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Il diffondersi delle tecniche di procreazione medicalmente assistita (PMA) ha portato ad un aumento dell’incidenza delle gravidanze gemellari, rendendo necessaria la discussione della maggiore frequenza di malformazioni congenite documentata nei nati da gravidanza plurima.  Contrariamente rispetto a quanto siamo abituati a credere, i gemelli non sono necessariamente identici, ma possono differire tra loro per anomalie congenite e/o genetiche: si definiscono concordanti i gemelli che presentano la stessa malformazione, mentre sono discordanti se uno solo dei gemelli presenta un’anomalia congenita, oppure se entrambi hanno anomalie congenite, ma distinguibili sotto il profilo eziopatogenetico.  Le anomalie di più comune riscontro nei gemelli sono le anomalie cardiache, del sistema nervoso centrale e dell’apparato gastroenterico. Gli stressi gemelli monocoriali possono presentare cariotipo discordante per anomalie cromosomiche (gemelli eterocarionti) o malattie monogeniche (gemelli eteroallelici).  I progressi della chirurgia pediatrica nell’ambito delle tecniche di separazione dei gemelli congiunti, in associazione all’uso estensivo dell’ecografia ostetrica nel primo trimestre, impongono agli ecografisti ostetrici la definizione diagnostica precoce dei casi di gemelli congiunti, così da poter fornire ai futuri genitori gli strumenti più idonei per una scelta consapevole circa la prosecuzione di una gravidanza.  Le informazioni disponibili in letteratura circa le anomalie congenite nei gemelli sono, purtroppo, ad oggi, frammentarie. Pertanto gli studiosi esperti hanno il dovere, nei casi di anomalie genetiche o fenotipiche in gravidanza gemellare, di pubblicare, nel medesimo report, i risultati delle analisi genetiche, degli esami istologici delle placente, delle eventuali autopsie o dell’esame clinico postnatale, così da contribuire, in modo concreto, ai futuri studi sulle anomalie nelle gravidanze gemellari.

Background: During COVID pandemic, many cancer patients (pts) refused to come to hospital, suspending therapies, with ominous consequences. Based on positive (+) results of DOMONCOVID, our homecare project for COVID+ cancer pts, we created a new model of assistance, ONCOHOME, delivering cancer care at home to immune-compromised pts. We aim to provide data on feasibility, efficacy and costs of this innovative model. Methods: ONCOHOME is a multicenter project involving 3 Cancer Center (CC) of the North of Italy: National Cancer Institute, San Raffaele in Milan and Cremona CC. We created an organizational homecare model based on a medical and nursing team with a car equipped for home visits and a secretariat managing patient calls, with a dedicated phone number. The team administers cancer care at home and provides pts with the same assistance usually delivered in hospital. Patient-reported outcome (PRO) assessment is performed. Results: From August 3rd 2020 to May 5th 2021, 79 cancer pts were assisted at home by Cremona team, receiving oral (62 pts), subcutaneous (10pts) or intravenous therapy (7 pts). All types of cancer were included. 77% of pts had a metastatic disease, 88% had a PS ECOG 0-1. Median duration of assistance was 126 days [range 2-270 days]. Most of the pts received oral chemotherapy (41pts). TKIs (25 pts), hormonal therapy (12 pts), supportive care with denosumab and zolendronic acid (5 pts ) and immunotherapy (1 patient, pt) were successfully administered at home, too. 13 pts required hospitalization due to clinical complications. In this group, only 2 pts were admitted to hospital due to severe toxicity;in particular, 1 pt treated with trifluridin/tipiracil developed febrile neutropenia and 1 pt treated with gefitinib reported Grade 3 diarrhea. Both pts were discharged and continued to be assisted at home. Conclusions: ONCOHOME showed that inpatient or outpatient cancer drug administration could be successfully replaced by home administration, for appropriate therapies and selected pts. This model is feasible at an affordable cost. The project is ongoing, planning to accrue other 100 pts for each center. ONCOHOME will be implemented with electronic devices for PRO evaluation, certified telemedicine service and non-invasive wearable smart tissue monitoring physiological parameters devices. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Objective: To evaluate perinatal outcomes in case of non-primary maternal cytomegalovirus (CMV) infection. Methods: We performed a retrospective cohort study of pregnant women with active CMV infection referred to our unit over a 15-year period (January 2000 to December 2014). Non-primary infection was diagnosed on the basis of the results of confirmatory serological and virological tests (avidity test, immunoblotting, real-time PCR-DNA). The vertical transmission rate and the percentage of symptomatic congenital infection were determined in this group of patients. Results: A total of 205 pregnant women were enrolled. Congenital infection occurred in 7 (3.4%) fetuses/neonates. Symptomatic disease was present at birth in 3 of the 7 congenitally infected neonates (1.5%). Two out of 3 symptomatic newborns presented a pathologic second-trimester ultrasound scan. Conclusion: Maternal immunity offers substantial protection against intrauterine transmission of CMV infection, but not against disease once the fetus is infected.

