B-flow/spatiotemporal image correlation M-mode: novel ultrasound method that detects decrease in spiral artery luminal diameter in first trimester in primate model of impaired spiral artery remodeling.

OBJECTIVE: To determine if B-flow/spatiotemporal image correlation (STIC) M-mode ultrasonography detects a decrease in spiral artery luminal diameter and volume flow during the first trimester in a non-human primate model of impaired spiral artery remodeling (SAR). METHODS: Pregnant baboons were treated daily with estradiol benzoate on days 25-59 of the first trimester (term, 184 days), or remained untreated. On day 60 of gestation, spiral artery luminal diameter (in seven untreated and 12 estradiol-treated baboons) and volume flow (in four untreated and eight estradiol-treated baboons) were quantified by B-flow/STIC M-mode ultrasonography. In addition, in 15 untreated and 18 estradiol-treated baboons, the percent of spiral arteries remodeled by extravillous trophoblasts was quantified ex vivo by immunohistochemical image analysis on placental basal plate tissue collected via Cesarean section on day 60. Findings were compared between treated and untreated animals. The correlation between spiral artery luminal diameter and percent of SAR was assessed in three untreated and six estradiol-treated baboons which underwent both B-flow/STIC M-mode ultrasound and quantification of SAR. RESULTS: The proportion of spiral arteries greater than 50 µm in diameter remodeled by extravillous trophoblasts was 70% lower in estradiol-treated baboons than in untreated animals (P = 0.000001). Spiral artery luminal diameter in systole and diastole, as quantified by B-flow/STIC M-mode in the first trimester of pregnancy, was 31% (P = 0.014) and 50% (P = 0.005) lower, respectively, and volume flow was 85% lower (P = 0.014), in SAR-suppressed baboons compared with untreated animals. There was a significant correlation between spiral artery luminal diameter as quantified by B-flow/STIC M-mode ultrasonography and the percent of SAR (P < 0.05). CONCLUSION: B-flow/STIC M-mode ultrasonography provides a novel real-time non-invasive method to detect a decrease in uterine spiral artery luminal diameter and volume flow during the cardiac cycle, reflecting decreased distensibility of the vessel wall, in the first trimester in a non-human primate model of defective SAR. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

When are amniotic fluid viral PCR studies indicated in prenatal diagnosis?

OBJECTIVE: To determine which prenatal ultrasound findings indicate the need to also obtain PCR studies for viral genome in women undergoing midtrimester amniocentesis. METHODS: This was a retrospective observational study on women that underwent amniotic fluid karyotyping and viral PCR testing for history or ultrasound based indication. Amniotic fluid was tested for adenovirus, cytomegalovirus, respiratory syncytial virus, enterovirus, Epstein-Barr virus, and parvovirus B19 using multiplex PCR study with multiple appropriate controls. Ultrasound findings were coded as normal or abnormal with 34 categories of ultrasound abnormality stratified into 18 subgroups. Relationships between these subgroups and karyotype/PCR results were tested by Pearson chi-square method or Fisher's exact test and overall logistic regression analysis. RESULTS: Amniotic fluid samples from 1191 patients were obtained for the study. Abnormal karyotype was detected in 5.4% of cases (64/1191), and PCR was positive in 6.5% of cases (77/1191). Abnormal fetal ultrasonographic findings were observed in 28.4% of cases (338/1191). There was an association between intrauterine growth restriction, nonimmune hydrops fetalis, hand/foot anomalies or neural tube defects (NTDs), and PCR positivity. NTDs were associated with PCR positivity in fetuses with normal karyotype and nuchal thickening, cardiac or ventral wall defects were specifically associated with aneuploidy. CONCLUSION: Amniotic fluid viral PCR testing should be considered for fetuses with intrauterine growth restriction, nonimmune hydrops fetalis, hand/foot anomalies, or NTDs. After aneuploidy is excluded, NTDs are associated with PCR positivity.

Duration of persistent abnormal ductus venosus flow and its impact on perinatal outcome in fetal growth restriction.

