Epidoxorubicin and paclitaxel as primary chemotherapy for T > 3 cm and T4 breast cancer patients.

UNLABELLED: The Anthracyclines/Taxanes combination is often used in adjuvant and advanced breast cancer. PURPOSE: To evaluate the toxicity and pathological response of sequential epidoxorubicin/paclitaxel combination as primary chemotherapy for T > 3 cm and T4 breast cancer patients. PATIENTS AND METHODS: Forty-eight patients with T2 > 3 cm, T3 and T4 breast tumours were treated with Epidoxorubicin (90 mg/m2, i.v.) on day one and paclitaxel (200 mg/m2 over 3 hours) on day 2 every 21 days for four courses. After the fourth cycle the patients underwent modified radical mastectomy or quadrantectomy plus axillary lymph node dissection followed by six courses of intravenous CMF regimen (days 1 and 8, every 4 weeks). Radiotherapy was given to patients undergoing conservative surgery or with T4 cancers. Tamoxifen was administered in ER or PgR positive patients. RESULTS: Out of the 48 patients enrolled into this trial, 43 were evaluable for toxicity and pathological response. Primary chemotherapy with epidoxorubicin and paclitaxel was well tolerated: no heart toxicity was observed during primary chemotherapy and follow-up. Primary toxicity consisted of myalgia, grade 1 neuropathy and grade 3 alopecia. Disappearance of invasive tumours in the breast with node negative was observed in 11.6% of patients: pathological partial response was shown in 56% of patients. On the whole major pathological response was achieved in 67% of our series: in the remaining 33% we found a stable disease or a size reduction less than 50%. No progressive disease was observed. Conservative surgery was performed in 64.5% of T2 and T3 tumours. CONCLUSION: These preliminary data showed that the epidoxorubicin/paclitaxel combination was safe and effective as primary chemotherapy for patients with T > 3 cm and T4 breast cancer patients.

Pathologic features of endometrial carcinoma in elderly women.

It has been estimated that more than two-thirds of cancers occur in people over 65 years of age: endometrial cancer (EC) is the most common gynaecologic cancer in the U.S. and represents the fourth most common malignancy in women. Some authors have reported that EC in elderly women was more aggressive, histologically less-differentiated and often non-endometrioid when compared with EC in the younger population. The purpose of this retrospective study is to evaluate the pathologic features of EC in women 70 years old or over compared with those of younger patients. Between 1987 and 1997, 174 patients with EC were surgically treated: 52 women were 70 years old or over. Two-thirds of both groups had surgical Stage I tumors: 54% of surgical Stage I tumors in the elderly had myometrial invasion more than 50% compared with 32% in the younger group (p<0.01). On the whole 37% of elderly patients had Stage IC tumors compared with 21% in younger women (p<0.01). Seventy-five percent of elderly women had Grade 2 or 3 tumors compared with 55% of younger patients (p<0.005). The majority of EC was endometrioid in both groups: 8% of elderly patients had clear-cell carcinomas compared with 4% of younger women (p not significant). No elderly patients showed nodal metastasis (0 out of 10): 9% of younger women had pelvic or para-aortic metastasis. The median follow-up was 78 months. The overall survival in the elderly and in the younger group was 80% and 93%, respectively (p<0.01): in elderly women overall survival significantly varied according to histotype and depth of myometrial invasion in Stage I tumors. In conclusion patients 70 years old or over have a high probability of surgical Stage I EC but a significantly higher probability of deep myometrial invasion and less-differentiated tumors than younger women: the prognosis w as good but poorer than for younger patients.

Obesity: internal medicine, obstetric and gynecological problems related to overweight.

Obesity is the major nutritional problem affecting industrialised society. According to a recent ISTAT survey, 41% of men and 19% of women in the Italian population suffer from obesity. Obesity is a complex pathological entity with a multiform and often indeterminable etiology. Studies of natural and adopted children and twins suggest that a clear hereditary, constitutional predisposing factor is present in obesity which interacts with environmental conditions. The genetic factor is also suggested by the statistical finding that if neither parent is obese, then only 7-10% of their children will be obese, whereas if one parent is obese, 40-50% of children will probably become obese, and if both parents are obese as many as 70-80% of children will be obese. The risks related to obesity can be broadly categorised as mechanical and metabolic. The former include arthrosis, osteoporosis, degenerative diseases affecting the joints and bone matrix, muscular hypotrophy and respiratory deficits. The major metabolic risks include hypercholesterolemia, altered glycoregulation and hyperuricemia. From an obstetric point of view, apart from the fact that obesity is often associated with sterility, excess weight can often lead to sometimes dramatic complications during pregnancy, involving major risks for both mother and fetus. From a gynecological point of view the links between obesity, tumours and menopause are well known.