Objective To verify the hypothesis that aberrant placental mRNA genes related to cardiogenesis can be detected in maternal plasma at the second trimester of pregnancy. Methods NanoString technology was used to identify aberrant genes, comparing 39 women carrying a fetus with a congenital heart defect (CHD) to 31 controls at 19-24 weeks of gestation. The genes with differential expression were subsequently tested using real time polymerase chain reaction. Linear discriminant analysis (LDA) was used to combine all the mRNA species with discriminant ability for CHD. A multivariable receiver operating characteristic (ROC) curve having the estimated discriminant score as an explanatory variable was generated. Results Six genes with differential expression, namely FALZ, PAPP-A, PRKACB, SAV1, STK4 and TNXB2, were found. The ROC curve yielded a detection rate of 66.7% at a false positive rate of 10%. A higher discriminant score (>75(th) centile) was reached for 14 CHD cases (82.4%) and only 1 control (5.8%). Two cases (11.8%) of heart rhythm disorders also yielded a discriminant score value >75(th) centile. Conclusion These data represent a step forward in the screening of CHDs. Additional studies are needed to detect more mRNAs with discriminant ability and to move the first trimester screening.

Objective To evaluate the incidence of infants with birth weight less than the 10th centile for small for gestational age (SGA) in primary maternal cytomegalovirus (CMV) infection and to determine whether SGA predicts poor neurodevelopmental outcome. Methods A retrospective cohort study, which included singleton live-born infants from pregnancies complicated by primary maternal CMV infection. Infants were classified as uninfected or infected based on viral virus isolation and real-time PCR in urine at birth. SGA neonates rate and long-term sequelae were evaluated. Results Between 2000 and 2012, 848 women with primary CMV infection were referred to our center with 588 infants assessed at birth. Congenital CMV infection was diagnosed in 119 cases (20%), of which 8 were SGA (6.7%) compared with 27 out of the 469 uninfected infants (5.7%) (p-value = 0.69). Among the 119 infected babies, 14 infants were symptomatic at birth or at postnatal follow-up (12%), of whom two were SGA compared with six out of the 105 asymptomatic neonates (5.7% versus 15%, respectively, p-value = 0.22). Conclusion Congenital CMV infection does not seem to be associated with a higher incidence of SGA, and long-term outcomes do not seem to be affected by isolated impaired fetal growth. © 2014 John Wiley & Sons, Ltd.

We previously studied a dose-dense TCF (TCF-dd) regimen demonstrating its feasibility and an activity comparable to epirubicin-based chemotherapy and TCF q3w in terms of overall survival and time to progression (TTP). We report here the final results of a phase II study of chemotherapy with a modified TCF-dd regimen in locally advanced or metastatic gastric cancer (MGC).Patients with histologically confirmed measurable MGC, not previously treated for advanced disease, received docetaxel 70 mg/m(2) day 1, cisplatin 60 mg/m(2) day 1, l-folinic acid 100 mg/m(2) days 1 and 2, followed by 5-fluorouracil (5-FU) 400 mg/m(2) bolus days 1 and 2, and then 600 mg/m(2) as a 22-h continuous infusion days 1 and 2, every 14 days, plus pegfilgrastim 6 mg on day 3. Patients aged ≥65 years received the same schedule with a dose reduction of 30 %.Study duration: December 2007-November 2010. Forty-six consecutive patients were enrolled (78 % male, 22 % female; median age, 66 years, range, 38-76 years; ECOG PS: 0, 48 %, 1, 46 %). Primary endpoint was overall response rate (ORR). A median of four cycles (range, one to six) was administered. Forty-three patients were evaluated for response (93.5 %) and all for toxicity: 3 complete response (CR), 25 partial response (PR), 10 stable disease (SD), and 5 progressive disease (PD) were observed, for an ORR by intention to treat (ITT) of 61 % (95 % CI 47-75). Median overall survival (OS) was 17.63 months (95 % CI, 13.67-20.67); median progression-free survival was 8.9 months (95 % CI, 6.5-13.4). Twenty-one patients (46.0 %) were treated at full doses without any delay, thus respecting the dose-dense criterion. Most frequent grade 3-4 toxicities were neutropenia (20 %), leukopenia (4 %), thrombocytopenia (2 %), anemia (2 %), febrile neutropenia (6 %), asthenia (22 %), diarrhea (4 %), nausea/vomiting (11 %), and hypokalemia (6 %). Overall, TCF-dd was shown to be safe.The TCF-dd regimen in locally advanced or MGC is confirmed to be feasible and very active and needs to be further tested in randomized studies.