OBJECTIVE: To study if the duration of individual Doppler abnormalities is an independent predictor of adverse outcome in fetal growth restriction (FGR) caused by placental dysfunction. METHODS: This was a secondary analysis of patients with FGR (abdominal circumference < 5(th) percentile and umbilical artery (UA) pulsatility index (PI) elevation) who had at least three examinations before delivery. Days of duration of absent/reversed UA end-diastolic velocity (UA-AREDV), low middle cerebral artery PI (brain sparing), ductus venosus (DV) and umbilical vein Doppler abnormalities were related to stillbirth, major neonatal morbidity and intact survival. RESULTS: One hundred and seventy-seven study participants underwent a total of 1069 examinations. The duration of an absent/reversed a-wave in the DV (DV-RAV) was significantly higher in stillbirths (median, 6 days) compared with intact survivors and those with major morbidity (median, 0 days for both; P = 0.006 and P = 0.001, respectively). Duration of brain sparing was also longer in stillbirth cases compared with intact survivors (median, 19 days vs. 9 days, P = 0.02). Stepwise multinomial logistic regression showed that gestational age at delivery was a significant codeterminant of outcome for all arterial Doppler abnormalities when the DV a-wave was antegrade. However, when present, the duration of DV-RAV was the only contributor to stillbirth (probability of stillbirth = 1/(1 + exp - (interval to delivery × 1.03 - 2.28)), r2 = 0.73). Receiver-operating characteristics curve statistics showed that a DV-RAV for > 7 days predicted stillbirth (100% sensitivity, 80% specificity, likelihood ratio = 5.0, P < 0.0001). In contrast, neither neonatal death nor neonatal morbidity was predicted by the days of persistent DV-RAV. CONCLUSIONS: The duration of absent or reversed flow during atrial systole in the DV is a strong predictor of stillbirth that is independent of gestational age. While prematurity remains the strongest predictor of neonatal risks it is unlikely that pregnancy can be prolonged by more than 1 week in this setting.

Prevalence of viral DNA in amniotic fluid of low-risk pregnancies in the second trimester.

AIM: The association between fetal viral infection and adverse pregnancy outcome is well documented. However, the prevalence of common viral pathogens in the amniotic fluid of normal pregnancies is not established. The purpose of this study was to determine this prevalence in asymptomatic patients. METHODS: This was a prospective observational study of patients at low risk for viral infection who were referred for second-trimester genetic amniocentesis. In patients with normal fetal anatomy on ultrasound and a normal fetal karyotype, a 2-ml aliquot of amniotic fluid obtained at amniocentesis was analyzed by multiplex polymerase chain reaction for cytomegalovirus (CMV), parvovirus B19, adenovirus, enterovirus, herpes simplex virus (HSV), respiratory syncytial virus (RSV) and Epstein-Barr virus (EBV). RESULTS: Among 686 patients, advanced maternal age was the most common indication for genetic testing (n = 469, 68.4%), followed by elevated aneuploidy risk on triple screen (n = 164, 23.9%), elevated maternal serum alpha-fetoprotein (n = 20, 2.9%), previous aneuploidy (n = 16, 2.3%) and family history of inheritable disease (n = 14, 2.1%). Forty-four (6.4%) amniotic fluid samples were positive for viral genome. A single genome was amplified in 41 samples (93%). In three samples, two viral genomes were identified. Adenovirus was most frequently identified (37/44), followed by CMV (5/44), EBV (2/44), enterovirus (2/44) and RSV (1/44). Parvovirus and HSV were not identified. There was a bimodal seasonal variation in prevalence, with the highest prevalence during the summer and late winter. CONCLUSION: Viral genome is commonly found in amniotic fluid with a sonographically normal fetus, and the prevalence follows a seasonal pattern. The mechanism, significance and effects of this asymptomatic viral presence require further study.

Popliteal lymph node metastasis from primary cutaneous melanoma.

AIMS: To document the incidence of popliteal lymph node involvement by metastatic melanoma and to consider the implications of this information for clinical management. METHODS: From the computerized database of the Sydney Melanoma Unit, all patients with primary melanomas located at or distal to the knee were identified and their records were examined. Experience with those patients who developed popliteal node metastases was then reviewed. RESULTS: Thirteen of 4262 patients (0.31%) with primary melanomas of the distal lower limb developed popliteal node metastases. Six of the 13 patients had previous, synchronous or subsequent groin node metastases. CONCLUSIONS: Popliteal lymph node involvement by metastatic melanoma is a rare event. The study results suggest only two indications for full popliteal node clearance-either a histologically positive sentinel node in the popliteal fossa or clinical evidence of metastatic disease in a popliteal node.

