Oesophageal atresia: sonographic signs may prenatally predict surgical complexity.

OBJECTIVE: Oesophageal atresia (OA) is a major anomaly of varying severity. The complexity of surgical correction highly depends on the gap length of missing oesophagus and the presence of a distal fistula. The aim of this study was to identify antenatal sonographic findings associated with presence of a distal fistula and type of surgical repair METHODS: Prenatal medical records of neonates postnatally diagnosed with OA were reviewed. Sonographic signs of OA (small/absent stomach, polyhydramnios, oesophageal pouch) and the trimester at sign detection were recorded and compared between (1) OA with and without a distal fistula and (2) early one-step versus delayed two-step anastomosis. Multivariate analysis was performed. RESULTS: Overall, 80 cases of OA were included. Absence of a distal fistula was significantly associated with higher rates of small/absent stomach (100% vs 28.6%, P<0.0001), oesophageal pouch (100% vs 24.3%, P<0.0001) and severe polyhydramnios (66.7% vs 22.9%, P=0.006), compared with OA with a distal fistula.Cases requiring a delayed two-step repair had higher rates of small/absent stomach (84.2% vs 16.7%, P>0.0001), severe polyhydramnios (47.4% vs 16.7%, P=0.008) and oesophageal pouch (73.7% vs 18.5%, P<0.0001), compared with those corrected in an early one-step anastomosis.Multivariate logistic regression found small/absent stomach and pouch to be significantly and independently associated with a delayed two-step anastomosis. CONCLUSION: OA without a distal fistula is associated with higher rates of prenatal sonographic signs. Both small/absent stomach and a pouch are independently associated with a delayed two-step anastomosis. These findings may help improve antenatal parental counselling regarding the anticipated surgical repair.

Do Serial Sonographic Assessments of Fetuses with Isolated Congenital Diaphragmatic Hernia Help Us Predict Survival?

OBJECTIVE: The aim of this study was to assess the ability of serial prenatal sonographic measurements, and specifically changes in the observed-to-expected lung-to-head ratio (O/E LHR) throughout gestation and to predict survival in congenital diaphragmatic hernia (CDH). METHODS: Retrospective study of CDH fetuses evaluated prenatally and treated postnatally in a single tertiary center, 2008-2020. Sonographic evaluations included side of herniation, liver involvement, and O/E LHR. All data were calculated to assess ability to predict survival. RESULTS: Overall, 94 fetuses were evaluated prenatally and delivered in our medical center. Among them, 75 had isolated CDH and 19 nonisolated. CDH was categorized as left (n = 76; 80.8%), right (n = 16; 17.0%), or bilateral (n = 2; 2.2%). Overall perinatal survival rate was 57% for all live-born infants, 68% in isolated CDH, and 40% in nonisolated (excluding 2 cases that underwent fetoscopic endoluminal tracheal occlusion and did not survive). The O/E LHR was lower in cases with perinatal death compared to survivors. In cases with multiple evaluations, the minimal O/E LHR was the most accurate predictor of survival and need for perinatal extracorporeal membrane oxygenation (ECMO) support. This remained significant when excluding twin pregnancies or when evaluating only isolated left CDH. In addition to disease severity, the side of herniation and liver position was associated with preoperative mortality. CONCLUSION: O/E LHR is associated with perinatal survival. In cases with multiple evaluations, the minimal O/E LHR is the most accurate and significant predictor of perinatal mortality and need for ECMO support.

In Vivo Expansion of Cancer Stemness Affords Novel Cancer Stem Cell Targets: Malignant Rhabdoid Tumor as an Example.

