A novel BRAF mutation in association with primary amelanotic melanoma with oral metastases.

BACKGROUND: In the context of amelanotic melanoma, little is known on the genetic or molecular background that determines the onset of this peculiar phenotype of melanoma and its sites of metastatic spread. However, it appears that amelanotic melanomas frequently lack BRAF mutations. OBJECTIVE: To report the genetical analysis of one case amelanotic melanoma developing oral metastasis. METHODS: The BRAF mutational status of the primary lesion was assessed by both Sanger sequencing and pyrosequencing. RESULTS: Both methodologies showed changes in three nucleotides: C1796T; G1798A and T1799A. These mutations should result in a rare double aminoacid substitution in codons 599 and 600 of the BRAF protein (BRAF T599I/V600K). CONCLUSION: This unusual mutation was associated with an uncommon clinical phenotype of the primary tumour and with an unusual site of metastatic spread. In the lack of comparable data, a potential association between the unusual mutation and clinical findings remains a matter of further studies.

The role of cetuximab in pre-treated refractory patients with metastatic colorectal cancer: outcome study in clinical practice.

We carried out a multicentric retrospective study on cetuximab + chemotherapy in pre-treated refractory patients outside clinical protocols, by registering the main clinical and pathological parameters. We evaluated 144 pre-treated patients. Cetuximab was administered usually in combination with irinotecan (93.8%). A 45% disease control rate (complete plus partial responses plus stable disease) was obtained in 55 patients and was related to absence of weight loss (p<0.0001) and high grade (> or =2) skin toxicity (p<0.0001). Median time to progression (TTP) was 4 months (95%CI 2.7-5.3) and median overall survival (OS) was 11.8 months (95%CI 8.5-15.1). Performance status << or =1, no weight loss and high grade (>or =22) skin toxicity were related both to a longer TTP (p=0.035, p=0.035, p=0.0017) and OS (p<0.0001, p<0.0001, p=0.006). According to multivariate analysis, the absence of weight loss was related to longer TTP (HR 0.331, p=0.004) and OS (HR 0.176, p<0.0001), and EGFR over-expression (3+) to longer TTP (HR 0.402, p=0.020).

Two-dimensional ultrasound is accurate in the diagnosis of fetal craniofacial malformation.

OBJECTIVE: To assess the accuracy of antenatal ultrasound in the diagnosis of craniofacial malformations and to compare two-dimensional with three-dimensional ultrasound. METHODS: This was a retrospective study in which the archives of our ultrasound laboratory were searched for cases with an ultrasound diagnosis of craniofacial malformation in the period 1986-2001. No attempt was made to look for false-negative diagnoses. RESULTS: Sixty cases with an antenatal diagnosis of a craniofacial malformation were found: 37 with cleft lip/palate; 17 with heterogeneous dysmorphisms (including mostly micrognathia and craniosynostosis) and 6 with miscellaneous craniofacial malformations. Associated anomalies were present in 48/60 (80%) cases, and holoprosencephaly (25 cases) was the most frequent of these. In 43 (72%) cases the diagnosis was made before 24 weeks' gestation. Postnatal follow-up was available for 43 cases and there was always complete correlation between antenatal and postnatal diagnoses. Cleft lip/palate was always accurately differentiated from cleft lip. Three-dimensional ultrasound was performed in 12 cases and was successful in 11. However, it did not provide further diagnostic information with regard to the two-dimensional scan. DISCUSSION: Current two-dimensional ultrasound in expert hands allows an accurate diagnosis of craniofacial abnormalities from early gestation. In our hands, three-dimensional ultrasound did not add any valuable diagnostic information. Three-dimensional ultrasound may facilitate the understanding of the lesion by the parents and facilitate communication with the plastic surgeons. However, these potential benefits need to be carefully weighed against the costs of the ultrasound instrumentation, increased examination time and training of personnel.

Absence of the ductus venosus: report of 10 new cases and review of the literature.

OBJECTIVE: To assess the clinical significance of the absence of the ductus venosus. DESIGN: A retrospective study with a review of the literature. METHODS: The archives of our ultrasound laboratory and the English literature were searched for cases with a prenatal diagnosis of absence of the fetal ductus venosus. RESULTS: Between 1985 and 2000, 10 fetuses were diagnosed in our center as having absence of the ductus venosus. The review of the literature revealed 23 cases. Three main patterns of abnormal venous circulation were documented: (1) umbilical vein bypassing the liver and connecting directly to the right atrium (46%); (2) umbilical vein bypassing the liver and connecting to the inferior vena cava mostly through one of the iliac veins (25%); (3) umbilical vein connecting to the portal circulation without giving rise to the ductus venosus (21%). Major anomalies, including chromosomal aberrations, were found in 8/33 (24%) cases. Hydrops developed in 11/33 (33%) cases. Twenty fetuses with isolated absence of the ductus venosus were delivered, and 5 (20%) died. The portal vein was found to be absent in half of the infants examined after birth. CONCLUSIONS: Our results and the review of literature suggest that absence of the ductus venosus is associated with a high incidence of fetal anomalies and adverse outcomes, including associated malformations, chromosomal aberrations, in utero heart failure and absence of the portal vein. Heart failure and absence of the portal vein seem particularly frequent when absence of the ductus venosus is associated with a connection of the umbilical vein to either the inferior vena cava or the right atrium.

