than 0.62 for the Doppler velocimetry and a diastolic midline estimating statistic of rhythm (MESOR) higher than 68 for the ABPM were considered abnormal. Patients were followed longitudinally until delivery. The occurrence of PE and low birth weight were considered as gestational outcomes endpoints. RESULTS: Overall, the mean gestational age at delivery was 36.3+/-3.4 weeks (range 29.4-41). Six out of 22 (27.2%) patients developed PE; 4 out of 22 (18%) newborns were small for gestational age (SGA) <5 degrees percentile. In the prediction of PE, ABPM in association with Doppler velocimetry showed a positive predictive value (PPV) of 42% and a negative predictive value (NPV) of 90%, for the development of low birth weight the PPV was 33% and the NPV 100%. CONCLUSION: This study shows that ABPM in association with Doppler velocimetry evaluation is a useful test to detect patients at high risk for the development of PE.

Width of the fetal lateral ventricular atrium between 10 and 12 mm: a simple variation of the norm?

OBJECTIVES: The prognosis of borderline forms of anomalies that can be detected by ultrasound is one of the most challenging issues in prenatal diagnosis. The aim of this study was to determine the prognosis for fetuses presenting with isolated mild ventriculomegaly (MVM). METHODS: Fetuses in which the width of the lateral ventricular atria was 10-12 mm and which had no other detectable chromosomal or morphological anomalies were followed by monthly ultrasound examinations until delivery. For the cases identified up to December 1997, postnatal information was gathered retrospectively through interviews. Children born from January 1998 onwards were included in a protocol involving planned neuropsychiatric visits at 12 and 18 months of age in which the Griffith scale was used to assess neurodevelopment. RESULTS: Between September 1992 and January 2001, 60 fetuses with isolated MVM were identified. Ventricular dilatation diminished in 18 cases (and became normal in nine of these) and stabilized in 42 cases. Information was obtained on 38 children born up to December 1997 and their neurodevelopment was found to be completely normal. The 22 children born from January 1998 onwards showed normal development at 12 and 18 months of age. CONCLUSIONS: When MVM is observed on prenatal ultrasound examination it can be very difficult to offer parents appropriate counseling. It is important to exclude aneuploidy or morphological abnormalities but even then there will be anxieties about long-term neurological outcome. Our data, which show normal neurodevelopment between 18 months and 10 years after birth in cases of MVM (10-12 mm), should provide a basis for reassuring counseling.

[Monitoring of pregnancy complicated by maternal-fetal isoimmunization. A comparison between two clinical protocols]. / Monitoraggio della gravidanza complicata da isoimmunizzazione materno-fetale. Due protocolli clinici a confronto.

AIM: Invasive techniques such as amniocentesis and cordocentesis are used for the diagnosis and treatment of fetus at risk for anemia due to maternal red-cell alloimmunization. The purpose of this study was to determine the value of non invasive measurements of the peak velocity middle cerebral artery in the fetus (PVMCA) for the diagnosis of fetal anemia. METHODS: From 1996 to September 2002, we studied 23 pregnancies with anti D title >1:32. In the 1(st) group of 11 women (from 1996 to 1999) fetal anemia was detected by invasive techniques (amniocentesis and cordocentesis). In the 2(nd) group of 12 women (from 1999 to 2002) fetal anemia was suspected on the basis of PVMCA. When PVMCA was significantly increased, cordocentesis was performed in order to rule out fetal anemia and to provide in utero transfusions. RESULTS: In the 1(st) period we performed 23 invasive techniques (7 amniocentesis and 16 cordocentesis) in 11 women, but we identified fetal anemia only in 4 cases. In the 2(nd) period we performed only 2 cordocentesis in women in which PVMCA was increased; the blood sampling confirmed fetal anemia in both cases. CONCLUSION: PVMCA and fetal hematocrit are highly significantly correlated: high values of PVMCA are associated with fetal anemia. Doppler velocity of PVMCA is related to fetal anemia with positive predictive value 100% and negative predictive value 100%. The middle cerebral artery blood velocity is a non invasive technique for detecting anemia in pregnancies complicated by alloimmunization.

Successful application of indirect in-situ polymerase chain reaction to tissues fixed in Bouin's solution.

