Spontaneous regression of low-grade cervical intraepithelial lesions is positively improved by topical bovine colostrum preparations (GINEDIE®). A multicentre, observational, italian pilot study.

OBJECTIVES: Human papillomavirus (HPV) is the causal agent of cervical cancer. The great majority of abnormal Pap test results - almost 90% - is referrable to either atypical squamous intraepithelial lesion or CIN1. For these lesions, worldwide agreement exists concerning the high rate - ranging from 40% to 70% - of spontaneous regression over a period of 1-5 years. Host's immune response is a key point influencing the natural history of these conditions. Bovine colostrum is a natural agent positively promoting several immune activities against bacterial and viral agents. The aim of this report was to evaluate the potential positive effect of bovine colostrum-containing vaginal tablets administered to CIN1 diagnosed patients in a prospective trial in regards to spontaneous regression rate. PATIENTS AND METHODS: A series of 256 consecutive patients with histologically proven CIN1 recruited in a multicentre, observational, Italian study. Patients have been enrolled in a 24-weeks protocol of treatment and re-tested at the end of the study. Rates of regression have been recorded. RESULTS: Overall regression rate to a negative histology at the end of the 6 month follow up was 75.5%. CONCLUSIONS: Regression to normal histology was observed in a very high rate of cases in a very short period compared to the natural history of these lesions. CIN1 patients could benefit from bovine colostrum topical administration in terms of significantly shortening the regression time.

Screening of foetal distress by assessment of umbilical cord lactate.

PURPOSE OF INVESTIGATION: Studies on umbilical cord blood for determination of lactate indicate that high levels seem to be correlated to foetal metabolism for anaerobic glycolysis taking place in oxygen-deprived tissues of the foetus. These findings may be of particular-deprived clinical importance when foetal distress or foetal hypoxemia is caused by perinatal events. METHODS: The maternal and foetal heart rates, acid-base values measured and the outcome of 94 pregnancies complicated by intrapartum foetal asphyxia have been reviewed, and the maternal and foetal acid-base and lactate levels during the course of labour and at delivery were studied in patients with evidence of metabolic acidosis. Lactate concentrations were measured during labour and at delivery in blood samples obtained from the foetal presenting part and from the umbilical cord with the use of a rapid electrochemical technique. The foetuses were evaluated by means of the Apgar score, intrapartum cardiotocography, observation of the presence of meconium stained amniotic fluid, and clinical features of distress at birth. RESULTS: Evidence of clinical foetal distress was not related to the severity of the asphyxia. An increased lactate level was found in asphyctic infants and a clear correlation between lactic acidosis and foetal distress was documented. Low Apgar scores were observed in infants with moderate or severe asphyxia at delivery. Scalp lactate correlated significantly with umbilical artery lactate, but not with 1-min or 5-min Apgar scores. The lactate concentration was higher in cases of instrumental delivery compared to spontaneous delivery. No perfect correlation was found between lactate level and neonatal outcome but there were not a significant number of neonates with immediate complications. The rate of forceps delivery in the distress group was significantly higher than that of the healthy foetuses, so spontaneous labour was less frequently associated with foetal distress than instrumental delivery. In the distress group, severe variable decelerations were generally recorded in the second stage of labour. The incidence of neonatal Apgar score < or = 7 in neonates with abnormal baseline foetal heart rate (FHR) was higher than in those with severe variable decelerations, mild variable decelerations, and transient tachycardia. Duration of the active second stage of labour was significantly with the presence of foetal lactate at the time of crowning of the foetal head and the presence of lactate in umbilical arterial and vein blood at delivery. Expulsion time > or = 45 minutes, compared with shorter active second stage, and acidaemia at birth implied larger arterial-venous lactate differences. The presence of foetal lactate at crowning was also significantly associated with the level of umbilical arterial-venous lactate difference. CONCLUSION: Lactate and pH values provide the best parameters to distinguish between asphyctic and normal newborns, with lactate having the most discriminating power. The prospective value of the discrimination functions derived from lactate and pH data is good when the foetuses are allocated into normal parameters but poor when an attempt is made to allocate the foetuses into pathologic ones, with a high false-negative rate. However, the discriminating ability is improved when pathologic foetuses are included into one single abnormal group. These results confirm the potential use of rapid foetal blood lactate measurements for the early diagnosis of intrapartum foetal distress.

Clinical, ethical, and medical legal considerations on emergency contraception.