Cancer stem cell (CSC) identification relies on transplantation assays of cell subpopulations sorted from fresh tumor samples. Here, we attempt to bypass limitations of abundant tumor source and predetermined immune selection by in vivo propagating patient-derived xenografts (PDX) from human malignant rhabdoid tumor (MRT), a rare and lethal pediatric neoplasm, to an advanced state in which most cells behave as CSCs. Stemness is then probed by comparative transcriptomics of serial PDXs generating a gene signature of epithelial to mesenchymal transition, invasion/motility, metastasis, and self-renewal, pinpointing putative MRT CSC markers. The relevance of these putative CSC molecules is analyzed by sorting tumorigenic fractions from early-passaged PDX according to one such molecule, deciphering expression in archived primary tumors, and testing the effects of CSC molecule inhibition on MRT growth. Using this platform, we identify ALDH1 and lysyl oxidase (LOX) as relevant targets and provide a larger framework for target and drug discovery in rare pediatric cancers.

Infants Born with Esophageal Atresia with or without Tracheo-Esophageal Fistula: Short- and Long-Term Outcomes.

BACKGROUND: The estimated incidence of esophageal atresia (EA) with or without tracheo-esophageal fistula (TEF) is 1:3500 live births. During childhood these patients have various co-morbidities, but the overall quality of life among adults is similar to that of the general population. OBJECTIVES: To evaluate short- and long-term co-morbidities and quality of life among infants born with EA ± TEF at a large single medical center. METHODS: Medical records of 65 children born over a 21 year period were reviewed for short- and long-term medical data. Telephone interviews were conducted with 46 of their parents regarding medical problems and quality of life after home discharge. RESULTS: The main long-term co-morbidities during the first 2 years of life, 4-6 years of age, and during adolescence (12-16 years) included gastro-esophageal reflux disease (GERD) in 56.5%, 35.8%, and 18.7%, respectively; stridor in 84.8%, 45.2%, and 12.5%, respectively; hyper-reactive airway disease (HRAD) in 43.5%, 35.5%, and 36.5%, respectively; recurrent pneumonia in 43.5%, 32.3%, and 18.8%, respectively; and overall recurrent hospitalizations in 87%, 41.9%, and 25%, respectively. The quality of life was reportedly affected among 100%, 75%, and 33.3% respectively. CONCLUSIONS: Long-term follow-up of patients with EA ± TEF indicates a high burden of co-morbidities during the first 6 years of life, with a gradual decrease in symptoms thereafter. Nevertheless, HRAD continued to impact the daily life of about one-third of the older adolescents, and GERD one-fifth. A long-term multidisciplinary follow-up should be conducted to prevent late onset complications that may affect the quality of life.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for disseminated intra-abdominal malignancies in children-a single-institution experience.

PURPOSE: Our purpose was to present our institutional experience with performing complete cytoreduction surgery and heated intraoperative chemotherapy (CRS-HIPEC) for children with disseminated intraabdominal malignancies, guided by a leading international center performing CRS-HIPEC in children. METHODS: Retrospective chart review of all cases of CRS-HIPEC in children in our institution, examining diagnosis, preoperative management, operative management, postoperative treatment, short term outcome including length of stay and complications, and long term outcome including survival and recurrence of disease. RESULTS: 9 children underwent CRS-HIPEC over 48months. The mean age of the patients was 8years. Tumors were: rhabdomyosarcoma (RMS), mesothelioma, Sertoli-Leydig, desmoplastic small round cell tumor, colon carcinoma and Wilms' tumor. Most patients received intraperitoneal cisplatin. Short term outcome was very good with median length of hospital stay of 13days and low rate of complications. Seven patients were alive at last follow up. Five patients developed a recurrent disease. Recurrence was intraabdominal in two of these patients. CONCLUSIONS: CRS-HIPEC for children with disseminated intraabdominal malignancies performed in a dedicated institution and with guidance by a leading international center can be performed safely. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: IV.

Minimal incision as a promising technique for resection of pilonidal sinus in children.