AIMS: To evaluate the value of polymerase chain reaction-in situ hybridization (PCR-ISH) for the detection of human papillomaviruses (HPV) in paraffin sections of cervical biopsies fixed either in 10% formalin or in Bouin's solution. METHODS AND RESULTS: We analysed 40 biopsies from Italian women infected with the human immunodeficiency virus type 1 (HIV 1). In-situ hybridization techniques were performed with commercial biotinylated probes. The PCR-ISH was carried out by the 'hot start modification'. Cervical intraepithelial neoplasia (CIN) was found in 23 of 40 patients (57. 5%); eight cases showed condylomatous features. Human papillomavirus was detected in 42.5% by ISH and in 65% by PCR-ISH. Sixty-nine per cent of positive biopsies contained HPV 16, 18, 31 and 33. HPV 6 and 11 were found only in condylomata acuminata samples. CONCLUSIONS: The results point to a high incidence of HPV infection as well as of CIN in HIV-positive patients. Human papillomavirus type 16 appears to be most frequently associated with CIN. Polymerase chain reaction-ISH is more sensitive than ISH in the detection and typing of HPV DNA both in clinical and in 'latent' infections. The two techniques yielded the same results with either formalin- or Bouin's-fixed material.

The use of carbon-dioxide laser surgery in the treatment of intraepithelial neoplasia of the uterine cervix.

From October 1989 to June 1997, 1841 patients (pts) suffering from different diseases of the lower genital tract have been treated with CO2 laser surgery in our Institution: among them, 782 were affected by cervical intraepithelial neoplasia (CIN). All pts underwent CO2 laser procedure for CIN after adequate colposcopic evaluation of the entire lower genital tract, colposcopic guided biopsy of the lesion, adequate pre-surgical work-up for possible infectious and coagulation associated disease. In 736 (94.1%) pts, the procedure was performed on an ambulatory basis while 46 pts (5.9%) were admitted for 1 or 2 days. A CO2 laser Sharplan 55 associated to a Zeiss operative colposcope was employed. The preoperative diagnosis of the 782 pts treated for CIN was 297 CIN1, 255 CIN2, 171 CIN3 and 59 CIS. Mean age was 33.6 years without statistical difference among the grade of disease: 605 pts underwent laser vaporization according to specific selection criteria. The depth of cervical destruction was less than 6 mm in 26 cases, between 6 and 10 mm in 549, between 11 and 15 mm in 157, more than 15 mm in 50 pts. 742 procedures were performed under local anesthesia and pain was absent in 667 pts. (89.9%), mild in 51 (6.8%), moderate in 19 (2.5%) and severe in 5 (0.7%). Intraoperative bleeding was severe in 30 pts. (3.8%), moderate in 77 (9.8%), mild in 204 (26.1%) and absent in 471 (60.2%). The conization procedure was shown to have a higher risk of bleeding but no direct relation was observed with the depth of cervical destruction. Late complications were scarce: 1.3% of late hemorrhages, 1.4% of stenosis of cervical external orifice and cervical endometriosis in 0.3%. In 76 pts (42%) of the 177 conizations the final pathology report was in accordance with the previous biopsy, in 56 (30.9%) a lower grade of CIN was observed, in 53 (29.3%) a worse grade of the lesion was retrieved. Among these latter pts. 10 showed a microinvasive and 2 an invasive cancer: both the invasive but only 3 of the 10 microinvasive cancer pts underwent a surgical procedure (2 radical and 3 extrafascial hysterectomies, respectively). After a mean follow up of 37 months our incidence of recurrence is 2.3% (18 pts): 5 CIN1, 7 CIN2, 3 CIN3, 2 CIS and 1 microinvasive disease. In 78% of the instances the recurrence has occurred within the first year of follow up. All 18 recurrences were successfully treated with further vaporization in 8 cases, conization in 9 and hysterectomy in 1. 93 term pregnancies occurred in 83 pts after CO2 laser treatment of CIN. No cervical incompetence occurred (no cervical cerclage employed) while the incidence of spontaneous abortion was not statistically significant. 82 pregnancies were delivered vaginally without significant variation of labor phase duration. The incidence of caesarian section (11.8%) was lower than the mean incidence in our Institution. These data confirm the successful complete restitutio ad integrum of the cervix after an adequate CO2 laser surgical procedure without any further risk of cervical incompetence, premature delivery or premature rupture of membranes. The use of CO2 laser surgery is recommended as modality treatment of choice in the management of cervical intraepithelial neoplasia.

[Ultrasonography of the uterine cervix in pregnancy. Curve of normality in a longitudinal and cross-sectional study]. / Studio ecografico del collo dell'utero in gravidanza. Curva di normalità in uno studio longitudinale e trasversale.