Relationship between arterial and venous Doppler and perinatal outcome in fetal growth restriction.

OBJECTIVE: The aim of this investigation was to assess the relationship between abnormal arterial and venous Doppler findings and perinatal outcome in fetuses with intrauterine growth restriction (IUGR). METHODS: Doppler velocimetry of the umbilical artery (UA), middle cerebral artery (MCA), inferior vena cava (IVC), ductus venosus (DV) and free umbilical vein was performed in 121 IUGR fetuses with a UA pulsatility index (PI) > 2 SD above the gestational age mean and subsequent birth weight < 10th centile for gestational age. Groups based on the last Doppler exam were: 1 = abnormal UA-PI only (n = 42, 34.7%), 2 = MCA-PI > 2 SD below the gestational age mean (= 'brain sparing') in addition to abnormal UA-PI (n = 29, 24.0%), 3 = DV or IVC peak velocity index (PVIV) > 2 SD above the gestational age mean and/or pulsatile UV flow (n = 50, 41.3%). Z-scores (delta indices) were calculated for Doppler indices. Perinatal mortality, respiratory distress (RDS), bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), circulatory failure and umbilical artery blood gases were recorded. RESULTS: Absence or reversal of umbilical artery end-diastolic flow was observed in 4 (9.5%) of fetuses in group 1, 10 (34.5%) fetuses in group 2 and 41 (82%) fetuses in group 3. A low middle cerebral artery pulsatility index was found in 39 (78%) fetuses in group 3. Multiple regression analysis with gestational age at delivery, delta indices and cord artery blood gas as independent parameters and individual perinatal outcomes as dependent variables was performed. In this analysis the association was strongest with gestational age for each complication. There were no significant differences in Apgar scores between groups. At delivery, 'brain sparing' was associated with hypoxemia and abnormal venous flows with acidemia. Perinatal mortality was highest in group 3 and stillbirth was only observed when venous flow was abnormal. All postpartum complications were more frequent in fetuses with abnormal venous flows. The only statistically significant relation between Doppler indices and outcome was the association between abnormal ductus venosus flow and fetal death (r2 = 0.24, P < 0.05). CONCLUSION: Growth restricted fetuses with abnormal venous flow have worse perinatal outcome compared to those where flow abnormality is confined to the umbilical or middle cerebral artery. In fetuses with low middle cerebral artery pulsatility, venous Doppler allows detection of further deterioration. While abnormal venous flows can be significantly associated with fetal demise, gestational age at delivery significantly impacts on all short-term outcomes.

Coronary artery blood flow visualization signifies hemodynamic deterioration in growth-restricted fetuses.

OBJECTIVE: To determine the relationship between fetal coronary blood flow (CBF) visualization in intrauterine growth restriction (IUGR), longitudinal changes in arterial and venous flow velocity waveforms and perinatal outcome. METHODS: A total of 48 IUGR fetuses (abdominal circumference below the 5th percentile for gestational age) with absent or reversed umbilical artery (UA) end-diastolic velocity (AREDV) were examined longitudinally by echocardiography attempting CBF visualization at each examination. Doppler evaluation of the middle cerebral artery, inferior vena cava (IVC), ductus venosus (DV) and umbilical vein (UV) was performed at each examination. Doppler measurements were correct for gestational age by conversion into Z-scores (delta-indices). Doppler results and outcome from fetuses in which CBF was visualized (group 1, n = 20) and those in which CBF was never visualized (group 2, n = 28) were compared. Outcome parameters analyzed included Apgar scores, cord arterial blood gases, perinatal mortality, respiratory distress, bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis and postpartum circulatory failure requiring pressor support. RESULTS: There was no difference in Doppler indices between groups at study entry. CBF visualization coincides with a significant increase of UA-, IVC- and DV delta-indices. The greatest rate of change was observed for indices in the ductus venosus which occurred in the 24 h preceding CBF visualization. Group 1 fetuses required earlier delivery (median 27 + 4, vs. median 30 + 0), had lower birthweight (682 +/- 305 g vs. 936 +/- 416 g), lower cord pH (7.21 +/- 0.1 vs. 7.27 +/- 0.06) and cord pO2 (13 +/- 4.5 vs. 24.1 +/- 13.5 mmHg) compared to group 2 (all values P < 0.05). Mortality was similar (group 1 = 6/20, 30%; group 2 = 6/28, 21.4%). CONCLUSIONS: In IUGR, fetuses with AREDV and centralization are at high risk for hypoxemia, acidemia and adverse outcome. CBF visualization coincides with deteriorating venous flows. Operator dependence of CBF visualization and the strong association with abnormal venous flow stresses the importance of venous Doppler surveillance in these fetuses.