Efficacy of Fat Mobilisation System (FMS) in the treatment of obesity and its utility in the resolution of gynecological problems related to overweight.

In industrialised countries the problem of overweight affects more than 50% of the adult population. Knowledge acquired over the past years has replaced the principally esthetic concept of obesity with the notion of a multifactorial pathology, the outcome of an imbalance in the individual's energy balance caused by an excessive food intake as well as an inadequate energy consumption. The Fat Mobilisation System (FMS), which is able to activate a fat clearance process following cold local application, has proved a valuable and well tolerated tool capable of influencing the entire system responsible for obesity. A group of 109 patients of both sexes, aged between 15 and 71 years old, with problems of overweight and/or figure faults linked to the localised accumulation of fat, underwent out-patient treatment in the form of bandaging with elasticated bandages soaked in active solution able to lower body temperature by 2-3 degrees C. The results were satisfactory in all cases. In particular, a group of 24 women (10 of a childbearing age, 7 in premenopause and 7 in menopause), in whom overweight was associated with gynecological problems, were evaluated by Department A of the Department of Gynecology and Obstetrics at the University of Turin. An improvement in gynecological symptoms was achieved in parallel to weight loss in all patients.

Antineoblastic activity of antioxidant vitamins: the role of folic acid in the prevention of cervical dysplasia.

The authors made a study on 90 patients affected by various degrees of uterine cervix dysplasia searching for folic acid plasmatic concentrations. The team members affected by CIN have been compared with a test team consisting of women with normal pap-test and vaginoscopy. The study proved that the average levels of folic acids have significantly decreased in cases of dysplasia compared with the test team. These results allow stating that low folic acid plasmatic concentrations may be associated with cervix neoplasms development.

Danazol in the treatment of endometrial hyperplasia.

The paper reports the results of a study performed in 62 menorrhagic women with endometrial hyperplasia treated with Danazol. The efficacy and tolerability of the above drug was found to be satisfactory.

Perinatal mortality and morbidity in premature birth.

In a study carried out in 100 cases of premature birth in Section "A" of the Department of Gynecology and Obstetrics of the University of Turin, the authors report a perinatal mortality rate of 5.4%. Perinatal morbidity was found to be very high (68.2%). These findings--which are perfectly in line with those reported in the literature--explain why premature birth is one of the most important topics of research in modern obstetrics.

Asymptomatic bacteriuria in pregnancy: a diagnostic and therapeutic approach.

Pregnancy is a predisposing factor for urinary tract infection and pregnant women suffering from this pathology are exposed to dangerous risks which may condition maternal wellbeing and fetal prognosis. The apparently paradoxal finding of a higher incidence of perinatal problems in pregnant women with asymptomatic bacteriuria compared to those with manifest infections may be explained by the fact that the latter are adequately treated, whereas asymptomatic bacteriuria, which is difficult to diagnose, may continue in a subtle form for the entire duration of pregnancy. This emphasises the importance of the early diagnosis of infection using a protocol based on urine tests and urine culture and the adequate treatment of all cases of asymptomatic bacteriuria in order to reduce the incidence of maternal and fetal complications (acute pyelonephritis, increased fetal morbidity and mortality). The choice of the antibiotic to be used must be made on the basis of the urine culture test, the stage of gestation, maternal clinical data and the characteristics of the antibiotic itself (pharmacokinetics, maternal and fetal toxicity). With regard to the treatment protocol, the "single-dose" protocol is currently preferred. After negative urine culture tests, all patients must carry out a complete urine test each month with hormonal and echographic monitoring of the fetoplacental unit.

Asymptomatic bacteriuria in pregnancy: maternal and fetal complications.

From an analysis of the data reported in the literature it is clear that pregnancy is a predisposing factor for urinary tract infection and that pregnant women with this pathology are exposed to dangerous risks which may influence maternal wellbeing and fetal prognosis. Authors do not concur on the specific risks to the mother and fetus, one reason being that the statistics reported to date reveal discrepancies relating to the presence of disorders prior to pregnancy and the environmental, working and socio-hygienic conditions of the populations studied. The apparently paradoxical finding of a higher incidence of perinatal problems in pregnant women with asymptomatic bacteriuria compared to manifest forms can be attributed to the fact that the latter are treated with adequate therapies whereas asymptomatic bacteriuria, which is difficult to diagnose, may persist throughout pregnancy. This underlines the importance of early diagnosis using a protocol which entails the execution of serial urine tests and urine cultures and adequate treatment of all cases of asymptomatic bacteriuria in order to reduce the incidence of urinary tract infections and materno-fetal complications. Non-treated asymptomatic bacteriuria in fact represents a considerable risk factor since it may lead to the onset of acute pyelonephritis in approximately 5% of pregnant women and may increase the risk of fetal mortality.

