Open Fetal Surgery for Ventricular-Amniotic Valve Implantation in Aqueductal Stenosis-Dependent Severe Fetal Hydrocephalus: A Case Report with 7-Year Follow-Up.

INTRODUCTION: Fetal ventriculomegaly is one of the most commonly diagnosed central nervous system pathologies of the second trimester, occurring with a frequency of 0.3-0.5/1,000 births. Severe fetal ventriculomegaly (SVM) may necessitate intrauterine intervention. Most such interventions have been made percutaneously with ultrasound guidance insertion of a pigtail catheter, which sadly often became obstructed or migrated. CASE PRESENTATION: Our case report presents the possibility of ventriculo-amniotic valve implantation (VAVI) by classic hysterotomy in isolated severe fetal hydrocephalus (IVSM) due to aqueductal stenosis. The patient was operated on similarly to open fetal surgery MOMS criteria at 24+4/7 GA, with an initial lateral ventricular dimension of 22.5 mm. A female newborn was delivered by elective cesarean section at 31+1/7 GA due to PPROM (Apgar 10' 8 points, birth weight 1,600 g), required CPAP, and removal of the drainage system due to infection and narrow lateral ventricles. Evans index (EI) gradual increase and clinical symptoms of high-pressure hydrocephalus after 10 days required a ventricle-peritoneal shunt (VPS) implantation. The newborn was discharged home after 28 days with stabile hydrocephalus (EI: 0.59-0.6), in good clinical condition. The 7-year follow-up was complicated by epilepsy, VPS shunt infections, delay in motor and intellectual functions (mild to moderate), and symptoms of atypical autism, the phenotype possibly related to a variant in ZEB2 gene. CONCLUSION: Intrauterine VAVI is a one-step procedure that is effective in draining CFS. The limitations of the method remain complications due to preterm labor and infection of the drainage system.

Decreased Maternal Morbidity and Improved Perinatal Results of Magnesium-Free Tocolysis and Classical Hysterotomy in Fetal Open Surgery for Myelomeningocele Repair: A Single-Center Study.

Fetal and maternal risks associated with open fetal surgery (OFS) in the management of meningomyelocele (MMC) are considerable and necessitate improvement. A modified technique of hysterotomy (without a uterine stapler) and magnesium-free tocolysis (with Sevoflurane as the only uterine muscle relaxant) was implemented in our new magnesium-free tocolysis and classical hysterotomy (MgFTCH) protocol. The aim of the study was to assess the introduction of the MgFTCH protocol in reducing maternal and fetal complications. The prospective study cohort (SC) included 64 OFS performed with MgFTCH at the Fetal Surgery Centre Bytom (FSCB) (2015-2020). Fetal and maternal outcomes were compared with the retrospective cohort (RC; n = 46), and data from the Zurich Center for Fetal Diagnosis and Therapy (ZCFDT; n = 40) and the Children's Hospital of Philadelphia (CHOP; n = 100), all using traditional tocolysis. The analysis included five major perinatal complications (Clavien-Dindo classification, C-Dc) which developed before the end of 34 weeks of gestation (GA, gestational age). None of the newborns was delivered before 30 GA. Only two women presented with grade 3 complications and none with 4th or 5th grade (C-Dc). The incidence of perinatal death (3.3%) was comparable with the RC (4.3%) and CHOP data (6.1%). MgFTCH lowers the risk of major maternal and fetal complications.

Fetoscopic Myelomeningocele Repair with Complete Release of the Tethered Spinal Cord Using a Three-Port Technique: Twelve-Month Follow-Up-A Case Report.

Open spina bifida is one of the most common congenital defects of the central nervous system. Open fetal surgery, which is one of the available therapeutic options, remains the gold standard for prenatal repairs. Fetoscopic closure may lower the number of maternal complications associated with open fetal surgery. Regardless of the approach, the outcome may be compromised by the development of tethered spinal cord (TSC) syndrome. At 24.2 weeks of gestation, a primipara was admitted due to fetal myelomeningocele and was deemed eligible for fetoscopic repair. Fetal surgery was performed at 25.0 weeks of gestation. It was the first complete untethering of the spinal cord and anatomic reconstruction (dura mater, spinal erectors, skin) achieved during a fetoscopic repair of spina bifida. Cesarean section due to placental abruption was performed at 31.1 weeks of gestation. VP shunting, with no need for revision, was performed at 5 weeks postdelivery due to progressing ventriculomegaly. No clinical or radiological signs of secondary tethering were observed. Neurological examination at 11 months postdelivery revealed cranial nerves without any signs of damage, axial hypotonia, decreased muscle tone in the lower extremities, and absent pathological reflexes. Motor development was slightly retarded. Complete untethering of the neural structures should always be performed, regardless of the surgical approach, as it is the only course of action that lowers the risk for developing secondary TSC.

