[Effects of folic acid supplementation on pregnancy outcomes: a review of randomized clinical trials]. / Revisione narrativa dei risultati degli studi clinici controllati sull'efficacia della supplementazione con folati nel migliorare l'esito della gravidanza.

Despite the causal association between defects of the metabolism of the folate (hyperhomocysteinemia) and risk of neural tube defects are both well documented, the association between folate deficiency and other pregnancy pathologies is still not entirely clear. The present article aims to gather the data published about the relationship between serum folate and pregnancy pathologies, distinguishing between the evidences emerged from the observational studies and the results of the clinical trials. We carried out a brief examination of the relationships between folate metabolism and homocysteine. Observational studies have suggested that a good level of folate in pregnancy is associated with higher birthweight, increased placental weight and fewer preterm birth. These results were not entirely consistent with findings from clinical trials. We have identified 12 randomized clinical studies with folate supplementation versus placebo. In the clinical studies where folic acid (FA) could improve pregnancy outcomes, its effect was not statistically significant, except for three studies where FA showed a significant decrease of low birthweight. With regard to preterm birth, pre-eclampsia and abruptio placentae, although in some observational studies AF was found to be associated with a reduction of these adverse outcomes, in currently available controlled clinical trials, FA supplementation had no statistically significant effects.

Induced abortion and risk of small-for-gestational-age birth.

OBJECTIVE: To investigate the possibility of an association between previous induced abortion and subsequent birth of a small-for-gestational-age (SGA) infant. DESIGN: Case-control study. SETTING: General and university hospitals. METHODS: Cases were 555 women who delivered SGA babies. Controls were 1966 women who gave birth at term (>37 weeks of gestation) to healthy infants of normal weight on randomly selected days at the hospital where cases had been identified. All women in the case and control categories were interviewed on the obstetric wards by one of a team of six interviewers. During the interviews, information was obtained regarding general socio-demographic factors, personal characteristics and habits, gynaecological and obstetric history, general anamnesis, family history of obstetric and gynaecological diseases, and the age of the father of the child. Further information on current pregnancy and delivery was also collected. We used conditional multiple logistic regression (with age as the matching variable), with maximum likelihood fitting, to obtain odds ratios and their corresponding 95% CIs. Included in the regression equations were terms for education, plus terms significantly associated in this data set with the risk of SGA birth (smoking in pregnancy, history of SGA, gestational hypertension and parity). POPULATION: Women admitted to a general and a university hospital. RESULTS: No significant increase in the risk of SGA birth was observed in women with a previous induced abortion [odds ratio (OR) 1.0; 95% CI 0.6-1.7]. The OR for SGA birth was 1.2 (95% CI 0.7-2.1) for preterm and 1.0 (95% CI 0.7-1.4) for term SGA births. CONCLUSION: This study found no association between risk of SGA birth and induced abortion.

Neonatal resuscitation of extremely low birthweight infants: a survey of practice in Italy.

Delivery room management of extremely low birthweight infants (ELBWIs) has been little studied. A questionnaire was sent to the heads of the 86 Italian neonatal intensive care units provided with on site delivery. The practice of and approach to the resuscitation of ELBWIs were very different among the centres surveyed, reflecting a paucity of evidence and consequent uncertainty among clinicians.

Adaptation and validation of an Italian version of the Prostate Cancer Specific Quality of Life Instrument (PROSQOLI).

OBJECTIVE: The Prostate Cancer Specific Quality of Life Instrument (PROSQOLI) is a measure of health-related quality of life (HRQoL) in advanced hormone-resistant prostate cancer. In this study, we aimed at performing a cross-cultural adaptation and validation of the Italian version of the PROSQOLI. PATIENTS AND METHODS: The original version of the PROSQOLI underwent several turnarounds of translations. A total of 472 patients treated with radical prostatectomy, radiotherapy or medical therapy were enrolled for the validation of the questionnaire. The PROSQOLI was administered together with the SF-12. Reliability indexes were calculated by using Cronbach alpha. To evaluate the validity of the construct, relationships between PROSQOLI and SF12 were assessed. The ANOVA test was used to evaluate the differences between groups of patients who had received different treatments. RESULTS: The reliability coefficient was 0.91. Item-to-total correlation indices were in most cases >0.70. The correlation between the scores of the PROSQOLI and those of the SF-12 questionnaire was high (r=0.8139, p<0.0001). The ANOVA test showed significant differences between groups (p<0.01) based on age, recurrence risk and treatment. CONCLUSIONS: The adaptation process showed that the PROSQOLI Italian version has high reliability and presents both convergent and discriminant validity. This version of the tool can be used to assess HRQoL in Italian men who underwent radical treatment for advanced prostate cancer.