[Ethical problems concerning artificial fecondation]. / Problematiche morali inerenti alla fecondazione artificiale.

In view of the seriousness of the facts regarding artificial fecondation as reported in the news and by the mass media, the various experiments carried out are analysed from the anthropological and ethical points of view. The purpose of these experiments is the procreation of a person and all those who are implicated in vital decisions-physicians, nurses, legislators and families-are invited to refrain from carrying out experiments or actions that might be damaging to the dignity of people and the couple in question.

[Vaginal delivery following previous cesarean section]. / Il parto vaginale nelle donne precesarizzate.

BACKGROUND AND AIM: The increased use of cesarean section (CS) over the past 30 years has raised a problem which has been much debated in obstetric practice: is it always necessary to repeat CS in women who have previously undergone cesarean section? The aim of this study was to establish whether women previously undergoing CS can start trial labour? METHODS: The authors examined 195 pregnant women who had previously undergone 1 or 2 CS. Medical history, clinical examination and maternal and fetal monitoring techniques were used to select the women who could start trial labour.

[Maternal morbidity in multiple pregnancies]. / La patologia gravidica nelle gravidanze multiple.

BACKGROUND: This study aimed to outline the clinical physiognomy of maternal morbidity in multiple pregnancies in order to improve maternal and feto-neonatal. METHODS: We reviewed the admissions to Department B of the Gynecology and Obstetrics Clinic at Turin University during the decade 1989-1998. Out of 17,445 pregnancies, we noted a 205 multiple pregnancies (1.17%), including 199 sets of twins, 5 triplets and 1 quadruplets. The percentages for the incidence of the various forms of maternal morbidity were compared to a control group of 1000 single births. RESULTS: Of 205 multiple pregnancies, 169 (82.43%) presented complications of varying severity and associated with statistically significant increase (always over 50%). These took the form of: premature birth (75.12%), PROM (28.29%), threat of premature birth (14.63%), phlebectasia (9.75%), anemia (8.78%), hyperemesis in the first quarter (8.29%), abortion (4.89%), polyhydramnios (4.39%), urinary tract infection (1.95%), detachment of the placenta (1.95%), liver pathology (1.46%), placenta previa (0.97%). CONCLUSIONS: The pathological picture revealed by this survey may seriously jeopardise the normal evolution of pregnancy, with severe repercussions for mother and fetus-neonate. These high-risk pregnancies should be included in a preventive programme of medical-social-outpatient and home assistance to guarantee early hospitalisation.

[Embryo-fetal diseases in multiple pregnancies]. / La embrio-fetopatie nelle gravidanze multiple.

BACKGROUND: Embryo-fetal diseases are the consequence of prenatal (progenetic and metagenetic or environmental) and intranatal (of a traumatic, infective, toxic nature) pathological factors. In multiple pregnancies this complex etiopathogenesis also includes an altered didymous embriogenesis. This study aimed to evaluate the pathologies affecting the fetus in multiple pregnancy, a special biological situation leading to the potential onset of severe fetal and neonatal damage. METHODS: The authors studied 205 patients with multiple pregnancies, including 199 bigeminal, 5 trigeminal and 1 quadrigeminal, admitted to the Department B of the Obstetrics and Gynecological Clinic of Turin University between 1989-1999. Possible embyro-fetal damage was examined using a chronological criterion: namely following the development of the multiple fetuses from the zygotic to the neonatal phase. RESULTS: Pregnancies were biamniotic bichorionic in 54% of cases, biamniotic monochorionic in 45% and monochorionic monoamniotic in 1%. There were a total of 154 (79.38%) premature births out of 194 and neonatal birth weight was always SGA (small for gestational age). 66.84% of newborns were LBW (<2500 g) and 7.14% were VLBW (<1500 g). Fetal mortality (2.29%) was higher than early neonatal mortality (1.53%). Perinatal mortality (3.82%) was three times higher than in all neonates from the same period (1.03%). CONCLUSIONS: The severe embryo-fetal and neonatal damage found in multiple pregnancies is a clinical reality that calls for adequate diagnostic and therapeutic measures, and above all specific medical and social prevention to limit maternal pathogenic risks.

[Preventable perinatal mortality]. / La preventabilità della mortalità perinatale.