BACKGROUND: The aim of the study was to establish a normality curve of cervical length variations during pregnancy in our pregnant women population, to be compared with pathological cases (risk of preterm labor and cervical incompetence). DESIGN: A prospective longitudinal and cross-sectional study in women with single pregnancy and without risk factors for preterm labor was carried on. SETTING: Obstetric and Gynecology Department, University of Brescia, Italy. POPULATION OR SAMPLE: One hundred and thirty-four pregnant women with single pregnancy, 112 cross-sectionally and 22 longitudinally followed, with labor at term, were selected. Sixty-eight were nulliparous, 66 pluriparous. Multiple pregnancy, previous placental and vaginal bleeding were excluded. METHODS: A transvaginal probe was used to assess uterine cervix and the patients were studied from the 12th to 41st gestational week. Statistical analysis was carried out by Student's "t"-test and Z-test. MEASURES: Cervical longitudinal diameter, internal uterine os and funneling were assessed. RESULTS: No statistically significant differences emerged in the curves with regard to nulliparous and pluriparous patients. The cut-off between normality and pathology, from the 24th to the 32nd gestational week (2ndSD), seems to correspond to a cervical length lower than 25 mm; a significant progressive decrement of the cervical longitudinal diameter begins from the 28th gestational week. CONCLUSIONS: These results allows the gathering of reference data about normality to compare with pathology (cervical incompetence and preterm delivery), which could be useful both for prevention and follow-up of these cases.

'Dual positivity' for neural tube defects and down syndrome at maternal serum screening: gestational outcome.

OBJECTIVE: To evaluate the gestational outcome of pregnancies screen-positive for both neural tube defects (NTD) and Down syndrome (DS) ('dual positivity'). METHODS: Among 10,667 mid-trimester women screened for DS and NTD with alpha-fetoprotein (AFP), unconjugated estriol (uE3), and human chorionic gonadotropin (hCG), delivered up to July 1996, we have selected cases with both an unexplained AFP value > or = 2.5 multiples of median (MoM) and a DS risk > or = 1:250. All these pregnant women were managed with amniocentesis and/or CVS, ultrasound scans, and Doppler velocimetry. We have collected all data about the gestations with 'dual positivity' and no obvious explanation for these findings (cases with fetal malformations related to raised AFP). RESULTS: Twelve women (1.1:1,000) showed unexplained 'dual positivity'. Abnormal karyotypes were found in 3 fetuses, and pregnancies were terminated: there were 2 triploidies with partial hydatiform mola, and 1 DS. In 9 cases the fetal karyotype was normal, but a confined placental trisomy 16 was found in 4. Of the 9 continuing gestations, 8 displayed fetal growth retardation (FGR). One gestation ended with fetal death at 27 weeks. All 9 fetuses were morphologically normal, and 8 were small for gestational age. CONCLUSIONS: 'Dual positivity' at NTD/DS screening may anticipate pregnancy complications. The finding of trisomy 16 confined to the placenta and FGR in 4 cases suggests that at least some fetuses with growth restriction may suffer from a distinct placental disease. Maternal serum screening may have implications different from DS and NTD, as demonstrated by the 2 cases with triploidy and incomplete hydatiform mola, the 4 cases with placental trisomy 16, and the 4 cases of FGR of the 5 fetuses without chromosome abnormalities. As the pathologic outcome of these pregnancies is more important than the mere serum screening results, we feel that these cases need a strict work-up, including CVS, amniocentesis and ultrasound studies to better address the obstetrical management.

Extended radical hysterectomy in early-stage carcinoma of the uterine cervix: tailoring the radicality.

The question of whether surgical treatment in early-stage cervical cancer should be aggressive or restricted to less radical techniques is still controversial. To answer this question it was thought useful to investigate the correlation of parametrial lymph node metastases with extension and stage of disease. Two-hundred and sixty-three consecutive primary radical surgical procedures were performed in our institute in clinical stage IB or stage IIA cervical cancer. Positive parametrial nodes were found in 6.9% of cases: 5% in stage IB (3% in the proximal part of the parametrium and 2% in the distal part, near the pelvic wall) and 16.3% in stage IIA (7% proximal and 9.3% distal) (P = 0.0193). During a median follow-up period of 92 months, disease recurred in 17.1% and 17.6% of cases, in negative and positive parametria, respectively. The 5-year overall and disease-free survival rates were 80.4% and 81.6% for patients with negative and positive parametria, respectively. From this experience it is concluded that the extent of radical hysterectomy should be related to the extent of the disease on the basis of modern knowledge of the pattern of spread. The principal key to prognosis remains pelvic and paracavoaortic nodal status.

Immunocytochemical localization of plasminogen activators in carcinomas in the cervix and vulva.

The presence of plasminogen activators (PA) in a variety of solid tumours appears to correlate, in a number of instances, with enhanced invasive and/or metastatic ability. Urokinase and tissue-type plasminogen activators (u-PA and t-PA) in normal and neoplastic tissues of cervix and of vulva were immunohistochemically identified by means of polycyclonal antibodies. In addition, frozen sections were analysed for u-PA and t-PA activity by in-situ zymography technique. Data collected in our study showed that in invasive cancer u-PA increased more in malignant cells as compared to normal cells in both the inactive and active enzymatic forms. The t-PA distribution pattern was related to angiogenesis while it did not relate to the degree of tumor differentiation. A synergic interaction between proteolytic tumoral activity and proteolytic inflammatory action could be hypothesized.