There is clinical utility in having a simple and low-cost method of predicting birth weight. To identify abnormal fetal growth, in fact, can reduce the risk of adverse perinatal outcomes. A longitudinal observational cohort study, including 1034 low-risk singleton pregnancies at term, was performed at the Division of Prenatal Medicine, St. Orsola-Malpighi Hospital, University of Bologna, Bologna (Italy) to derive a reliable equation based on maternal characteristics. The following formula was obtained: estimated birth weight (g) = 1485.61 + (symphysis-fundal height (cm) × 23.37) + (11.62 cm × maternal abdominal circumference) + [body mass index (BMI) × (-6.81)] + (parity (0 = nulliparous, 1 = multiparous) × 72.25). Based on study results, 92% of the estimated weights were within the 10% of the actual weight at delivery. The role of obstetric and maternal factors in term birth weight prediction is, therefore, confirmed. Prospective estimations are needed to validate the model proposed. Key words: Symphysis-fundal height, multivariable birth weight prediction, term of pregnancy

Objective To evaluate the outcome of pregnancies complicated by placental insufficiency and abnormal umbilical artery Doppler prior to viability. Design A retrospective cohort study. Setting Italy. Population Singleton pregnancies with fetal growth restriction and absence of end-diastolic velocities (AEDVs) in the umbilical arteries prior to 24 weeks. Methods A retrospective cohort study of singleton pregnancies with fetal growth restriction and AEDVs in the umbilical arteries prior to 24 weeks. Main outcome measures Fetal growth restriction and AEDVs in the umbilical arteries prior to 24 weeks. Results Of 16 fetuses first seen at 20–23 weeks, only 12 survived and one of these developed cerebral palsy. Severe hypertensive disorders occurred in three mothers. In four women, the Doppler waveforms progressively improved and developed a normal pulsatility. These fetuses had a better outcome than those that had persistent alterations: they were delivered later (34 versus 28 weeks), had a larger birthweight (1598 versus 630 g) and developed fewer complications. Conclusions Placental insufficiency with AEDV in the umbilical arteries prior to fetal viability is associated with a high probability of perinatal death and neonatal complications. However, progressive amelioration of Doppler indices occurs in a subset of women, and these fetuses have a much better outcome.

Aim: To evaluate pregnancy outcome in women with fetal membranes at or beyond external os who underwent exam-indicated cerclage or conservative management. Material and Methods: Retrospective cohort study including 52 patients with fetal membranes at or beyond external os between 17 and 27 weeks of gestation, treated in two third-level hospitals, between January 2001 and April 2009. The outcomes of interest of the study, prolongation of pregnancy and neonatal survival rate, were stratified according to type of management, parity, clinical conditions and blood tests at admission and calculated using the Kaplan–Meier algorithm. Results: Of 52 women, 37 received exam-indicated cerclage and 15 were managed conservatively. The rate of patients still pregnant beyond 180 days within the cerclage group differed significantly from those of the conservative management group (80% vs 0%, respectively) (P-value

Objective: To verify the hypothesis that aberrant placental mRNA genes related to cardiogenesis can be detected in maternal plasma at the second trimester of pregnancy. Methods: NanoString technology was used to identify aberrant genes, comparing 39 women carrying a fetus with a congenital heart defect (CHD) to 31 controls at 19–24 weeks of gestation. The genes with differential expression were subsequently tested using real time polymerase chain reaction. Linear discriminant analysis (LDA) was used to combine all the mRNA species with discriminant ability for CHD. A multivariable receiver operating characteristic (ROC) curve having the estimated discriminant score as an explanatory variable was generated. Results: Six genes with differential expression, namely FALZ, PAPP-A, PRKACB, SAV1, STK4 and TNXB2, were found. The ROC curve yielded a detection rate of 66.7% at a false positive rate of 10%. A higher discriminant score (>75th centile) was reached for 14 CHD cases (82.4%) and only 1 control (5.8%). Two cases (11.8%) of heart rhythm disorders also yielded a discriminant score value >75th centile. Conclusion: These data represent a step forward in the screening of CHDs. Additional studies are needed to detect more mRNAs with discriminant ability and to move the first trimester screening.

Preterm birth is the leading cause of perinatal morbidity and mortality worldwide [1]. It contributes to 70% of neonatal mortality and approximately half of long-term neurodevelopmental disabilities [2]. The obstetrics precursors leading preterm birth are delivery for maternal or fetal indications, spontaneous preterm labour with intact membranes and preterm premature rupture of membranes (pPROM) [3]. It is estimated that about 30-35% of all preterm births are indicated, 40-45% follow spontaneous preterm labour and 25-30% occur after pPROM [3]. Premature infants born at a gestational age of 32 weeks or less are obviously at greatest risk. The term “extreme low birthweight” (ELBW) is used to identify newborns with birthweight less than 1000 g. Although their prevalence is less than 1%, these newborns disproportionately account for nearly one-half of all perinatal deaths [4]. Antecedent risk factors for ELBW neonates, though geographically heterogeneous, include nulliparity and multiple gestations, each accounting for one-third and one-fourth of all births, respectively [5]. Spontaneous preterm labor precedes 34% of these deliveries and premature rupture of membranes in 25%. The pregnancy is complicated by hypertensive disease in about 20% of cases and bleeding and chorioamnionitis in 18%, respectively. Moreover, small for gestational age infants rate ranged from 16 to 20%. When the frequencies of these factors is compared between the United States and other countries, PROM rate is similar between the groups (25% vs. 26%, respectively), while others are not (chorioamnionitis: 18% vs. 37%, respectively). These variations may be due to publication bias, differences in maternal demographic characteristics, differences underlying burden of maternal or fetal illness, and/or differences in obstetrical practice patterns.