Multiple fraction per day radiation therapy for inoperable esophageal cancer.

Experience with a multiple fractions per day radiation therapy program for inoperable esophageal cancer is reported. The treatment program consisted of 3 daily fractions of 1.6 Gy, with a 4 hr interval between fractions, for 5 consecutive days (24 Gy). After a rest period of 2 weeks, a second course of radiation was given with the same dose and fractionation for a total dose of 48 Gy in an overall treatment time of 4 weeks. Thirty-four patients were treated between February 1981 and July 1983. Acute reactions consisted of mild esophagitis noted in 30% of patients. No treatment related complications were reported. Median survival was 7 months and the 2- and 5-year survival rates were 12 and 9%, respectively. Tumor size and Karnofsky performance status were found to be the most important prognostic indicators for prolonged survival. Prompt palliation of symptoms was noted. Thirty-three per cent of patients had complete resolution and 41% had partial improvement of symptoms after completion of treatment. Four patients (12%) obtained complete tumor regression with negative biopsy at endoscopic examination and 2 of them are free of disease at 58 and 64 months. A partial response was reported in 12 patients (35%) for a median duration of 5 months (3-26). Treatment with multiple fractions per day was feasible in patients with esophageal cancer and could be preferred to more conventional fractionations for promptness of palliation and the shorter treatment time. The expected therapeutic gain is discussed.

Radiotherapy enhanced by cis-platinum in stage III non-small cell lung cancer: a phase II study.

From January 1984 to December 1986, 94 patients with unresectable, locally advanced, non-small cell lung cancer (NSCLC) were treated to assess both the efficacy and the toxicity of a combined modality treatment including radiation therapy (45 Gy/15 fractions/3 weeks) and daily low dose cDDP (6 mg/m2). The overall response rate for the 90 evaluable patients was 54.3% with 16.6% of complete responses. At a minimum follow-up of 4 years, the overall median survival time was 12 months. Provided adequate hydration is ensured, the cDDP regimen chosen as a radiosensitizer can be safely combined with radiation therapy.

Accelerated split course regimen in the treatment of brain metastases.

Between July 1981 and December 1983, 63 patients, with brain metastases were treated with an accelerated split course regimen; irradiation was given to the whole brain in 3 daily fractions of 160 cGy each (with 4-h interval between the fractions), for 5 days a week. The cycle was repeated after 2 weeks to a total dose of 4800 cGy. Male-female ratio was 3:1 (48 males and 15 females). Median age was 58 years (range 24 to 75). The most frequent site of primary tumor was lung (squamous cell carcinoma in 33 patients and oat cell carcinoma in 8 patients), breast in 6 patients, melanoma in 3 patients, other sites in 8 patients and unknown cancer in 5 patients. Thirty-five patients had multiple brain metastases localizations. In 33 patients (52.3%), metastases were present in other sites outside the central nervous system. Two patients failed to complete the scheduled treatment: one because of early death and the other by refusal of therapy during treatment. We obtained complete remission (CR) in 4 patients and partial remission (PR) in 24 patients. The median survival time was 21 weeks. The overall response rate was 42.5%. Toxicity was not considerable. The treatment results were not influenced by the site of primary tumor or by disease spreading; only the neurologic status before radiotherapy and the response to treatment influenced survival. The results we obtained are similar to those reported by other studies; however, with the accelerated split course regimen the treatment time was reduced and a shorter period of hospitalization was required.

Paternal and maternal smoking habits before conception and during the first trimester: relation to spontaneous abortion.

