An 18-year Study of Malignant Melanoma in Childhood and Adolescence.

Malignant melanoma is rare in childhood and adolescence. Diagnostic uncertainty and misdiagnosis often lead to delayed treatment. METHODS: We evaluated children and adolescents under 20 years of age presenting with malignant melanoma at our institution over an 18-year period. Data were collected, analyzed, and interpreted, following which findings were compared with the existing literature. RESULTS: Twenty-four patients were included in the study with mean follow-up of 61.8 months. Males comprised 54% of cases. On presentation, 33% of children had melanoma of s thickness 2-4 mm and 34% had stage III disease. Younger children presented with thicker melanomas, differing subtypes, and more advanced stage disease compared with older children. Extremities were the most common sites affected (42%). Dissection of the draining lymph node basins was undertaken in 38% of cases. Overall survival was 92%. CONCLUSIONS: Tumor subtype, biology, hormonal influence, and lymph node status are all important prognostic factors in malignant melanoma in childhood and adolescence. Compared with adults, children presenting with thicker melanomas and more advanced stage disease generally have more favorable outcomes and a better survival. Plastic surgeons, commonly encountering skin lesion in children, must maintain a high index of suspicion so that early excision and sentinel lymph node biopsy may be promptly offered to patients with melanoma.

Does oral carbohydrate supplementation improve labour outcome? A systematic review and individual patient data meta-analysis.

BACKGROUND: Labour is a period of significant physical activity. The importance of carbohydrate intake to improve outcome has been recognised in sports medicine and general surgery. OBJECTIVES: To assess the effect of oral carbohydrate supplementation on labour outcomes. SEARCH STRATEGY: MEDLINE (1966-2014), Embase, the Cochrane Library and clinical trial registries. SELECTION CRITERIA: Randomised controlled trials (RCT) of women randomised to receive oral carbohydrate in labour (<6 cm dilated), versus placebo or standard care. DATA COLLECTION AND ANALYSIS: Authors were contacted to provide data. Individual patient data meta-analyses were performed to calculate pooled risk ratios (RR) and 95% confidence intervals (CI). MAIN RESULTS: Eight RCTs met the inclusion criteria. Six authors responded, four supplied data (n = 691). Three studies used isotonic drinks (one placebo-controlled, two compared with standard care), and one an advice booklet regarding carbohydrate intake. The mean difference in energy intake between the intervention and control groups was small [three studies, 195 kilocalories (kcal), 95% CI 118-273]. There was no difference in the risk of caesarean section (RR 1.15, 95% CI 0.83- 1.61), instrumental birth (RR 1.26, 95% CI 0.96-1.66) or syntocinon augmentation (RR 0.99, 95% CI 0.86-1.13). Length of labour was similar (mean difference -3.15 minutes, 95% CI -35.14 to 41.95). Restricting the analysis to primigravid women did not affect the result. Oral carbohydrates did not increase the risk of vomiting (RR 1.09, 95% CI 0.78-1.52) or 1-minute Apgar score <7 (RR 1.23, 95% CI 0.82-1.83). AUTHORS' CONCLUSION: Oral carbohydrate supplements in small quantities did not alter labour outcome. TWEETABLE ABSTRACT: Oral carbohydrate does not affect labour. But the difference between intervention and control equals 10 teaspoons sugar.

Antenatal magnetic resonance imaging versus ultrasound for predicting neonatal macrosomia: a systematic review and meta-analysis.

BACKGROUND: Fetal macrosomia is associated with an increased risk of adverse maternal and neonatal outcomes. OBJECTIVES: To compare the accuracy of antenatal two-dimensional (2D) ultrasound, three-dimensional (3D) ultrasound, and magnetic resonance imaging (MRI) in predicting fetal macrosomia at birth. SEARCH STRATEGY: Medline (1966-2013), Embase, the Cochrane Library and Web of Knowledge. SELECTION CRITERIA: Cohort or diagnostic accuracy studies of women with a singleton pregnancy, who had third-trimester imaging to predict macrosomia (>4000 g, >4500 g or >90th or >95th centile). DATA COLLECTION AND ANALYSIS: Two reviewers screened studies, performed data extraction and assessed methodological quality. The bivariate model was used to obtain summary sensitivities, specificities and likelihood ratios. MAIN RESULTS: Fifty-eight studies (34 367 pregnant women) were included. Most were poorly reported. Only one study assessed 3D ultrasound volumetry. For predicting birthweight >4000 g or >90th centile, the summary sensitivity for 2D ultrasound (Hadlock) estimated fetal weight (EFW) >90th centile or >4000 g (29 studies) was 0.56 (95% CI 0.49-0.61), 2D ultrasound abdominal circumference (AC) >35 cm (four studies) was 0.80 (95% confidence interval [95% CI] 0.69-0.87) and MRI EFW (three studies) was 0.93 (95% CI 0.76-0.98). The summary specificities were 0.92 (95% CI 0.90-0.94), 0.86 (95% CI 0.74-0.93) and 0.95 (95% CI 0.92-0.97), respectively. CONCLUSION: There is insufficient evidence to conclude that MRI EFW is more sensitive than 2D ultrasound AC (which is more sensitive than 2D EFW); although it was more specific. Further primary research is required before recommending MRI EFW for use in clinical practice. TWEETABLE ABSTRACT: Systematic review of antenatal imaging to predict macrosomia. MRI EFW is more sensitive than ultrasound EFW.