Prenatal diagnosis of congenital cytomegalovirus infection.

We report here the results of a study on the prenatal diagnosis of congenital cytomegalovirus (CMV) infection. The study was carried out by both PCR and virus isolation from amniotic fluid (AF) for 82 pregnant women at risk of transmitting CMV for the detection of (i) seroconversion to CMV immunoglobulin G (IgG) positivity during the first trimester of pregnancy, (ii) symptomatic CMV infection in the mother during the first trimester of pregnancy or intrauterine growth retardation detected by ultrasound or abnormal ultrasonographic findings suggestive of fetal infections, and (iii) seropositivity for CMV-specific IgM. For 50 women, fetal blood (FB) was also obtained and tests for antigenemia and PCR were performed. The results indicate that AF is better than FB for the prenatal diagnosis of CMV infection. PCR with AF has a sensitivity (SNS) of 100%, a specificity (SPE) of 83.3%, a positive predictive value (PPV) of 40%, and a negative predictive value (NPV) of 100%; rapid virus isolation with the same material has an SNS of 50%, an SPE of 100%, a PPV of 100%, and an NPV of 94.7%. Fewer than 10% of the women positive for IgM by enzyme immunoassay (EIA) had a congenitally infected fetus or newborn infant. When EIA IgM positivity was confirmed by Western blotting (WB) and the WB profile was considered, the percent transmission detected among women with an "at-risk" profile was higher than that observed among IgM-positive women and was the same as that among women who seroconverted during the first trimester of pregnancy (transmission rates of 29 and 25%, respectively).

Changes of biological features in breast cancer cells determined by primary chemotherapy.

BACKGROUND: To evaluate the changes in the biological features of breast cancer cells induced by primary chemotherapy (PCT) and their possible relationship with the response to therapy we performed an extensive immunohistochemical study before and after PCT. PATIENTS AND METHODS: PCT was administered to 29 women with breast cancer. On specimens obtained by tru-cut and post-chemotherapy surgery we analyzed the following parameters: histology, histologic grade, apoptotic index, hormone receptor levels, Ki67, PCNA, EGFr, bcl-2, p53, p170. The significance of the changes induced by PCT and their correlations with the type of response were evaluated. RESULTS: Twelve patients achieved a partial response with PCT. No baseline biological parameter correlated with the type of response. After PCT we observed a significant increase in the apoptotic index (p = 0.000), PCNA (p = 0.036), EGFr (p = 0.005), and p170 expression (p = 0.001), regardless of the type of chemotherapy administered (anthracyclines, 25 cases, or CMF, 4 cases). Responder patients displayed a significant decrease in ER levels (p = 0.015), whereas in non responders there was an increase in PCNA (p = 0.008) and EGFr expression (p = 0.002). The apoptotic index and p170 expression rose after PCT regardless of the type of response. CONCLUSIONS: PCT induced significant variations in the phenotype of breast cancer cells. These changes might reflect the selection of new neoplastic clones with different biological properties and so could facilitate the choice of appropriate chemotherapy agents.

Distribution of abnormal karyotypes among malformed fetuses detected by ultrasound throughout gestation.

A karyotype was obtained from 755 fetuses with structural anomalies detected by sonography between 13 and 40 weeks' gestation. Gestational age was found to have no influence on the prevalence of chromosomal aberrations. The incidence in the second and third trimesters of pregnancy was 15.7 and 17.5 per cent, respectively. The contribution of the different malformations to such proportions did, however, change throughout gestation. Cystic hygroma was by far predominant in the early second trimester, cardiac defects in the late second trimester, and duodenal atresia in late pregnancy. Our findings confirm that karyotyping of malformed fetuses is highly advisable; the importance of chromosomal investigation is not dependent on the gestational age at detection of the structural defect as the likelihood of finding a chromosomal anomaly during the second and third trimesters is quite similar. Spontaneous intrauterine selection of chromosomally abnormal fetuses is most likely counterbalanced by the limited accuracy of prenatal ultrasound in recognizing many fetal anomalies early in pregnancy.

Biometry of early pregnancy with transvaginal sonography.

A prospective cross-sectional study was performed in 248 pregnant women between 5 and 12 weeks' menstrual age with transvaginal sonography to establish biometric charts of the gestational sac, embryonic crown-rump length and biparietal diameter, amniotic sac and yolk sac to be used for assessment of gestational age and prediction of pregnancy failure. Polynomial regression analysis was applied and demonstrated a statistically significant positive correlation that could be described in all cases as a quadratic function, between gestational age and all the measurements with the exclusion of the yolk sac. Centile charts of both growth models and dating models were tabulated. The interrelationship between different measurements, including the gestational sac, crown-rump length, biparietal diameter and amniotic sac was also evaluated to produce age-independent charts. The dating model of the crown-rump length was found to have mean values similar to those described in transabdominal studies. The 95% reference interval was, however, 8.4 days, which was not lower than those reported in most transabdominal studies. It was concluded that transvaginal sonography was more able than the abdominal route to allow measurement of the crown-rump length in very early gestation, but did not yield a greater accuracy in predicting gestational age.