PURPOSE: This study examined the association between maternal smoking before and during the first trimester of pregnancy and spontaneous abortion. METHODS: We have been conducting a hospital-based case-control study on risk factors for spontaneous abortion in the greater Milan area. We collected information from 782 cases of spontaneous abortions and 1543 controls (women who delivered at term healthy infants). RESULTS: With respect to never smokers, the odds ratio (OR) were 0.7 (95%, confidence interval (CI), 0.5-1.0) for women who quit smoking and 1.3 (95% CI, 1.0-1.6) for those who continued during pregnancy. Women who smoked more than 10 cigarettes/day in the first trimester were at increased risk of miscarriage, with an OR of 1.4 (95% CI, 1.0-2.1). No relationship was evident between the number of cigarettes smoked before conception and the risk of abortion. Likewise, no association emerged between paternal smoking and miscarriage. Moreover, no significant interaction or modification effect was obtained when strata of age and other major characteristics were investigated. CONCLUSIONS: The risk of abortion associated with cigarette smoking during the first trimester of pregnancy was measurable and noticeable in this population, and accounted for 9% (95% CI, 6-13%) of all cases. The increased risk of spontaneous abortion in women smoking during pregnancy is a further reason to encourage pregnant women to quit.

Serum bone alkaline phosphatase in the follow-up of skeletal metastases.

The efficacy of bone alkaline phosphatase (ALP) isoenzyme measurement, using a lectin precipitation method, in confirming metastatic sites was assessed in 65 patients with cancer and skeletal (n = 44), hepatic (n = 15) or lymph node (n = 6) metastases; the control group consisted of 33 healthy adults. In all subjects, total ALP activity and osteocalcin were also assayed. Our results confirm that isoenzyme analysis is more specific than total enzymatic activity measurement in the identification of bone metastases: the mean for total ALP values was increased in all patients, while significantly high mean values of bone fraction (p < 0.05 by ANOVA) were observed only in patients with bone secondaries. In the serial monitoring of 9 patients with skeletal metastases, bone ALP values correlate with pain symptomatology: a progressive decrease in bone isoenzyme activity was observed in patients with a complete remission of pain after radiotherapy, while a progressive increase in activity was observed in the presence of increased bone pain. The measurement of bone isoenzyme activity is useful in screening for skeletal metastases; levels appear to correlate with the course of bone symptomatology, thus providing useful objective evidence of response to treatment.

Results of three consecutive combined treatments for malignant gliomas. Ten-year experience at a single institution.

Between 1978 and 1988, 108 consecutive patients with malignant gliomas were treated. The patients were divided into 3 groups as follows: Group I, surgery if possible, otherwise biopsy followed by whole-brain irradiation to a total dose of 34 Gy in 4 fractions, VCR (2 mg i.v.), and BCNU (80 mg/m2 i.v.) repeated every 6 weeks; Group II received irradiation as Group I plus VP16 (75 mg/m2) every 3 weeks and BCNU (50 mg/m2 i.v.) every 6 weeks; Group III received 60 Gy in 30 fractions to the tumor bed plus VCR (2 mg i.v.), BCNU (50 mg/m2 i.v.), and CDDP (15 mg/m2 i.v.) every 6 weeks. In group I, 28 patients had stable disease (SD) and 2 patients showed disease progression (PRO). Median survival time was 9 months (range 1-18). In Group II 22 SD's were observed. Median survival time was 6 months (2-16). In the third group of patients 29 SDs and 14 partial remissions (PR) were recorded. Median survival time in this group was 13 months (range: 3-59+ months). In general, the group of patients treated with radical or subtotal surgery and the group of patients included in neurologic classes I-II and with performance status (PS) > or = 70 had a longer survival. In our experience, patients with grade III and IV astrocytoma receiving treatments similar to those described above showed no difference in survival and response. Regardless of treatment, none of the patients experienced severe toxicity.

Determinants of response to intracervical prostaglandin E2 for cervical ripening. Gruppo di Studio sull'Induzione del Travaglio di Parto.