PURPOSE: To evaluate functional and long-term outcome of a minimal incision technique for resection of pilonidal sinus in children. PATIENTS AND METHODS: All children who underwent surgery for pilonidal sinus in our institution between October 2008 and March 2015 were included. We performed a retrospective chart review and a follow-up telephone survey. Demographic, clinical and outcome data were compared between patients who underwent either minimal incision or wide excision surgery. RESULTS: Study groups included 21 cases of minimal incision procedure and 21 cases of wide excision procedure with similar demographic and clinical characteristics. Postoperative functional outcome was significantly better in the minimal incision group with fewer days on analgesics (0 versus 2.5, P=0.005), fewer sick days (4 versus 14, P<0.001), and fewer days to full activity (10 versus 45, P<0.001). Reoperation rate was 28% for minimal incision and 9% for wide excision (P=0.238). Overall long-term favorable outcome (no reoperation/recurrent abscess/continued symptoms) rate was 62% after minimal incision and 45% after wide excision (P=0.354). CONCLUSION: The minimal incision is a promising technique for resection of pilonidal sinus in children as it is associated with better postoperative functional outcome and comparable long-term outcome compared with wide excision. LEVEL OF EVIDENCE: Therapeutic study- level III.

Nonobstructive Diffuse Dilated Bowel Loops: Prenatal Diagnosis, Fetal Characteristics and Neonatal Outcomes.

OBJECTIVES: The purpose of this study was to describe the characteristics and outcomes of fetuses with a diagnosis of nonobstructive diffuse dilated bowel loops. METHODS: We conducted a retrospective study of all pregnancies with fetal diagnosis of nonobstructive diffuse dilated bowel loops over 14 years in a large tertiary referral center. Fetomaternal and neonatal characteristics and outcomes were assessed. RESULTS: Seven fetuses had sonograms showing diffuse dilated bowel loops; none of them had intestinal obstruction after labor. The median gestational age at diagnosis was 33 weeks 1 day (range, 27 weeks-34 weeks 1 day). The median gestational age at delivery was 34 weeks 1 day (range, 32 weeks 4 days-39 weeks 1 day). Four cases had premature rupture of membranes beyond 32 weeks. Four among the 7 had gastrointestinal manifestations. Three cases presented with hematochezia, which resolved with conservative treatment. One fetus had intractable diarrhea, had a diagnosis of rare microvillus inclusion disease, and died of sepsis after 92 days. Not a single case of Hirschsprung disease was observed in our group. CONCLUSIONS: Nonobstructive diffuse dilated bowel loops diagnosed in the second half of pregnancy are associated with premature rupture of membranes and premature labor. As neonatal gastrointestinal complications may be anticipated, prenatal parental counseling with a neonatologist and pediatric gastroenterologist should be conducted.

A case series of congenital hepatic hilar cyst: recommendations for diagnosis and management.

BACKGROUND: Congenital hepatic hilar cysts are rare. Some are simple and do not require intervention, but some biliary cystic malformations impose the risk of morbidity and mortality. OBJECTIVES: To assess a series of five patients presenting with congenital hepatic hilar cysts. METHODS: We retrospectively reviewed all cases presenting to our pediatric surgical service between January 2010 and December 2012 and found to have a congenital hepatic hilar cyst. Data regarding clinical, radiological, operative and pathological features were analyzed. RESULTS: Five children with congenital cyst of the hepatic hilum were identified; four of them were diagnosed prenatally. Four children had undergone surgical intervention: one with intrahepatic choledochal cyst, one with epidermoid cyst, and two with biliary atresia and an associated cyst of the common bile duct. In another case of choledochal cyst the treatment was conservative. All children except one had a good prognosis; one child with biliary atresia required liver transplantation. CONCLUSIONS: The differential diagnosis of congenital hepatic hilar cyst includes a broad spectrum of pathologies. It is essential to diagnose biliary atresia as early as possible. Signs such as smaller cysts in association with a hypoplastic gallbladder and direct hyperbilirubinemia may be suggestive of biliary atresia.

Do immunocompromised children benefit from having surgical lung biopsy performed?