Adjuvant therapy in stage-I epithelial ovarian cancer: an open question.

From January 1980 to December 1991, 137 patients suffering from Stage I EOC, were treated in our Institute. All patients underwent primary surgery with intensive staging procedures in 82% of cases; 12 patients underwent USO. Sixty-one out of 137 patients did not receive complementary treatment, 66 patients were treated with chemotherapy and 10 patients with i.p. P32. Three risk categories were identified, according to stage and grade: R1 = Stage IA-B G1 (45 cases); R2 = Stage IA-B G2-3 (31 stage); R3 = Stage IC all grades (53 cases). Forty out of 45 R1 cases did not receive adjuvant therapy; 12/31 R2 cases underwent surgical treatment only, 16/31 received adjuvant chemotherapy and 3/31 i.p. P32; 39/53 R3 patients were treated with chemotherapy and 6 with i.p. P32. Twenty-six patients (18.9%) suffered from a neoplastic relapse. Overall actuarial 5- and 10-year survival was: R1 = 96.3% and 89.9%; R2 = 79.6% and 79.6%; R3 = 79.2% and 62.3% respectively. There was no difference in survival between R2 treated and untreated patients, while difference emerged in R3 patients between chemotherapy and i.p. P32 groups. Five-year actuarial survival for the 26 patients suffering from recurrence was 40.5%.

Histological human papillomavirus induced lesions: typization by molecular hybridization techniques.

The viral typization in Human Papillomavirus (HPV) infections of the lower female genital tract is relevant both from the epidemiological and the clinical point of view. We have tested DNA from specimens obtained by guided biopsies on neoplastic and benign lesions, using single probes of the different virus types (6, 11, 16 and 18) by Dot-blot and Southern blot analysis. According to previous studies HPV 16 and 18 have been detected in neoplastic lesions, while 6 and 11 were more frequently found associated to condylomata. Negative specimens and intermediate were 36% of the total. In our experience both methods have shown same sensibility.

[Immunohistochemical localization of laminin, collagen IV and fibronectin in dysplasias and neoplasms of the cervix uteri]. / Localizzazione immunoistochimica di laminina, collagene IV e fibronectina nelle displasie e neoplasie della cervice uterina.

The distribution of intrinsic components (Laminin and Type IV Collagen) and extrinsic component (Fibronectin) of the Basement Membrane (BM) has been studied in normal uterine cervix (16 cases), in cervical dysplasia (14 cases) and in invasive carcinoma (45 cases). We found that BM staining for Laminin and Type IV collagen is linear and continuous underlying normal and dysplastic epithelium (CIN 1-CIN 2), it shows minor breaks in continuity and alterations of linearity in situ carcinomas (CIN 3), and it disappears in microinvasive areas. In well differentiated invasive carcinomas only focal disruptions of BM around neoplastic nests is noted; in contrast, in moderately and poorly differentiated neoplasias, is found a progressive reduction and loss of staining for Laminin and Type IV Collagen. The results of this study suggest that the distribution patterns of BM intrinsic components are in relation to the histological grade of cervical neoplasias and their invasion ability. On the contrary Fibronectin doesn't show any distribution pattern related to the grade of cervical neoplasias, its immunostaining increased with the rise of both connective tissue stroma production and of vascularity.

Extended operations for extracolic invasion by colon cancer.

Out of 618 cases of colon cancer treated between 1976 and 1986, 25 had an unusual local invasion. They underwent radical surgery with total resection of one or more adjacent organs. This group is made of 17 female and 8 male patients, with an average age of 58 years. All the patients underwent resection of the colon with radical excision of the locally invaded organs. Only one case of postoperative death is recorded. Postoperative surgical complications were rare. This experience confirms that colic resection extended to adjacent organs invaded by the tumor gives a low risk of relapse and satisfying long term results in relatively young patients with good general conditions and without remote metastases.

Treatment of primary invasive cervical cancer. Considerations on 997 consecutive cases.

From 1965 to 1979 997 consecutive cervical cancer patients were treated at the University of Brescia. Stage I B and II A low risk patients underwent radical surgery, followed by Co60 external pelvic radiation when positive nodes and/or adverse pathological factors on the specimens were encountered. In stage I B the 5-year survival was 95.9% and 82.7% in the two groups and in stage II A 93.3% and 76.5% respectively. Bulky and large tumors were treated by intracavitary radium followed by radical hysterectomy and, if indicated, by Co60 external beam pelvic radiation. All other patients and all stage II B were treated by radiotherapy. The results of primary radical surgery may reflect the favourable preselection of cases. Postoperative radiation teletherapy in case of adverse pathological factors is of benefit to the patients.