Incidence of malignant melanoma in Auckland, New Zealand: highest rates in the world.

The calculation of incidence rates of melanoma in New Zealand has been hampered in the past by incomplete registration of cases. The aim of this study was to document the incidence of melanoma in the Auckland Caucasian population and to define the pathologic characteristics of these lesions. Data were collected for the Auckland region from the New Zealand Cancer Registry and the Auckland Melanoma Unit database for 1995 and combined with census statistics to give the crude and age-standardized rates for invasive melanoma. The results were analyzed by gender, morphology, body site, and thickness. The crude annual incidence for invasive cutaneous malignant melanoma was 77.7/100,000. The age-standardized annual rate was 56.2/100,000 with no statistically significant differences in the rates for males and females. The cumulative risk of developing melanoma over a lifetime, from age 0 to 74, was 5.7% overall. The age-specific rates steadily increase with advancing age. The lesions were generally thin; 64% were less than 0.76 mm, and only 7% were thicker than 3.00 mm. In conclusion, the Caucasian population in the Auckland region has the highest incidence of melanoma in the world.

Sporadic primary hyperparathyroidism in young patients: a separate disease entity?

HYPOTHESIS: Sporadic primary hyperparathyroidism (1 HPT) in young persons is thought to be extremely rare. The exact incidence is unknown and little is known of the characteristics of the disease. METHODS: From 1976 to 1998, 33 patients aged 19 years or younger underwent operation for sporadic 1 HPT at a single institution. Data were recorded regarding the clinical, surgical, pathologic, and biochemical aspects, as well as long-term patient follow-up. RESULTS: There were 17 male subjects and 16 female subjects ranging in age from 9 to 19 years (median age, 17 years). Thirty-one (94%) were symptomatic: 14 (42%) had renal stones, 9 (27%) had bone disease, 1 (3%) had pancreatitis, and 7 (21%) had vague nonspecific symptoms alone. The high incidence of symptoms was matched by correspondingly high biochemical values (mean serum calcium level, 3.02 mmol/L [12.1 mg/dL]) and large adenomas (mean weight, 967 mg). Five patients (15%) underwent exploration for persistent/recurrent 1 HPT. Thirty-one patients (94%) were normocalcemic postoperatively. One patient was temporarily hypocalcemic. No patient had vocal cord paralysis or paresis. Two patients developed recurrent disease in the mean follow-up period of 10.3 years. None have shown evidence of an inherited disorder. CONCLUSIONS: It appears that 1 HPT in young patients presents as a more severe disease, in terms of symptoms, biochemistry, and extent of pathologic findings. Physicians should be aware that 1 HPT does occur in young persons in a nonfamilial setting and that it may be responsible for a wide spectrum of symptoms. As in the adult population, 1 HPT is safely and effectively treated with surgical intervention.

Indications, technique, and efficacy of alcohol injection of enlarged parathyroid glands in patients with primary hyperparathyroidism.