Objective The aim of this study was to evaluate the incidence of cervical lacerations with cerclage removal planned before labor compared to after the onset of labor by a systematic review of published studies. Study design Searches were performed in electronic databases from inception of each database to November 2014. We identified all studies reporting the rate of cervical lacerations and the timing of cerclage removal (either before or after the onset of labor). The primary outcome was the incidence of spontaneous and clinically significant intrapartum cervical lacerations (i.e. lacerations requiring suturing). Results Six studies, which met the inclusion criteria, were included in the analysis. The overall incidence of cervical lacerations was 8.9% (32/359). There were 23/280 (6.4%) cervical lacerations in the planned removal group, and 9/79 (11.4%) in the removal after labor group (odds ratio 0.70, 95% confidence interval 0.31–1.57). Conclusions In summary, planned removal of cerclage before labor was not shown to be associated with statistically significant reduction in the incidence of cervical lacerations. However, since that our data probably did not reach statistical significance because of a type II error, further studies are needed.

Objective: To evaluate radiologic findings and outcomes of cerebellar injuries in fetuses with severe anemia due to RhD alloimmunization undergoing intrauterine transfusions.Methods: Imaging of multiplanar neurosonography and magnetic resonance imaging (MRI) were reviewed. Pregnancy outcomes were recorded.Results: Cerebellar injuries were identified after the first intravascular transfusion in four fetuses. Two of these cases were previously reported. The median hemoglobin concentration was 2.1 g/dL. Prenatal neurosonography identified an echogenic collection involving the cerebellum suggestive for hemorrhage in three cases. A progressive hypoplasia of a hemisphere was demonstrated at follow-up examination in one of these cases. Hypoplasia of a cerebellar hemisphere was seen in the fourth fetus. Ultrasound diagnosis was confirmed by prenatal MRI in two cases. In the third case, the postnatal MRI showed as additional finding vermian involvement. One pregnancy was terminated and autopsy confirmed the presence of infratentorial hemorrhage. The remaining infants were delivered alive. At time of writing, a truncal ataxia was diagnosed in the child with vermian hypoplasia, while the other children have met all age-appropriate milestones.Conclusions: A severe anemia seems to put the fetus at risk of cerebellar damage, despite successful intravascular transfusion.

e15538 Background: The presence of BM in AGC is a relatively uncommon finding and has a poor prognosis [Leporini C. 2015]. At diagnosis the presence of BM occurs in approximately 10-15% of pts with AGC.[Park 2011; Silvestris 2013]. Aim of this study is to describe the main features of pts with AGC and BM at diagnosis and the prognostic implications. Methods: A consecutive series of AGC followed at Cremona Oncology Division from November 2004 to Dicember 2016 and included in three consecutive prospective trials [Dalla Chiesa M. 2011; Tomasello G. 2013], were analyzed. All pts were treated with a modified DCF (docetaxel, cisplatin, fluorouracil) given as a dose-dense regimen, every 14 days. We analyzed pts with BM at diagnosis (BMaD) and pts without BMaD. We evaluated baseline clinical and pathological parameters, the presence of coagulation disorders (CD) together with efficacy measures in the two groups. Results:218 pts with AGC were identified (38 with BMaD and 180 without BMaD).Main pts characteristics and results are reported in the Table below. Conclusions: The presence of BM at diagnosis in pts with AGC is not a rare event (21%) and identifies a population with a significantly poorer outcome and a higher incidence of CD, that need a clinical monitoring of coagulation parameters. More efforts are required to understand the reasons of the different prognosis and to find specific treatments to improve the survival. [Table: see text]

At 32 weeks of gestation, a peripheral maternal blood sample was collected for measurement of mRNAs for Ki-67, KiSS-1 metastasis-suppressor (KISS1), PLAC1, PlGF, VEGF and Flt-1 genes. Amounts of mRNA samples were expressed in terms of copies per millilitre and were also measured in 32 pregnant women at 31 to 33 gestational weeks with normal placentation (controls). All the cases included in the study were dated by ultrasound in the first trimester. Copies were converted into multiples of the median (MoM) of unaffected pregnancies. Normal distribution was tested by Kolmogorov–Smirnov test. As we had only one case of placenta accreta data were examined and compared only by visual inspection.Our results are consistent with a possible involvement of KISS1, PLAC1 and VEGF genes in placenta accreta development. These results could allow a more in depth follow-up during the pregnancy in centers where molecular genetics laboratories are available