PURPOSE OF INVESTIGATION: To evaluate how many women required the so-called "emergency contraception" at our outpatient service and what the actual role is of this kind of pharmacological administration in interfering with ovulation and pregnancy, paying particular attention to the ethical and medico-legal aspects of this subject. METHODS: During the period from 1 December 1998 to 30 November 2003, emergency contraception was prescribed to a total of 1,160 women. With regard to the contraceptives used, in most cases (1,132, 97.6%) a combined oral estrogen-progestogen pill (ethinyloestradiol 0.05 mg plus levonorgestrel 0.25 mg) was prescribed; in some cases (20 patients, 1.8%) danazol (400 mg), in four women (0.3%) a progestin-only pill (levonorgestrel 0.75 mg), and in four other women (0.3%) an intrauterine device. RESULTS: It does not come out that there were any pregnancies in our study patients since none of them, who were told to come back for follow-up, were seen at our termination of pregnancy service or delivery room. CONCLUSION: The "Yuzpe regimen" of a combined oral estrogen-progestogen pill has been the most commonly used method for emergency contraception. A new method recently proposed, a progestin-only pill with levonorgestrel 0.75 mg, is having better results than the previous one, with a lower incidence of side-effects and higher efficacy. Moreover, the treatment with this method does not interfere in case of a pregnancy already being carried and cannot interrupt it.

Fetal and neonatal ovarian cysts: what's their real meaning?

PURPOSE OF INVESTIGATION: The management of fetal ovarian cysts is still controversial despite the improvement in prenatal diagnosis with ultrasonography. Some studies suggest an aggressive management, while others opt for a conservative one. The prognosis of the majority of congenital ovarian cysts is good since they have a benign origin. Sometimes, however, complications such as torsion or rupture can occur which often require surgical intervention after delivery. In this paper we report our experience and a brief review of the literature. METHODS: The authors report on 32 pregnant women in whom ultrasonography revealed the presence of an echo-rare or echo-free area in the fetal abdomen suggestive of an ovarian cyst. All women were followed-up during pregnancy with serial ultrasound examinations. Postnatal ultrasound controls confirmed the prenatal diagnosis in all cases. The diameters of the cysts ranged from 2.7 to 7.5 cm. RESULTS: In the 16 cases (50%) in which the cyst diameter was below 4 cm, periodic ultrasound examinations revealed a tendency towards spontaneous regression of the cysts. In the other 16 cases (50%) in which the cyst diameter exceeded 4 cm, cystectomy was necessary due to subsequent complications (torsion in 6 cases, 37.5%, and intracystic hemorrhage in the other 10, 62.5%). CONCLUSION: The most appropriate clinical approach in the management of benign feto-neonatal ovarian cysts is to adopt a wait-and-see policy, assessing the course of the condition by means of periodic ultrasound monitoring. Only when tumefactions measure more than 4 cm in diameter with attendant complications is surgical therapy indicated. Without complications, however, aspiration of the cystic contents is possible even in ovarian cysts exceeding 4 cm in diameter.

The use of intravenous methotrexate in the treatment of ectopic pregnancy.

Between January 1996 and December 2001, at the Department of Gynecology, Perinatology and Human Reproduction of the University of Florence, 49 ectopic pregnancies were submitted to medical treatment. The treatment schedule consisted of the administration of 100 mg of intravenous methotrexate (MTX). The patients included in this study fulfilled the following requisites: gestational period <8 weeks; diameter of the ectopic gestational sac <4 cm; serum level of human chorionic beta-gonadotropin (beta-hCG) <5000 IU/ml; absence of clinical and ultrasound signs of tube rupture with initial hemoperitoneum; hematochemical tests compatible with chemotherapic treatment. All patients were followed with a dosage of serum beta-hCG repeated every 2-3 days after chemotherapy and with an ultrasound every 3-4 days. In case of documented success of treatment the patient was hospitalized for no more than 3 days after administration of the drug. In 1 case therapy took place in a day-hospital regimen. Medical treatment was effective in 35 patients out of 49 (71.4%) and led to negative beta-hCG in a median time of 11 days, with a range between 2 and 48 days. In the 14 non-responsive cases (28.6%), after a mean time of 6 days we proceeded to a traditional surgical approach or laparoscopy. In none of the cases did we find significant pharmacological toxicity, while in 9 patients (18.3%), severe painful symptoms appeared immediately after treatment, but resolved within 24 hours. Our results are interesting and in agreement with other experiences found in the literature. In our opinion, the advisability of a second administration in case of slow response, the comparison with an analogous intramuscular treatment, a more precise definition of the eligibility criteria, long-term follow-up of the patients, especially in case of subsequent pregnancies should all be further considered.

Role of ultrasound evaluation of nuchal translucency in prenatal diagnosis.