Alternative technique of intrauterine myelomeningocele repair to decrease the incidence of unfavorable maternal and fetal outcomes.

OBJECTIVES: The aim of the study was to determine the effectiveness of an alternative method of open fetal surgery to prevent severe unfavorable prenatal events, both for the mother and the fetus. MATERIAL AND METHODS: In this study, the previously published results for a cohort of 46 patients, who had undergone intrauterine myelomeningocele repair (IUMR) at our Center by 2014, constituted the retrospective control group (CG). The MOMS protocol had been applied for hysterotomy, with an automatic uterine stapling device. The study group (SG) n = 57 was assembled during a prospective observation. IUMR was performed using an alternative method of hysterotomy, with the typical opening and closure of the uterus, without automatic stapling device, as described by Moron et al. Additionally, our single-center results were compared with the post-MOMS findings of other centers: CHOP (Children' S HOSPITAL OF PHILADELPHIA: ) and VUMC (Vanderbilt University Medical CENTER: ). RESULTS: No cases of delivery before 30 weeks of gestation (0%, 0/55) were observed in the study group, which is a statistically significant difference (p < 0.05) as compared to controls (15/44). Statistically significantly lower incidence of chorioamniotic separation (5.4% (3/55) vs CHOP 22.9% (22/96), p < 0.001) and contractile activity resulting in preterm labor (16.3% (9/55) vs CHOP 37.5% (36/96), p < 0.05) was found in the study group. Premature rupture of the membranes was statistically significantly less common in the study group as compared to controls, CHOP and VUMC (SG 12.7% (7/55) vs CG 52.2% (24/46), p < 0.001; vs CHOP 32.3% (31/96), p < 0.001; vs VUMC 22% (9/43), p < 0.01, respectively). CONCLUSIONS: The presented IUMR method is associated with improved perinatal outcomes, i.e., lower rates of preterm delivery at < 30 weeks of gestation, preterm premature rupture of membranes, and uterine contractility resulting in preterm delivery. That, in turn, results in lower prematurity rates and, consequently, more favorable neonatal outcomes.

In utero myelomeningocele repair reduces intensification of inflammatory changes in the dura mater and the skin.

Objective: Chemical and mechanical injury in myelomeningocele (MMC) during the fetal life results in functional disorders of multiple organs. Prenatal MMC repair reduces sequelae of spinal cord injury.Design: Histopathological evaluation of dura mater and skin specimens to assess the severity of inflammatory changes.Setting: Histopathological laboratory and operated patients.Participants: 45 cases (Group I)-intrauterine surgery due to MMC and 42 cases (Group II)-postnatal surgery.Outcome measures: Specimens of the skin and of the dura mater adjacent directly to the uncovered section of the spinal cord were collected for assessment. The specimens were histopathologically evaluated to assess the severity of inflammatory changes.Results: The analysis of the severity of inflammatory changes in the skin and the dura mater showed only small lymphocytic infiltration in 5 fetuses (Group I). Medium and large infiltration in the skin and the dura mater was found in all children who underwent postnatal surgery (Group II). Lymphocytic and granulocytic infiltration in the skin and the dura mater were statistically significantly more prevalent in children who underwent postnatal surgery compared to the group of children who underwent prenatal surgery (P < 0.000003).Conclusions: By reducing the time of exposure to damaging factors, prenatal MMC repair statistically reduces the risk of inflammatory changes in the exposed spinal cord and spinal nerves. Prenatal closure of spina bifida before 24 week of gestation does not reduce the severity of inflammatory changes in the exposed spinal cord.

Alternative Hysterotomy Technique for the Reduction of Prenatal Complications of Intrauterine Myelomeningocele Repair.