BACKGROUND: Surgical lung biopsy is considered a gold standard for the evaluation of pulmonary disease in immunocompromised children. However, in the literature, its accuracy and the rate of complications vary. OBJECTIVE: We aimed to evaluate the yield of surgical lung biopsies in the management of persistent pulmonary findings in immunocompromised children. METHODS: We performed a retrospective review of clinical records of immunocompromised children who underwent surgical lung biopsies, and evaluated the impact that preoperative factors had on outcomes. RESULTS: Twenty-five patients underwent 27 surgical lung biopsies. The underlying immunodeficiency included allogeneic stem cell transplantation (n = 12), chemotherapy for solid tumors (n = 6), hematologic malignancy (n = 4), primary immunodeficiency (n = 4) and chronic steroid use (n = 1). Biopsies provided a specific histopathologic or microbiologic diagnosis in 10 cases (37%). No preoperative factor predicted a diagnostic biopsy. Five of the 27 biopsies were beneficial for the patients (18%). A major complication related to the procedure was reported for 1 biopsy (4%). CONCLUSIONS: We conclude that surgical lung biopsy in pediatric immunocompromised patients appears to be safe, but has a relatively low diagnostic yield and an even lower yield with regards to the benefit it provides.

More than a gut feeling - sonographic prenatal diagnosis of imperforate anus in a high-risk population.

OBJECTIVES: The objective of this article is to investigate whether sonographic identification of the fetal anal mucosa (AM) can assist in the diagnosis of anal atresia (AA) in fetuses referred for congenital anomalies of kidney and urinary tract (CAKUT) malformation. METHODS: During a 3-year study period, 245 fetuses referred for CAKUT were prospectively examined for the presence of the AM on an axial trans-perineal view. The prenatal findings were confirmed clinically. RESULTS: The AM was identified in all but two fetuses. The diagnosis of AA was confirmed clinically. In two additional cases, the babies were born with imperforated anus. In the first case, the AM was identified prenatally. The baby was born with a thin membrane covering the anal pit, which was easily penetrated revealing a patent anal canal. The second case was a false-negative, in which the echogenic ischial tuberosity was falsely mistaken for the AM. None of the cases earlier had bowel dilatation or enterolithiasis. Overall, the incidence of AA in our group was 30-fold relative to the general population (1.2% vs 0.04%). CONCLUSIONS: In a CAKUT population, absence of the AM in the posterior perineal triangle in the axial trans-perineal view emerges as an important sonographic marker for prenatal diagnosis of AA.

Umbilical cord hernias: prenatal diagnosis and natural history.

OBJECTIVES: The purpose of this study was to describe the characteristics and outcomes of umbilical cord hernias diagnosed prenatally. METHODS: We conducted a retrospective study of all pregnancies with the diagnosis of a fetal umbilical cord hernia during a 5-year period. All women received care from a multidisciplinary team and underwent complete meticulous sonography for structural malformations as well as fetal echocardiography and amniocentesis. RESULTS: Between 2004 and 2009, isolated fetal umbilical cord hernias were diagnosed in 8 pregnant women. The gestational ages at the time of referral ranged from 16 to 28 weeks (median, 20 weeks). In 1 case, intrauterine fetal death occurred at 35 weeks due to rupture of the umbilical cord. All remaining cases were delivered at 36 to 40 weeks, and the neonates underwent corrective surgery with good outcomes. CONCLUSIONS: Despite 1 case complicated by intrauterine fetal death in this study, the outcome of an isolated fetal umbilical hernia seems favorable.

Congenital diaphragmatic hernia: 22 years experience in a single tertiary medical center.

BACKGROUND: Over the last two decades, the epidemiology, treatment strategy and mortality rate for congenital diaphragmatic hernia have changed. OBJECTIVES: To retrospectively analyze our experience with CDH of the last 22 years. METHODS: We reviewed the charts of all infants suffering from CDH between 1985 and 2007. Prenatal and maternal as well as perinatal and neonatal data were collected, including outcome parameters. The 71 infants that we identified were divided into two historical groups: from 1985 to 1995 (group 1, 23 patients) and from 1996 to 2007 (group 2, 45 patients). RESULTS: There was an increase in the incidence of prenatal diagnosis and a subsequent significant decrease in gestational age at diagnosis in group 2 (25 weeks gestation, compared with 30 weeks gestation in group 1, P = 0.018). In addition, we noted a trend toward a reduced number of infants with right-sided hernia and associated cardiac anomalies. The timing to post-delivery surgery was significantly longer in group 2 (20 hours in group 1 vs. 53 hours in group 2, P < 0.001). A significant reduction in postoperative mortality was demonstrated in group 2 compared with group 1 (13.5% vs. 38.7% respectively, P = 0.04), CONCLUSION: Our data suggest a higher survival rate for operated infants in group 2 during the last decade, probably due to changes in preoperative methods of treatment as well as later surgery timing compared to group 1. We speculate that today's cases of congenital diaphragmatic hernia are probably milder than in the past due to earlier and more detailed prenatal diagnosis and subsequent termination of pregnancies for the more severe forms of the disorder.