BACKGROUND: Nuchal translucency (NT) is the ultrasonographic pattern of the accumulation of subcutaneous fluid (> or = 3 mm) behind the fetal neck. The measurement of NT thickness by ultrasound examination at 11-14 weeks of gestation has been associated with maternal age and to be an effective screening tool for trisomy 21; with an invasive method rate of 5%, about 75% of trisomical pregnancies can be identified. With the association of some biochemical markers like maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) to ultrasonography at 11-14 weeks, it is possible to identify about 90% of chromosomal abnormalities. An increase of NT also allows us to identify most other chromosomal abnormalities, a large number of major cardiac defects, skeletal dysplasias, and genetic syndromes. In monochorial twins the discordance in the measurement of NT represents an early sign of twin-to-twin transfusion syndrome (TTTS). METHODS: The objective of our study was to assess the detection of fetal structural defects with an ultrasound scan at 11-14 weeks of gestation. We submitted 3,157 pregnant women to a routine ultrasound examination at 11-14 weeks. The patients were then submitted to ultrasound scan in the second or third trimester of pregnancy. An isolated increased NT thickness was not considered an abnormality, but these patients, nonetheless, were submitted to an early echocardiographic evaluation. Fetal structural abnormalities were classified as major or minor and of early or late onset. RESULTS: A detection rate of 4.3% (135 cases) of abnormalities was found and 22.6% of these (30 cases) were diagnosed by ultrasound scan at 11-14 weeks, including seven cardiac defects associated with increased NT. The antenatal ultrasound detection rate was 73.5%, and 33.2% were diagnosed in the first trimester assessment. A rate of 76.8% of the major defects were diagnosed by the prenatal scan and 35.8% by the scan at 11-14 weeks. Fetal structural defects with the ultrasonography at 11-14 weeks were diagnosed in about 24.3% of the cases, therefore, a second trimester abnormality is important in routine antenatal care to increase the prenatal assessment of fetal anomalies. CONCLUSIONS: As for the introduction of every new technique in routine clinical practice, the operators who perform the ultrasound scan at 11-14 weeks should be submitted to adequate training and to strict quality control.

Radical vaginal hysterectomy with extraperitoneal pelvic lymphadenectomy in cervical cancer.

OBJECTIVE: The aim of this work was to examine three types of radical vaginal hysterectomy with different degrees of radicality, performed in order to reduce surgical complications and sequelae in different indications, and to test the feasibility of a new simple and quick technique for extraperitoneal pelvic lymphadenectomy to be used in combination with radical vaginal hysterectomy for treatment of cervical cancer. In this way the advantages of vaginal surgery (e.g.: unnecessary general anaesthesia, reduced surgical trauma, applicability to obese and poor surgical risk patients, fast time-saving procedure) can be preserved. METHODS: We compared retrospectively the long-term results of radical vaginal and radical abdominal operations in a large series of stage IB-IIA cervical cancer patients treated at our institution in Florence from 1968 to 1983. Furthermore, we analysed the results of our experience from 1995 to 1998, when we performed extraperitoneal pelvic lymphadenectomy, followed by radical vaginal hysterectomy, on 48 patients affected by cervical cancer. Extraperitoneal pelvic lymphadenectomy was performed through two small abdominal incisions (6-7 cm). Twenty-two patients (45%) were obese (BMI>30 kg/m2) and 20 were poor surgical risks. FIGO stage was: IB1 in 18 cases, IB2 in eight, IIA in six, IIB in 12, IIIB in four. Neoadjuvant chemotherapy was given in 12 cases and preoperative irradiation was given in ten. General and regional anaesthesia were used in 30 (62.5%) and in 18 (37.5%) cases, respectively. RESULTS: As for past experience, in stage IB the five-year survival of 356 patients who underwent radical vaginal hysterectomy and that of 288 who had radical abdominal hysterectomy with pelvic lymphadenectomy were 81% and 75%, respectively (p<0.05). Surgical complications were fewer with no mortality in the first group. In stage IIA, survival rates were 68% for radical vaginal hysterectomy and 64% for radical abdominal hysterectomy, in 76 and 64 cases, respectively (p=n.s.). As for the more recent experience, median operative time for extraperitoneal pelvic lymphadenectomy was 20 minutes for each side (range 15-36). In each patient a median of 26 lymph nodes were removed (range 16-48). Positive nodes were found in 12 cases (25%). Median operative time for radical vaginal hysterectomy was 40 minutes (range 30-65). Extraperitoneal pelvic lymphadenectomy complications included: lymphocyst, five cases (10%) and retroperitoneal hematoma, one (2%); all occurred at the beginning of the experience. Radical vaginal hysterectomy complications included: ureteral stenosis, one (2%) and uretero-vaginal fistula, one (2%). All complications occurred in patients who received radiotherapy or chemotherapy preoperatively. Median hospital stay was ten days (range 6-20). CONCLUSIONS: The results of our work demonstrate that our technique for extraperitoneal pelvic lymphadenectomy shows a good applicability to cervical cancer patients submitted to radical vaginal hysterectomy, which has a high rate of cure for stage IB and IIA as shown by our past experience. The procedure of extraperitoneal pelvic lymphadenectomy was quick, easy, and safe, and its realization was not detrimental to the advantages of radical vaginal hysterectomy. Our experience supports the continued use of this combined extraperitoneal and vaginal approach in the treatment of cervical cancer. Moreover, the three classes of radical vaginal hysterectomy allow tailoring the type of the operation to the clinical and physical characteristics of the patients.