INTRODUCTION: The main aim of the fetal surgery of myelomeningocele (MMC) is the improvement in prognosis for children with this defect and at the same time high safety of the procedure for mother and fetus. OBJECTIVE: The aim of the study was to determine the effectiveness of alternative hysterotomy technique for fetal surgery of MMC in prevention of essential perinatal complications. METHODS: Forty-nine pregnant women diagnosed with fetal MMC (fMMC) who underwent classic hysterotomy without the use of stapler formed the study cohort. Two cases of intrauterine fetal death or neonatal death in the immediate perioperative period in the study group (SG) were excluded from further analyses. In the historical control group (46 patients) from our center hysterotomy was performed according to Management of Myelomeningocele Study (MOMS) protocol. The study cohort's outcomes were compared with the historical controls and with post-MOMS results in Children's Hospital of Philadelphia (CHOP) and Vanderbilt University Medical Center (VUMC). RESULTS: In the SG we did not observe delivery before 30 weeks of gestation (0/47; 0%) and the incidence of chorionamniotic membrane separation (CMS, 3/47; 6%) and preterm premature rupture of membranes (PPROM, 7/47; 15%) was lower compared to the other groups. Preterm delivery as a result of uterine contractions occurred significantly less frequently in the SG (8/47; 17%). Fetal surgery with classic hysterotomy resulted in rare use of magnesium sulfate (3/47; 6%). CONCLUSIONS: The alternative hysterotomy technique for fetal surgery of MMC results in low occurrences of CMS, PPROM, preterm delivery, and the rare use of tocolytics.

Open fetal surgery for myelomeningocele - is there the learning curve at reduction mother and fetal morbidity?

OBJECTIVES: We aimed to show how increased experience of a surgery team in fMMC repair influences maternal and fetal/neonatal outcomes. MATERIAL AND METHODS: We compare perinatal results of fMMC repair in our Fetal Surgery Center (FSC) in cohort groups for the early period (2005-2011 year; previous - PFSC, n = 46) and current period (2012-2015 year; current - CFSC, n = 74) to results of the randomized Management of Myelomeningocele Study (MOMS, 78 patients). RESULTS: The maternal morbidity due to fMMC repair was low and there was no difference comparing CFSC to PFSC and MOMS. The frequency of iatrogenic preterm labor (iPTL) ≤ 30 weeks of gestation decreased from 34.1% in PFSC to 23.9% in CFSC. Iatrogenic preterm premature rupture of membranes (iPPROM) was a common complication after fMMC repair in all cohorts. The total reduction rate of hindbrain hernation (HH) was similar in CFSC - 90.3% and PFSC - 82.1%. CONCLUSIONS: The increasing experience of our surgery team in fMMC repair majorly decreased the risk of iPTL.

[Prenatal myelomeningocele repair - a chance to improve the quality of life].

Spina bifida (myelomeningocele) is the most prevalent developmental defect of the nervous system. In different regions of the world it affects from 0.3 to 5 per 1000 of living neonates. It is known that the defect develops during the early fetal life however no explicit cause has been found yet. Recently it has been accepted that one of the major factors contributing to spina bifida is deficiency of folic acid in the mother's body before and during pregnancy. The first attempts to cure myelomeningocele were taken in ancient times. More extensive knowledge of aetiology and effects of spina bifida and development of new surgical techniques allowed for management not only of the defect itself but also the consequent complications. Prenatal spina bifida repair has been performed in the USA for 20 years now while European surgeons (Poland and Switzerland) have operated myelomeningocele for 12 years. Comparative analysis carried out to evaluate the patients operated for spina bifida prenatally and postnatally pointed that those after fetal repair demand the use of ventriculoperitoneal shunt for hydrocephalus twice less frequently. Thanks to shortened exposure of the spinal cord and the spinal nerves to the toxic effect of amniotic fluid and reduced exposure to mechanical injuries, prenatal myelomeningocele repair offers better opportunities to improve motor, urinary and alimentary functions, contributing then statistically to higher quality of lives of children with spina bifida.

The Use of Indomethacin with Complete Amniotic Fluid Replacement and Classic Hysterotomy for the Reduction of Perinatal Complications of Intrauterine Myelomeningocele Repair.