Background: Growing evidence indicates that unilateral lung irradiation for breast cancer may "prime" the development of migratory lung infiltrates with histologic features of bronchiolitis obliterans organizing pneumonia. Objective: Our purpose was to evaluate the cytologic and immunocytologic features of bronchoalveolar lavage in this condition. Methods: We analyzed the profile bronchoalveolar lavage cell differentials and lymphocyte subpopulations of 11 women with bronchiolitis obliterans organizing pneumonia syndrome after radiation therapy for breast cancer in comparison to 9 healthy women. Results: The bronchoalveolar lavage analysis demonstrated a significant increase in the percentage of lymphocytes (36.7% ± 5.4% vs 8.6% ± 1.1%, P = .0002), neutrophils (3.8% ± 1.2% vs 0.6% ± 0.2%, P = .005), eosinophils (2.4% ± 1% vs 0.3% ± 0.1%, P = .01), and mast cells (1.4% ± 0.6% vs 0.1% ± 0.02%, P = .05) with a significant decrease in the percentage of macrophages (56.1% ± 6% vs 90.3% ± 1.4%, P = .0002) in patients with bronchiolitis obliterans organizing pneumonia compared with the control subjects. The percentage of CD3 + cells was significantly increased in patients with bronchiolitis obliterans organizing pneumonia (93.7% ± 1.3% vs 70.9% ± 4%, P = .0004), with a significant decrease in CD4 + cells (32.7% ± 4.7% vs 55.4% ± 2.6%, P = .002) and a significant increase in CD8 + cells (61.2% ± 4.8% vs 37.5% ± 2.9%, P = .003) in comparison to control subjects. The CD4/CD8 ratio was significantly reduced in patients with bronchiolitis obliterans organizing pneumonia compared with control subjects (0.6% ± 0.1% vs 1.5% ± 0.1%, P = .001). Conclusion: These data add to the view that unilateral lung irradiation for breast cancer may "prime" the development of a syndrome quite similar to idiopathic bronchiolitis obliterans organizing pneumonia. (J Allergy Clin Immunol 2000;105:239-44.)

OBJECTIVE: To derive a birth weight predictive equation and to compare its diagnostic value with that of ultrasound. METHODS: A longitudinal observational cohort study, including singleton pregnancies at term, was performed at St. Orsola-Malpighi Hospital, University of Bologna (Italy). A birth weight prediction formula, including symphysis-fundal height (SFH), BMI, maternal abdominal circumference (mAC) and parity was derived from a general linear model (GLM) (retrospective study). Moreover, on a new series of patients, the fetal weight was estimated by using both GLM and ultrasound using Hadlock formula (prospective study). The residual analysis and the intraclass correlation coefficient (ICC) were used to test the accuracy of methods in predicting birth weight. RESULTS: Between January and November 2012, 1034 patients were included in the retrospective study and 44 in the prospective one. The following GLM was derived: estimated birth weight (g) = 1485.61 + (SFH (cm) × 23.37) + (11.62 (cm) × mAC) + [BMI × (-6.81)] + (parity (0 = nulliparous, 1 = multiparous) × 72.25). When prospectively applied, the GLM and ultrasound provided a percentage of prediction within ±10% of the actual weight of 73% and 84%, respectively. Ultrasound estimation, as opposite of GLM one, was significantly associated with neonatal weight (R(2 )= 0.388, F = 26.607, p value

Objective: To present our experience of symptomatic cerebral cavernous malformations (CCMs) in pregnancy and to review the literature on the topic. Methods: We retrospectively collected a case series of symptomatic CCMs during pregnancy or the puerperium. A literature search was performed to identify all similar reports. Results: We collected 16 cases of symptomatic CCMs. Haemorrhage occurred in 10 patients. Two patients opted for termination of pregnancy. Delivery occurred preterm in four cases, in only one case due to neurological symptoms at 30 weeks' gestation. Caesarean section was performed in 9 cases; concern over CCM was the indication for delivery in eight of these cases. Four out of 16 patients underwent neurosurgery, three during pregnancy. Conclusion: Symptomatic CCMs seldom require neurosurgery either during or after pregnancy and are not associated with preterm delivery.

Objective: To develop a model for prediction of late preeclampsia (PE; which develops at or after 34 weeks' gestation) based on maternal history and characteristics, mean arterial pressure (MAP), and circulating levels of mRNA for the placenta-specific 1 (PLAC1) gene in maternal plasma at 14-18 weeks' gestation. Method: This was a screening study of singleton pregnancies at 14-18 weeks' gestation including 43 women that subsequently developed PE and 200 that were unaffected by PE. A Gaussian model was fitted to the log distribution of the multiple of the median (log MoM) PLAC1 mRNA in the PE group and in the unaffected group. Likelihood ratios for log MoM of circulating levels of mRNA for the PLAC1 gene were used to combine the a priori risk from maternal characteristics with MAP to produce patient-specific risks for each case. Results: Screening by maternal characteristics (including BMI, woman's mother's history of PE, previous PE, and parity) (a priori risk) and MAP detected 46.8% of all cases of late PE at a fixed false-positive rate (FPR) of 10%. The addition of PLAC1 yielded a detection rate (DR) of 62.8% at the same level of FPR. PLAC1 alone yielded a DR of 30.2%. Conclusion: In late PE, molecular markers can be used to improve the DR of screening and can be a valid option for the biochemical approach.