BACKGROUND: Percutaneous alcohol ablation of the parathyroid gland (PAAP) has been proposed as an alternative treatment for primary hyperparathyroidism in patients unsuitable for surgery. The current study aimed to determine the (1) selection criteria, (2) associated morbidity, and (3) efficacy of PAAP. METHODS: From 1987 to 1998, 36 patients with primary hyperparathyroidism (mean age 65 years) underwent PAAP. The indications for PAAP were (1) medical comorbidity, (2) technically unsafe reoperative surgery, (3) partial ablation of a single remaining gland, and (4) patient choice. RESULTS: There were no long-term complications. Two patients had temporary recurrent laryngeal nerve injury and 4 had temporary hypocalcemia. Over a median follow-up of 16 months, 12 (33%) of the patients remained eucalcemic. For analysis purposes patients were separated into 2 separate groups: 29 with attempted complete ablation and 7 with partial ablation of a single remaining gland only. Ten of the complete ablation group (34%) remained eucalcemic. In the partial ablation group only 2 remained eucalcemic, but all had adequately controlled serum calcium levels. CONCLUSION: PAAP should be considered for hyperparathyroid patients with excessive reoperative morbidity or prohibitive medical comorbidity or those in whom the intent is to partially ablate a single remaining enlarged gland. In these patients close follow-up of serum calcium is required, and repeat treatments may be necessary because recurrence of hypercalcemia is likely.

Epitrochlear lymph nodes as a site of melanoma metastasis.

BACKGROUND: The incidence of epitrochlear lymph node metastasis for patients with melanomas on the hand or forearm is disputed, and management guidelines for these nodes are unclear. METHODS: The records of 13,139 consecutive melanoma patients were reviewed to document the incidence of metastatic disease in epitrochlear nodes. The frequency of direct lymphatic drainage to epitrochlear nodes was determined for 109 patients with melanomas of the distal upper limb who had undergone preoperative lymphoscintigraphy. RESULTS: Nine of 801 patients (1.1%) with upper limb primary melanomas developed metastatic disease in an epitrochlear node, and one other patient with an occult primary tumor did so. Six of these ten patients underwent elective axillary node dissection at the time of surgery for epitrochlear node disease, and three were found to have metastatic disease in an axillary node. Epitrochlear node metastasis occurred in only two of 83 (2.4%) patients with upper extremity melanoma who underwent therapeutic axillary dissection. Of the 109 patients who underwent lymphoscintigraphy, four (3.7%) demonstrated lymphatic drainage to an epitrochlear node. CONCLUSIONS: Epitrochlear nodal involvement from melanoma of the distal upper extremity is rare, and routine epitrochlear node clearance at the time of either elective or therapeutic axillary dissection for upper extremity melanoma is not indicated. However, it is desirable to perform an axillary dissection whenever surgery for metastatic disease in an epitrochlear node is performed.

Isolated limb infusion with cytotoxic agents: a simple alternative to isolated limb perfusion.

Isolated limb perfusion (ILP) with cytotoxic agents is an effective but complex procedure. Isolated limb infusion (ILI) has been developed as a simpler alternative. Catheters are inserted percutaneously into the axial artery and vein of the affected limb and a pneumatic tourniquet is inflated proximally. Cytotoxic agents are then infused through the arterial catheter and circulated with a syringe for 15 to 20 minutes. Progressive hypoxia occurs, but normothermia is maintained. To date, 175 ILIs have been performed: 164 for melanoma and 11 for other tumours. Results obtained are similar to those obtained by conventional ILP. Morbidity is low and treatment of frail and elderly patients who would not tolerate ILP is possible. An elective double ILI protocol can be used to obtain the additional benefits of fractionated chemotherapy. The possibility of increasing ILI response rates by using other drugs and drug combinations and by multiple fractionated dosing is being investigated.

Prenatal diagnosis of ring chromosome 6.

An amniocentesis was performed on a gravida 1, para 0 23-year-old female because of high maternal serum alpha-fetoprotein and nuchal thickening/cystic mass apparent on the fetal ultrasound. Detailed ultrasound examination revealed multiple anomalies including brain abnormalities. The fetus was found to have a mosaic female karyotype: 45,XX, - 6/46,XX,r(6) (p25q27) (62 per cent:38 per cent). This is the first report of a prenatally diagnosed case of ring chromosome 6.

Intrauterine thoracentesis of fetal cystic lung malformations.