BACKGROUND: Using a critical systematic analysis of perinatal mortality, this study aims to examine, on the basis of current medical and scientific knowledge, whether there are still situations in which feto-neonatal death could be prevented and to define and evaluate the feasibility of realising this goal. METHODS: The concept of preventable feto-neonatal death refers to the number of individuals who could have survived with better pre-, intra and postnatal care. In other words, it indicates the number of deaths that could have been avoided in an almost perfect health organisation and therefore, by reference, the number of inevitable deaths (not preventable). In this field it is important to distinguish between clinically preventable, where there are preventable factors at the time of hospitalisation and during the clinical phase of the disease, and extra-clinically preventable when these factors, if potentially present during the preclinical phase of disease, disappear owing to the gravity of conditions at the time of hospitalisation. Using data from maternal and neonatal clinical records, death certificates and autopsy findings, the authors examined the perinatal mortality rate in Department B of the Gynecological and Obstetrics Clinic of Turin University during the period 1979-1998. The results of these two decades were compared in terms of clinical practice. RESULTS: The perinatal mortality rate fell significantly (p<0.01) during the period 1989-1998: 1.02 vs 1.77%. It is worth underlining that this was mainly the result of a marked reduction (over 50%) in late fetal mortality: 0.43 vs 0.98% (p<0.01). Early neonatal mortality also diminished, although not significantly (0.59 vs 0.79%). In order to evaluate preventable deaths, perinatal mortality was subject to a detailed critical analysis to analyse its chronological evolution: prenatal, intranatal, early neonatal. During the second period examined, the preventable nature of perinatal mortality, although slightly lower, applied to 36.35% of cases. It is important to underline that although clinically preventable deaths were unfortunately still present (approx. 10%), most cases (approx. 90%) referred to extra-clinically preventable deaths. CONCLUSIONS: On the basis of current medical and scientific knowledge, the authors outline the directives for medical and specialist obstetric and social care required in the specific fight against preventable perinatal deaths. Recent progress in basic scientific research, especially in the genetic field, may make a vital contribution to limit and reduce the coefficient of feto-neonatal pathology that is still beyond control.

[Estrogen and progestin treatment in postmenopause. Effects on the endometrium]. / Trattamento con estrogeni e progestinici in età post-menopausale. Effetti sull'endometrio.

BACKGROUND AND AIMS: It has been well demonstrated that menopausal disorders resulting from the lack of estrogens may be delayed and partly eliminated by appropriate hormone replacement therapy. The aim of this study was to demonstrate the absolute innocuity of the association of estrogen and progestin. METHODS: The authors used an association of conjugated equine estrogens and medroxi-progesterone acetate to treat menopausal syndrome in 80 women aged between 48 and 55 years old. The study lasted 2 years. RESULTS AND CONCLUSIONS: The results obtained showed the good tolerability and marked efficacy of the drugs used, as well as the absolute innocuity in relation to the target organs, namely the breast and endometrium. No cases of endometrial hyperplasia with atypical development or malignant evolution were reported during the study and there was a significant improvement in lipid metabolism, vasomotor or psychomotive disorders, as well as increased trophism of the genitourinary tract and skeleton.

[Abnormal uterine bleeding during climacteric. Correlation between transvaginal ultrasonography, hysteroscopy and histology]. / Sanguinamenti uterini anomali in climaterio. Correlazioni fra ecografia transvaginale, isteroscopia e istologia.

BACKGROUND AND AIMS: The authors evaluated the accuracy of ultrasonographic findings compared to hysteroscopic and histological results in the diagnosis of anomalous uterine bleeding in menopause. METHODS: Forty-eight women suffering from the above pathology and attending the Preventive Gynecology outpatient clinic of Department C of the Gynecology and Obstetrics faculty at Turin University during the period between September 1996 and July 1997, underwent first ultasonography using a transvaginal probe and then outpatient hysteroscopy with endometrial biopsy. RESULTS: A total overlap between the ultrasonographic image, hysteroscopic results and histological diagnosis was only obtained in the group of menopausal patients. CONCLUSIONS: In line with the data reported in the literature, the authors imposed a cut-off endometrial thickness of 4 mm above which further diagnostic tests were performed using hysteroscopy with targeted biopsy.

[Observations on vaginal delivery in women with previous cesarean section]. / Considerazioni attuali sull'assitenza al parto delle donne con pregresso taglio cesareo.

