Norbert Szunyogh

Spontaneous Regression of a Breast Carcinoma: A Case Report

Spontaneous regression of malignant tumors is a rare event. It is defined as partial or total disappearance of a proven malignant tumor without adequate medical treatment. The causes of this phenomenon are various. Nevertheless, malignant tumors do regress occasionally for no apparent reason, as evidenced by many clinical observations. We report a case of a 68-year-old woman, who was presented with a several-month history of a painless firm lump, initially of 1 cm in diameter and growing to a large solid regular tumor of 2.5 × 2.5 cm in size, in the upper outer quadrant of her right breast. Preoperative histopathological diagnosis revealed ductal invasive carcinoma. Later on, while awaiting surgical treatment, she suffered an arm injury requiring a 1-month delay of surgery. After recovery, on the date of surgery the tumor disappeared, and, in addition, it was not found in tissue specimens obtained from quadrantectomy. After 78 months of follow-up there was no evidence of relapse. In this report, we discuss clinical and histopathological findings, patient management and possible mechanisms of cancer regression.

Human epithelial growth factor receptor 2[Ile655Val] polymorphism and risk of breast fibroadenoma.

Studies on the association between the Ile to Val polymorphism at codon 655 of the human epithelial growth factor receptor 2 (HER-2) gene and susceptibility to breast cancer have been reported for almost all ethnic populations, with both positive or negative conclusions. No study, however, has yet been focused on the possible association between this gene and its predisposition to benign breast lesions, especially on risk for fibroadenoma. We aimed to study the association of the single nucleotide polymorphism V655 HER-2 gene polymorphism with histologically verified breast fibroadenoma risk. We conducted a molecular epidemiological case–control study of 70 breast fibroadenoma cases without cellular atypia and 172 healthy female controls. We found that the Val variant allele and genotype frequency of this polymorphism is higher in cases with fibroadenoma; however, this difference was not significant (allele Val 655: 27.86 and 22.67% in fibroadenoma and controls, respectively; genotype Ile/Val: 35.71 and 38.37% and Val/Val: 10.0 and 3.49% in fibroadenoma and controls, respectively). Applying logistic regression analysis, we found an increased risk of fibroadenoma formation in carriers of the Val allele (odds ratio=1.17; 95% confidence interval=0.67–2.05), in which the highest risk was associated with homozygous genotype (odds ratio=3.07; 95% confidence interval=0.97–9.72), but this risk was not significant. Stratification by age (cut-off 45 years) revealed the highest risk of fibroadenoma among young women homozygous for the Val allele (odds ratio=3.30). The risk, however, was slightly increased (odds ratio=1.24) among older carriers of the aberrant allele in their genotype as well, but it was not significant. In spite of insignificant differences, our results indicate that HER-2 Ile655Val polymorphism, especially in a homozygous form might play some role in the etiology of breast fibroadenoma formation. The significance of this susceptibility, however, will have to be verified by larger studies.

Atypical ductus venosus blood flow pattern during a prolonged fetal heart rate deceleration in labor

The incidence of atypical ductus venosus (DV) waveforms is under-reported in the literature. We read with interest the article of Smrcek et al.1 on seven cases of atypical DV waveform patterns due to structural cardiac defects. In all seven cases severe tricuspid valve regurgitation was present. Such a phenomenon may be accompanied by systolic notching and may cause reduced peak systolic velocity (S-wave) compared to the peak diastolic velocity (D-wave) in the DV, especially after the conversion from tachycardia to sinus rhythm. Besides such cases with structural heart defects, atypical DV waveforms can be observed as a result of different fetal positions in healthy fetuses2,3. We report on a case with an atypical DV waveform at the very last moments of a term labor, recorded during a prolonged deceleration. At the time of examination the fetal heart rate (FHR) was 80 beats per min (Figure 1). This coincided with a sudden decrease in arterial oxygen saturation, measured by pulse oxymetry, from 40% to values below 10% (Figure 2). A similar characteristic DV pattern was observed by Gudmundsson et al.4 during hypoxemia-induced bradycardia in ovine fetuses. An explanation for this could be that fetal heart rate affects central venous pressure and DV blood flow velocities in a parabolic fashion4. Accordingly, an increase in venous pressure and a corresponding decrease or absence of enddiastolic blood velocities during atrial contraction occur regularly but are dependent on the severity of bradycardia. In our case, a hypoxia-induced deceleration of the FHR (bradycardia) occurred, which lasted several

Uterine activity and ductus venosus flow velocity patterns during the first stage of labor