Fractional volume of placental vessels in women with diabetes using a novel stereological 3D power Doppler technique.

OBJECTIVES: In maternal diabetes the placenta is large with abnormal vascular development and increased villous volume. We used a novel stereological 3D power Doppler ultrasound technique to investigate differences in-vivo in the placental fractional volume of power Doppler signal (FrVol-PD) between women with and without diabetes. METHODS: We recruited 17 pregnant women with pre-gestational diabetes and 20 controls, all with anterior placentae. Each subject had ultrasound scans (Voluson 730 Expert) every 4 weeks between 12 and 32 weeks gestation. 3D power Doppler data were acquired and the placenta manually outlined using VOCAL (4D View). Power Doppler signal within the resultant volume was counted in a 3D manner adapting the random but systematic techniques used in stereology. RESULTS: Subjects were of similar age, BMI and parity. From 16 weeks the mean (SD) placental FrVol-PD was higher in the non-diabetic than in the diabetic group: 16 weeks - 0.125 (0.03) versus 0.108 (0.03), 20 weeks - 0.144 (0.05) versus 0.104 (0.03), 24 weeks - 0.145 (0.05) versus 0.128 (0.03), 28 weeks - 0.159 (0.05) versus 0.133 (0.02) and 32 weeks - 0.154 (0.03) versus 0.123 (0.04). These differences were significant between control and diabetic subjects [F(1,35) = 4.737, p = 0.036] and across gestation [F(3,140) = 8.294, p < 0.001]. CONCLUSION: Using a novel stereological-based ultrasound technique we have demonstrated the reliability of this application in the placenta. This technique shows promise for non-invasive assessment of placental function: further studies are required to identify if structural changes in a diabetic placenta are accompanied by altered function, manifest as reduced perfusion demonstrable in-vivo.

Measurement of fetal fat in utero in normal and diabetic pregnancies using magnetic resonance imaging.

OBJECTIVES: To assess the reliability of magnetic resonance imaging (MRI) to measure fetal fat volume in utero, and to study fetal growth in women with and without diabetes in view of the increased prevalence of macrosomia in the former. METHODS: We studied 26 pregnant women, 14 with pre-gestational diabetes and 12 non-diabetic controls. Fetal assessment took place at 24 weeks' gestation and again at 34 weeks by standard ultrasound biometry followed by MRI at 1.5 T. Fetal fat volume was determined from T1-weighted water-suppressed images using a semi-automated approach based on pixel intensity and taking into account partial volume effects. Fetal volume was also determined from the MRI images. Fetal weight was calculated using published fat and lean tissue densities. RESULTS: There was little fetal fat at 24 weeks' gestation, but at 34 weeks the fetal fat content was considerably higher in the women with diabetes, with a mean fat content of 1090 ± 417 cm(3) compared with 541 ± 348 cm(3) in the controls (P = 0.006). Measurements of fetal fat volume showed low intra- and interobserver variability at 34 weeks, with intraclass correlation coefficients consistently above 0.99. Birth-weight centile correlated with fetal fat volume (R(2) = 0.496, P < 0.001), percentage of fetal fat (R(2) = 0.362, P = 0.008) and calculated fetal weight (R(2) = 0.492, P < 0.001) at 34 weeks. CONCLUSIONS: MRI appears to be a promising tool for the determination of fetal fat, body composition and weight in utero during the third trimester of pregnancy.

Utero-placental haemodynamics in the pathogenesis of pre-eclampsia.