OBJECTIVE: This study presented outcomes of classical hysterotomy with modified antiprostaglandin therapy for intrauterine repair of foetal myelomeningocele (fMMC) performed in a single perinatal centre. STUDY DESIGN: Forty-nine pregnant women diagnosed with fMMC underwent classic hysterotomy with anti-prostaglandin management, complete amniotic fluid replacement and high dose indomethacin application. RESULTS: The average gestational age (GA) at delivery was 34.4 ± 3.4 weeks, with no births before 30 weeks GA. There were 2 foetal deaths. Complete reversal of hindbrain herniation (HH), assessed in magnetic resonance imaging at 30-31 weeks GA was found in 72% of foetuses (mostly with HH grade I prior to fMMC repair). Our protocol resulted in rare use of magnesium sulphate (6%), low incidence of chorioamniotic membrane separation - chorioamniotic membrane separation (6%), preterm premature rupture of membranes - preterm premature rupture of membranes (pPROM; 15%) and preterm labour - preterm labour (PTL; 17%). The postoperative wound continuity of the uterus was usually stable (in 72% of patients), with low frequency of scar thinning (23%). CONCLUSION: Our protocol results in rare use of tocolytics, and the low occurrences of CMS, pPROM and PTL in relation to other study cohorts: Management of Myelomeningocele Study, Children's Hospital of Philadelphia, and Vanderbilt University Medical Centre.

Changes in Platelet Count and Size Indices in Adolescent Patients With Anorexia Nervosa.

The significance of platelet size indices has not been widely analyzed in anorexia nervosa (AN). It seems important to get more knowledge on the easily available indices of platelet function obtained by routine complete blood count analysis in patients with AN. We analyzed platelet count (PLT), platelet distribution width (PDW), and mean platelet volume using an automated blood cell counter in 25 females with AN and healthy age- and gender-matched nonatopic controls. Mean PLT was significantly lower in patients with AN than in the control group. Platelet distribution width values in patients with AN were significantly higher than those in the controls. Platelet distribution width values significantly correlated with the disease duration and rate of body weight loss in the anorectic patients. Anorexia nervosa in adolescents is associated with a decrease in PLT along with an increased PDW, which may be an indicator of dysregulated thrombopoiesis.

Current views on fetal surgical treatment of myelomeningocele - the Management of Myelomeningocele Study (MOMS) trial and Polish clinical experience.

Myelomeningocele (MMC) is the most frequent congenital defect of the central nervous system for which there is no satisfactory alternative to postnatal treatment. On the contrary prenatal MMC surgery is conducting before birth and is aimed at protecting from Chiari II malformation. The main goal of fetal MMC repair is to improve development and life quality of children with Chiari II malformation. Management of Myelomeningocele Study (MOMS) which was published in 2011 clearly confirmed effectiveness of prenatal surgery. In this paper we compare MOMS results with our own clinical experience. Thanks to high effectiveness and significant improvement in safety of maternal-fetal surgery prenatal MMC surgery become a new standard of treatment.

Myometrial contractility influences oxytocin receptor (OXTR) expression in term trophoblast cells obtained from the maternal surface of the human placenta.

BACKGROUND: Oxytocin (OXT) acts through its specific receptor (OXTR) and increased density of OXTR and/or augmented sensitivity to OXT were postulated as prerequisites of normal onset of labor. Expression of OXTR in the placental term trophoblast cells has not yet been analyzed in the context of contractile activity of the uterus. Here we examine comparatively OXT contents in the placental tissue adjacent to the uterine wall and expressions of OXTR in this tissue and corresponding isolated placental trophoblast cells. METHODS: Twenty eight placentae after normal labors at term (group I, N = 14) and after cesarean sections performed without uterine contractile activity (group II, N = 14) have been collected. Tissue excised from the maternal surface of examined placenta was used for OXT concentration measurement, cytotrophoblast cell cultures preparation and immunohistochemistry of OXTR. Concentration of OXT was estimated in the tissue homogenates by an enzyme immunoassay with colorimetric detection. Cytotrophoblast cells were isolated using Kliman's method based on trypsin, DNase, and a 5-70% Percoll gradient centrifugation. The cultures were incubated for 5 days in normoxia. Both placental specimens and terminated cytotrophoblast cultures were fixed and embedded in paraffin before being immunostained for OXTR. Using light microscopy with computed morphometry for quantitative analysis, OXTR expressions were estimated in calibrated areas of the paraffin sections. RESULTS: There were not significant differences between the groups in respect to the mean OXT concentration. However, in both groups the median value of OXT concentration was significantly (p < 0.05) higher in the tissue obtained from the peripheral regions of the maternal surface of the placenta, compared to the samples from the central region of this surface. In placental tissue the mean expression of OXTR in group I was significantly (p < 0.05) increased by approximately 3.2-fold and 3.45-fold (the samples collected from central and peripheral regions, respectively) compared to the values obtained in group II. In the isolated primary trophoblast cultures the differences were even more evident (p < 0.02) and the mean change in OXTR expression in group I comprised approximately 6.9-fold increase and 6.5-fold increase (the samples collected from central and peripheral regions, respectively) compared to the values obtained in group II. CONCLUSIONS: Upregulation of OXTR within placental trophoblast cells localized close or adherent to uterine wall may play a crucial role in labor with efficient contractile activity (vaginal delivery). Further studies may disclose if this local OXT/OXTR signaling is utilized in the third stage of labor to elicit placental detachment or contribute in a more versatile way throughout the labor period.