Objective: To analyze the effects of uterine contractions on ductus venosus (DV) pulsatility during the first stage of labor. Methods: Twenty healthy women were examined. Measurements were taken at three stages of cervical dilatation (< 4 cm, 4–7 cm and ≥ 8 cm) during and between contractions. Peak velocity during ventricular systole (S) and atrial contraction (A), pulsatility index for veins (DV PIV), ductus venosus index (DVI) and the S/A ratio were measured. Results: The DV was observed successfully in 16 cases. The mean S velocity did not change significantly (64 cm/s during and 65 cm/s between contractions). The mean A velocity decreased significantly from 35 cm/s measured between contractions to 29 cm/s during contractions (P < 0.0001). The mean DV PIV and DVI were significantly higher during contractions (0.72 and 0.55) than between contractions (0.57 and 0.45) (P < 0.0001). There were no significant differences in means between stages of cervical dilatation. Conclusion: Significant differences during and between uterine contractions can be observed in DV pulsatility during normal labor.

Ductus venosus Doppler measurement during labor.

Abstract Objectives: To assess ductus venosus (DV) indices during the first stage of labor and the effect of ruptured membranes, meconium stained liquor and epidural analgesia (EDA). Methods: Prospective cross-sectional study. Eighty-one women with low-risk singleton term pregnancies participated, 51 had normal labor (Group 1), and 30 experienced ruptured membranes and/or stained liquor (Group 2). Of the latter group 14 received EDA. The effect of various interventions and application of EDA on the ductus venosus index (DVI) and pulsatility index for veins (DV PIV) were tested. Results: The feasibility rate was 94%. A significant increase of DV indices (DVI, DV PIV) was found in group 2 (P<0.001 and P<0.0005, respectively). The A-velocity was also significantly lower in group 2 (P<0.02). A markedly significant increase of DV indices (P<0.0001) among participants receiving EDA was observed in group 2. The mean±SD indices were: 0.53±0.10 for the DVI and 0.68±0.14 for the DV PIV in those women. There was a significant positive correlation of DV indices with the duration of amniorrhea in group 2 (PIV: r=0.66; P<0.002; DVI: r=0.68; P<0.001). Conclusions: Long-term amniorrhea seems to affect the fetal venous circulation reflected in increased DV waveform indices.

Human and software error in ductus venosus Doppler waveform analysis

Ductus venosus waveform analysis has become increasingly affected by technical errors; however, these errors could be avoided if more attention was paid during sampling and analysis. The most common misevaluations include incorrect tracing, under‐ or overestimation of the peak systolic velocity, overestimation of the end‐diastolic velocity, and, as a consequence, incorrect calculation of the pulsatility index facilitated either by human or software error. This article proposes practical suggestions to avoid technical errors in ductus venosus waveform analysis.

OC114: Ductus venosus systolic and early diastolic wave indices: new markers of pre‐terminal changes in cardiac function

Objective: The atrial contraction wave is the single most important component of the ductus venosus (DV) indices used in predicting acidosis and adverse outcome. Based on the assumption that some pre-terminal changes in cardiac compliance and performance are rather reflected in the systolic and early diastolic components of the DV waveform, we aimed to establish and test new indices suitable for clinical use. Methods: DV velocities of 381 low-risk pregnancies were used to establish reference ranges for systolic pulsatility [DV-SPuls = (systolic peak − systolic nadir)/systolic peak] and early diastolic pulsatility [DV-DPuls = (diastolic peak − systolic nadir)/diastolic peak]. The DV-SPuls and DV-DPuls were determined in 123 cases where the DV Doppler recording was done ≤2 days before Cesarean section and where arterial cord pH and base excess (BE) were available at delivery, and in 15 cases of intrauterine fetal death (IUD). Power-transformation was used to achieve normality and fractional polynomial regression to calculate reference ranges, and SD-score statistics to assess deviation from the reference means. P < 0.05 was considered significant. Results: Arterial cord pH < 7.15 (n = 12), BE <−8.7 (n = 10), and particularly IUD (n = 15) were associated with increased DV-SPuls and DV-DPuls (overall p < 0.0001, and no overlap of 95%CI) when compared with the reference population. The DV-SPuls and DVDPuls were particularly high in cases with IUD (means were 2.4 and 3.1 SDs above means for the reference population) and also significantly higher than in fetuses that had arterial cord pH < 7.15 and BE <−8.7 (no overlap of 95%CI). Conclusions: Changes in the ductus venosus waveform during systole and early diastole are linked to alterations in acid base status at birth and intrauterine death. Augmented pulsations in this part of the DV wave may give valuable additional information on pre-terminal deterioration of the fetal circulation.