Pre-eclampsia is associated with insufficient adaptations of spiral arteries which theoretically alter haemodynamics within the intervillous space. Such changes could damage the syncytiotrophoblast and release factors which instigate maternal endothelial dysfunction. We tested this hypothesis using an in vitro dual perfusion model of the human placenta, representing putative changes in flow arising from these spiral artery maladaptations. Whilst fetal-side flow rates remained constant (6 ml/min) perfusion rates on the maternal side were increased from 14 ml/min to 45 ml/min. As well as increasing placental derived intervillous hydrostatic pressures, and changes in flow dynamics observed by colour Doppler, these elevated flow rates resulted in morphologic damage, vacuolation and shedding of the syncytiotrophoblast, focal features previously defined in pre-eclampsia. The collected maternal perfusates recovered under high flow conditions also contained significantly elevated levels of biochemical markers of syncytial damage, including lactate dehydrogenase, alkaline phosphatase and human chorionic gonadotrophin. There were also significant elevations in chemokines GROalpha and RANTES, compared with the low flow perfusions. The soluble components of the maternal high flow rate perfusions decreased the number and proliferation of HUVECs after 24h exposure. These results could not be attributed to GROalpha or RANTES alone or in combination. This study provides evidence that alterations in intervillous flow have the potential to influence both the integrity of the syncytiotrophoblast and the liberation of potentially pathogenic soluble factors. This therefore offers a putative link between utero-placental maladaptations in pregnancy and the vascular endothelial complications of pre-eclampsia.

Changes in myometrial 'perfusion' during normal labor as visualized by three-dimensional power Doppler angiography.

OBJECTIVES: Myometrial contractions are one of the most important aspects of effective labor. For cells within the myometrium to work efficiently they need to be well oxygenated and this requires an adequate blood supply. This study used quantitative three-dimensional (3D) power Doppler angiography to calculate the percentage change in myometrial blood flow during a relaxation-contraction-relaxation cycle of active labor. METHODS: Transabdominal 3D power Doppler ultrasound imaging was used to acquire volumetric data during the first stage of spontaneous labor in 20 term, nulliparous women. 3D datasets were acquired during a single cycle of uterine relaxation, contraction and subsequent relaxation for each subject. The resultant datasets were analyzed independently by two investigators on two occasions using Virtual Organ Computer-aided AnaLysis to define a volume of interest within the myometrium; the power Doppler signal within this volume was quantified to provide 3D indices of vascularity: vascularization index (VI), flow index (FI) and vascularization flow index (VFI). The percentage change in these indices, during a uterine contraction, was calculated from the baseline value during the initial uterine relaxation phase (taken as a maximum of 100%). RESULTS: Myometrial blood flow fell significantly during the uterine contraction and returned during the subsequent relaxation phase of the cycle (P < 0.001 for VI and VFI, P = 0.002 for FI). From the initial baseline relaxation value, VI dropped to 43.9%, FI to 85.5% and VFI to 40.8% during uterine contraction, and returned to 86.7%, 98.1% and 89.1%, respectively, during the subsequent relaxation. The intraclass correlation coefficients in blood flow measurements of 0.982-0.999 between the two investigators were indicative of good interobserver reliability. CONCLUSIONS: This study confirms that myometrial perfusion, as measured by quantitative 3D power Doppler angiography, significantly falls during uterine contractions, returns during the subsequent relaxation phase, and can be quantified reliably from stored datasets. Further work is now required to establish clinical applicability for this non-invasive investigation.

In vitro dual perfusion of human placental lobules as a flow phantom to investigate the relationship between fetoplacental flow and quantitative 3D power doppler angiography.

Flow phantoms have been used to investigate and quantify three-dimensional power Doppler data but this is the first study to use the in vitro, dual perfused, placental perfusion model. We used this model to investigate and quantify the effect of variation in fetal-side flow rates and attenuation on 3D power Doppler angiography. Perfusion of a placental lobule was commenced within 30 min of delivery and experimentation was successful in 8 of the 18 placenta obtained. Fetal and maternal perfusate was modified Earle's bicarbonate buffer which, following equilibration, was supplemented on the fetal side with whole heparinised cord blood. Imaging was performed with a Voluson-i ultrasound machine. A 'vascular biopsy' the thickness of the placental lobule was defined and signal quantified within using VOCAL (GE Medical Systems, Zipf, Austria). Three vascular indices are generated: vascularisation index (VI) defined as the percentage of power Doppler data within a volume of interest; flow index (FI), the mean signal intensity of the power Doppler information; and vascularisation flow index (VFI), a combination of both factors derived through their multiplication. Attenuation was investigated in this model with the addition of tissue mimic blocks. Our results showed a predictable relationship between flow rates and the vascular indices VI and VFI. However the FI was a less reliable predictor of flow; thus it should be interpreted with caution. The power Doppler signal was markedly affected by attenuation leading to a complete loss of information at a depth of 6 cm in the model used. In conclusion this model can be adapted to provide a phantom to analyse and quantify 3D power Doppler signals and demonstrates that vascular indices within a tissue remain related to volume flow. This model provides further evidence that depth dependent attenuation of signal needs to be accounted for in any in vivo work where the probe is not in direct contact with the tissue of interest.