BACKGROUND: The significant increase in cesarean sections both before (52.73%) and during labour (89.82%) observed in the 1990s compared to the period 1970-1980 prompted the authors to review the cases of women admitted to Department B of the Gynecology and Obstetrics Clinic at the University of Turin and to study the number of women with previous cesarean sections undergoing labour. The aim of this study was to throw light on this complex question and to reduce the incidence of surgical births wherever possible. METHODS: Two groups of pregnant women with previous cesarean sections were studied in Department B of the Gynecology and Obstetrics Clinic at the University of Turin: one group included women undergoing cesarean sections between 1990-1998, and the other included women undergoing cesarean sections between 1970-1980. The authors analysed the indications for repeat cesarean section and the percentage of vaginal births. RESULTS: The results show that during 1970-1980 the percentage of vaginal births was 24.34% (259 vaginal births out of 1593 patients), whereas between 1990-1998 the percentage of vaginal births fell to 10.18% (51 vaginal births out of 1060 patients). CONCLUSIONS: The high percentage of repeat cesarean sections found in the 1990s is not only due to strictly medical reasons, but also to ethical and political motives, and above all the maternal desire not to undergo natural labour.

[Delivery in multiple pregnancies]. / Il parto nelle gravidanze multiple.

BACKGROUND: A knowledge of clinical physiognomy in pathologies related to multiple births is indispensable for improving maternal and feto-neonatal prognosis. This study is a contribution to the solution of this problem. METHODS: A meta-analysis of data for multiple births at Department B of the Gynecology and Obstetrics Clinic at the University of Turi during the decade 1989-1998 was carried out, focusing on the arrangement and presentation of fetuses, the various types of birth, the gestational age at which birth occurred, the weight of neonates, neonatal mortality and maternal morbidity. RESULTS: Out of 11,523 births, there were a total of 194 (1.68%) multiple births, including 190 sets of twins and 4 triplets. 154 (79.38%) premature births were reported; 20 occurred <32(nd) week (10.29%). There was a high incidence of podalic presentation (26.30%) and shoulder presentation (5.61%) among twins; 202 were delivered using a cesarian section (51.53%) and 190 by vaginal birth (48.47%), of which 172 (90.52%) spontaneously. Surgical birth was an important means of extracting fetuses rapidly from a pathological environment. two hundred and sixty-two neonates (66.84%) were LBW (<2500 g), including 28 (7.14%) VLBW (>1500 g). The perinatal mortality rate was 3.82%. Maternal complications mainly occurred during the placental state, in the immediate postpartum and in puerperio. CONCLUSIONS: The authors feel that a more careful medical and social assistance, preventive hospitalisation, early recognition of the risk, constant monitoring for the optimal timing of birth, and lastly, qualified medical assistance during labour (expert gynecologist, trained obstetric staff) with other medical personnel (anesthetist, neonatal specialist) represent winning strategies to solve the problems arising during multiple pregnancies.

[Therapy for cervical intraepithelial neoplasia and fertility]. / Terapia delle lesioni preinvasive del collo dell'utero e fertilità

BACKGROUND: We reviewed the case records of patients of childbearing age treated with various types of surgical techniques for cervical intraepithelial neoplasia (CIN) to determine the impact of surgical treatment on their fertility. METHODS: Between 1983 and 1997 a total of 486 women with CIN received surgical treatment at out unit. Laser vaporization was used in 196 cases, cold-knife conization in 163 and REP in 127. The outcome of the various treatments was then compared. RESULTS: Independent of the surgical technique used, the percentage of pregnancies achieved after surgery was high: 93.33 and 96.66% of patients treated with laser vaporization and REP, respectively, and 87.69% of those who received cold-knife conization. The differences did not reach statistical significance nor were significant differences observed in the number of abortions or in the method of birth delivery (spontaneous, Cesarean section). However, a higher percentage of premature births was noted among women who received cold-knife conization (31.57%), which was statistically significant in the comparison among the three groups. CONCLUSIONS: The results from our study indicated which techniques for the treatment of CIN may be preferable. Compared with the other two techniques, cold-knife conization bears higher costs (hospitalization, general anesthesia) and has been superceded by laser vaporization and REP as evaluated in this series. When cold-knife conization must be used, cerclage of the cervix uteri should be performed in the event of future pregnancy. In contrast, laser vaporization and REP can be performed in an outpatient setting with local anesthesia. These techniques, because they are conservative, afford the advantages of complete lesion removal and maintenance of reproductive capability. Another important consideration is that REP is less costly and allows histological examination of the surgical specimen.

[Endoscopic treatment of polycystic ovary syndrome. Preliminary data]. / Trattamento endoscopico della sindrome dell'ovaio policistico. Dati preliminari.

Four women suffering from polycystic ovary syndrome recalcitrant to routine ovulation inducers have been submitted to electro-cauterization and ovarian resection. Hormonal changes after 24 hours and the incidence of ovulatory cycles in the 6 months subsequent to the execution of these surgical techniques are reported.