Elevated levels of exhaled nitric oxide in patients with anorexia nervosa.

BACKGROUND: Nitric oxide (NO) is involved in eating behavior and inflammatory response. Moreover, there is evidence that NO production is altered in patients with anorexia nervosa (AN). AIM: To assess whether the overproduction of NO in AN can affect NO level in exhaled air. MATERIALS AND METHODS: Exhaled NO level was studied in 23 girls with AN and compared with that of healthy age- and gender-matched nonatopic controls. RESULTS: Exhaled NO levels were significantly higher in girls with AN compared with healthy age-matched controls. CONCLUSIONS: It appears that anorexia nervosa was accompanied by a higher level of exhaled NO, likely resulting from a systemic increase in NO production because of the severe catabolic state.

Comparison of prenatal and postnatal treatments of spina bifida in Poland--a non-randomized, single-center study.

OBJECTIVE: The aim of this study was a comparison of the outcomes of intrauterine myelomeningocele (MMC) repairs (IUMR) in type II Chiari malformation (II CM) fetuses with clinical data of newborns and infants operated on postnatally. METHODS: The study group (SG) comprised 46 pregnant women whose type II CM children underwent IUMR, while 47 pregnant women whose type II CM children were operated on postnatally constituted the control group (CG). A total of 24 SG and 20 CG patients reached the endpoint of the study. RESULTS: High incidence of prelabor rupture of membranes (24 (52.2%), CI: 3.74 (1.69-8.26) (p < 0.001) was noted in the group of prenatal surgeries as compared to controls. The need for ventriculoperitoneal shunt implantation was statistically significantly lower (p < 0.008) in the group of children after IUMR as compared to controls (5 (27.8%) and 16 (80%), respectively, CI: 0.35 (0.16-0.75). None of the postnatally treated CG children can walk without adaptive equipment. In contrast, two children from the SG (2 (11.1%) CI: 1.86 (1.00-3.48) p < 0.05) are able to walk independently. CONCLUSIONS: Prenatal MMC closure significantly lowers further adverse evolution of the II CM. Further studies are needed, especially on preventive measures for preterm labor and iatrogenic preterm prelabor rupture of membranes (iPPRM) in the postoperative course of IUMR.

[Prenatal MRI as a method of controlling fetal pathology]. / Prenatalne badanie MR jako metoda kontroli patologii plodu.