Torsion of the cryptorchid testis--can it be salvaged?

PURPOSE: The literature concerning undescended testis mainly concentrates on the increased risks of infertility and development of germ cell tumors. Yet the UDT also appears to be at higher risk for torsion compared to the normally descended testis, and this issue is relatively poorly addressed. We reviewed all cases of torsion of UDTs operated on at our hospital during the last 20 years in an attempt to characterize better this condition and its salvageability. MATERIALS AND METHODS: In this retrospective clinical study we reviewed and analyzed all cases of testicular torsion involving UDT operated on at our hospital between 1984 and 2004. RESULTS: A total of 11 children were operated on at our hospital for torsion of undescended testis between 1984 and 2004. Patient age ranged from 1 month to 18 years (median 7.5 months). In all cases unilateral torsion of undescended testis was diagnosed, with 73% of cases involving the left side. Clinical symptoms included inguinal swelling and erythema associated with a tender, firm mass palpated in the groin area and an empty ipsilateral hemiscrotum. Doppler ultrasound examination was routinely performed in the last 7 patients to confirm the diagnosis. During inguinoscrotal exploration severe ischemia or overt necrosis of the testis was found in 5 of 11 cases. Three of these 5 cases were managed by orchiectomy, while in the other 2 cases the testis subsequently vanished. In the 6 patients who exhibited some improvement following detorsion and warming of the tissue the testes were preserved and orchiopexy was performed. Followup was available in only 5 patients, with vanishing of the torsed testis observed in 4 and a normal testicle detected 21 years postoperatively in 1 patient who was diagnosed early. CONCLUSIONS: This series clearly demonstrates poor rates of surgical salvage, which we mainly attribute to delays in parental response and in primary physician referral to the hospital. Parents, who have a pivotal role in early diagnosis, were usually unaware of this urological emergency, and some were surprisingly unaware of the presence of cryptorchidism. By increasing the awareness regarding this entity among members of the medical community and parents, we hope that torsion of the cryptorchid testis (literally, "hidden testis") will no longer necessarily be synonymous with "crypt-torsion" ("hidden torsion").

[Preoperative laboratory screening in healthy children: what is necessary?].

This study was designed to evaluate the current practice of preoperative laboratory testing in healthy children undergoing elective surgery in a single tertiary general hospital, and compare it to the guidelines published by the American and Israeli societies of pediatric anesthesia. We also evaluated the effects of a pre-designed educational program on that practice. This was a prospective, two stage study. In stage one, data was collected on the practice of the preoperative laboratory tests obtained from children scheduled for elective surgeries. We then conducted training, dedicated to criteria and indications for preoperative laboratory testing in children prior to elective surgery. Following the training, we conducted a second phase observation and data on a second group of children was collected and analyzed. Comparing the two groups of children enabled the evaluation of the benefit of the pre-designed educational program. Two hundred and forty children scheduled for elective surgery during the four months of the study period, were surveyed. In stage one, we enrolled and documented preoperative laboratory data obtained for 150 children. In stage two, we collected data on 90 children. Overall, the incidence of unnecessary laboratory tests in the preoperative period was reduced significantly (by 32.5%, p < 0.001). The incidence of non-indicated tests performed, was also reduced significantly (by 23.1%, P = 0.015). We conclude that the use of unnecessary testing of children before elective surgery is common. A training program designed to address this issue can lead to a reduction in unnecessary testing.