OBJECTIVE: To analyze the determinants of response to intracervical prostaglandin E2 (PGE2) in cervical ripening. STUDY DESIGN: A total of 250 women with normal pregnancy, parae three or less, with intact membranes between 40 and 42 weeks of gestation and Bishop's score < or = 4 were treated with 0.5 mg PGE2 intracervical repeated after 12 hours if cervical Bishop's score was still < or = 4. RESULTS: After the first administration of PGE2, labor was induced in 106 (42.4%) women. Nulliparae had a significant longer interval from the first PGE2 dose to delivery and more failures of treatment and caesarean sections than parae. There was a tendency towards a shorter interval between the first administration and delivery and a decrease in the frequency of treatment failures with increasing Bishop's score, but the finding was not statistically significant. No fetal or neonatal death occurred. There were eight neonates at one min and three neonates at five min with an Apgar score less than seven. There were 22 neonates admitted to Neonatal Intensive Care Unit. There were 20 cases of jaundice. CONCLUSIONS: The study confirms that the main determinant of treatment failure with PGE2 gel in cervical ripening is nulliparity.

Placental ratio in pregnancies at different risk for intrauterine growth.

OBJECTIVE: We have analyzed the placental/birthweight ratio in women at increased risk of intrauterine growth retardation and pregnancy-induced hypertension and in women with pregnancy 'complicated' by these conditions. STUDY DESIGN: A total of 89 women with small gestational age (SGA) infants, 355 with appropriate gestational age infants (200 in the uncomplicated pregnancy group) and 28 with large for gestational age (LGA) infants were considered. RESULTS AND CONCLUSION: The mean placental weight showed a significant increase from the SGA to the LGA in the two groups. The placental ratio tended to increase from the LGA group to the SGA one both in infants of women with uncomplicated pregnancy and with pregnancy complicated by intrauterine growth retardation or pregnancy-induced hypertension; these findings were statistically significant.

Solitary thyroid metastasis from a renal cell carcinoma diagnosed and treated 12 years before: a case report.

The authors report a case of a solitary thyroid metastasis in a 62-year-old woman. The clinical history of the patient and the histologic findings are consistent with a renal origin of the tumor.

Hyperthermia in clinical practice: preliminary results and current problems in the treatment of 21 patients.

From February 1988 through February 1991, 21 patients were managed by superficial hyperthermia and radiotherapy. Nineteen patients had received previous treatment; the most common histology was breast carcinoma. Twenty-six cycles of combined hyperthermia and radiotherapy were delivered: 4 complete responses (15.4%), 17 partial responses (65.4%), 1 minimal partial response (3.8%), 3 stable diseases (11.6%) and 1 disease progression (3.8%) were obtained. The median duration of response was 7 months (range 1-16) for responding and 4 months (range 2.5-4) for non-responding patients. The toxicity encountered (confined mostly to epithelitis--7/21 patients) was completely reversible. In our experience, hyperthermia combined with radiotherapy proved to be an effective treatment. However, some problem that emerged during treatment planning and delivery showed the need for further development and research into hyperthermic devices and thermometry systems.

Radiation therapy combined with chemotherapy for inoperable pancreatic carcinoma.

From March 1985 to July 1989, 22 patients with unresectable pancreatic adenocarcinoma entered the study to receive external beam irradiation with chemotherapy. Radiation therapy consisted of 60 Gy in 3 courses (20 Gy each course) delivered over a period of 2 weeks, with a 2-week rest between the courses. Chemotherapy consisted of 5 fluorouracil, 500 mg/m2, plus cisplatinum, 20 mg/m2, administered on days 1, 2 and 3 of each radiation therapy course. Of the 22 evaluable patients, 10 were males and 12 females; their median age was 63 years (range, 32-77), and their median performance status was 80 (range, 60-90). After treatment, 12 partial remissions and 6 no changes were reported. In 4 cases, abdominal progression of disease during treatment required interruption of the therapy program. At the start of treatment, abdominal pain was the most important symptom in 17 patients; improvement of abdominal pain was observed in 10 cases (76%) after treatment and lasted for a median of 5 months. Median survival time was 7.5 months, and time to progression was 6.2 months. Median follow-up was 7 months (range, 14 days -38). In 2 cases, persistent hematologic toxicity did not permit completion of therapy, and in another 3 cases grade II hematologic toxicity required a 2-week rest period over the normal split-course program. In another 4 cases, grade I hematologic toxicity did not require any delay in the therapy program. Our results are comparable with those achieved in other major studies and are acceptable in terms of survival time, palliation of symptoms and toxicity. In our experience, the combination of radiotherapy plus 5-fluorouracil and cisplatinum does not seem to offer any advantage over the combination of radiation therapy and 5-fluorouracil.

Postoperative radiotherapy in locally advanced head and neck cancer.