Idiopathic bronchiolitis obliterans organizing pneumonia (BOOP) is characterized by air space inflammation and fibrosis of unknown origin. The pathogenesis of the inflammatory reaction and fibrosis in fibrotic lung disorders remains unclear; however, recent attention has focused on the potential role of the mast cell in the genesis of fibrosis. To determine whether mast cells are implicated in the pathogenesis of BOOP, mast cells were identified in BAL fluid and in transbronchial lung biopsy specimens from 11 patients affected by BOOP and 17 control subjects. Mast cells and tryptase were significantly increased in BAL fluid of patients with BOOP (p=0.001 and p=0.03, respectively). In lung tissue of patients with BOOP, there was an increased number of mast cells per square millimeter of lung tissue with respect to control group (p=0.001). Seventy-three percent of mast cells were found in the alveolar septa, 18% within alveoli often plunged in organizing pneumonia, 4% among alveolar lining cells, and 6% along blood vessels. No mast cells were located within alveoli in control subjects. Mast cell degranulation was evident in lung tissue specimens of patients with BOOP but not in those of control subjects (p=0.01). This study shows the importance of mast cells and mast cell activation in the pathogenesis of BOOP.

Objectives: To evaluate whether transvaginal ultrasound cervical length (TVU CL) can predict antepartum bleeding (APB) in women with low-lying placenta. Study design: A retrospective study was performed including pregnancies with low-lying placenta for which third trimester TVU CL was available. Multiple pregnancies were excluded. Short cervix was defined as TVU CL ≤25mm. Outcomes of interest were compared with respect to the TVU CL. Results: Forty three cases of singleton pregnancies complicated by low-lying placenta in third trimester were identified. Short cervix was reported in 8 cases (19%). APB (75% vs. 31 %, p = 0.02), blood transfusions (25% vs. 3%, p = 0.02), lower birth weight (2246 vs. 2985g, p = 0.02), and neonatal intensive care unit (NICU) admissions (50% vs. 17%, p = 0.04) were more frequent in the women with short cervix. Rate of unplanned cesarean delivery for APB was similar between both the groups (25% vs. 28%, p = 0.83). Conclusions: In women with low-lying placenta persisting into third trimester, short cervical length can be used as a predictor for APB

Background: Second trimester emergency cerclage is an option for pregnant women presenting bulging fetal membranes. Despite a significant prolongation of pregnancy might be achieved, serious fetal and maternal events have been reported. Exclusion of infections through preprocedure amniocentesis has been proposed. Methods: A 37-year-old woman, gravida 4 para 1, was admitted at 21 weeks of gestation to our University Hospital due to bulging fetal membranes. An amniocentesis was performed in order to exclude an actual amniotic infection. Our Microbiology Department found a negative amniotic culture for bacteria and Mycoplasma and a normal glucose and interleukin-6 level, so a cervical cerclage was performed. The patient was discharged home on oral erythromycin. Results: After 48 h, the patient complained of hyperpyrexia, shivers and reduced fetal movements. Ultrasound at admission showed absent cardiac activity and after cerclage removal a non-viable fetus was delivered vaginally. Piperacillin and tazobactam were started, but the clinical course of the patient deteriorated and she developed a cold septic shock and was submitted to hysterectomy and transferred to the ICU of our hospital. Conclusion: This report heralds that even after negative amniocentesis, a life-threatening infection may not be excluded in women candidate for emergency cerclage due to bulging fetal membranes.