Fetal pulmonary malformations comprise a rare but often lethal group of congenital anomalies. Until recently, diagnosis and therapy were directed postnatally and therefore some cases of fetal compromise were inevitably missed. We present 2 cases in which intermittent thoracentesis of fetal cystic lung malformations resulted in a successful outcome. Intrauterine thoracentesis should be considered in the second and third trimester of pregnancy in cases which demonstrate early fetal compromise.

Elevated MSAFP levels and congenital heart defects: lack of an association.

This study was undertaken to evaluate the relationship between elevated maternal serum alpha fetoprotein (MSAFP) levels and congenital heart defects. Thirty-two infants with isolated major congenital heart defects and whose mothers had had MSAFP screening were identified. In only one case was the MSAFP greater than 2.3 multiples of the median. A review of our experience with women with elevated MSAFP levels did not document a higher rate of congenital heart malformations than would be expected based on estimated frequencies in the general population.

Spontaneous resolution of a cystic hygroma in a fetus with Turner syndrome.

The prenatal detection of a cystic hygroma (CH) in a fetus with a 45,X karyotype is described. The cystic hygroma underwent spontaneous resolution and a healthy baby with Turner syndrome was subsequently born. The implications for genetic counselling are discussed.

Bioethical issues in perinatology--is the future now?

The rapid progress of the science of perinatology has produced a broad range of capabilities in our approach to the fetus. Advances in diagnostic methodology, both invasive and noninvasive, enable early identification and potentially, early correction, of a multitude of disorders. The laboratory correlates of this progress have kept pace, with possibilities in the areas of fetal surgery and genetic manipulation which seemed fantasy only a few years ago. Important moral issues which had been deferred because of our physical limitations must now be addressed. As instigators of the scientific stampede, perinatologists must assume a major role in the ethical inquiry as well.

Fetal biophysical profile score and the nonstress test: a comparative trial.

In this prospective blind study, 735 patients with high-risk pregnancies referred for antepartum testing of fetal well-being were randomly assigned to either a fetal biophysical profile scoring (375 patients) or a nonstress testing scheme (360 patients). Management was based on the results of antepartum tests, but the method of testing used was not disclosed. Fetal biophysical profile scoring resulted in a significantly higher positive predictive value in regards to low Apgar scores. Sensitivity, specificity, and accuracy, although higher with fetal biophysical profile scoring, did not demonstrate significant differences when compared with the nonstress test. The negative predictive value between the two methods was similar. All major anomalies were detected during ultrasound scanning, whereas none of these anomalies were detected by heart rate testing alone.

Factors influencing morbidity in termination of pregnancy.

This study analyzes the morbidity of therapeutic abortion and identifies predisposing factors. A retrospective case evaluation of 2,105 pregnancy terminations was performed. Major complications occurred in 5% of those undergoing curettage procedures, 41% of women undergoing prostaglandin amnioinfusion, and 17% of those who had hysterotomy as a method of abortion. Age, parity, and history of previous pregnancy termination, had little effect on morbidity. Surgical/technical factors and reliance on amnioinfusion and hysterotomy as procedures of choice for pregnancy termination contributed significantly to the high morbidity rates. This contribution, however, was overshadowed by the influence of patient delay, physician delay, and limited abortion facilities, resulting in 35.4% of pregnancy terminations being performed in the midtrimester. Improvements in abortion technique may lower the incidence of complications, but the need for more appropriate facilities is emphasized.

PIP: The morbidity of pregnancy termination in a large university hospital in Winnipeg, Manitoba, Canada is described, and predisposing factors are analyzed. A retrospective case evaluation of 2105 pregnancy terminations was performed. Major complications occurred in 5% of those undergoing curettage procedures, 41% of women undergoing postaglandin amnioinfusion, and 17% of those who had hysterotomy as a method of abortion. Age, parity, and history of previous abortion had little effect on morbidity. Surgical/technical factors and reliance on amnioinfusion and hysterotomy as procedures of choice for abortion contributed significantly to the high morbidity rates. The influence of patient delay, physician delay, and limited abortion facilities was greater, resulting in 35.4% of abortions being performed during the midtrimester. The variable most significantly associated with abortion-related morbidity was choice of procedure. Patients undergoing midtrimester abortions had 7 times the risk of major complications compared to those having 1st trimester abortions.