This retrospective study was conducted on 255 consecutive patients with locally advanced squamous-cell carcinoma of the oral cavity, oropharynx, larynx or hypopharynx, treated at the Radiotherapy Department of Pordenone General Hospital between January 1975 and December 1985. All patients underwent radical surgery followed, after an interval ranging from 10 days to 2.9 months, by radiotherapy given either through a 6 MeV linear accelerator or a cobalt-60 unit. Field extension and dose delivered were comparable in relation to stage and involvement of the surgical resection margins. The aims of the study were to evaluate the survival rate and to analyze the clinical parameters which can influence the disease-free survival. The adjusted overall 5-year survival rate was 71%; stage, performance status at diagnosis, and site of the primary tumor were significant factors in determining patient prognosis, whereas infiltration of resection margins was not significant in determining loco-regional control of disease. Seventy-five patients relapsed and 67 died of cancer-related diseases whereas death in 52 patients was not related to the head and neck cancer. The combined modality treatment consisting of surgery followed by radiotherapy was well tolerated and proved to be effective in the treatment of locally advanced head and neck tumors.

[Timing of radiotherapy in the treatment of breast carcinoma. Review of the literature]. / Timing della radioterapia nel trattamento del carcinoma mammario. Revisione della letteratura.

Combined modality treatments are indicated for most patients with breast cancer. The definition of a proper treatment schedule and of the timing of each modality is a relevant issue that affects the feasibility and the clinical outcome of the treatment. A review of the literature was done on the timing of radiation therapy (RT) in the post-operative treatment of breast cancer. Retrospective studies and randomized clinical trials addressing the issue were considered and grouped according to the combined modality treatments performed. With regard to breast conserving surgery and adjuvant RT, it was verified that a delay up to 8 weeks between breast surgery and start of RT is not associated with an increased risk of local failure if compared with RT started within 4 weeks. Concerning breast conserving surgery followed by adjuvant RT and chemotherapy, the choice of the best schedule is still a complex unresolved issue. More results on sequential schedule of adjuvant RT and chemotherapy from recently published randomized studies are available. The reconstruction of the breast after conservative surgery is rarely necessary and is usually performed immediately after surgical treatment. With regard to mastectomy followed by adjuvant RT and breast reconstruction, it appears from some retrospective studies that autologous tissue transfer offers better results over implants. Concerning the transverse rectus abdominis muscle (TRAM) procedure, either immediate reconstruction before RT or delayed reconstruction after RT was feasible without significative differences in complication rates. Further randomized clinical studies are required to address the unresolved issues linked to the timing of RT. At present the treatment plan should be based on the patient's individual circumstances with regard to risk of metastasis and local failure.

[Follow-up of children in obstetrical clinical trials: research experience in Italy]. / Il follow-up dei bambini nei trial clinici ostetrici: esperienze di ricerca in Italia.

The effectiveness of treatments for the mother exposed to adverse events in pregnancy is not always interpreted in the light of possible effects on the child. The follow-up of infants is an important component of obstetric and perinatal audit not only in randomised clinical trials but as part of routine health care. The results of the 18 month's follow-up of children born from women recruited in the Italian Study of Aspirin in Pregnancy and in the Italian Trial on Nifedipine in Pregnancy are discussed. No significant differences emerged between treatment and no-treatment groups with respect to indicators of development and health status. Malformations, diseases, and other health problems showed no specific patterns and were much the same in the groups. Our findings suggest that the use of low-dose aspirin and calcium channel blocker nifedipine in pregnancy is safe with respect to the risks of malformation and of major impairment in development at 18 months of age.

[Epidemiology of identical twin pregnancy]. / Epidemiologia della gravidanza gemellare.

On the basis of MEDLINE and manual search, we looked at the main papers in English literature published from 1976, regarding risk factors for spontaneous (i.e. not related to fertility drug use) multiple births. The constant frequency of monozygotic (MZ) pregnancies over time and in different geographic areas suggests that determinants of MZ twins are largely unchanged over time and that genetic mechanism may act a role. On the contrary, temporal and geographic trends observed in dizygotic (DZ) pregnancies suggest that environmental factors play a role in determining this condition. At present maternal age and hereditary components are the better defined determinants for spontaneous multiple births.