OP11.08: Factors influencing ductus venosus Doppler waveforms during labor

Bangkok, Thailand between June 1999 and May 2003. The measurement of four-quadrant amniotic fluid index was performed by ultrasonography in the early intrapartum period. The amniotic fluid index 5 cm. The incidence of poor perinatal outcome was 16.67%. An intrapartum amniotic fluid index of ≤ 5 cm, in comparison with > 5 cm, is associated with an increased risk of poor perinatal outcome (P < 0.05). The sensitivity, specificity, positive and negative predictive values and accuracy of four-quadrant amniotic fluid index ≤ 5 cm for predicting perinatal outcome were 72%, 89.86%, 58.69%, 94.13%, and 86.88%, respectively. Conclusion: An intrapartum amniotic fluid index of ≤5 cm is associated with a significantly increased risk of poor perinatal outcome. The amniotic fluid index measurement is an effective diagnostic test to identify fetus at risk in the intrapartum period of the high risk pregnancy.

OC193: The effects of epidural analgesia on the fetus: a Doppler ultrasonographic study

Objectives: To evaluate sonographic detection of fetal head rotation during the second stage of labor and to establish a correlation with station. Methods: A group of unselected women in labor underwent serial 2D ultrasound in the second stage. Before each ultrasound examination the station and rotation of the head were clinically assessed by two expert examiners. Rotation of the head was assessed with translabial ultrasound in a transverse view of the maternal pelvis by evaluating the angle between the midline of the fetal brain and the anteroposterior diameter of the pelvis. Results: Sixty women were included in the study group with a total of 168 and a median of three ultrasound and clinical examinations performed for each fetus (range, 1–6). Spontaneous vaginal delivery occurred in 43 (72%), whereas ventouse delivery or Cesarean section were performed in 11 (18%) and six (10%) cases respectively. Rotation was hardly seen on ultrasound with station 0 or + 1 (23/51, 45%), while it was usually well identified with station + 2 and more (117/117, 100%). Rotation of ≥ 45◦ was usually found with station + 2 or less in 70/75 (93%). Rotation of < 45◦ was found with station ≥ +3 or more in 45/65 cases (69%). The 11 ventouses were all applied with rotation of < 45◦ and were all easily performed. Of six Cesarean sections, rotation was undetectable or ≥ 45◦ in one and three cases respectively. Conclusions: Sonographic detection of fetal head rotation in labor is feasible by visualizing the midline of the fetal brain and comparing it with the anteroposterior diameter of the maternal pelvis. Rotation is strongly associated with fetal station and can therefore help the assessment of labor progression in the second stage, as well the choice of operative delivery.

OP21.09: Abnormal umbilical venous drainage bypassing the fetal liver is associated with impaired fetal growth

Objectives: Intra-abdominal umbilical vein (UV) distension is sometimes seen in cases of fetal demise. We hypothesize that such a UV distension may be a post-stenotic dilatation due to an umbilical ring constriction. Here we explore whether a stricture of the UV is related to UV distension and to adverse outcome. Methods: Referred high-risk pregnancies underwent Doppler assessment that included assessment of the UV at the umbilical ring. UV blood velocity >90th percentile at this site and gestational age (GA) was defined as a UV constriction. An intra-abdominal UV diameter >90th percentile was defined as distension. Pregancies were followed up with repeat observations. Placental weight and fetal outcome were noted. Results: Thirteen fetuses (11 singletons and two twins) that had UVstricture but no major anomalies were included. Median GA at first examination for 10 survivors was 27 (19–36) weeks and for three fetal deaths 24 (19–24) weeks. There was a median of 5 (range, 2–9) observations in each fetus (total 66). Nine of 13 fetuses had both UV constriction and dilatation at first examination. UV constriction >97.5th percentile and GA <24 weeks were related to birth weight <5th percentile (P < 0.05) and fetal death (P < 0.05). In subsequent observations UV constriction varied to values <90th percentile in seven of 13 fetuses. In the rest (6/13) the UV constriction resolved for the rest of pregnancy. In all cases a relatively large placental weight was seen. Furthermore, a UV distension that extended from the abdominal wall to the ductus venosus was related to increased placental weight (P < 0.05). Conclusions: UV stricture at the umbilical ring seems to be commonly linked to intra-abdominal UV distension. This supports the assumption that the UV distension is often a post-stenotic dilatation. We speculate that it is the venous constriction that restricts hemodynamic responsiveness and carries the risk of complications (rather than the distention).