OBJECTIVE: To compare the fetal loss rate

146 Background: Gastric cancer is a highly aggressive disease. No established standard first-line regimens are currently available. Aim of this study is to evaluate efficacy of dose-dense chemotherapy with DCF combined with P in patients (pts) with locally advanced or metastatic cancer of the stomach or GEJ. Methods: HER2 negative, ECOG PS 0-1, not previously treated pts, received up to 4 cycles of therapy with Panitumumab 6 mg/kg d 1, Docetaxel 60 mg/m2 d 1, Cisplatin 50 mg/m2 d 1, L-Folinic acid 100 mg/m2 d 1 and 2, followed by 5-FU 400 mg/m2 bolus d 1 and 2, and then 600 mg/m2 as a 22 h c.i. on d 1 and 2, every 2 weeks, plus Pegfilgrastim 6 mg on d 3. Pts aged ≥ 65 years were treated with the same chemotherapy schedule with a dose reduction by 30%. Pts with disease control after 4 cycles, received P until progression. Results: From 05/2010 to 01/2014, 52 consecutive pts were enrolled (75% M, 25% F; median age: 64.5 y, range: 42-75; metastatic 90%, locally advanced inoperable 10%; 96% adenocarcinoma; 13 pts with GEJ cancer). Primary end point was overall response rate (ORR). At 31 Aug 2014 cut-off date, 1 pt is still on treatment, 2 lost at f-up, 11 alive and 39 dead. 50 pts evaluable for response and all for toxicity. A median of 4 cycles (range 0-6) was administered. 3 CR, 29 PR, 10 SD and 8 PD were observed, for an ORR (by ITT) of 62% (95% CI, 48%-75) and a DCR of 81%. 26 pts entered the maintenance phase with only P and received a median 7.3 cycles (range 1-46). Median TTP was 4.8 months (95% CI, 4.1-6.9) and median OS was 9.4 months (95% CI, 7.4- 11.6). Most frequent grade 3-4 toxicities were: leucopenia (29%), neutropenia (19%), febrile neutropenia (13%), anemia (10%), asthenia (27%), mucosytis (13%), anorexia (17%), nausea/vomiting (12%), diarrhea (15%), ipokalemia (12%), and skin rash (25%). Two toxic deaths were registered (pulmonary aspergyllosis due to febrile neutropenia and gastric hemorrhage). Conclusions: Dose-dense chemotherapy combined with P is a very active regimen in gastric cancer. Due to a not negligible toxicity profile, it may represent a treatment option in neoadjuvant setting. Clinical trial information: 2009-016962-10.

4112 Background: TCF is a standard first line option for GEC. The Norton-Simon hypothesis suggests that chemotherapy efficacy can be enhanced by decreasing intervals between cycles. We previously reported on the high activity of TCF-dd in GEC (Tomasello 2010). The aim of this study is to investigate the efficacy and safety of this intensified dose-dense regimen in a single-center large cohort of patients (pts). Methods: 150 pts with measurable or evaluable GEC, PS 0-2, with adequate organ function, treated in our center from 2004 to 2012 received TCF-dd: Docetaxel (60-85 mg/m2 d 1), Cisplatin (50-75 mg/m2 d 1), l-Folinic Acid (100 mg/m2 d 1-2), 5-FU (400 mg/m2 bolus d 1-2, and 600 mg/m2 as a 22 h continuous infusion d 1-2), plus Pegfilgrastim 6 mg d 3, every 14 days. Pts aged ≥ 65 years received the same schedule with a dose reduction by 30%. Analysis was based on the intention to treat population. Results: At a median follow-up of 44 months, 128 pts were evaluable for response, all for survival. Median age 65 (range 31-81), M:F 112:38. 17 pts (11%) with locally advanced inoperable GEC, 133 pts (89%) with metastatic GEC. Metastatic sites: liver 40%, peritoneum 31%, bone 14%, lung 12%. A median of 4 cycles (range 1-7) per patient was administered. 33% required a dose reduction. 33% were treated without any delay. 10 CR, 74 PR, 24 SD and 20 PD were observed, for an ORR of 66% (95% CI 57-74). Median OS was 13 months (95% CI 9.7-14.2). Most frequent grade 3/4 toxicities: neutropenia (34%), asthenia (28%), thrombocytopenia (17%), hypokalemia (16%), diarrhea (11%), febrile neutropenia (10%), anemia (9%), and stomatitis (4%). 11 pts (7%) [7 metastatic, 4 locally advanced] became operable after TCF-dd and underwent surgery. We identified 12 metastatic pts (8%) with overall survival > 3 years and 7 (5%) still maintaining a long lasting CR at the time of the current analysis. Conclusions: TCF-dd in GEC is very active and may be an option for conversion therapy. Toxicity can be relevant and requires a careful monitoring.

e15086 Background: Gastric cancer is more common in elderly pts with its highest incidence around the seventh decade of life. Most oncologists are reluctant to treat this population with the most active polichemotherapy combinations because of safety concerns. Subgroup analyses of elderly pts enrolled in European studies show limited and conflicting data.We previously reported on the feasibility and high activity of a dose-dense TCF regimen (Tomasello 2010). This is a retrospective analysis of efficacy and safety of this schema in the elderly pts subgroup (≥ 65 years). Methods: From Nov 2004 to Jan 2013, 119 consecutivepts with MGC, PS 0-2, not previously treated, received Docetaxel 70 mg/m2 d1, Cisplatin 60 mg/m2 d1, l-Folinic Acid 100 mg/m2 d1-2, followed by 5-FU 400 mg/m2 bolus d1-2, and then 600 mg/m222 h c.i. d1-2, every 2 weeks, plus Pegfilgrastim 6 mg on day 3. Pts aged ≥ 65 years (60) received the same schedule with doses reducted by 30%. Results: Overall pts characteristics: 76% male, 24% female; median age: 65, range 31-81. A median of 4 cycles was administered. 102 pts were evaluable for response (86%) and all for toxicity. In pts aged ≥ 65 y, we observed 5 CR (8%), 26 PR (43%), 10 SD (17%) and 7 PD (12%); in younger pts: 3 CR (5%), 32 PR (54%), 9 SD (15%) and 10 PD (17%); ORR by ITT was 56% (95% CI 45-64). Median OS was 11,2 months (95% CI 9,4-14,1); in elderly and younger pts was 11,2 (95% CI 7,3-15,1) and 11,8 (95% CI 9,2-16,2), respectively. Out of 48 evaluable pts aged ≥ 65 years, 24 (50%) were treated at full doses without any delay. In the elderly most frequent grade 3-4 toxicities were: neutropenia (13%, p