BACKGROUND: It has been shown that MRI offers the possibility of more detailed assessment of fetal pathology than sonography. It is used not only to diagnose but also to follow up some prenatal diseases. It is a basis of in utero treatment and the tool of monitoring its efficacy The purpose of the study was to present the authors' experience with prenatal MRI as a method of follow-up of fetal pathology and of monitoring invasive fetal therapy MATERIAL AND METHODS: The study group consisted of 31 fetuses that underwent two MRI examinations. The first exams were performed at the gestational age of 19-28 weeks (mean: 23.6 weeks), the follow-up between week 20 and 37 (mean: 30.5). The MRI examinations were performed using 1.5 T scanners. SSFSE/T2-weighted images, TSE/ or GRE/T1-weighted images, DWI, FIESTA, EPIGRE were performed. RESULTS: In 5 cases MRI allowed to exclude a suspected pathology: brain anomaly in a healthy fetus, septo-optic dysplasia in a healthy fetus, right-sided CDH in case of a left-sided pathology pentalogy of Cantrell, lack of bladder in a fetus with a small, thick-walled bladder In 4 cases an additional pathology was detected on MRI: CCAM/ pulmonary sequestration with self-regression, cerebellar hypoplasia, rhombencephalosynapsis, tethered cord with syringohydromyelia. In 4 cases MRI was used just to follow-up and showed evolution of the disease in 2 cases: regression of intracerebral hemorrhage, progression of kidney disease. Finally, in 18 cases MRI was performed before and after an open fetal surgery of myelomeningocele showing good outcome in 10 cases and a wide spectrum of complications in 8 neonates: from edema of the transplant only in 4 to recurrent MC in 1. CONCLUSIONS: Maternal uterus constitutes a natural "incubator" for the fetus--it is easier and safer to perform diagnostic procedure in utero than in a seriously ill newborn. MRI is a method of choice in the diagnosis and of follow-up in cases of open fetal surgery.

Three pregnancies in a Marfan syndrome patient after a mitral and tricuspid valve surgery.

Marfan syndrome is an autosomal dominant disorder of connective tissue with up to 25% of cases related to a spontaneous mutation. It has been associated with perinatal loss, preterm labor and, potentially a rupture of the maternal aortic arch. We present a case of a woman diagnosed with Marfan syndrome after a miscarriage of her first pregnancy. At the time of diagnosis she had mild aortic bulb dilation and insufficiency of the mitral and tricuspid valves. She underwent cardiosurgical correction, after which she had two uneventful pregnancies. This case suggests that preconceptional correction of valve defects in women with Marfan syndrome may decrease the risk of cardiac decompensation during future pregnancies. Additionally close clinical follow up and the appropriate use of beta-adrenergic blockade may decrease the risk of aortic rupture, a significant risk factor for mortality in pregnant women.

[Total pelvic exenteration in vaginal cancer--case report]. / Calkowite wytrzewienie narzadów miednicy mniejszej z powodu raka pochwy--opis przypadku.

Vaginal cancer is a rare neoplasm and in about 65% to 90% of cases it is a metastatic one. It is diagnosed in women aged from 60 to 70 years, but it can also appear in younger patients. Squamous cell carcinoma is the most frequently found histopathological type. Risk factors for the development of vaginal cancer are thought to be similar to those of cervical cancer. We present a case of a 52-year old woman with vaginal cancer treated with brachytherapy. Due to neoplasm recurrence, additional examinations were performed in the course of one year. The patient was qualified for total pelvic exenteration. A leakage from the abdominal wound was observed post operatively. It was successfully noninvasively treated. In 3 months time she was hospitalized because of the superficial abdominal abscess which was located next to the left ureterostomy. The patient undergoes regular gynecological, surgical and urological control examinations. So far the results do not show any recurrence of the neoplastic process. Total pelvic exenteration should be considered in selected groups of patients.

[Endometrial cancer in a 25-year-old patient. Case study]. / Rak blony sluzowej macicy u 25-letniej pacjentki. Opis przypadku.

Endometrial cancer is one of the most frequently diagnosed malignant neoplasms among women. In Poland, it is in the fourth place in terms of incidence. The highest morbidity concerns women aged 50-70 years, however it may also appear in women in their reproductive period. Endometrial cancer concerns about 3% of premenopausal women. We present a case of a 25-year-old patient who underwent endometrial curettage because of irregular menstrual bleeding for the last 5 months. Histopathology revealed endometrial cancer. We attempted to apply a conservative treatment. During the next 6 months the patient was treated with lynestrenol. After one month of hormonal therapy endometrial curettage was repeated. In histopathology endometrial tissues corresponding to the hormonal treatment were found. After 6 months of treatment hysteroscopy with endometrial biopsy followed by endometrial curettage, were performed. Hormonal treatment resulted in disease regression. About 5 months after successful treatment the patient conceived spontaneously. One year after she gave birth to her first child, she conceived spontaneously once more. Both children were born vaginally. In selected cases of atypical hyperplasia and early endometrial cancer in young women the attempt of hormonal treatment is acceptable.