4097 Background: MGC is a chemosensitive tumour. According to the Norton-Simon hypothesis, a reduction of tumor burden could best be achieved by shortening the interval between the cycles, and the resistance might be overcome by switching from initial chemotherapy to a new, non cross-resistant one. We previously reported on the high efficacy of a new strategy using 2 sequential, non cross-resistant chemotherapy regimens in MGC (Cancer Chemother Pharmacol 11 Jan; 67 (1): 41-8). Aim of this study is to evaluate this therapeutic approach in a larger case series. Methods: 43 patients (pts) treated at our centre from November 04 to April 11 were included. All pts were chemo-naïve and received 4 cycles of TCF-dd (see reference above for doses) every 2 weeks. Subsequently and irrespective of their response, they received 4 cycles of COFFI (see reference above ) every 2 weeks. In both regimens pegfilgrastim 6 mg sc on day 3 was included. Results: Median age: 63; 74% male. PS 0-1. After the first regimen (TCF-dd) 43 pts were evaluable for response.We registered 3 CR, 27 PR, 7 SD, 5 PD and 1 not evaluable for an ORR at ITT of 70% (95% CI, 58-85). All pts proceeded to the second regimen (COFFI) and 40 pts were evaluable for response. The 3 CR observed after TCF-dd were maintained. Among the 27 pts with PR after TCF-dd, 2 achieved CR, 14 improved the response, 6 maintained PR, 3 progressed. Among the 7 pts with SD after TCF-dd, 1 achieved CR, 3 achieved PR, 2 progressed and 1 is not valuable. Among the 5 pts with PD after TCF-dd, 1 achieved CR, 4 achieved RP. After COFFI we observed 5 CR, 21 PR, 9 SD and 5 PD. The ORR in the 40 pts was 60% (95% CI, 50-80). Considering both regimen ORR was 93%. mTTP was 12.1 months (95% CI, 8,1-16,2). mOS was 16.1 months (95% CI, 12.7-21.6). At Dec '11, 4 out of 8 pts who achieved CR are alive and disease free. Most frequent G3-4 toxicities were: astenia (32%), neutropenia (35%), anemia (14%), neurotoxicity (21%). Conclusions: The study confirms that a sequential dose-dense strategy using TCF-dd followed by COFFI is feasible and highly effective and deserves to be tested in a randomized study which is on going.

an association with small for gestational age neonates? Giuliana Simonazzi, Alessandra Curti, Brunella Guerra, Margherita Contoli, Paola Murano, Chiara Puccetti, Antonio Farina, Nicola Rizzo Department of Obstetrics and Gynecology, St. Orsola Malpighi Hospital, Bologna, Italy, Department of Obstetrics and Gynecology, St. Orsola Malpighi Hospital, Bologna, Italy, bologna, Italy OBJECTIVE: to evaluate the rate of small for gestational age (SGA) neonates in primary cytomegalovirus (CMV) infection and the performance of prenatal ultrasound in prediction of SGA. STUDY DESIGN: Retrospective study including primary CMV infections referred to our Hospital between 2007 and 2011. Neonates were classified as uninfected, infected asymptomatic and symptomatic. Abdominal circumference (AC) and estimated fetal weight (EFW) were used to build up a ROC curve for evaluating the detection rate (DR) of ultrasound in prediction of infected SGA neonates. RESULTS: Follow-up was available in 209 cases. Sixty-two neonates (29%) resulted infected at birth; 14 were symptomatic (22%); congenital neurosensory hearing loss was diagnosed in all cases, one of them presented also a brain anomaly. The overall SGA rate was 10% and the distribution did not differ in the groups (8% vs 12% vs 21%, respectively). Prenatal ultrasound data were available in 130 cases. Uterine artery Doppler was altered in 2 cases (15%), both within uninfected group. According to prediction of SGA in maternal infection, a cut off of 10th centile of EFW achieved a DR of 25% (FPR of 6%). Within infected neonates, instead, a DR of 25% and 50% was achieved by AC and EFW, respectively (at FPR of 10%) and correspondent cut-off value were 22th and 10th centile. CONCLUSION: congenital CMV infection does not seem to be associated with increased rate of SGA neonates. Ultrasound not identify properly SGA neonates in case of both primary maternal infection or congenital infection. Neurosensory hearing loss is very frequent in infected SGA neonates.